Preparation and characterization of corn cob activated carbon coated with nano-sized magnetite particles for the removal of Cr(VI).
Activated carbon prepared from corn cob biomass, magnetized by magnetite nanoparticles (MCCAC) was used for the adsorption of hexavalent chromium from aqueous solution. The adsorbent was characterized by SEM, TEM, XRD, VSM, surface functionality and zero-point charge. The iron oxide nanoparticles were of 50 nm sizes and the saturation magnetization value for the adsorbent is 48.43 emu/g. Adsorption was maximum at pH 2. Isotherm data were modeled using Langmuir, Freundlich and Temkin isotherm. The prepared MCCAC had a heterogeneous surface. The maximum monolayer adsorption capacity was 57.37 mg/g. Kinetic studies were carried out and the data fitted the pseudo second-order equation. The mechanism of the adsorption process was studied by incorporating the kinetic data with intraparticle diffusion model, Bangham equation and Boyd plot. The adsorption was by chemisorption and the external mass transfer was the rate-determining step. A micro column was designed and the basic column parameters were estimated.


Nondirected, Site-Selective Arylation of Quinone Imine Ketals Derived from Arylamines: One-Pot Access to meta-Substituted Anilines.
Herein, we develop a metal-free, nondirected, site-selective, one-pot approach to meta-arylation of arylamines. This Brønsted acid-catalyzed, direct C-C bond formation offers a broad substrate scope and scalability and creates the ideal conditions for overriding the conventional site-selectivity to furnish meta-substituted anilines. Additionally, the protocol applies to the meta-allylation of anilines and has been extended to afford late-stage functionalization and synthesis of medicinally privileged arylated diamines and densely functionalized anilines. The control experiments and density functional theory studies provide evidence for the proposed mechanism and selectivity.


Gliadin nanoparticles for oral administration of bioactives: Ex vivo and in vivo investigations.
This study aims to provide a thorough characterization of Brij O2-stabilized gliadin nanoparticles to be used for the potential oral administration of various compounds. Different techniques were used in order to evaluate their physico-chemical features and then in vivo studies in rats were performed for the investigation of their biodistribution and gastrointestinal transit profiles. The results showed that the gliadin nanoparticles accumulated in the mucus layer of the bowel mucosa and evidenced their ability to move along the digestive systems of the animals. The incubation of the nanosystems with Caenorhabditis elegans, used as an additional in vivo model, confirmed the intake of the particles and evidenced their presence along the entire gastrointestinal tract of these nematodes. The gliadin nanoparticles influenced neither the egg-laying activity of the worms nor their metabolism of lipids up to 10 μg/mL of nanoformulation. The systems decreased the content of the age-related lipofuscin pigment in the nematodes in a dose-dependent manner, demonstrating a certain antioxidant activity. Lastly, dihydroethidium staining showed the absence of oxidative stress upon incubation of the worms together with the formulations, confirming their safe profile. This data paves the way for the future application of the proposed nanosystems regarding the oral delivery of various bioactives.


A pH-triggered delayed-release chronotherapeutic drug delivery system of aceclofenac for effective management of early morning symptoms of rheumatoid arthritis.
Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication. The aim of the present work was to develop and optimise a pH-triggered delayed-release colon-specific aceclofenac microspheres and to accomplish chronotherapy of RA. A 3-factor, 3-level Box-Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats. The particle size and encapsulation efficacy of these microspheres were 117.36 ± 10.54 µm and 85.06 ± 5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation revealed delayed anti-inflammatory activity in carrageenan-induced rats and anti-arthritic activity in freund's adjuvant-induced arthritis rats. The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA.


Responses to photodynamic therapy in patients with polypoidal choroidal vasculopathy consisting of polyps resembling grape clusters.
To investigate the responses to photodynamic therapy (PDT) in patients with polypoidal choroidal vasculopathy (PCV) that show large aneurysmal dilation with internal angio-architecture consisting of diverse patterns of curvilinear vessels and polyps resembling grape clusters. Retrospective, interventional case series. Twenty-two eyes of 22 patients were included. All patients initially received PDT monotreatment. The main outcome measures were the rates of complete polyp regression on indocyanine green angiography and initial favorable responses observed clinically. Also, the rates of recurrent exudative changes were evaluated at the 2-year follow-up. We focused on changes in the vascular features and their clinical association. Complete regression of polypoidal lesions was observed in 21 eyes (95%) after a mean of 1.7 PDTs. However, favorable clinical responses were achieved in only 9 eyes (41%), and 6 of them had recurrent exudation. Main vessels, previously consisting of the polypoidal lesion frame, persisted. Additionally, aberrant vessels with a thin radiating or tortuous configuration were observed in the area where large aneurysmal dilation was present. Leakage from this vascular complex or an expanded vascular complex was observed in a total of 14 eyes (64%) during the 2-year follow-up, contributing to persistent (8 eyes) or recurrent (6 eyes) exudation. This seemed to represent secondary choroidal neovascularization (CNV). In another 4 eyes (18%), fibrous changes developed immediately after PDT. Polyps recurred in 8 eyes (38%). This PCV pattern frequently evolved into typical CNV after PDT, resulting in persistent or recurrent exudation despite the disappearance of polypoidal structures.


Atherosclerosis in diabetes: the role of hyperinsulinemia.
Non-insulin-dependent diabetes (NIDDM) is a major cause of premature morbidity and mortality among adults. Macrovascular disease of coronary and peripheral vessels is the primary cause of death in these patients. Numerous experimental and epidemiologic studies have suggested that hyperinsulinemia accelerates the development of atherosclerosis. In experimental models, insulin promotes diet-induced lesion development and overrides lesion regression and estrogen protection against atherosclerosis. Local hyperinsulinemia induced by selected arterial infusion accelerates atherosclerosis in the perfused artery. Insulin has been shown to stimulate subintimal smooth muscle and fibroblast cells in culture, and to increase the uptake and local synthesis of lipid by these cells. Insulin may also induce inhibition of fibrinolysis. Several prospective studies performed on nondiabetic patients show that either fasting or postprandial insulin levels are a sensitive predictor of the development of coronary disease independent of other risk factors. Two recent studies in NIDDM patients confirm this finding and suggest that glycemic control may not be a significant factor in the development of macrovascular disease. Diseases of carbohydrate tolerance, ie, NIDDM, impaired glucose tolerance, obesity, are frequently associated with elevated circulating insulin levels, either physiologically or secondary to treatment. Given the high prevalence of cardiovascular disease in these populations, modifying therapy to minimize hyperinsulinemia should be an important consideration in a treatment program. Use of oral agents such as glipizide or gliclazide, which induce less diurnal hyperinsulinemia, may be advantageous when compared to traditional oral agent or insulin therapy.


Does transient hyperprolactinemia during ovarian hyperstimulation interfere with conception or pregnancy outcome?
The significance of transiently increased serum prolactin (PRL) levels on pregnancy rates in in vitro fertilization (IVF) is unknown. The aim of this study was to evaluate PRL levels in IVF patients who conceived and in matched controls who did not. Thirty-seven IVF cycles resulting in pregnancy and 74 nonpregnant cycles were compared. Prolactin was measured before ovarian stimulation with clomiphene citrate, and human menopausal gonadotropin and estradiol (E2) and PRL were measured 8 hours after human chorionic gonadotropin (hCG) administration at midcycle. Before ovarian stimulation, serum PRL levels were not different in the pregnant and nonpregnant women (11.1 +/- 0.6 [mean +/- standard error] micrograms/l and 10.1 +/- 0.4 micrograms/l, respectively). After hCG, PRL levels were significantly higher in the pregnant women than in the nonpregnant women (20.8 +/- 1.6 and 16.0 +/- 0.9 micrograms/l, respectively; P less than 0.005) and more pregnant than nonpregnant women had elevated PRL levels (49% versus 28%, respectively; P less than 0.05). There was no correlation between PRL and E2 in either group. The abortion rate was not different between the women with elevated PRL (22.2%) and the normoprolactinemic women (31.6%). These results do not support treatment of transient hyperprolactinemia with dopamine agonists in IVF patients.


Purification and properties of phaseolamin, an inhibitor of alpha-amylase, from the kidney bean, Phaseolus vulgaris.
Kidney beans, Phaseolus vulgaris, contain a proteinaceous inhibitor of alpha-amylase, which we have named phaseolamin. The inhibitor has been purified to homogeneity by conventional protein fractionation methods involving heat treatment, dialysis, and chromatography on DEAE-cellulose, Sephadex G-100, and CM-cellulose. Phaseolamin is specific for animal alpha-amylases, having no activity towards the corresponding plant, bacterial, and fungal enzymes, or any other hydrolytic enzyme tested. Optimal inhibitory activity is expressed during preincubation of enzyme and inhibitor at pH 5.5 and 37 degrees. Substrate prevents inhibition. Measurement of the stoichiometry on inhibition showed that a 1:1 complex of alpha-amylase and inhibitor is formed. Complex formation was demonstrated by chromatography on Sephadex G-100. The phaseolamin-amylase complex is dissociated at low pH values, apparently as a result of destruction of the enzyme; the complex cannot be dissociated by other conditions unfavorable for inhibition (low temperature or high pH). Phaseolamin inhibits hog pancreatic alpha-amylase in a noncompetitive manner.


Three-dimensional evaluation of heel raise test in pediatric planovalgus feet and normal feet.
Planovalgus foot is a common pediatric deformity which may be associated with pain. To evaluate flexibility of the foot, the heel raise test is used. During this test the arch and hindfoot are assessed. Several studies have described planovalgus foot based on 3D gait and standing analysis. However, no studies have evaluated foot flexibility during heel raise using an objective 3D analysis. Therefore, the purpose of this study is to evaluate the flexibility of planovalgus feet during the heel raise test using an objective 3D assessment and to determine whether any hypotheses can be generated about potential differences between painful and painless flexible planovalgus feet and reference feet. Here, 3D foot analysis was conducted in 33 children (7 reference feet, 16 painless, and 10 painful flexible planovalgus feet) during the heel raise test. To identify the characteristics of planovalgus foot, the concept of 3D projection angles was used as introduced in the Heidelberg Foot Measurement Method (HFMM), with a modified marker set. All feet showed dynamic movements of the medial arch and hindfoot from valgus to varus position during heel raise. Reference feet had the smallest range of motion, perhaps due to joint stability and absence of foot deformity. Painful and painless flexible planovalgus feet demonstrated similar movements. No significant differences were found between the painful and painless groups. However, the kinematics of the pain group seemed to differ more from those of the reference group than did kinematics of the painless group. This assessment is a new, practical, and objective method to measure the flexibility of small children's feet.


Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels.
There is controversy in the literature on the role of the fusion TMPRSS2-ERG in the pathogenesis and progression of prostate cancer. The quantitative differences in TMPRSS2-ERG fusion expression have received very limited attention in the literature. We have quantitatively analyzed the mRNA levels of TMPRSS2-ERG, ERG, PTEN, and AR (n = 83), as well as ERG immunostaining (n = 78) in a series of prostate tumors. Among the TMPRSS2-ERG cases (n = 57), high fusion levels were associated with GS ≥8 (P = 0.025). ERG mRNA overexpression was associated with GS ≥8 (P = 0.047), and with stage T3-T4 tumors (P = 0.032). Among the ERG overexpressing cases (n = 54), higher expression levels were found in 92.3% of GS ≥8 tumors (P = 0.02). ERG immunostaining, regardless of staining intensity, was also associated with high stage (P = 0.05). There was a statistical association between ERG immunostaining and PSA progression-free survival (Log Rank test, P = 0.048). Decreased PTEN expression was associated with TMPRSS2-ERG (P = 0.01), ERG mRNA overexpression (P = 0.003) and ERG immunostaining (P = 0.007). Furthermore, decreased PTEN expression, alone (P = 0.041) and also combined with TMPRSS2-ERG (P = 0.04) or with ERG overexpression (P = 0.04) was associated with GS ≥7 tumors. Although more studies are needed to further clarify their role, our findings emphasize that the expression levels of the TMPRSS2-ERG fusion and ERG mRNA, rather than their mere presence, are related to a more aggressive phenotype, have an effect on prognosis and could be molecular markers of progression for prostate cancer. Furthermore, ERG immunohistochemistry could be also a potentially useful prognostic factor.


A palpable, obstructing carcinoma of the colon incarcerated within a large ventral hernia.
Uncovering the etiology of a bowel obstruction in a patient with a hernia represents a diagnostic dilemma. Although the hernia is often initially the presumptive cause of the bowel obstruction, obstructive carcinoma or another pathological process hidden by the hernia are important considerations. Here we describe a case of a man with an obstructing neoplasm of the colon within a large ventral hernia, whose constipation was initially attributed to incarceration of the hernia.


An efficient and simple method for measuring (226)Ra using the scintillation cell in a delayed coincidence counting system (RaDeCC).
A delayed coincidence counter (RaDeCC), developed to determine ultra-low levels of (223)Ra (half life = 11.1 days) and (224)Ra (half life = 3.6 days) in seawater, was adapted to measure (226)Ra (half life = 1622 years). After pre-concentration of Ra from seawater onto MnO(2)-coated fiber we show in this study that the (226)Ra activity can be determined using the RaDeCC's ability to record alpha decay of its daughters as total counts. For sufficient ingrowth of (222)Rn, the Mn-fiber is hermetically sealed in a column for a few days. Then, the ingrown (222)Rn is circulated through the RaDeCC air-loop system followed by shutting down of the pump and closure of the scintillation cell for equilibration. Counting may be completed within a few hours for seawater samples. Sample measurements with this method agreed well with data obtained using gamma-ray spectrometry. This proves that a set of Ra isotopes ((223)Ra, (224)Ra, and (226)Ra), commonly used for geophysical studies such as mixing rates of different water masses and submarine groundwater discharge, can be efficiently and rapidly measured using the RaDeCC.


EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.
Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.


Digital Twins for Bioprocess Control Strategy Development and Realisation.
New innovative Digital Twins can represent complex bioprocesses, including the biological, physico-chemical, and chemical reaction kinetics, as well as the mechanical and physical characteristics of the reactors and the involved peripherals. Digital Twins are an ideal tool for the rapid and cost-effective development, realisation and optimisation of control and automation strategies. They may be utilised for the development and implementation of conventional controllers (e.g. temperature, dissolved oxygen, etc.), as well as for advanced control strategies (e.g. control of substrate or metabolite concentrations, multivariable controls), and the development of complete bioprocess control. This chapter describes the requirements Digital Twins must fulfil to be used for bioprocess control strategy development, and implementation and gives an overview of research projects where Digital Twins or "early-stage" Digital Twins were used in this context. Furthermore, applications of Digital Twins for the academic education of future control and bioprocess engineers as well as for the training of future bioreactor operators will be described. Finally, a case study is presented, in which an "early-stage" Digital Twin was applied for the development of control strategies of the fed-batch cultivation of Saccharomyces cerevisiae. Development, realisation and optimisation of control strategies utilising Digital Twins.


Prostatic Artery Embolization (PAE) Using Polyethylene Glycol Microspheres: Safety and Efficacy in 81 Patients.
To evaluate the safety and efficacy of prostatic artery embolization (PAE) using polyethylene glycol microspheres (PEGM) in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH). This multicentric prospective study enrolled 81 patients who underwent PAE with 400 ± 75 µm PEGM (HydroPearl®, Terumo, Japan). Results from baseline and 1-, 3-, 6-, and 12-month follow-ups were assessed for subjective outcomes including International Prostate Symptoms Score (IPSS), Quality of life (QoL), and International Index of Erectile Function, and objective outcomes such as peak urinary flow (Qmax) and post-void residual volume (PVR). The visual analogue scale, satisfaction questionnaire, prostatic volume, and prostatic specific antigen levels were also evaluated. Complications were documented using the modified Clavien-Dindo classification. Technical success was obtained in all patients. Clinical success was achieved in 78.5% of patients. Before PAE, 54.3% of patients had an indwelling catheter which was removed in 75% of them after procedure. A statistically significant decrease was observed in IPSS and QoL from baseline to 12 months (20.14 vs 5.89; 4.8 vs 0.63, P < .01), respectively. Objective outcomes also showed a statistically significant improvement in Qmax (+ 114.9%; P < .01), achieving a maximum urinary flow of 14.2 mL/sec, and PVR (decrease 58%; P < .05) at 12 months. Minor complications (Clavien-Dindo grades I-II) occurred in 13.6% of patients, without major complications observed. PAE with PEGM is safe and effective treatment in patients with symptomatic BPH, with a significant improvement in both subjective and objective outcomes.


DNP and ATP induced alteration in disease development of Phomopsis longanae Chi-inoculated longan fruit by acting on energy status and reactive oxygen species production-scavenging system.
As compared with P. longanae-inoculated longans, DNP treatment for P. longanae-inoculated longans exhibited higher fruit disease index and pericarp browning index, lower ATP amount and energy charge level, lower activities of SOD, CAT and APX, lower amounts of AsA and GSH, lower levels of DPPH radical scavenging activity and reducing power, higher O2- generating rate and MDA amount. However, supply of ATP for P. longanae-inoculated longans showed the contrary effects. These results gave convincing evidence that DNP treatment for accelerating pericarp browning and disease development of harvested longans caused by P. longanae was due to decreases of energy production and ROS scavenging capacity, and increases of O2- accumulation and membrane lipid peroxidation. Whereas, supply of ATP for retarding pericarp browning and disease development of harvested longans caused by P. longanae was due to increases of energy production and ROS scavenging capacity, and reductions of O2- accumulation and membrane lipid peroxidation.


Dickkopf1 induces enteric neurogenesis and gliogenesis in vitro if apoptosis is evaded.
Neurogenesis in the postnatal enteric nervous system (ENS) is controversially discussed. Yet, deciphering the regenerative potential of the ENS is essential for our understanding and therapy of human enteric neuropathies. Dickkopf1 (DKK1) is a Wnt-antagonist and involved in the homeostasis of various tissues. We hypothesize that DKK1 could function as a negative regulator on the proliferation of ENS-progenitors in the postnatal gut of mice and human infants. Here, we provide evidence that DKK1 is expressed in the murine and human ENS. If applied to ENS-progenitors in vitro, DKK1 leads to an increased proliferation, however, followed by extensive apoptosis. Yet, once we block apoptosis, DKK1-stimulation markedly increases enteric neurogenesis in murine and human ENS-progenitors. Thus, DKK1 is a strong, ambivalent regulator of the ENS-progenitor cell pool in mice and humans. These results are fundamental steps to reshaping our understanding of the homeostasis of the ENS in health and disease.


Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case-case-control study.
We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.


Chitosan nanoparticles as a rice growth promoter: evaluation of biological activity.
The agriculture sector is the building block of an economy with more than 60% of the world population depending on it for livelihood. Among the many crops, rice is the most important income source. It is the staple food for more than half of the world population. In spite of its huge demand, rice production has been dwindling due to various constraints. Chitosan nanoparticles (ChNP) are an excellent choice for agricultural applications owing to its non-toxic, biodegradable nature. Chitosan is an interesting polymer and is then partially or fully deacetylated chitin. In the present study, the effectiveness of ChNP as a growth promoter in improving the yield and biological activity of rice has been analyzed. 1 mg/ml of ChNP was applied as a seed, soil, foliar and combination treatments and the growth and yield parameters were measured to understand the best mode of application. The combination treatment of seed, soil and the foliar application was found to be most efficient. The cellular uptake of ChNP was also studied to deduce the mechanism of action. The soil toxicity of ChNP was studied prior to application and was found to be non-toxic.


Immobilized smart RNA on graphene oxide nanosheets to specifically recognize and adsorb trace peptide toxins in drinking water.
The contaminations of peptide toxins in drinking water lead directly to sickness and even death in both humans and animals. A smart RNA as aptamer is covalently immobilized on graphene oxide to form a polydispersed and stable RNA-graphene oxide nanosheet. RNA-graphene oxide nanosheets can resist nuclease and natural organic matter, and specifically adsorb trace peptide toxin (microcystin-LR) in drinking water. The adsorption data fit the pseudo-second-order kinetics and the Langmuir isotherm model. The adsorption capacity of RNA-graphene oxide nanosheets decreases at extreme pH, temperature, ionic strength and natural organic matter, but it is suitable to adsorb trance pollutants in contaminated drinking water. Compared with other chemical and biological sorbents, RNA-graphene oxide nanosheets present specific and competitive adsorption, and are easily synthesized and regenerated. Aptamer (RNA) covalently immobilized on graphene oxide nanosheets is a potentially useful tool in recognizing, enriching and separating small molecules and biomacromolecules in the purification of contaminated water and the preparation of samples.


