Granuloma annulare with alopecia areata in a 6-year-old girl: a case report.
Dermatologic signs and symptoms can be the manifestations of a single disease or different diseases, and it is proven that some are associated with one another. These connections are not fully understood, but the answer lies in the pathophysiology of each disease. We report the case of a 6-year-old Middle-Eastern girl who presented with two skin lesions on the dorsum of her foot, along with scaling of her soles and palms, face skin discoloration, and areas of patchy alopecia on her scalp. She was diagnosed as a case of acute onset of granuloma annulare with alopecia areata and dermatitis. The treatment regimen for the patient's scalp consisted of topical minoxidil and betamethasone and three sessions with 1-month intervals of triamcinolone acetonide intralesional injections, which demonstrated modest effectiveness in treating alopecia areata. Granuloma annulare is a benign inflammatory illness with no known cause that might be difficult to cure. The clinical course and prognosis might vary greatly depending on the disease subtype, and associating symptoms and diseases, such as alopecia areata, should be considered.


A dynamic model to measure retention of solid and liquid digesta fractions in chickens fed diets with differing fibre sources.
Dietary fibres impact multiple digestive processes, and insights into the effects of various types of fibre on digesta retention time are required to optimise current feed formulation systems. Therefore, the objective of this study was to apply a dynamic modelling approach to generate estimates for the retention time of solid and liquid digesta in broilers fed different fibre sources. A maize-wheat-soybean meal control diet was compared against three diets in which wheat was partially substituted with oat hulls, rice husks, or sugar beet pulp (3% w/w). Non-starch polysaccharide (NSP) digestibility was evaluated in broilers between 23 and 25 days of age (n = 60 birds/treatment) using titanium dioxide (TiO2, 0.5 g/kg) as a marker, after feeding the experimental diets for 21 days. Digesta mean retention time (MRT) was measured in another 108 birds at 30 days of age by the administration of an oral pulse dose of chromium sesquioxide (Cr2O3) as solid marker and Cobalt-EDTA as liquid marker, and subsequent measurement of marker recovery in compartments of the digestive tract (n = 2 or 3 replicate birds/time point/treatment). Marker recovery models to estimate fractional passage rates for solid and liquid digesta in crop, gizzard, small intestine, and caeca compartments of the gastrointestinal tract were developed to predict MRT of solid and liquid digesta for each dietary treatment. The models were composed of a series of first-order differential equations, representing the variation of marker concentration in a compartment over time. Estimated MRT of solid and liquid digesta in the gizzard varied from 20 min for oat hulls and 34 min for rice husks diets to 14 min for sugar beet pulp and 12 min for control diets. In the caeca, liquid MRT was decreased compared to the control diet (989 min) for the sugar beet pulp diet (516 min), while it was increased for both the oat hulls and rice husks diets (≈1 500 min). Overall, these estimates are greater than those previously reported, suggesting that liquid digesta retention in the caeca previously has been underestimated. Digestibility of total NSP was increased by dietary fibre inclusion, regardless of the fibre type, although degradation of constituent sugars of NSP varied among diets. In conclusion, the inclusion of fibre sources at a low level (3% w/w) in the diet of broiler modulated retention time mainly in the gizzard and caeca, and increased digestibility of NSP.


Structure-/disease-modifying agents for osteoarthritis.
OA is the most common articular disease. Age is its most notable risk factor. With the aging of the population of the developed world, there will be a growing need for better understanding of OA and for superior therapies. There is increasing appreciation for the role of inflammation in OA. There also is the realization that OA is not only a disease of cartilage, but of the entire joint. This has led to increasing interest in structure/disease modification as the goal in OA therapy. However, there are no universally proven structure-/ disease-modifying interventions.


[Hormones in ischemic heart disease with the presence of coronary atherosclerosis].
The activity of the pituitary hormones (ACTH, STH, TTH, FSH, LH), the adrenal hormones (cortisol, aldosterone), the kidney hormone (renin), and the thyroid hormones (thyroxine tri-iodthyronine), the thyroxine binding capacity of blood proteins and the activity of the hormones of the pancreas (insulin) and the sex glands (testosterone, estradiol) were studied in 26 males suffering from ischemic heart disease verified by means of selective coronarography and in 20 healthy males with no atherosclerosis of the coronary arteries of the heart. Patients with ischemic heart disease were found to be marked by increased activity in the blood of ACTH, TTH, cortisol, aldosterone, insulin, and estradiol and reduced concentration of STH, thyroxine, and testosterone. These shifts in the activity of the hypothalamo-hypophyseal system and in its subordinate hormonal systems play an important role in the origin of the atherosclerotic process and assosiated ischemic heart disease.


Abdominal aortic aneurysms in heart transplanted patients.
In the AA's opinion, the dilatation of the abdominal aorta is not a contraindication to heart transplantation. From July 1994 to February 1998, 3 out of 80 heart transplanted patients, required a replacement of their abdominal aorta because of an infrarenal aortic aneurysm. The first patient (62 years old) did not have an aneurysm by time of heart transplantation: his aneurysm (5.1 cm wide) was resected 2 years later. The other two patients (m, 44 years old; m, 60 years old) had a dilatation of 3.1 and 3.5 cm of the abdominal aorta by time of cardiac transplantation: 15 months later, the aneurysms measured 5.8 and 7 cm, respectively, and had been resected. Two resections were performed through a retroperitoneal approach. All 3 patients had uneventful postoperative course. Before heart transplantation the aorta must be screened for dilatation or aneurysm, which can be enlarged by operation. Such lesions can be operated on, with low risks, and should not be a contraindication to heart transplantation.


Prevalence of antimicrobial resistance in a full-scale drinking water treatment plant.
Antibiotic resistance in drinking water has received increasing attention in recent years. In this study, the occurrence and abundance of antibiotic resistance genes (ARGs) in a drinking water treatment plant (DWTP) was comprehensively investigated using metagenomics. Bioinformatics analysis showed that 381 ARG subtypes belonging to 15 ARG types were detected, and bacitracin had the highest abundance (from 0.26 × 10-2 to 0.86 copies/cell), followed by multidrug (from 0.57 × 10-1 to 0.47 copies/cell) and sulfonamide (from 0.83 × 10-2 to 0.35 copies/cell). Additionally, 933 ARG-carrying contigs (ACCs) were obtained from the metagenomic data, among which 153 contigs were annotated as pathogens. The most abundant putative ARG host was Staphylococcus (7.9%), which most frequently carried multidrug ARGs (43.2%). Additionally, 38 high-quality metagenome-assembled genomes (MAGs) were recovered, one of which was identified as Staphylococcus aureus (Bin.624) and harboured the largest number of ARGs (n = 16). Using the cultivation technique, 60 isolates were obtained from DWTP samples, and Staphylococcus spp. (n = 11) were found to be dominant in all isolates, followed by Bacillus spp. (n = 17). Antimicrobial susceptibility testing showed that most Staphylococcus spp. were multidrug resistant (MDR). These results deepen our understanding of the distribution profiles of ARGs and antibiotic resistant bacteria (ARB) in DWTPs for potential health risk evaluation. Our study also highlights the need for new and efficient water purification technologies that can be introduced and applied in DWTPs.


Current and future developments in laser surgery.
Following the first application of the laser in surgery, the development of its instrumentation and techniques in many surgical disciplines has been rapid. An overview is provided of the present and future use of surgical lasers. New laser systems and developments include high-output argon lasers; more miniaturization and flexibility; combinations of lasers; copper and gold head lasers; and selection beam lasers.


Native mass spectrometry for understanding dynamic protein complex.
Biomolecules have evolved to perform specific and sophisticated activities in a highly coordinated manner organizing into multi-component complexes consisting of proteins, nucleic acids, cofactors or ligands. Understanding such complexes represents a task in earnest for modern bioscience. Traditional structural techniques when extrapolating to macromolecules of ever increasing sizes are confronted with limitations posed by the difficulty in enrichment, solubility, stability as well as lack of homogeneity of these complexes. Alternative approaches are therefore prompted to bridge the gap, one of which is native mass spectrometry. Here we demonstrate the strength of native mass spectrometry, used alone or in combination with other biophysical methods such as analytical ultracentrifugation, small-angle neutron scattering, and small-angle X-ray scattering etc., in addressing dynamic aspects of protein complexes including structural reorganization, subunit exchange, as well as the assembly/disassembly processes in solution that are dictated by transient non-covalent interactions. We review recent studies from our laboratories and others applying native mass spectrometry to both soluble and membrane-embedded assemblies. This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato.


Use of forest corridors by boreal Xestia moths.
We studied movements of the noctuid moths Xestia speciosa and X. fennica in a fragmented forest landscape including old-growth spruce forest corridors in eastern Finland. We individually marked and released 1,796 adults of the habitat generalist X. speciosa and 683 individuals of X. fennica, which prefers old-growth spruce forests. Moths were recaptured with 60 sugar-bait traps that were placed within habitat corridors, in the non-habitat matrix and in surrounding old-growth forest patches. Both species favoured the corridors during their movements and tended to avoid entering the matrix. We analysed recapture rates and movements of the recaptured moths. Results suggest that X. speciosa moves longer distances than X. fennica. Though corridors clearly canalized movements by both species, the impact of old-growth forest corridors at the larger landscape scale was less clear in X. fennica. Movement behaviour of the two sexes differed more than that of the two species.


The accelerating epidemic of hypertension among rural Chinese women: results from Liaoning Province.
The objective of the study was to assess prevalence, awareness, treatment, and control of hypertension and its risk factors in rural women in Liaoning Province in northeast China. We conducted a cross-sectional analysis of 23,178 women of minimum age 35 years, living in rural Liaoning province in northeast China. We measured their blood pressure (BP) and investigated associated factors. Hypertension was defined as an average systolic BP > or =140 mm Hg, and/or an average diastolic BP > or =90 mm Hg, and/or self-report of current treatment for hypertension with antihypertensive medication. The overall prevalence of hypertension in this study was 38.6%. Among those with hypertension, 32.8% were aware that they had high BP, 27.4% were being treated with antihypertensive medications, and in 1.4% of the women the hypertension was controlled. Multivariate analysis revealed that higher age, Mongolian ethnicity, higher body mass index (BMI), higher waist circumference (WC), excessive salt intake, smoking, alcohol consumption, lipid disorder, diabetes, and family history of hypertension were associated with the prevalence of hypertension; a higher level of education (high school or beyond) and a higher income level were inversely related to hypertension prevalence. Our results indicate that hypertension is highly prevalent in rural women in Liaoning province and it is associated with known risk factors. There are unacceptably low percentages of those with hypertension who are aware of their condition, are receiving treatment, and in whom hypertension is controlled. Our study suggests the urgent need for a public health program to improve the prevention, detection, and treatment of hypertension in rural Chinese women.


VAC® therapy a therapeutic alternative in giant omphalocele treatment: a multicenter study.
Giant omphalocele is associated to morbidity and mortality because of the strain the reintegrated herniated mass places on the hemodynamic equilibrium and breathing functions of affected infants. Currently, care management consists in a reintegration in one time or progressive reintegration. We report here a multicenter retrospective study about alternative management by VAC® therapy for giant omphaloceles. The study included three patients (1 girl, 2 boys) presenting with giant omphaloceles, born at full term in three different University Hospitals (prenatal diagnosis, normal karyotype). VAC® therapy was implemented at different times according to the cases (at Day 11, Month 1 and Month 5 after birth). The initial pressure applied was -10 mmHg progressively increased to -50 mmHg. A middle size VAC GranuFoam Silver® Dressing was used in all cases. Wound healing occurred at Month 4 for the first case, Month 6 and Month 8 for the other two. VAC® therapy is a good alternative for the care management of giant omphaloceles with more advantages especially when using prosthetic material. We also aimed at refining the most adapted indications in these specific situations, and finally we envisioned a harmonization of care for these children.


Obstructive jaundice caused by a giant liver hemangioma with Kasabach-Merritt syndrome: a case report.
Hemangioma is the most common benign tumor of the liver. Liver hemangioma (LH) usually remains asymptomatic, but the most common symptoms associated with LH are abdominal pain and discomfort. LH is an uncommon cause of bile duct dilatation and obstructive jaundice. An 83-year-old Japanese woman who received hemodialysis at another hospital was referred to our hospital because of abnormal liver function and obstructive jaundice. Abdominal computed tomography and magnetic resonance imaging revealed a 13-cm tumor in liver segments IV-V and intrahepatic bile duct dilatation. Endoscopic retrograde cholangiopancreatography revealed extrinsic compression of the bile duct at the hepatic hilar region. Laboratory tests showed that the patient had low platelet counts and low fibrinogen levels. Because the patient had hyperbilirubinemia and Kasabach-Merritt syndrome, we performed a segmentectomy of liver segments IV and V. Histological examination showed hemangioma of the liver. The patient's thrombocytopenia and coagulopathy improved immediately after surgery. In conclusion, LH is a very rare cause of obstructive jaundice. LH has the potential to compress the bile duct and cause obstructive jaundice.


Ascites, renal abnormalities, and electrolyte and acid-base disorders associated with liver disease.
Ascites and renal dysfunction are often associated with decreased liver function and reflect the complex abnormalities of water, protein, electrolyte, and acid-base metabolism that may complicate severe liver disease. This article discusses the pathophysiology and management of ascites, polydipsia and polyuria, decreased renal function, and acid-base and electrolyte alterations that can complicate liver disease.


Cimetidine use and the risk for prostate cancer: results from the VITAL cohort study.
The histamine-2 (H(2)) blocker cimetidine may alter androgen, zinc, and prolactin levels, which could alter prostate cancer risk. Increased risk for men filling more than 20 cimetidine prescriptions was reported previously. We examined the association between cimetidine use and prostate cancer risk in a cohort in western Washington State. Participants were 33,506 men, 50 to 76 years old, enrolled in the VITamins And Lifestyle cohort (VITAL). H(2)-blocker use during the prior 10 years was self-reported through baseline questionnaire between October 2000 and December 2002. Men were followed up for subsequent prostate cancer by linkage to the Surveillance, Epidemiology and End Results cancer registry. We identified 548 incident invasive prostate cancer cases diagnosed from baseline to December 31, 2003. Overall, no association between ever use of cimetidine or years of cimetidine use and prostate cancer risk was observed. However, daily cimetidine use for 10 years was associated with increased risk (relative risk, 2.35; 95% confidence interval, 1.05-5.26) compared with nonuse of any H(2) blockers. Use of other H(2) blockers was not associated with prostate cancer. Additional studies are needed to determine whether long-term daily cimetidine use is associated with increased prostate cancer risk in other populations, and if so, the reason for this association.