Association between glial fibrillary acidic protein, glial-derived neurotrophic factor, and fatty acid-binding protein-2 at birth in the incidence of necrotizing enterocolitis in preterm infants.
This study aimed to analyze the relationship between glial fibrillary acidic protein (GFAP), glial-derived neurotrophic factor (GDNF), and fatty acid-binding protein-2 (FABP-2) in preterm infants on the incidence of NEC. Preterm infants with a birth weight <1,500 g and gestational age <34 weeks were included in this study. Biomarker examination was performed using the umbilical vein blood at birth (first sample). Biomarker examination was repeated if the infant developed symptoms of NEC using peripheral vein blood (second sample). Infants were observed for 14 days. If NEC did not exist, a biomarker examination was performed at 14 days. This study included 30 preterm infants, nine infants experienced NEC. The values of GFAP, GDNF, and FABP-2 (median and range) in the group with NEC were higher than those in the group without NEC in both the first samples {GFAP [1.40 (0.20-6.50) vs. 0.30 (0.10-1.30) P = 0.014], GDNF [2.84 (1.05-14.11) vs. 1.56 (1.07-3.48) P = 0.050], and FABP-2 [621.70 (278.40-2,207.00) vs. 294.20 (211.40-597.50) P = 0.002]} and second samples {GFAP [2.40 (0.30-3.10) vs. 0.30 (0.10-0.60) P = 0.003], GDNF [2.99 (0.56-10.30) vs. 1.46 (0.85-2.24) P = 0.019], and FABP-2 [646.8 (179.20-1,571.00) vs. 314.90 (184.70-521.60) P = 0.040]}. In infants with NEC, the median values of GFAP [2.40 (0.30-3.10) vs. 1.40 (0.20-6.50) P = 0.767], GDNF [2.99 (0.56-10.30) vs. 2.84 (1.05-14.11) P = 0.859], and FABP-2 [646.80 (179.20-1,571.00) vs. 621.70 (278.40-2,207.00) P = 0.953] in the second sample were higher than those in the first sample. Logistic regression demonstrated that GFAP at birth (Odds Ratio [OR] = 15.629, 95% Confidence Interval [CI] = 1.697-143.906, P = 0.015) and FABP-2 levels at birth (OR = 1.008, 95% CI = 1.001-1.015, P = 0.033) were significantly associated with an increased risk of NEC. Increased GFAP, GDNF, and FABP-2 at birth are associated with NEC occurrence within two weeks of birth. These findings suggest that early-onset NEC is associated with intestinal injury that occurs during the perinatal or even prenatal period.


Comparison of cryoglobulinemia in children and adults.
Cryoglobulinemic vasculitis is a systemic vasculitis resulting from circulating immune complex deposition in the small vessels and is characterized by variable clinical features, including purpura, Raynaud's syndrome, ulcerations, arthralgia, glomerulonephritis, and peripheral neuropathy. Cryoglobulinemia can also result from hepatitis C virus (HCV) infection. The clinical spectrum and associated or underlying diseases of cryoglobulinemia in different age groups is not well understood. This study investigated the demographic, clinical, serologic features, and associated or underlying diseases in children and adult patients with cryoglobulinemia. The retrospective study included 114 patients (18 children, 96 adults) who presented with cryoglobulinemia between 2000 and 2010 at the Chang Gung Memorial Hospital. Their medical records were reviewed and serological and virologic assessments were analyzed. In this group of patients, children had a significantly higher prevalence of prolonged fever (16.7% vs. 3.13%; p=0.018), arthralgia (66.67% vs. 16.67%; p<0.001), arthritis (66.67% vs. 15.63%; p<0.001) and cutaneous involvement (77.78% vs. 50%; p=0.03) compared with adults. Both the adult and children groups had a greater frequency of hepatitis B virus (HBV) infection (20.8% and 5.6%, respectively), than HCV infection (12.5% and 0%, respectively). Children with cryoglobulinemia had a significantly higher prevalence of prolonged fever, arthralgia, arthritis and cutaneous involvement compared with adults.


Toxicological evaluation of the flavour ingredient 4-amino-5-(3-(isopropylamino)-2,2-dimethyl-3-oxopropoxy)-2-methylquinoline-3-carboxylic acid.
A toxicological evaluation of 4-amino-5-(3-(isopropylamino)-2,2-dimethyl-3-oxopropoxy)-2-methylquinoline-3-carboxylic acid(S9632; CAS 1359963-68-0), a flavour with modifying properties,was completed for the purpose of assessing its safety for use in food and beverage applications. No Phase I biotransformations of S9632 were observed in rat or human microsomes in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S9632 was not found to be mutagenic or clastogenic in vitro, and did not induce micronuclei or indicate interactions with the mitotic spindle in an in vivo mouse micronucleus assay at oral doses up to 2000 mg/kg. In subchronic oral toxicity studies in rats, the NOEL was 100 mg/kg/day (highest dose tested) for S9632 when administered as a food ad-mix for 90 consecutive days. Furthermore, S9632 demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOEL of 1000 mg/kg/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats.


Treatment of bladder cancer at the Rotterdam Radiotherapy Institute (R.R.T.I.) with special reference to bladder radium implantation and preoperative radiotherapy followed by cystectomy.
Between 1950 and 1972, a total of 2,031 cases of bladder cancer were treated in the R.R.T.I. The policy differed according to size and stage of the disease as well as to the general condition of the patient. Best results were achieved by radium implantation of solitary lesions less than 5 cms in diameter. Preoperative radiotherapy followed by cystectomy was the treatment of choice for cases of T3 category. The remaining T1 and T2 cases were treated surgically, while T4 cases were managed with external irradiation alone.


Reproducibility and repeatability of transabdominal uterine artery Doppler velocimetry between 10 and 14 weeks of gestation.
To assess the intraobserver repeatability and interobserver reproducibility of Doppler flow velocity measurements of the uterine arteries in pregnant women between 10 and 14 weeks of gestation. In this prospective study, Doppler velocimetric indices (maximum peak systolic velocity, end-diastolic velocity, peak systolic velocity/end-diastolic velocity ratio, pulsatility index and resistance index) were measured twice by the same trained observer in each uterine artery of 63 women. In 47 of these women, a second trained observer then repeated the measurements. In addition, both observers classified qualitatively the blood flow with regard to the presence or absence of an early diastolic notch. The coefficient of variation, intraclass correlation coefficients, within observer and between observers repeatability coefficient and Cohen's kappa coefficient were calculated. The best parameter in terms of repeatability and reproducibility in both uterine arteries was the resistance index with a low coefficient of variation and high intraclass correlation coefficient. The other parameters (pulsatility index, peak systolic velocity/end-diastolic velocity ratio, peak systolic velocity and end-diastolic velocity) performed poorly with high coefficients of variation on both sides. Agreement between the repeated observations (inter- and intraobserver) with regard to the presence or absence of an early diastolic notch was good. Doppler velocimetry of uterine artery blood flow is technically feasible between 10 and 14 weeks of gestation. This study demonstrates that this technique is prone to measurement errors. Quantitatively, the resistance index appears to be the most repeatable and reproducible measurement at this gestational age. Qualitative assessment of the waveform morphology also shows high levels of intra- and interobserver agreement.


Predicting Overall Survival Using Preoperative Nutritional and Inflammation Status for Colorectal Cancer.
It has been shown that nutritional status and inflammation correlate with survival in patients with various cancer types. In this study, we evaluated several kinds of nutritional and inflammation parameters in preoperative blood samples and constructed new risk model predicting survival in patients with colorectal cancer. We retrospectively examined 286 patients with stage I-III colorectal cancer who had undergone curative resection at Teikyo University Hospital. The association between overall survival (OS) and nutritional status and inflammation factors were examined using Kaplan-Meier curves and log-rank tests. Serum albumin, cholesterol and C-reactive protein concentration, neutrophil count and platelet count were shown to be correlated with OS. We constructed a new risk model (nutrition inflammation status, NIS) using these factors, and compared it with other nutrition and inflammation models. NIS was useful as a new model for predicting OS in patients undergoing curative resection for colorectal cancer, compared with known models.


Wide spread scars, hypertrophic scars, and keloids.
Patients with a wide scar may complain of having a "keloid," yet have a hypertrophic or a wide spread scar. The plastic surgeon should make the appropriate clinical diagnosis, because therapy varies depending on the condition present. A wide spread scar is best treated with excision and closure. A buried dermal flap may help to prevent recurrence, which is nevertheless likely to some degree. A hypertrophic scar can be distinguished from a keloid on clinical grounds. Although both may be red, nodular, and itchy, the keloid overgrows the original wound boundary and is much more likely to recur after surgical excision. Nonsurgical treatment of hypertrophic scars and keloids is similar, using repeated intralesional injections of Kenalog 40 mg per cc and sustained pressure on the lesion when possible. Surgical treatment differs for hypertrophic scars or keloids. Scar excision and closure, and selective Z-plasty, may be used in hypertrophic scars. In keloids, aggressive surgery is usually avoided, unless the lesion has a narrow pedicle. Surgery of keloids should be accompanied by intra- and postoperative Kenalog-40 injections, and on occasion by sustained pressure. Very large keloids may be resistant to medical management, and too aggressive for surgery owing to a high likelihood of recurrence. These difficult lesions serve as the impetus for continued biochemical and tissue culture research, seeking a biochemical means of control keloids.


Rational design of artificial Lewis pairs coupling with polyethylene glycol for efficient electrochemical ammonia synthesis.
Ammonia (NH3) synthesis at mild conditions by electrocatalytic nitrogen reduction (eNRR) has received more attention and has been regarded as a promising alternative to the traditional Haber-Bosch process. Lewis acid-base pairs (LPs) can chemisorb and react with nitrogen by electronic interaction, while the tuning of the microenvironment near electrode can hinder hydrogen evolution reaction (HER) thus improving the selectivity of the eNRR. Herein, the FeOOH nanorod coupled with LPs on the surface (i.e., Fe, Fe-O) was synthesized, which could effectively drive eNRR. Meanwhile, polyethylene glycol (PEG) was introduced to serve as a local non-aqueous electrolyte system to inhibit HER. The prepared FeOOH-150 catalyst achieved outstanding eNRR performance with an NH3 yield rate of 118.07 μg h-1mgcat-1 and a Faradaic efficiency of 51.4 % at -0.6 V vs. RHE in 0.1 M LiClO4 + 20 % PEG. Both the experiment and DFT calculations revealed that the interaction of PEG with Lewis base sites could optimize nitrogen adsorption configuration and activation.