Effectiveness and Cost-effectiveness of an Empowerment-Based Self-care Education Program on Health Outcomes Among Patients With Heart Failure: A Randomized Clinical Trial.
Strategies that enhance self-care of patients with heart failure reduce mortality and health care use. To examine whether an empowerment-based self-care education program was more effective and cost-effective to improve self-care, health status, and hospital service use than a didactic education program in patients with heart failure. In this double-blind randomized clinical trial, a consecutive sample of 988 patients with heart failure from the cardiac clinics of 2 regional hospitals underwent eligibility screening from February 1, 2017, to May 31, 2019, using the criteria of age of 55 years or older, heart failure diagnosed 6 months before screening, and New York Heart Association class II to IV. A total of 236 participants were randomized to the empowerment (n = 118) or education (n = 118) group. The 12-week, group-based, empowerment-based education program included self-care assessment, goal-orientated actions in symptom recognition and response, fluid and dietary modification, and lifestyle management. Didactic education covered the same topics without empowerment strategies. The primary outcome was self-care measured by the Self-care Heart Failure Index (SCHFI) maintenance, management, and symptom perception subscales at posttest and 3-month end points. Secondary outcomes included measures of knowledge, confidence, health-related quality of life, and health service use. Direct, indirect, and social costs of the 2 programs were collected for cost-effectiveness analysis. A total of 236 Chinese patients (mean [SD] age, 70 [8.0] years; 149 [63.1%] men) were included in the study. The empowerment group reported significantly greater improvement in SCHFI management scores (mean difference, 13.76; 95% CI, 5.89-21.62; Cohen d = 0.46 at posttest and Cohen d = 0.35 at 3 months) and symptom perception scores (mean difference, 20.36; 95% CI, 13.98-26.75; Cohen d = 0.84 at posttest and Cohen d = 0.61 at 3 months). The empowerment group had lower risks of emergency department attendance (incidence rate ratio, 0.55; 95% CI, 0.31-0.95; P = .03) and hospital admission (incidence rate ratio, 0.38; 95% CI, 0.21-0.68; P = .001) and better improved self-care knowledge (change in score [empowerment minus education], 1.29; 95% CI, 0.48-2.09) and confidence (change in score [empowerment minus education], 7.98; 95% CI, 1.91-14.05). Empowerment was cost-saving and cost-effective at T2 compared with the education group for quality-adjusted life-years, with an incremental cost-effectiveness ratio of -114 485. In this randomized clinical trial, an empowerment approach led to clinically relevant improvement in symptom perception and self-care management among patients with heart failure. Its cost-effectiveness in improving these prognostic factors also benefits the patient-reported outcome. Chinese Clinical Trial Registry: ChiCTR-IOR-16008254.


Metastatic spinal cord syndromes: imaging appearances and treatment planning.
Metastatic spinal cord syndromes usually result from neural compression by adjacent vertebral disease but are occasionally caused by intradural or intramedullary disease. MRI is the most accurate method for evaluation of such syndromes. Knowledge of the relevant imaging appearances and therapeutic options enables the radiologist to make an accurate assessment of the extent of disease and contribute information relevant to treatment planning.


Response rate and toxicity of etoposide (VP-16) in squamous carcinoma of the lung: report from the Lung Cancer Treatment Study Group.
In two multicenter studies, 325 patients with advanced squamous lung cancer were randomized to receive either no treatment v oral etoposide (VePe-sid) 300 mg/m2 on days 1 and 2 for 6 cycles, or the same dose of oral etoposide v the same dose of oral etoposide plus cyclophosphamide 300 mg/m2 IV on days 1 and 2, each given for 6 cycles. A total of 175 patients in both trials received oral etoposide alone. All patients assigned to treatment were included in the results. Remissions occurred in 20 (11%) patients (CR in 1; PR in 19). Leukopenia occurred in 2% of patients and other toxicity was acceptable.


Interferon gamma downregulates IL-8 production in primary human colonic epithelial cells without induction of apoptosis.
In acute or chronic inflammatory bowel disease (IBD) interferon gamma (IFNgamma) is still considered to be an important pro-inflammatory mediator. In the present study we investigated the impact of IFNgamma on interleukin-8 (IL-8) production as a read-out for cell activation in intestinal epithelial cell (IEC) lines and primary human colonic epithelial cells (CEC). Primary cultures of human CEC were established from the mucosa of patients without inflammatory disease. CEC, HT-29 or Caco-2 cells were incubated with either IFNgamma, tumor necrosis factor (TNF)alpha or IL-10. IL-8 and IL-1Ra secretion was determined by ELISA. Competicon PCR was used for quantification of IL-8mRNA. Apoptosis was quantified by propidium iodine incorporation and fluorescence activated cell sorting (FACS) analysis. In contrast to HT-29 cells in primary human CEC 100 U/ml IFNgamma inhibited IL-8 secretion significantly to 70+/-15% of unstimulated primary CEC (p<0.005) more effectively than IL-10 (87+/-21% versus unstimulated cells, n.s.). In HT-29 cells, IL-8 secretion was induced to 405+/-101% of unstimulated cells. In Caco-2 cells, IFNgamma had no significant effect on IL-8 secretion. The effect in HT-29 and CEC was concentration dependent. In primary CEC, 200 U/ml IFNgamma further reduced IL-8 secretion to 48+/-18% of unstimulated CEC (p<0.05). Whereas IL-8 mRNA was strongly upregulated in HT-29 cells, no upregulation or even a downregulation was found in CEC. Pre-incubation with 100 U/ml IFNgamma did not increase the susceptibility to apoptosis mediated by anti-Fas antibody (CH-11) in primary CEC, whereas HT-29 cells showed increased rates of apoptosis after priming with IFNgamma. In contrast to HT-29, IFNgamma downregulated IL-8 secretion and did not induce IL-8 mRNA expression in primary human CEC. This effect was not due to induction of apoptosis.


Reactive adsorption of SO2 on activated carbons with deposited iron nanoparticles.
The effect of iron particle size anchored on the surface of commercial activated carbon on the removal of SO(2) from a gas phase was studied. Nanosize iron particles were deposited using forced hydrolysis of FeCl(3) with or without H(3)PO(4) as a capping agent. Dynamic adsorption experiments were carried out on either dry or pre-humidified materials and the adsorption capacities were calculated. The surface of the initial and exhausted materials was extensively characterized by microscopic, porosity, thermogravimetric and surface chemistry. The results indicate that the SO(2) adsorption capacity increased two and half times after the prehumidification process owing to the formation of H(2)SO(4) in the porous system. Iron species enhance the SO(2) adsorption capacity only when very small nanoparticles are deposited on the pore walls as a thin layer. Large iron nanoparticles block the ultramicropores decreasing the accessibility of the active sites and consuming oxygen that rest adsorption centers for SO(2) molecules. Iron nanoparticles of about 3-4 nm provide highly dispersed adsorption sites for SO(2) molecules and thus increase the adsorption capacity of about 80%. Fe(2)(SO(4))(3) was detected on the surface of exhausted samples.


Functional orthopedic magnetic appliance (FOMA) II--modus operandi.
A new functional appliance (FA) to correct Class II dentoskeletal malocclusions is introduced. The functional orthopedic magnetic appliance (FOMA) II uses upper and lower attracting magnetic means (Nd2Fe14B) to constrain the lower jaw in an advanced sagittal posture. In vitro, a special gauge transducer measured the magnetic attractive path and forces. In vivo, 13 prepubertal female Macaca fascicularis monkeys received facial implants and were treated for 4 months with the following appliances: conventional FA (four subjects), FOMA II (five subjects), a combined FOMA II + FA (two subjects), and sham (control) appliance (two subjects). The in vitro results showed the following: vertico-sagitally displaced upper and lower magnets attracted ultimately along an oblique line with a terminal horizonal slide to become fully superimposed; the functional performance improved when the magnetic interface acted as a magnetic inclined plane; and the magnetic force was able to guide and constrain the mandible toward the constructive protrusive closure position (CPCP) (1.2 mm, F = 570 gm) from levels below the habitual rest position (3 mm, F = 219 gm) and the electromyographic (EMG) relaxed position (8.5 mm, F = 45 gm). The in vivo results demonstrated the following: functional performance increased in FOMA II (22%) and in the combined FOMA II + FA (28%) over the conventional FA; mandibular length increased significantly in the treated animals (means = 2.83 +/- 0.70 mm) over the control animals (means = 0.43 +/- 0.08 mm); incisor proclination was lower in magnetic appliances (means = 4.57 +/- 1.76 degrees) than in the conventional FA (means = 8.75 +/- 1.85 degrees); mandibular elongation and condylar posterior inclination resulted from posterosuperior endochondral growth (increased cell proliferation and/or hyperplasia of functional chondroblasts) and by bony remodeling of the condylar neck (apposition posterior border, resorption anterior border), respectively; virtually no anterior displacement of the postglenoid spine (means = 0.19 +/- 0.68 mm) nor the articular eminence (means = 0.36 +/- 0.69 mm) was found. Increased lower posterior alveolar height (means = 1.71 +/- 0.82 mm) is a major impediment in the correction of excessive lower anterior facial height. The results of the study highly recommend the exploration of the clinical application of the FOMA II.


Optimal aeration area of cathode electrode in the batch type of microbial fuel cells with non-woven interface.
Microbial fuel cells (MFCs) are based on the biochemical reaction of microorganisms to decompose organic wastewater for converting chemical energy into power energy. MFCs are considered an environmentally friendly technology that is gaining popularity due to their simultaneous digestion and energy production abilities. To enhance its real application in wastewater treatment, this study proposes to use a non-woven material for replacing the usage of expensive membranes in MFCs. In addition, the study aims to consider a series of different aeration areas of cathode electrodes for finding an optional design. Results have shown that the adoption of non-woven with 0.45 μm can effectively prohibit the diffusion of oxygen into the anode chamber. Moreover, the non-woven material played an important role as an interface between the anode and cathode, enhancing the MFC performance. The usage of suitable non-woven material can replace the role of the membrane when applied in real wastewater applications. The results have shown that the case study where a combination of a 50% aeration area of the cathode electrodes with 25% exposure of the cathode plate in the air yielded relatively better aeration in terms of a higher current density of 250 mA/m2, higher power density of 220 mW/m2, and higher open voltage circuit of 0.4 V, compared to other case studies considered. These results indicate the optimal aeration configuration for MFCs applied in commercial wastewater treatment in the future.


Complete genome sequence of deoxynivalenol-degrading bacterium Devosia sp. strain A16.
The strain A16, capable of degrading deoxynivalenol was isolated from a wheat field and identified preliminarily as Devosia sp. Here, we present the genome sequence of the Devosia sp. A16, which has a size of 5,032,994 bp, with 4913 coding sequences (CDSs). The annotated full genome sequence of the Devosia sp. A16 strain might shed light on the function of its degradation.


Cooperative activation of Src family kinases by SH3 and SH2 ligands.
Src family nonreceptor tyrosine kinases are kept in a repressed state by intramolecular interactions involving the SH3 and SH2 domains of the enzymes. Ligands for these domains can displace the intramolecular associations and activate the kinases. Here, we carried out in vitro activation experiments with purified, down-regulated hematopoietic cell kinase (Hck), a Src family kinase. We show that SH3 and SH2 ligands act cooperatively to activate Src family kinases: the presence of one ligand lowers the concentration of the second ligand necessary for activation. To confirm the findings in intact cells, we studied Cas, a Src substrate that possesses SH2 and SH3 ligands. In contrast to wild-type Cas, mutant forms of Cas lacking the SH3 or SH2 ligands were unable to stimulate Src autophosphorylation when expressed in Cas-deficient fibroblasts. Cells expressing the Cas mutants also showed decreased amounts of activated Src at focal adhesions. The results suggest that proteins containing ligands for both SH3 and SH2 domains can produce a synergistic activation of Src family kinases.


Effect of dextran and dextran modifications on the thermal and proteolytic stability of conjugated bovine testis beta-galactosidase and human serum albumin.
In order to study carbohydrate-induced protein stabilization bovine testis beta-galactosidase and human serum albumin were conjugated with dextran, partially acetylated dextran and partially methylated dextran. The conjugates and the free proteins were compared with respect to thermal stability at 50 degrees C and resistance to proteolytic digestion by subtilopeptidase A. Both beta-galactosidase and serum albumin were stabilized by conjugation with polysaccharide. However, higher stability was achieved by conjugating the proteins with the hydrophilic polysaccharides, dextran and acetylated dextran, than by conjugation with the hydrophobic polysaccharide, methylated dextran. The results are discussed in relation to possible explanations of carbohydrate-induced protein stabilization.


Translation and validation of the patient-Generated Subjective Global Assessment against the Mini-Nutritional Assessment for patients with gastric cancer.
This study aimed to (1) translate the PG-SGA into Korean according to a translation guideline, (2) validate the translated version against the Mini-Nutritional Assessment, and (3) determine the prevalence of malnutrition in patients with gastric cancer. The translation of the PG-SGA was based on the Guidelines for Translation by the International Society for Pharmacoeconomics and Outcomes Research Task Force for Translation and Cultural Adaptation Group. The translated version was validated in 226 patients with gastric cancer, using the area under the receiver operating characteristic curve analysis (AUC-ROC), measures of sensitivity, specificity, and the Youden index. The prevalence of malnutrition was analyzed using descriptive statistics. The AUC-ROC Korean version of the PG-SGA was 0.85, and a score of 12 was the most optimal cut-off score, with a sensitivity of 78.6% and a Youden index of 0.54. One-third of participants were malnourished, and 70% of them had more than one physical symptom affecting their food intake. The Korean version of the PG-SGA is an effective and valid assessment tool for evaluating malnutrition in patients with gastric cancer. A new cut-off score could be used in patients with gastric cancer to assess malnutrition.