Mast cell tumors in three ferrets.
Pruritic open skin lesions (5 mm diameter) on the thorax, neck, or head of 3 ferrets were diagnosed as mast cell tumors. Diagnosis of the tumors was based on histologic examination of biopsy specimens. Histologic diagnosis was necessary because the lesions had been treated as mycotic or bacterial ulcers and did not respond to conventional treatment. Excised mast cell tumors did not recur, and malignant behavior of the tumors was not observed.


A case of mesenteric panniculitis in a patient with Tangier disease.
Mesenteric panniculitis is a rare disease caused by idiopathic inflammation of adipose tissue, most commonly affecting the mesentery of the small bowel. We present a unique case of mesenteric panniculitis in a patient with Tangier disease; a rare genetic disorder caused by mutations in the ABCA1 gene, leading to deficiency of high-density lipoprotein in the blood and accumulation of cholesterol esters within various tissues. The accumulation of cholesterol esters in body tissues in patients with Tangier disease may contribute to the pathogenesis of mesenteric panniculitis; although there is limited evidence to support this hypothesis due to the rarity of concurrent disease.


Improvement of bowel dysfunction with sacral neuromodulation for refractory urge urinary incontinence.
Sacral nerve stimulation (SNS) is approved for urologic indications in the USA and, recently, fecal incontinence. This study described concomitant bowel dysfunction and improvements in bowel and urinary symptoms and quality of life (QOL) in women with refractory urge urinary incontinence (UUI) receiving SNS. Women (N = 36) with refractory UUI receiving SNS were prospectively enrolled. Surveys and exams were completed at baseline and follow-up, with symptom and QOL scores measured using validated scales (0-100, none-worst). A total 24 women were followed up at a median of 4.0 months post-implantation. Of these, 20 (83%) had bowel dysfunction, 13 (54%) used bowel medications at baseline, and 11 (45%) continued them after SNS. The mean/median urinary (54.8 to 32.6) and bowel (23.4 to 14.1) symptom scores improved significantly, as did urinary (64.2 to 14.3) but not bowel (2.4 to 0.0) QOL scores. Bowel dysfunction is common in women with refractory UUI. SNS improves urinary symptoms and QOL, but improvement in bowel symptoms does not translate into significant QOL changes.


Increased risk for complications following removal of hardware in patients with liver disease, pilon or pelvic fractures: A regression analysis.
Indications for removing orthopedic hardware on an elective basis varies widely. Although viewed as a relatively benign procedure, there is a lack of data regarding overall complication rates after fracture fixation. The purpose of this study is to determine the overall short-term complication rate for elective removal of orthopedic hardware after fracture fixation and to identify associated risk factors. Adult patients indicated for elective hardware removal after fracture fixation between July 2012 and July 2016 were screened for inclusion. Inclusion criteria included patients with hardware related pain and/or impaired cosmesis with complete medical and radiographic records and at least 3-month follow-up. Exclusion criteria were those patients indicated for hardware removal for a diagnosis of malunion, non-union, and/or infection. Data collected included patient age, gender, anatomic location of hardware removed, body mass index, ASA score, and comorbidities. Overall complications, as well as complications requiring revision surgery were recorded. Statistical analysis was performed with SPSS 20.0, and included univariate and multivariate regression analysis. 391 patients (418 procedures) were included for analysis. Overall complication rates were 8.4%, with a 3.6% revision surgery rate. Univariate regression analysis revealed that patients who had liver disease were at significant risk for complication (p=0.001) and revision surgery (p=0.036). Multivariate regression analysis showed that: 1) patients who had liver disease were at significant risk of overall complication (p=0.001) and revision surgery (p=0.039); 2) Removal of hardware following fixation for a pilon had significantly increased risk for complication (p=0.012), but not revision surgery (p=0.43); and 3) Removal of hardware for pelvic fixation had a significantly increased risk for revision surgery (p=0.017). Removal of hardware following fracture fixation is not a risk-free procedure. Patients with liver disease are at increased risk for complications, including increased risk for needing revision surgery following hardware removal. Patients having hardware removed following fixation for pilon fractures also are at increased risk for complication, although they may not require a return trip to the operating room. Finally, removal of pelvic hardware is associated with a higher return to the operating room.


Flat adenoma and flat mucosal carcinoma (IIb type)--a new precursor of colorectal carcinoma? Report of two cases.
Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence."


Simultaneous determination of retinoic acid and hydroquinone in skin ointment using spectrophotometric technique (ratio difference method).
An innovative spectrophotometric method was developed for simultaneous determination of compounds with interfering spectra in binary mixtures without previous separation, showing significant advantages over the conventional methods regarding minimal data manipulation and applicability. The proposed method was applied for the determination of retinoic acid and hydroquinone in laboratory-prepared mixtures with mean percentage recoveries 100.13 ± 0.31 and 99.99 ± 0.04, respectively, and in their pharmaceutical formulation with mean percentage recoveries 100.13 ± 0.86 and 100.07 ± 0.58, respectively. The method was validated according to USP guidelines and can be applied for routine quality control testing.


The more developmental assets, the less internet gaming disorder? Testing the cumulative effect and longitudinal mechanism during the COVID-19 pandemic.
The COVID-19 pandemic has triggered the dramatical development and prosperity of online games, while worldwide people are suffering from it. Considering the high prevalence, serious impacts, and huge development potential of internet gaming disorder (IGD), it is extremely necessary to develop a protective model to prevent and intervene with it among young people. Based on the developmental assets theory, the present study adopted a two-wave longitudinal design to evaluate the cumulative effects of developmental assets on IGD, as well as the underlying mechanisms during this specific period. Data were collected from a sample of 1023 adolescents in Hubei province, Central China through self-report questionnaires. The results indicated that (1) developmental assets were negatively associated with adolescents' IGD concurrently and longitudinally; (2) the overall developmental assets had cumulative effects in linear patterns on adolescents' IGD, concurrently and longitudinally; and (3) internal developmental assets mediated the relationship between external developmental assets and adolescents' IGD longitudinally. Theoretically, the present study supports the developmental assets theory and expands the literature about developmental assets and IGD in younger generations. Practically, the present study provides guidance for prevention and intervention of IGD among adolescents during and after the COVID-19 pandemic. Comprehensive measures should be taken to assist in developing positive internal and external resources to promote youth thriving.


Association of Ankle Dorsiflexion and Landing Forces in Jumping Athletes.
Dorsiflexion range of motion restriction has been associated with patellar tendinopathy, but the mechanisms of how dorsiflexion restriction could contribute to knee overload remain unknown. Peak ankle dorsiflexion and ankle dorsiflexion excursion are negatively associated with peak vertical ground-reaction force (vGRF) and loading rate, and with peak patellar tendon force and loading rate, and positively associated with peak ankle plantar flexor moment. Cross-sectional study. Level 4. Kinematic and kinetic data of 26 healthy recreational jumping athletes were measured during a single-leg drop vertical jump. Pearson's correlation coefficients were calculated to establish the association between peak ankle dorsiflexion and ankle dorsiflexion excursion with peak vGRF and vGRF loading rate, with peak patellar tendon force and patellar tendon force loading rate, and with peak ankle plantar flexor moment. Ankle dorsiflexion excursion negatively correlated with peak vGRF loading rate (r = -0.49; P = 0.011) and positively correlated with peak ankle flexor plantar moment (r = 0.52; P = 0.006). In addition, there was a positive correlation between peak ankle dorsiflexion and peak vGRF (r = 0.39; P = 0.05). Ankle kinematics are associated with vGRF loading rate, ankle flexor plantar moment and peak vGRF influencing knee loads, but no association was observed between ankle kinematics and patellar tendon loads. These results suggest that increasing ankle dorsiflexion excursion may be an important strategy to reduce lower limb loads during landings but should not be viewed as the main factor for reducing patellar tendon force.


Quantitative magnetic resonance imaging for evaluating of the cerebrospinal fluid kinetics with 17O-labeled water tracer: A preliminary report.
The aim of this study was to evaluate the feasibility of kinetic analysis of cerebrospinal fluid (CSF) using 17O-labeled water tracer. Four subjects (two idiopathic normal pressure hydrocephalus (iNPH) and two possible AD dementia patients) were prospectively included. Injectable formulation of 17O-labeled water containing 10 mol% of H217O (PSO17), was intrathecally administered to the subjects with the lateral decubitus position between the 3rd and 4th lumbar vertebrae. MRI acquisitions were performed in four-time points, before PSO17 administration, 1, 8, and 24 h after PSO17 administration. The 3-dimensional fast spin echo sequence was used. After image registration for all four-time points data, polygonal regions of interest (ROIs) were set in the 14 regions to obtain the signal intensity of CSF. Each signal intensity within the ROI was converted to 17O concentration [%]. The peak concentration at one hour after administration, the slope of concentration changes after PSO17 administration [%/s], and the root mean square error (RMSE) for evaluating the performance of a fitting were calculated. There was no significant difference in peak concentration between the iNPH and AD group. The slope in the AD group (-2.25 ± 1.62 × 10-3 [%/h]) was significantly smaller than in the iNPH group (-1.21 ± 2.31 × 10-3 [%/h]), which suggests the speed of CSF clearance in the iNPH group was slower than AD group. The RMSE indicating the fit to the concentration change in the AD group (4.86 ± 4.74 × 10-3) was also significantly smaller than in the iNPH group (8.64 ± 7.56 × 10-3). The kinetic evaluation of CSF using 17O-labeled water was feasible, and this preliminary study suggests that the differentiation of iNPH and possible AD dementia can be achieved using this method.