Microsurgical treatment of cerebral aneurysms at the bifurcation of the internal carotid artery.
With microtechnique, meticulous dissection and identification of critical anatomical structures become realities, contributing substantially to the improved results in the treatment of internal carotid artery bifurcation aneurysms.


Nitrates and calcium antagonists for silent myocardial ischemia.
Continuous Holter monitoring of patients with coronary heart disease can show transient ischemic episodes occurring spontaneously with or without angina throughout the day. A controlled double-blind trial was conducted comparing the effects of isosorbide-5-mononitrate (IS-5-MN) and nifedipine in patients with documented transient ischemic episodes. Seventy-five percent of the ischemic episodes were not accompanied by pain. Twenty patients with documented coronary heart disease were included; 15 finished the 4-week study (1 patient had headaches, 1 thyrotoxicosis, 1 hypertensive crisis and 2 unstable angina). On a dual-channel FM-recorded electrocardiogram, ischemic episodes were counted when ST deviation was greater than 1 mm for greater than 1 minute. Patients received IS-5-MN (20 mg 3 times a day or 50 mg in a sustained-release tablet) or nifedipine (20 mg in a sustained-release tablet 3 times a day) in random order over four 1-week periods. At the end of each week, Holter monitoring was repeated and showed reductions of episodes by 67% and 67% after weeks of IS-5-MN therapy and 56% and 58% after weeks of nifedipine therapy (all p less than 0.05). Painful and painless episodes were reduced to a similar extent. Individual responses showed great variability, and in all treatment periods not more than half of the patients were completely free of ischemic episodes. One of the 12 patients did not respond to either way of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of caries risk in schoolchildren: salivary buffering capacity and bacterial counts, sugar intake and caries experience as predictors of 2-year and 3-year caries increment.
Six variables which are capable of measurement at the chairside were assessed for their ability to identify children who would experience high caries increments during the subsequent 2 or 3-year period. The predictor variables measured in 84 urban schoolchildren, aged 11-12 years at baseline, were: baseline caries experience, salivary buffering power, counts of salivary Streptococcus mutans and lactobacilli, and two estimates of between-meal sugar intake. All the predictor variables showed statistically significant correlations with either 2-year or 3-year caries increment. Approximately 25% of subjects were identified as high risk individuals on the basis of a 2-year DFS increment of 5 and above, or a 3-year increment of 8 and above. None of the predictor variables achieved the target predictive value of 80%, either individually or in combination. The combination of Streptococcus mutans counts and buffering capacity measurements at baseline correctly identified low risk during the 3-year period in 78% of individuals (specificity), but only identified 12 out of 19 individuals (63%) at high risk (sensitivity), giving a predictive value of 75%. The predictive value for baseline caries experience was 66%. The results of the present study indicate that the salivary diagnostic tests have potential, but need further development before they can be used with confidence in clinical practice.


[Clinical epidemiology and prevention of contact allergies. The Information Network of Departments of Dermatology (IVDK) as a register and surveillance system].
A total of 56 departments of dermatology from Germany, Austria, and Switzerland collaborate to study the clinical epidemiology of contact allergies (CA). Data generated in the course of the diagnostic work-up of CA (e.g., patch test data) have been stored since 1989 in the data center in Göttingen, Germany, including data for more than 200,000 patients (March 2011). These data can be used as a register and as a surveillance system. Analysis of the register may identify and quantify risk factors of sensitization to an allergen, which is exemplified with the case of the allergen para-phenylenediamine. It turned out that-in addition to the risk factor hair dyeing-other important risk factors must be considered. In contrast, data collected every 6 months (from approximately 6,000 patients) allow for time-trend analyses of allergens, thus, identifying allergens of concern, which is of utmost importance for early preventive intervention. Here, the epidemiology of allergies to epoxy resins serves as an example. Continuous monitoring of contact allergens will also be mandatory in the future, as the CA premarketing screening systems will have imperfect predictive values with regard to human CA risk. Unfortunately, the (current) national regulatory framework severely hampers clinical surveillance/epidemiology of contact sensitization and, thus, prevention of contact allergy.


Exploring the N-terminal role of a heterologous protein in secreting out of Escherichia coli.
Escherichia coli is commonly used as a host for the extracellular production of proteins. However, its secretion capacity is often limited to a frustratingly low level compared with other expression hosts, because E. coli has a complex cell envelope with two layers. In previous report, we identified that the catalytic domain of a cellulase (Cel-CD) from Bacillus subtilis can be secreted into the medium from recombinant E. coli in large quantities without its native signal peptide. In this study, we proved the N-terminal sequence of the full length Cel-CD played a crucial role in transportation through both inner and outer membranes. By subcellular location analysis, we verified that the secretion was a two-step process via the SecB-dependent pathway through the inner membrane and an unknown pathway through the outer membrane. However, the N-terminal region of Cel-CD is polar and hydrophilic, which showed no similarities to other typical signal sequences. Random mutagenesis experiment suggested that the N-terminal sequence is a compromising result of transportation through inner and outer membranes. This is the first report that a "non-classical signal peptide" can guide recombinant proteins out of the cells from cytoplasm. Biotechnol. Bioeng. 2016;113: 2561-2567. © 2016 Wiley Periodicals, Inc.


A tiling resolution DNA microarray with complete coverage of the human genome.
We constructed a tiling resolution array consisting of 32,433 overlapping BAC clones covering the entire human genome. This increases our ability to identify genetic alterations and their boundaries throughout the genome in a single comparative genomic hybridization (CGH) experiment. At this tiling resolution, we identified minute DNA alterations not previously reported. These alterations include microamplifications and deletions containing oncogenes, tumor-suppressor genes and new genes that may be associated with multiple tumor types. Our findings show the need to move beyond conventional marker-based genome comparison approaches, that rely on inference of continuity between interval markers. Our submegabase resolution tiling set for array CGH (SMRT array) allows comprehensive assessment of genomic integrity and thereby the identification of new genes associated with disease.


Anaerobic biodegradation of acetochlor by acclimated sludge and its anaerobic catabolic pathway.
Acetochlor is a chloroacetamide herbicide that has been widely used for weed control in recent decades. The contamination from its residue in the environment has raised major serious concerns. The aerobic degradation of acetochlor has been well studied; however, little is known regarding its anaerobic degradation. In the study, anaerobic sludge with high acetochlor degradation efficiency was obtained by pressure acclimation in a continuous flow anaerobic reactor. The acetochlor degradation dynamics followed a first-order kinetic reaction equation. The acclimated sludge could degrade six chloroacetamide herbicides with the degradation efficiencies observed as alachlor > acetochlor > propisochlor > butachlor > pretilachlor > metolachlor, and the N-alkoxyalkyl structure of these herbicides significantly affected their biodegradability. Five metabolites, 2-ethyl-6-methyl-N-(ethoxymethyl)-acetanilide, N-(2-methyl-6-ethylphenyl) acetamide, N-2-ethylphenyl acetamide, N-2-ethylphenyl formamide and 2-ethyl-N-carboxyl aniline were identified, and a putative anaerobic acetochlor degradation pathway, initiated by dechlorination, was subsequently proposed. During acclimation, the community diversity of both eubacteria and archaea in the anaerobic sludge decreased, while the abundance of microbes belonging to genera Sporomusa, Sporobacterium, Dechloromonas, Azotobacter and Methanobacterium were significantly increased and dominated the acclimated sludge, and showing a positive correlation with the acetochlor degradation capacity. These findings should be valuable to elucidate the mechanisms associated with the anaerobic catabolism of acetochlor and facilitate the engineering application of anaerobic treatment for removing acetochlor from wastewater.