[Drug-induced eosinophilic pneumonia].
Eosinophilic pneumonia is a lung disorder characterized by eosinophilic pulmonary infiltration and blood eosinophilia. It can be caused by a variety of drugs. Especially in mild forms and in chronically neurologically ill patients, it can be difficult to spot. We report the case of a 46-year-old woman suffering from multiple sclerosis who developed nitrofurantoin-induced eosinophilic pneumonia.


Spatiotemporal distribution and environmental control factors of halocarbons in the Yangtze River Estuary and its adjacent marine area during autumn and spring.
The oceanic production and release of volatile halocarbons (VHCs) to the atmosphere play a vital role in regulating the global climate. In this study, seasonal and spatial variations in VHCs, including trichlorofluoromethane (CFC-11), methyl iodide (CH3I), dibromomethane (CH2Br2), and bromoform (CHBr3), and environmental parameters affecting their concentrations were characterized in the atmosphere and seawater of the Yangtze River Estuary and its adjacent marine area during two cruises from October 17 to October 26, 2019 and from May 12 to May 25, 2020. Significant seasonal variations were observed in the atmosphere and seawater because of seasonal differences in the prevalent monsoon, water mass (Yangtze River Diluted Water), and biogenic production. VHCs concentrations were positively correlated with Chl-a concentrations in the surface water during autumn. The average sea-to-air fluxes of CH3I, CH2Br2, and CHBr3 in autumn were 19.7, 4.0, and 7.6 nmol m-2 d-1, respectively, while those in spring were 6.3, 6.4, and -3.6 nmol m-2 d-1. In the ship-based incubation experiments, ocean acidification and dust deposition had no significant effects on VHCs concentrations. The concentrations of CH2Br2 and CHBr3 were significantly positively correlated with phytoplankton biomass under lower pH condition (M3: pH 7.9). This result indicated that CH2Br2 and CHBr3 concentrations were mainly related to the biological release.


Does Adolescent Alcohol Harm Minimization Policy Exposure Reduce Adult Alcohol Problems? A Cross-National Comparison.
Adolescent alcohol use carries risks for problem behaviors, such as injury and school dropout, as well as increases the risk of alcohol dependence later on, making public health approaches that curb youth alcohol use a key concern. The present study uses a two-state comparison of alcohol-related policies in Victoria, Australia and Washington State, U.S. (harm minimization in Australia and zero tolerance in the U.S.) to examine whether youth alcohol use in each state is related to alcohol-related problems in young adulthood. Data were drawn from the International Youth Development Study (N = 1,965) that followed youth in Victoria and Washington states from age 13 years, with follow-up at ages 14 and 15 years, and then again at age 25 years. Multiple-group structural equation modeling was used to test whether early alcohol use was equally related to alcohol problems (measured by the Alcohol Use Disorder Identification Test) at age 25 years and whether the relationship was moderated by family and school environments that were tolerant of youth drinking and by gender. Youth in Victoria reported greater rates of alcohol use compared with youth in Washington, as well as more permissive family and school environments. Early alcohol use was equally associated with Alcohol Use Disorder Identification Test problems at age 25 years in the two nations, and none of the moderators significantly changed the association. Results suggest that harm minimization policies adopted in Victoria are less effective at reducing alcohol problems during young adulthood compared with the stricter zero-tolerance approaches adopted in Washington State.


Impact on survival of addition of etoposide to primary chemotherapy in diffuse large B-cell lymphoma: a Swedish Lymphoma Registry study.
No randomised study in the rituximab era has been performed specifically to evaluate addition of etoposide to treatment of diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the outcome with three chemotherapy regimens (R-CHOP-21, R-CHOP-14 and R-CHOEP-14) in a population-based cohort in terms of overall survival, adjusted for clinical prognostic factors. Through the Swedish Lymphoma Registry, 3443 patients with DLBCL were identified 2007-2012. Among all patients, there was no evidence of a difference between the regimens, after adjustment for prognostic factors. However, when restricted to patients aged up to 65, R-CHOEP-14 was associated with superior outcome compared to both R-CHOP-21 (hazard ratio: 0.49, 95% confidence interval: 0.3-0.9, p = 0.028) and R-CHOP-14 (hazard ratio: 0.64, 95% confidence interval: 0.4-1.0, p = 0.06), when adjusted for prognostic factors. Results were consistent in an additional stratified analysis with patients grouped according to age and IPI-score. In conclusion, we could show that R-CHOEP-14 was associated with superior overall survival in patients with DLBCL aged up to 65 years, indicating that this may be a valid treatment option for this patient population. To further investigate which patient groups that may benefit the most from treatment intensification, R-CHOEP-14 should be compared to R-CHOP-21 in a randomised setting. Copyright © 2015 John Wiley & Sons, Ltd.


Value of multidisciplinary collaboration in acute and chronic pancreatitis.
Multidisciplinary collaboration (MDC) has been widely adopted in healthcare to optimize patient care. MDC brings several specialized healthcare providers to the table using several methods, including multidisciplinary meetings (MDMs), multidisciplinary clinics, teleconferences, and online multidisciplinary expert panels, to reach the goal of achieving the best diagnosis and treatment plan for complex diseases. Diagnosis and management of acute/chronic pancreatitis is complex which necessitates the development and utilization of MDC. The key members of pancreatitis MDM include gastroenterologists, radiologists, pathologists, hepatobiliary surgeons, chairperson, and a coordinator. After selection of admitted or referred patients, the availability of required information is reviewed, and then each case is discussed. The final diagnosis and treatment plan is confirmed by consensus, especially for complex cases that require endoscopic intervention or pancreatectomy and patients with the possibility of pancreatic adenocarcinoma. It has been shown that MDMs have improved the clinical outcome of patients with acute/chronic pancreatitis. In addition to MDM, the feasibility of multidisciplinary clinics, teleconferences, and online multidisciplinary expert panels for the management of pancreatic disorders has been investigated. Understanding structure, potential advantages, and limitations of MDC will help clinicians and healthcare systems in developing an optimized MDC to improve the management of acute/chronic pancreatitis. This narrative review summarized prior recommendations and explored the impact of MDC on clinical outcomes of patients with pancreatitis. Our recommendations offer a generalizable method that can be utilized by healthcare systems.


Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review.
Polyphenols are a class of naturally sourced compounds with widespread distribution and an extensive array of bioactivities. However, due to their complex constituents and weak absorption, a convincing explanation for their remarkable bioactivity remains elusive for a long time. In recent years, interaction with gut microbiota is hypothesized to be a reasonable explanation of the potential mechanisms for natural compounds especially polyphenols. This review aims to present a persuasive explanation for the contradiction between the limited bioavailability and the remarkable bioactivities of polyphenols by examining their interactions with gut microbiota. We assessed literatures published before April 10, 2023, from several databases, including Scopus, PubMed, Google Scholar, and Web of Science. The keywords used include "polyphenols", "gut microbiota", "short-chain fatty acids", "bile acids", "trimethylamine N-oxide", "lipopolysaccharides" "tryptophan", "dopamine", "intestinal barrier", "central nervous system", "lung", "anthocyanin", "proanthocyanidin", "baicalein", "caffeic acid", "curcumin", "epigallocatechin-3-gallate", "ferulic acid", "genistein", "kaempferol", "luteolin", "myricetin", "naringenin", "procyanidins", "protocatechuic acid", "pterostilbene", "quercetin", "resveratrol", etc. RESULTS: The review first demonstrates that polyphenols significantly alter gut microbiota diversity (α- and β-diversity) and the abundance of specific microorganisms. Polyphenols either promote or inhibit microorganisms, with various factors influencing their effects, such as dosage, treatment duration, and chemical structure of polyphenols. Furthermore, the review reveals that polyphenols regulate several gut microbiota metabolites, including short-chain fatty acids, dopamine, trimethylamine N-oxide, bile acids, and lipopolysaccharides. Polyphenols affect these metabolites by altering gut microbiota composition, modifying microbial enzyme activity, and other potential mechanisms. The changed microbial metabolites induced by polyphenols subsequently trigger host responses in various ways, such as acting as intestinal acid-base homeostasis regulators and activating on specific target receptors. Additionally, polyphenols are transformed into microbial derivatives by gut microbiota and these polyphenols' microbial derivatives have many potential advantages (e.g., increased bioactivity, improved absorption). Lastly, the review shows polyphenols maintain intestinal barrier, central nervous system, and lung function homeostasis by regulating gut microbiota. The interaction between polyphenols and gut microbiota provides a credible explanation for the exceptional bioactivities of polyphenols. This review aids our understanding of the underlying mechanisms behind the bioactivity of polyphenols.


Is anterior knee pain a predisposing factor to patellofemoral osteoarthritis?
Adolescent anterior knee pain has traditionally been described as running a benign and self-limiting course. Studies more recently have questioned this supposition. This study aimed to assess how many patients who had undergone patellofemoral arthroplasty for isolated patellofemoral arthritis had previously suffered from adolescent anterior knee pain, knee instability and trauma. This group was then compared to a control group of medial unicompartmental arthroplasty patients. Both groups were surveyed by postal questionnaire, with a >75% response rate from each group. 22% of the patellofemoral arthroplasty group described adolescent or early adulthood anterior knee pain as compared to 6% in the medial unicompartmental arthroplasty group (p<0.001). Patients in the patellofemoral group had also suffered significantly more patellofemoral instability and trauma than the medial unicompartmental group (p<0.001 and p=0.02, respectively). A significant number of patients with patellofemoral arthritis have described preceding anterior knee pain in their adolescence and early adult years, raising the question as to whether anterior knee pain may be one of the contributing factors to patellofemoral osteoarthritis in later years.


Peripheral blood monocytes from patients with HBV related decompensated liver cirrhosis can differentiate into functional hepatocytes.
Peripheral blood monocytes (PBMCs) have the potential to differentiate into various progenitor cells. Here we have investigated the differentiation potential of PBMCs derived from patients with HBV related decompensated liver cirrhosis into hepatocyte-like cells. In our clinical trial, the PBMCs from 2 patients were mobilized by the recombinant human granulocyte colony stimulating factor, followed by leukapheresis and transplantation of PBMCs. PBMCs, induced by recombinant human hepatocyte growth factors, were identified by the expression of hepatocyte markers and specific biological functions with biochemical assays in vitro. Patients showed a lasting clinical amelioration for more than one year after transplantation, and hepatocyte-like cells were identified by expressing liver specific genes, synthesizing albumin, urea, aspirate transaminase, and glycogen, which were all similar to the human normal hepatic cell line QZG. Our results clearly demonstrated that mobilized PBMCs from patients with HBV related decompensated liver cirrhosis could differentiate into functional hepatocyte-like cells, indicating the possibility of autologous cell transplantation for treating patients with HBV related decompensated liver cirrhosis.


Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study.
Adiponectin is an adipocytokine with lowered blood levels in obesity and Type 2 diabetes mellitus. We sought to define the specific effects of different alleles of the gene encoding adiponectin. We studied the associations of adiponectin gene sequence variations with body fat distribution and insulin indices in 503 White and 276 Black subjects of the HERITAGE Family Study cohort and subjects from a Finnish population. The His111 allele frequency of the Tyr111 His polymorphism in Finnish Type 2 diabetic subjects (n=254) was higher (5.1%) than in control subjects (n=270) (2.6%; P = 0.033). In the HERITAGE cohort, the His111 allele was associated with a lower insulin sensitivity index (P = 0.018) and a higher acute insulin response to glucose (P = 0.0098) in Whites. Other variants showed associations with adiposity and plasma lipid values only in Blacks. Among Blacks, the IVS2+G62T variant was associated with body fat (P = 0.002) and total cholesterol values (P = 0.005), and the Gly15Gly variant with cholesterol (P = 0.009) and triglyceride (P = 0.05) levels. The haplotype derived from these two polymorphisms was associated with total body fat, while the IVS2+G62T and Tyr111His-haplotype was associated with body fat and disposition index. The carriers of the His111 allele may have a higher risk of developing Type 2 diabetes mellitus. Racial differences were found between Blacks and Whites in body composition and lipids according to ACDC genotypes. Sequence variants in the adiponectin gene appear to be associated with diabetes and diabetes-related phenotypes.


Multi-scale goal distance representations in human hippocampus during virtual spatial navigation.
Goal-directed navigation relies on both coarse and fine-grained coding of spatial distance between the current position of a navigating subject and a goal destination. However, the neural signatures underlying goal distance coding remain poorly understood. Using intracranial EEG recordings from the hippocampus of drug-resistant epilepsy patients who performed a virtual spatial navigation task, we found that the right hippocampal theta power was significantly modulated by goal distance and decreased with goal proximity. This modulation varied along the hippocampal longitudinal axis such that theta power in the posterior hippocampus decreased more strongly with goal proximity. Similarly, neural timescale, reflecting the duration across which information can be maintained, increased gradually from the posterior to anterior hippocampus. Taken together, this study provides empirical evidence for multi-scale spatial representations of goal distance in the human hippocampus and links the hippocampal processing of spatial information to its intrinsic temporal dynamics.


Characterization of occupational sensitization by multiallergen immunoblotting in workers exposed to laboratory animals.
Studies have estimated that 10% to 23% of workers exposed to laboratory animals report symptoms of laboratory animal allergy. To determine the level of occupational sensitization in workers exposed to laboratory animals and to develop a diagnosis system based on a multiallergen IgE immunoblot. A total of 75 workers exposed to laboratory animals were initially studied with skin prick tests performed with animal epithelia extracts. The workers with suspected occupational disease and positive skin prick test results were further studied with the ImmunoCAP system to determine specific IgE levels to urine and epithelia allergens and with multiallergen IgE immunoblotting to detect specific IgE levels to epithelia allergens and bovine serum albumin. Twenty of the 75 workers were studied with ImmunoCAP and multiallergen IgE immunoblotting. Nine were polysensitized and 3 were sensitized to only one animal. The results obtained by ImmunoCAP and multiallergen IgE immunoblotting were concordant except for in 3 workers, who had low or negative values of specific IgE determined by ImmunoCAP but positive allergen detections by immunoblotting. On the basis of the results of the study and the clinical symptoms related by workers, 16% were diagnosed as having occupational allergy. Multiallergen immunoblotting by means of a unique test offers a graphic representation of sensitization to the different animals to which workers are exposed, providing additional information on the clinical symptoms caused by the involved allergens. The results presented suggest that this system can improve the diagnosis of laboratory animal allergy by obtaining a sensitization profile for each exposed worker.


Food-borne heterocyclic amines. Chemistry, formation, occurrence and biological activities. A literature review.
This review summarizes the abundant literature on food-borne heterocyclic amines, their chemistry and formation, their occurrence in food, their biological activities including mutagenicity, induction of DNA damage and carcinogenicity. Pharmacokinetics and biotransformation are also discussed. Factors that influence these effects are given consideration, with special emphasis on dietary factors that might counteract detrimental biological effects. The annual per capita intake of heterocyclic amines via food is estimated. Risk extrapolations that have been published suggest that food-borne heterocyclic amines are relevant for human cancer etiology.


Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: determination of interobserver variability and correlation to clinical outcome after 2 years.
In an observational study, the validity and reliability of magnetic resonance imaging (MRI) for the assessment of autologous chondrocyte transplantation (ACT) in the knee joint was determined. Two years after implantation, high-resolution MRI was used to analyze the repair tissue with nine pertinent variables. A complete filling of the defect was found in 61.5%, and a complete integration of the border zone to the adjacent cartilage in 76.9%. An intact subchondral lamina was present in 84.6% and an intact subchondral bone was present in 61.5%. Isointense signal intensities of the repair tissue compared to the adjacent native cartilage were seen in 92.3%. To evaluate interobserver variability, a reliability analysis with the determination of the intraclass correlation coefficient (ICC) was calculated. An "almost perfect" agreement, with an ICC value >0.81, was calculated in 8 of 9 variables. The clinical outcome after 2 years showed the visual analog score (VAS) at 2.62 (S.D. +/-0.65). The values for the knee injury and osteoarthritis outcome score (KOOS) subgroups were 68.29 (+/-23.90) for pain, 62.09 (+/-14.62) for symptoms, 75.45 (+/-21.91) for ADL function, 52.69 (+/-28.77) for sport and 70.19 (+/-22.41) for knee-related quality of life. The clinical scores were correlated with the MRI variables. A statistically significant correlation was found for the variables "filling of the defect," "structure of the repair tissue," "changes in the subchondral bone," and "signal intensities of the repair issue". High resolution MRI and well-defined MRI variables are a reliable, reproducible and accurate tool for assessing cartilage repair tissue.


Feasibility and Accessibility of a Tailored Intervention for Informal Caregivers of People with Severe Psychiatric Disorders: a Pilot Study.
This study aimed to assess the acceptability and feasibility of a new tailored intervention for informal caregivers: the Ensemble (Together) program. An open pre-post within-subject comparison pilot study was conducted. Twenty-one informal caregivers completed the five-session Ensemble program. Two measurement tools were used: The Brief Symptom Inventory (BSI) and the Life Orientation Scale (LOT-R). The results showed that informal caregivers were in need of individual support and were ready to participate in the Ensemble program independent of the patient's diagnosis or stage of illness. The participants were very satisfied, and 95.4% completed the program. The preliminary results also showed that in five sessions, informal caregivers' Global Severity Index measured by the BSI and their optimism about their future (measured by the LOT-R) were significantly improved. This pilot study provided preliminary results concerning the feasibility and acceptability of the tailored Ensemble program and indicates the need for a randomized trial. The Ensemble program is appropriate for both the acute and chronic phases of disease. Individualized brief and useful interventions for informal caregivers may provide more positive outcomes in care.


Sources and composition of natural and anthropogenic hydrocarbons in sediments from an impacted estuary.
Hydrocarbons in estuarine sediments provide information on sources of sedimentary organic matter (OM), and they are thus useful for tracing natural and anthropogenic OM inputs to the estuary. Here, we assessed the amounts, compositions and sources of natural and anthropogenic hydrocarbons from the sediments of a large, ecologically important estuary, Mobile Bay in Southeast USA. TOC/TN ratios and δ13C of organic carbon suggest that the bulk natural OM was sourced from marine phytoplankton and bacteria mixed with marsh and terrigenous C3 plants. Normal alkanes show high proportions of long-chain compounds with a high Carbon Preference Index, indicating the importance of C3 plants-derived OM in Mobile Bay. High concentrations of biogenic hopanes and perylene indicate microbial sources and degradation played an important role in shaping OM compositions. Anthropogenic hydrocarbons, αβ-hopanes and polycyclic aromatic hydrocarbons (PAHs), were widely detected in Mobile Bay sediments. The source diagnostic ratios of hopanes and steranes suggest they were sourced from coal and diesel combustions. The source diagnostic ratios of PAHs, together with a positive correlation between PAHs and total mercury, suggests that PAHs originated primarily from coal combustion. We proposed two ratios, αβ-hopanes/(ββ-hopanes+hopenes) and 16 PAHs/perylene, to evaluate anthropogenic versus natural contributions of hydrocarbons. These ratios were higher in the western estuary than in the eastern estuary, suggesting elevated anthropogenic hydrocarbon inputs to the western estuary. Correspondingly, the toxic equivalent quantity (TEQBaQ) of PAHs showed a higher ecological risk for the western estuary. This spatially uneven distribution of hydrocarbon pollutants can be attributed to more concentrated urban and industrial areas on the western shore, suggesting the importance of adjacent pollution sources. Collectively, our results provide new insights into the origins and dynamics of natural and anthropogenic OM and highlight the significance of coal combustion in contributing hydrocarbon pollutants in Mobile Bay sediments.