Endoscopic drainage of pancreatic fluid collections and pancreatic necrosis.
PFCs are heterogeneous, with different underlying pathology and pathophysiology. Each type of PFC is amenable to drainage, although not in every patient. Collections with only a fluid component that have either apposition to the gastric or duodenal wall demonstrated by CT or communication with the main pancreatic duct demonstrated by pancreatography can be drained endoscopically using transmural or transpapillary approaches, respectively. Collections containing significant amounts of solid debris that are treated endoscopically require placement of an irrigation system to evacuate solid debris. Endoscopists considering endoscopic therapy of a pancreatic collection must identify the type of collection being drained and exclude masqueraders of PFCs such as cystic neoplasms. EUS-guided drainage, if available, may decrease the complications of bleeding and perforation during transmural entry of PFCs. Refinement in endoscopic techniques to improve the safety and studies comparing the efficacy of endoscopic therapy with that of other drainage methods are needed.


Amazon river dolphins (Inia geoffrensis) use a high-frequency short-range biosonar.
Toothed whales produce echolocation clicks with source parameters related to body size; however, it may be equally important to consider the influence of habitat, as suggested by studies on echolocating bats. A few toothed whale species have fully adapted to river systems, where sonar operation is likely to result in higher clutter and reverberation levels than those experienced by most toothed whales at sea because of the shallow water and dense vegetation. To test the hypothesis that habitat shapes the evolution of toothed whale biosonar parameters by promoting simpler auditory scenes to interpret in acoustically complex habitats, echolocation clicks of wild Amazon river dolphins were recorded using a vertical seven-hydrophone array. We identified 404 on-axis biosonar clicks having a mean SLpp of 190.3 ± 6.1 dB re. 1 µPa, mean SLEFD of 132.1 ± 6.0 dB re. 1 µPa(2)s, mean Fc of 101.2 ± 10.5 kHz, mean BWRMS of 29.3 ± 4.3 kHz and mean ICI of 35.1 ± 17.9 ms. Piston fit modelling resulted in an estimated half-power beamwidth of 10.2 deg (95% CI: 9.6-10.5 deg) and directivity index of 25.2 dB (95% CI: 24.9-25.7 dB). These results support the hypothesis that river-dwelling toothed whales operate their biosonars at lower amplitude and higher sampling rates than similar-sized marine species without sacrificing high directivity, in order to provide high update rates in acoustically complex habitats and simplify auditory scenes through reduced clutter and reverberation levels. We conclude that habitat, along with body size, is an important evolutionary driver of source parameters in toothed whale biosonars.


Winter birth in association with a risk of brain tumor among a Finnish patient population.
The aim of this study was to analyze whether winter birth is related to risk of brain tumor in a clinical sample of patients from northern Finland. The study group comprised 101 patients suffering from a primary brain tumor. When comparing births in winter to births in other seasons, a 1.39-fold (95% CI 1.01-1.77) excess of winter births among patients was observed compared to respective births in the general population (p = 0.026). Especially patients with pituitary adenomas exhibited a 2.5-fold (95% CI 1.5-4.4) excess of winter births. The authors conclude that the season-of-birth effect in brain tumor patients should not be neglected when the actual and important tumorigenesis is investigated.


Superselective vagotomy sparing blood vessels in the rat. A useful tool in stress ulcer prevention.
In male Sprague-Dawley rats a microsurgical technique for highly selective vagotomy (HSV; syn. proximal gastric vagotomy) and for superselective vagotomy (SSV; cutting of proximal vagal fibers but sparing the blood vessels) has been developed. Basal acid secretion in both preparations was appr. 60% lower than in sham-operated controls. Acid response to 2-Deoxy-D-glucose (35 mg/kg/h over 4 h) was negative in HSV and SSV rats, whereas in sham rats acid output rose significantly. HSV, during mild stress (= control conditions), renders rats more susceptible to gastric stress ulcerations, whereas SSV with intact mucosal blood flow protects gastric mucosa almost completely. Although SSV, during severe restraint stress, cannot prevent the stress-induced breakdown of mucosal blood flow, gastric ulcerations are reduced to 40% of HSV and sham-operated control rats. SSV appears an elegant tool in stress ulcer research.


Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation?
The implantation of the blastocyst and early development of the placenta are crucial for the success of implantation and pregnancy. However, the formative stages of human placental development are largely unknown because of their existence in a 'black box' where access to samples is extremely limited for ethical reasons. In this review we discuss our current knowledge of early placental formation from the time of implantation at 3 weeks of gestation to approximately 5-6 weeks of gestation, encompassing both the significant anatomical findings derived from the unique specimens obtained in the mid-20th century and the renewed study of this period over the past 10 years as novel models of implantation have been developed.


Flood inundation mapping- Kerala 2018; Harnessing the power of SAR, automatic threshold detection method and Google Earth Engine.
Flood inundation maps provide valuable information towards flood risk preparedness, management, communication, response, and mitigation at the time of disaster, and can be developed by harnessing the power of satellite imagery. In the present study, Sentinel-1 Synthetic Aperture RADAR (SAR) data and Otsu method were utilized to map flood inundation areas. Google Earth Engine (GEE) was used for implementing Otsu algorithm and processing Sentinel-1 SAR data. The results were assessed by (i) calculating a confusion matrix; (ii) comparing the submerge water areas of flooded (Aug 2018), non-flooded (Jan 2018) and previous year's flooded season (Aug 2016, Aug 2017), and (iii) analyzing historical rainfall patterns to understand the flood event. The overall accuracy for the Sentinel-1 SAR flood inundation maps of 9th and 21st August 2018 was observed as 94.3% and 94.1% respectively. The submerged area (region under water) classified significant flooding as compared to the non-flooded (January 2018) and previous year's same season (August 2015-2017) classified outputs. Summing up, observations from Sentinel-1 SAR data using Otsu algorithm in GEE can act as a powerful tool for mapping flood inundation areas at the time of disaster, and enhance existing efforts towards saving lives and livelihoods of communities, and safeguarding infrastructure and businesses.


Does left ventricular size impact on intrinsic right ventricular function in hypoplastic left heart syndrome?
The size of the remnant left ventricle (LV) may influence right ventricular function and thus long-term outcome in palliated hypoplastic left heart syndrome (HLHS). We therefore sought to assess the impact of the size of the hypoplastic LV on intrinsic RV function in HLHS patients after Fontan surgery. Fifty-seven HLHS patients were studied 2.5 (range: 0.8-12.6) years after Fontan-type palliation with the pressure-volume conductance system. The patient cohort was divided into two groups according to the median LV area index (group 1: LV area index ≤ 1.33 cm(2)/m(2), n=29; group 2: LV area index>1.33 cm(2)/m(2), n=28). The slopes of the end systolic elastance (Ees) and the preload recruitable stroke work relation (Mw) were not different between group 1 and 2 (Ees: 2.70 ± 1.92 vs. 3.68 ± 2.68 mmHg/ml; Mw: 52.75 ± 14.98 vs. 51.09 ± 16.63 mmHg x ml; P=NS for all). Furthermore, the systolic responses to dobutamine were not statistically different between groups. However, the slope of the end diastolic stiffness (Eed) was higher in group 2 and catecholaminergic stimulation resulted in a decrease in Eed in group 2 (group 1: 0.40 ± 0.26 vs. 0.52 ± 0.45; group 2: 0.68 ± 0.44 vs. 0.47 ± 0.38 mmHg/ml, P<0.01). Furthermore Eed was lowest in patients with mitral atresia/aortic atresia, the anatomic subgroup with the smallest LV remnant. Intrinsic systolic RV function is not affected by the size of the hypoplastic LV in survivors of surgical palliation of HLHS. Diastolic stiffness, however, was higher in patients with a larger LV remnant.