Effect of repeated convulsive seizures on brain gamma-aminobutyric acid metabolism in three sublines of mice differing by their response to acoustic stimulations.
The turnover rates and steady-state levels of gamma-aminobutyric acid (GABA) have been determined in 15 brain areas of three sublines of inbred mice differing in their susceptibility to audiogenic seizures: Rb3, which is seizure resistant; Rb2, which develops clonic seizures; and Rb1, which develops tonic-clonic seizures. In the Rb1 subline, GABA steady-state levels are lower than in the Rb3 subline in three of the 15 areas examined (cerebellum, anterior colliculus, and amygdala), whereas in the Rb2 subline, steady-state levels are either higher (posterior colliculus and hippocampus) or lower (amygdala) than in the Rb3 subline. GABA turnover rates differ in three brain areas in Rb1 (amygdala, raphe, and hypothalamus) and in a single area (amygdala) in Rb2 when compared with Rb3. Only one area has similar variations of GABA turnover rate and steady-state levels in the two susceptible sublines: the amygdala. After 2 weeks of repeated auditory stimulations (two times a day, 8,000 Hz, 100 dB), additional alterations in GABA metabolism are observed: mainly large increases in GABA turnover rates (from 40% to three- to fourfold). The Rb2 subline displays a greater number of alterations (increases of turnover rates in pons, cerebellum, anterior and posterior colliculus, amygdala, olfactory bulbs and tubercles, striatum, and frontal cortex) than the Rb1 subline (increases of turnover rates in cerebellum, posterior colliculus, olfactory tubercles, raphe, and frontal cortex and a decrease in hypothalamus). In the Rb3 subline, increases of the turnover rate in amygdala and olfactory tubercles and decreases in olfactory bulbs and hippocampus are observed.(ABSTRACT TRUNCATED AT 250 WORDS)


A polyclonal antiserum against the rabbit progesterone receptor recognizes the human receptor: immunohistochemical localization in rabbit and human uterus.
A polyclonal antiserum, raised in guinea pigs immunized with the 116,000 Mr rabbit uterine progesterone receptor (PR), was used to demonstrate immunoreactive PR in frozen fixed sections of rabbit and human uterus. In both species, PR localization was exclusively nuclear. For the rabbit uterus, staining intensity was greatest in the myometrium, followed by endometrial stroma, glands, and luminal epithelium. In premenopausal human endometrium and myometrium there was intense staining of nuclei from proliferative phase glands and myometrium. In the secretory phase the glands failed to stain, yet immunostaining persisted in the myometrium.


Contralateral Interhemispheric Transfalcine Transprecuneus Approach: Advancing Operative Angles to Deep-Seated Lesions.
The reach to expose the peritrigonal/atrial territories poses special challenges. The highly functional overlying cortices and white matter tracts, such as the optic radiations lateral to the ventricle, postcentral gyrus laterally and more superficially, and the thalamus anteroinferiorly, constrain the surgical corridors to the atrium. Standard interhemispheric or transcortical approaches involve significant retraction and resection of the normal parenchyma. In this offering, the authors describe the contralateral posterior interhemispheric transfalcine transprecuneus approach (PITTA), which provides flexible working angles while protecting the functional brain tissues. In summary, the PITTA is founded on the concept of using a contralateral operative trajectory to augment a more tangential working angle to the more difficult-to-reach lateral target through a midline route. The PITTA emphasizes the importance of operative working angles (versus necessary operative space) through less disruptive exposures as a more viable parameter for achieving desirable results.


Etiology of acute diarrhea due to enteropathogenic bacteria in Beijing, China.
Acute diarrhea is of great concern due to considerable morbidity and mortality worldwide. The causative bacteria leading to acute diarrhea in general population remains unclear in China. This study was conducted to determine the etiology of acute diarrhea using a sentinel hospital-based surveillance network in Beijing. Active surveillance was implemented from April 2010 to December 2011 on two random days per week by enrolling every tenth diarrheal patients admitted to seventeen intestinal clinics. Shigella spp., Vibrio spp, Salmonella spp., diarrheagenic Escherichia coli and other genera of bacteria, were investigated from 4803 outpatients with acute diarrhea by microbiological methods. The pathogenic bacteria recovered out from fecal samples of 968 (20.2%) patients had the following profile: Shigella spp. (5.9%) was the most prevalent pathogen, Vibrio parahaemolyticus (5.2%), Salmonella spp. (3.9%) and enteropathogenic E. coli (EPEC) (0.9%) had from the second to fourth highest prevalence, respectively. Of the 55 co-infections detected, V. parahaemolyticus was the most common pathogen from 28 cases (50.9%), with the main combination of V. parahaemolyticus and Salmonella. The highest proportion of all causative bacteria was found in adults aged 20-39 year and in summer as well as early autumn. The clinical symptoms associated with specific bacterial infection, such as fever, abdominal pain, tenesmus, nausea, vomiting, and watery and bloody stool, were observed frequently in diarrheal patients. Shigella spp., V. parahaemolyticus, Salmonella spp., and EPEC are important enteropathogenic bacteria causing acute diarrhea in Beijing. To execute reasonable interventions, the comprehensive and continuous surveillance is needed to identify the prevalence of different enteropathogeic bacteria.


Biotic stress induced demolition of thylakoid structure and loss in photoelectron transport of chloroplasts in papaya leaves.
Papaya mosaic virus (PMV) causes severe mosaic symptoms in the papaya (Carica papaya L.) leaves. The PMV-induced alterations in photosystem II (PS II) structure and photochemical functions were probed. An increase in chlorophyll a (Chl a) fluorescence polarization suggests pathogen-induced transformation of thylakoid membrane to a gel phase. This transformation in physical state of thylakoid membrane may result in alteration in topology of pigments on pigment-binding proteins as reflected in pathogen-induced loss in the efficiency of energy transfer from carotenoids to chlorophylls. The fast Chl a fluorescence induction kinetics of healthy and PMV-infected plants by F(O)-F(J)-F(I)-F(P) transients revealed pathogen-induced perturbation on PS II acceptor side electron transfer equilibrium between Q(A) and Q(B) and in the pool size of electron transport acceptors. Pathogen-induced loss in photosynthetic pigments, changes in thylakoid structure and decrease in the ratio of F(V)/F(M) (photochemical potential of PS II) further correlate with the loss in photoelectron transport of PS II as probed by 2,6-dichlorophenol indophenol (DCPIP)-Hill reaction. Restoration of the loss by 1,5-diphenyl carbazide (DPC), an exogenous electron donor, that donates electron directly to reaction centre II bypassing the oxygen evolving system (OES), leads towards the conclusion that OES is one of the major targets of biotic stress. Further, the data suggest that chlorophyll fluorescence could be used as a non-invasive handy tool to assess the loss in photosynthetic efficiency and symptom severity in infected green tissues vis-a-vis the healthy ones.


Cooperative dual medical ontology representation learning for clinical assisted decision-making.
Predicting clinical events and providing assisted decision-making using Electronic Health Records (EHRs) play a central role in personalized healthcare. Despite the promising performance achieved for diagnosis and procedure predictions, most of the existing predictive models regard different medical codes as the same type and generally ignore the dependence between diagnoses and procedures in patients' admission history. To address these issues, we propose an end-to-end cooperative dual medical ontology representation learning framework for clinical assisted decision-making. The framework consists of two primary modules: (1) dual medical ontology representation learning to facilitate the learning of medical concepts and (2) task dependent multi-task prediction to capture the correlation between diagnoses and procedures in patients' admission history. We evaluate our method with EHRs from the MIMIC-III Clinical Database, covering 6321 patients and 16335 visits. Experiments conducted on the MIMIC-III dataset show that the proposed model achieves the best performance, with a top-20 accuracy of 58.20% for diagnosis prediction and a top-20 accuracy of 75.85% for procedure prediction. In addition, a series of experimental analyses and case studies further illustrate the excellent performance of our model. We propose an end-to-end cooperative dual medical ontology representation learning framework, which achieves superior performance on multi-task diagnosis and procedure predictions. The source code is available at https://github.com/mhxu1998/CoDMO.


Complete Genome Sequences of Rhizobium leguminosarum bv. phaseoli BT01, Rhizobium sp. Strain BT03, and Rhizobium sp. Strain BT04, Isolated from Black Turtle Bean Nodules in Ontario, Canada.
We report the complete genome sequences of three Rhizobium strains isolated from nodules of heritage black turtle bean (Phaseolus vulgaris) plants grown in a community garden in Ontario, Canada. The genomes are between 6.91 Mb and 7.98 Mb long and consist of five to seven DNA replicons.


Rational design of α-Fe2O3 nanocubes supported BiVO4 Z-scheme photocatalyst for photocatalytic degradation of antibiotic under visible light.
The Z-scheme BiVO4/α-Fe2O3 photocatalyst was synthesized by a simple hydrothermal method. The photocatalyst is composed of α-Fe2O3 nanocubes with a regular cubic structure and the BiVO4 particles distributed on the surface of the α-Fe2O3 nanocubes. The photocatalytic performance of Z-scheme BiVO4/α-Fe2O3 photocatalyst was investigated in terms of its capacity for photodegradation of tetracycline hydrochloride. Improved photocatalytic activity was observed for Z-scheme BiVO4/α-Fe2O3 photocatalyst compared with pure BiVO4 and α-Fe2O3 nanocubes under visible light irradiation. Studies of its morphology, physicochemical properties and photoelectrochemical behaviors demonstrated that BiVO4 loading on the surface of α-Fe2O3 nanocubes forms a Z-scheme heterojunction, which increases the specific surface area and significantly promotes the separation of photoinduced carriers. The main active species were determined to be OH and h+ by ESR technique and trapping experiments. We propose a possible photocatalytic mechanism of Z-scheme BiVO4/α-Fe2O3 photocatalyst system. This study may also provide a novel and eco-friendly demonstration of a useful strategy for the design and preparation of special structure photocatalytic materials.


Biochemical and immunologic abnormalities in peripheral blood T lymphocytes of patients with hemophilia A.
Subset distribution, ecto-5'nucleotidase (5'NT) activity, and the generation of allospecific cytotoxic T lymphocytes (CTL) were investigated in peripheral blood T lymphocytes from 39 hemophilia A patients divided into three groups: group A and group B (HIV-patients with CD4:CD8 ratio less than 1 and greater than 1 respectively), and group C (HIV + patients). 5'NT activity was significantly decreased compared with healthy controls in groups B and C. In group B, this deficiency was attributable to expansion of CD8 + CD11 + suppressor cells. In group C, activated (HLA-DR+) CD8+ cells were also present and contributed to 5'NT deficiency. The suppressor cell expansion seemed to be mainly related to AHF infusions, whereas HLA-DR expression was related to HIV infection. CD11+ and HLA-DR+ cells were also expanded in the CD4+ subpopulation of all three groups, whereas CD4+ CD28+ lymphocytes were significantly decreased in group C only. Lastly, alloreactive cytotoxicity was decreased in group B and was normal in groups A and C.