Spontaneous rupture of solid pseudopapillary tumor of pancreas: A case report and review of literature.
Solid pseudopapillary tumors (SPT) account for 1% to 3% of all pancreatic tumors. They have low malignant potential with a favorable prognosis, and predominantly occur in young women. The pathogenesis and clinical behavior of SPT are still uncertain. In addition, most ruptures of SPT were associated with blunt abdominal trauma, while spontaneous ruptures seemed to be quite rare. Up to now, there have been only 3 spontaneous ruptured SPT cases reported worldwide. Here, we reported a 22-year-old female patient with left lower abdominal pain. Computed tomography (CT) showed that a hemorrhagic complex solid cystic mass located in the lesser omentum sac. According to pathological findings of tumor specimen, the diagnosis of solid pseudopapillary tumor (SPT) of the pancreas was made. Distal pancreatectomy and splenectomy was carried out. The patient recovered to normal status within 10 days after surgery. Besides, we reviewed about 50 cases in literatures to find out the clinical characteristics and differential diagnostic strategies of SPT.


Half-lives of different sized mRNAs for the PKA subunit RI alpha are regulated differently in response to inhibition of transcription and translation.
The RI alpha mRNA level is induced 3-5 times by FSH or cAMP analogs in primary cultures of rat Sertoli cells. In rat tissues, the RI alpha gene gives rise to three different mRNAs of different size: 3.2, 2.9 and 1.7 kb. In the present study we report that the 1.7 kb transcript has a shorter half-life than the two other mRNAs. In cells which had been pre-stimulated with a cAMP analog, inhibition of transcription stabilizes the two larger, but not the smaller sized RI alpha mRNA. However, in contrast, inhibition of protein synthesis stabilizes all the RI alpha mRNAs. Thus, degradation of various mRNAs coding for the same protein reveals different dependencies on transcription and translation.


Differential recognition of the serologically defined HLA-A2 antigen by allogeneic cytotoxic T cells. I. Population studies.
Human alloimmune cytotoxic T cells, sensitized selectively against the HLA-A2 antigen, were tested on a panel of selected target cells. Five HLA-A2 positive outlier cells could be identified. These outlier cells were only weakly lysed by HLA-A2 specific CTLs, although they were serologically indistinguishable from the other HLA-A2 positive, strongly lysed target cells. Furthermore, it was found that the outlier cells were poor cold target inhibitors in contrast to the other HLA-A2 positive target cells, which showed adequate inhibition of specific lysis of HLA-A2 positive target cells. Population studies indicate that the frequency of such HLA-A2 outlier cells may be approximately 10%.


Role of Prolactin in the Regulation of Bicarbonates Biodynamics in Female Rat Model of Cholestasis of Pregnancy.
We studied possible involvement of prolactin in the regulation of bicarbonate biodynamics using female rat model of cholestasis of pregnancy induced by transplantation of the donor pituitary under the renal capsule of a recipient (hyperprolactinemia) and bile duct ligation (cholestasis). The concentration of bicarbonates in the bile and blood, their excretion, clearance, and reabsorption, as well as glomerular filtration rate and excretion of sodium ions were assessed. It was found that the main effect of prolactin was directed to the kidney-regulated pool of bicarbonates and consisted in stimulation of their clearance and inhibition of reabsorption, which led to a decrease in bicarbonate blood concentration. Parallel influence of prolactin on the clearance of bicarbonates and sodium ions was observed.


Establishing best practice in violence risk assessment and violence prevention education for nurses working in mental health units.
To explore and evaluate extant and potential methods used in risk assessment and aggression prevention training. This study was also designed to consider the most appropriate method for educating nurses in use of a novel risk assessment instrument linked to a structured nursing intervention protocol (the electronic application of the Dynamic Appraisal of Situational Aggression and Aggression Prevention Protocol). Organisational and personal concerns have led to the development of training programs designed to prevent and manage aggression in mental health units. This descriptive qualitative study explored experts' opinions about effective training approaches. Data were collected via focus groups (a total of four discrete groups), with each of the four focus groups repeated after four weeks. A semi-structured guide was used to guide the focus group discussions. Seventeen experts with experience coordinating and facilitating training in prevention and management of aggression in mental health units in New Zealand and Australia participated in this study. Three themes emerged from the data 1) existing training can be "like pulling teeth without anaesthetic" 2) the need to "breathe life" into the training and 3) a vision of the "gold standard" for practice and training. Training is optimal when it is place-based, responsive to local needs and inclusive of relevant clinical, cultural, consumer/carer and contextual factors. Training may benefit from a focus on the application of the knowledge, skills and attitudes learnt and there is a need for ongoing reinforcement of training in the clinical setting, beyond initial introduction and provision of information and orientation to relevant skills.


Phosphate fertilization affects rhizosphere microbiome of maize and sorghum genotypes.
Despite the lower reactivity of natural phosphates compared to soluble fertilizers, their P bioavailability can increase over the cultivation years, due to the physicochemical processes and the activity of soil microbiota. Therefore, this work aimed to evaluate the α and β diversity of the rhizosphere microbiota of maize and sorghum genotypes grown under different sources and doses of phosphate fertilizers. Four commercial maize and four sorghum genotypes were grown under field conditions with three levels of triple superphosphate (TSP) and two types of rock phosphate sources: phosphorite (RockP) and bayóvar (RP) during two seasons. Maize and sorghum presented a significant difference on the genetic β diversity of both rhizosferic bacterial and arbuscular mycorrhizal fungi. Moreover, P doses within each phosphate source formed two distinct groups for maize and sorghum, and six bacterial phyla were identified in both crops with significant difference in the relative abundance of Firmicutes and Proteobacteria. It was observed that RockP fertilization increased Firmicutes population while Proteobacteria was the most abundant phylum after TSP fertilization in maize. In sorghum, a significant impact of fertilization was observed on the Acidobacteria and Proteobacteria phyla. TSP fertilization increased the Acidobacteria population compared to no fertilized (P0) and RockP while Proteobacteria abundance in RockP was reduced compared to P0 and TSP, indicating a shift toward a more copiotrophic community. Our results suggested that the reactivity of P source is the predominant factor in bacterial community' structures in the maize and sorghum rhizosphere from the evaluated genotypes, followed by P source.