A false sense of security? Can tiered approach be trusted to accurately classify immunogenicity samples?
Detecting and characterizing of anti-drug antibodies (ADA) against a protein therapeutic are crucially important to monitor the unwanted immune response. Usually a multi-tiered approach that initially rapidly screens for positive samples that are subsequently confirmed in a separate assay is employed for testing of patient samples for ADA activity. In this manuscript we evaluate the ability of different methods used to classify subject with screening and competition based confirmatory assays. We find that for the overall performance of the multi-stage process the method used for confirmation is most important where a t-test is best when differences are moderate to large. Moreover we find that, when differences between positive and negative samples are not sufficiently large, using a competition based confirmation step does yield poor classification of positive samples.


Self-supporting electrocatalyst constructed from in-situ transformation of Co(OH)2 to metal-organic framework to Co/CoP/NC nanosheets for high-current-density water splitting.
Transition metal phosphide (TMP) emerges as a promising electrocatalyst for overall water splitting (OWS). However, conventional TMP materials require exogenous metal ions to participate in coordination reactions, which usually suffer from active site blocking, pronounced intrinsic impedance, and inevitable catalyst shedding at high current density. Herein, a novel in-situ construction strategy has been developed to grow N-doped carbon (NC) enwrapped Co/CoP nanosheets directly onto Co foam (abbreviated as CoF) through a three-step transformation of Co to Co(OH)2 to Co-Metal-Organic Framework (Co-MOF) to Co/CoP/NC. In the entire preparation process, Co metal is only provided by the CoF substrate without external metal sources. Such in-situ construction yields tight contact at the interface of the heterogeneous catalyst, leading to much-reduced impedance and boundary vacancy, while the porous nitrogen-doped carbon backbone further endows the catalyst with the exposure of massive active sites, promotes mass transfer, and possesses high electrical conductivity. The Co/CoP/NC/CoF requires overpotentials of only 64 mV/263 mV@10 mA cm-2 and 414 mV/481 mV@400 mA cm-2 for both HER/OER in 1.0 M KOH, respectively. Remarkably, it reveals excellent OWS catalytic activity with a cell voltage of 1.56 V@10 mA cm-2 and 1.88 V@200 mA cm-2. This strategy of in-situ interface engineering transformation provides new ideas for direct device processing and construction of highly-efficient transition-metal-based OWS electrode materials.


Time-course distribution of fluorescent microplastics in target tissues of mussels and polychaetes.
The majority of the plastic produced in the last century is accumulated in the environment, leading to an exacerbated contamination of marine environments due to transport from land to the ocean. In the ocean, mechanical abrasion, oxidation, and photodegradation degrade large plastics into microplastics (MPs) - 0.1 μm to 5 mm (EFSA, 2016) which are transported through water currents reaching the water surface, water column, and sediments. Further, they can be accumulated by aquatic and benthic species, entering the trophic chain and becoming a potential threat to humans. In the present research, we aimed to decipher the accumulation and distribution time-courses between different organs or target tissues of organisms inhabiting coastal areas such as mussels Mytilus galloprovincialis and polychaetes Hediste diversicolor. Both were exposed in microcosm experiments to fluorescent polystyrene MPs (1 μm) which were spiked at two doses (103 and 105 particles/mL) for 1, 4, 24, and 72 h. Mussels and polychaetes were digested with 10% KOH and filtered to quantify the number of MPs incorporated. Different anatomical parts of the body were selected and processed for cryosectioning and posterior microscopic localisation of MPs. Both species accumulate MPs spiked in water column, mainly after exposure to the highest dose. In mussels, particles were found in distinct parts of the digestive tract (stomach, digestive diverticula, ducts) and gills. Even if the majority of MPs were localised in the lumen of the digestive tract, in some cases, were inside the digestive epithelium. The identification of MPs and their internalization in the digestive system was studied using Raman spectroscopy. A decreasing trend with time regarding MPs number in the digestive tract (stomach) of mussels was observed while the opposite was recorded for polychaetes and sediments. The combination of microscopical observations of frozen sections and Raman, appeared to be accurate methodologies to address MPs abundances and to reveal their localisation in different organs. This work has enabled to understand the distribution and fate of MPs in different environmental compartments and it could contribute to gain knowledge about their impact after ingestion by coastal organisms.


Sustainable preparation of luminescent carbon dots from syringe waste and hyaluronic acid for cellular imaging and antimicrobial applications.
Addressing the global challenge of persistent waste through an eco-conscious strategy to transform it into valuable and versatile materials holds great significance in today's swiftly evolving world. By adopting a sustainable approach, we can repurpose waste syringes composed of polytetrafluoroethylene (PTFE) into fluorescent carbon dots (CDs) using a simple hydrothermal process. This research harnessed hyaluronic acid to carbonize and modify discarded plastic syringes, resulting in the creation of luminescent syringe carbon dots (SCDs). Rigorous analysis employing diverse techniques delved into their optical attributes, size distribution, and surface characteristics. Extensive biocompatibility assessments using established assay methods confirmed the safety of the derived SCDs, unveiling their potential antibacterial and antifungal traits. Additionally, a confocal microscope was employed to evaluate the cellular imaging capabilities of SCDs on HeLa cells. Notably, at bactericidal concentrations, SCDs exhibited mild cytotoxicity towards mammalian cells, showcasing cell viability surpassing 91.07% at 1 mg/mL. This pioneering exploration paves the way for potential applications of SCD-based nano-bactericides across various biomedical domains. The initial outcomes established herein mark a significant stride towards the creation of cost-effective and ecologically sound fluorescent probes for biomedical imaging, aimed at combating microbial infections. By ingeniously reutilizing polyethylene terephthalate (PET), this investigation offers a sustainable remedy to address the ecological predicaments linked with plastic waste. In doing so, it charts a course towards contributing to the development of affordable, eco-friendly solutions, heralding a promising prospect for a cleaner, healthier environment.


Improving Inter-Helix Contact Prediction With Local 2D Topological Information.
Inter-helix contact prediction is to identify residue contact across different helices in α-helical integral membrane proteins. Despite the progress made by various computational methods, contact prediction remains as a challenging task, and there is no method to our knowledge that directly tap into the contact map in an alignment free manner. We build 2D contact models from an independent dataset to capture the topological patterns in the neighborhood of a residue pair depending it is a contact or not, and apply the models to the state-of-art method's predictions to extract the features reflecting 2D inter-helix contact patterns. A secondary classifier is trained on such features. Realizing that the achievable improvement is intrinsically hinged on the quality of original predictions, we devise a mechanism to deal with the issue by introducing, 1) partial discretization of original prediction scores to more effectively leverage useful information 2) fuzzy score to assess the quality of the original prediction to help with selecting the residue pairs where improvement is more achievable. The cross-validation results show that the prediction from our method outperforms other methods including the state-of-the-art method (DeepHelicon) by a notable degree even without using the refinement selection scheme. By applying the refinement selection scheme, our method outperforms the state-of-the-art method significantly in these selected sequences.


Detection of quantitative trait loci for carcass traits in the pig by using AFLP.
For evaluation of the suitability of Amplified Fragment Length Polymorphism (AFLP) for detection of quantitative trait loci in farm animals, a combination of AFLP and selective genotyping has been applied as a rapid screening method for marker-QTL associations. Focusing on loci affecting eye muscle area, six extreme discordant sib pairs were selected from a Duroc x Berlin Miniature Pig F2 experimental cross and examined by using 48 AFLP primer combinations. Two prominent AFLP markers were converted into simple codominant PCR markers ( STS-Bo1 and STS-Bo3) and assigned to Sscr4 by physical and linkage mapping. Single marker analysis indicated association of the STS markers with a putative QTL influencing eye muscle area. Interval mapping confirmed the presence of a significant QTL for eye muscle area (Pgenomewide < 0.01) on the Sscr4, with STS-Bo1 being the closer marker. At the same location, significant effects (Pgenomewide < 0.01) on carcass length and backfat thickness were also detected. Our results demonstrate the capability of the combination of AFLP analysis and selective genotyping as a method for detection of genome regions containing QTL in livestock.


Re-examining the role of the dorsal fan-shaped body in promoting sleep in Drosophila.
The needs fulfilled by sleep are unknown, though the effects of insufficient sleep are manifold. To better understand how the need to sleep is sensed and discharged, much effort has gone into identifying the neural circuits involved in regulating arousal, especially those that promote sleep. In prevailing models, the dorsal fan-shaped body (dFB) plays a central role in this process in the fly brain. In the present study we manipulated various properties of the dFB including its electrical activity, synaptic output, and endogenous gene expression. In each of these experimental contexts we were unable to identify any effect on sleep that could be unambiguously mapped to the dFB. Furthermore, we found evidence that sleep phenotypes previously attributed to the dFB were caused by genetic manipulations that inadvertently targeted the ventral nerve cord. We also examined expression of two genes whose purported effects have been attributed to functions within a specific subpopulation of dFB neurons. In both cases we found little to no expression in the expected cells. Collectively, our results cast doubt on the prevailing hypothesis that the dFB plays a central role in promoting sleep.


STAT1 Inhibits MiR-181a Expression to Suppress Colorectal Cancer Cell Proliferation Through PTEN/Akt.
Signal transducers and activators of transcription 1 (STAT1) exhibits tumor-suppressor properties by inhibiting oncogenic pathways and promoting tumor immunosurveillance. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Recently, miR-181a has been reported to be associated with poor prognosis of colorectal cancer (CRC). Using human colorectal cancer cell lines, we demonstrated that STAT1 suppresses both LoVo and SW480 cell growth by down-regulating miR-181a. STAT1 regulates the expression of miR-181a through binding to the elements in the miR-181a's promoter region. Further, we revealed that miR-181a accelerates CRC cell proliferation through phosphatase and tensin homolog on chromosome ten (PTEN). In addition, PTEN protein was upregulated in response to STAT1 overexpression or miR-181a inhibition, downregulated in response to STAT1 knockdown or miR-181a overexpression. Without changes on the AKT protein level, p-AKT was downregulated by STAT1 overexpression or miR-181a inhibition while upregulated by STAT1 knockdown or miR-181a overexpression, indicating PTEN/Akt pathway activated in STAT1/miR-181a regulation of CRC cell proliferation. Taken together, our findings shed new light on the STAT1/miR-181a/PTEN pathway in colorectal cancer and add new insight regarding the carcinogenesis of colorectal cancer. J. Cell. Biochem. 118: 3435-3443, 2017. © 2017 Wiley Periodicals, Inc.