Continuous, high capacity reconstitution of nutrient media from concentrated intermediates.
We designed an Integrated Media Preparation System (IMPS) for continuous, on-line preparation of cell culture media and delivery to intermediate storage vessels or directly to a bioreactor. Key components of the IMPS include: a high precision, continuous fluid mixing device; formulation-specific liquid medium concentrates; validated process controls and membrane filtration; and automated dispensing into large volume flexible plastic containers. The IMPS system is designed to produce sterile, single-strength liquid medium from common raw materials at a delivery rate of 1000-3000 liters per hour and will manufacture homogenous batches from several thousand liters to over 60,000 liters. Fortified nutrient media prepared from multi-component 50X concentrates have been demonstrated to accelerate bioreactor seed chains, increase product yield, and reduce the overall manufacturing cost of nutrient medium. A productivity matrix will analyze the fully-loaded costs and contrast alternative methods for media preparation against projected biological yield.


MicroRNA21 promotes interstitial fibrosis via targeting DDAH1: a potential role in renal fibrosis.
Scarring of the kidney directly promotes loss of kidney function. A thorough understanding of renal fibrosis at the molecular level is urgently needed. One prominent microRNA, miR-21, was previously reported to be up-regulated in renal fibrosis, but its mechanism is unclear. In the present study, an unbiased search for downstream messenger RNA targets of miR-21 using the HK-2 human tubular epithelial cell line was performed. Effects of the target gene in renal fibrosis and underlying mechanism were explored. Results show that forced expression of miR-21 significantly increased cell apoptosis, interstitial deposition, and decreased E-cadherin level of the HK-2 cells. Conversely, inhibition of miR-21 promoted the opposite effects. We identified that miR-21 directly interacted with the 3'-untranslated region of the suppressor of dimethylarginine dimethylaminohydrolase 1 (DDAH1) by dual-luciferase assay. Moreover, pcDNA3.1-DDAH1 pretreatment could effectively reduce α-SMA, collagen I, fibronectin expression, and promoted E-cadherin expression, as well as inhibiting HK-2 cell apoptosis, while all those effects can be attenuated by pretreatment with the Wnt/β-catenin signaling activator Licl. Taken together, our results suggest that miR-21 may regulate renal fibrosis by the Wnt pathway via directly targeting DDAH1. Therefore, this study may provide novel strategies for the development of renal fibrosis therapy.


From sewage sludge ash to a recycled feed phosphate - digestibility of precipitated calcium phosphate in broiler chickens and growing pigs.
Today, EU is largely (∼92%) dependent on the import of phosphates as most mines are located outside Europe. Because of the limited availability, phosphorus (P) is included on the list of Critical Raw Materials. Precipitated calcium phosphate (PCP) recovered from sewage sludge ash is a novel and sustainable option to replace mined P as raw material in feed phosphates, e.g. monocalcium phosphate (MCP) or dicalcium phosphate, but the digestibility has not yet been tested in vivo. The aim was therefore to determine PCP and MCP apparent ileal digestibility (AID) of P in broiler chickens and apparent (ATTD) and true (TTTD) total tract digestibility of P in growing pigs. A chicken study comprised 240 Ross 308 chickens that were housed in groups of eight from day 21 to day 28. Five diets were used, a basal diet and two test diets, which contributed either 0.075% (low) or 0.150% (high) additional P for each of the test sources (MCP and PCP). The basal and test diets were composed to achieve increasing levels of P and AID was calculated with regression analysis. In the pig study, eight individually housed pigs were used in a change-over study with two experimental periods. The pigs were fed a basal P-free diet in a preperiod to be able to estimate endogenous P losses and then two different diets in two periods using a change-over design, where MCP and PCP were the only P source, providing in total 0.33 (basal diet), 4.42 (MCP) and 3.53 (PCP) g kg-1P, respectively. The AID of P in PCP and MCP for chickens was 58.4 and 75.1% (P = 0.166). The ATTD and TTTD of P in PCP for pigs were 58.4 and 67.2%, respectively, which was lower (P < 0.001) than the corresponding values for MCP (82.1 and 89.1%), respectively. The digestibility of calcium (Ca) did not differ in the chicken diets with high inclusion levels of PCP and MCP (54.7 and 55.3%, respectively, P = 0.535), but was lower for PCP than MCP in the pig study (57.8 and 70.8% respectively, P = 0.001). In conclusion, the digestibility of P in PCP for chickens did not differ from conventional MCP, whereas for pigs, it was lower, but could be a viable alternative to other common sources of P.


The utility of DHL-HisZnNa, a novel antioxidant, against anticancer agent-induced alopecia in breast cancer patients: a multicenter phase II clinical trial.
Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of anticancer drugs; however, there are currently no mechanisms to completely prevent CIA. In this study, we performed a clinical trial to examine whether sodium N-(dihydrolipoyl)-l-histidinate zinc complex (DHL-HisZnNa), an alpha-lipoic acid derivative, prevents CIA in patients with breast cancer. Between July 2014 and May 2015, we performed a multi-center, single arm, clinical trial involving 103 breast cancer patients who received adjuvant chemotherapy at three medical institutions in Japan. During chemotherapy, a lotion containing 1% DHL-HisZnNa was applied daily to the patients' scalps. The primary endpoint was the incidence of grade 2 alopecia; the secondary endpoints were the duration of grade 2 alopecia, alopecia-related symptoms, and drug-related adverse events. Alopecia was evaluated by three independent reviewers using head photographs taken from four angles. Safety analysis was performed for 101 patients who started the protocol therapy. After excluding one patient who experienced disease progression during treatment, 100 patients who received at least two courses of chemotherapy underwent efficacy analysis. All original 101 patients developed grade 2 alopecia, the median durations of which were 119 days (112-133 days) and 203 days (196-212 days) in the groups treated with four and eight courses of chemotherapy, respectively. Mild or moderate adverse events potentially related to DHL-HisZnNa were observed in 11 patients. Alopecia-related symptoms were observed in 53 patients (52%). The application of 1% DHL-HisZnNa to the scalp did not prevent CIA. However, this drug may promote recovery from CIA. UMIN000014840.


Mortality Patterns Among Industrial Workers Exposed to Chloroprene and Other Substances: Extended Follow-Up.
To update the U.S. portion of an historical cohort mortality study of workers with potential exposure to chloroprene (CD) and vinyl chloride (VC) with focus on lung and liver cancer. Subjects were 6864 workers from two sites with vital status determined through 2017 for 99% of subjects and cause of death for 97.2% of deaths. Historical exposures to CD and VC were estimated quantitatively. We performed external and internal mortality comparisons. External comparisons revealed mostly deficits in deaths; internal comparisons revealed no consistent evidence of exposure-response relationships with CD or VC. Our update continues to support the conclusion that the risk of death from lung or liver cancer is unrelated to exposure to CD or VC at levels experienced by workers in the two U.S. sites.


Primary care pediatricians and job satisfaction: a cross sectional study in the Lazio region.
The Order of Physicians and Dentists of the Province of Rome aims at focusing on the satisfaction of healthcare personnel as an essential factor for the quality of medical care in the health sector. The aim of this study is to assess and prioritize the factors that can be linked to a higher or lower degree of job satisfaction in Primary Care Pediatricians (PCPs). This study is a cross sectional survey. A questionnaire was administered to all primary care pediatricians registered to the Order, exploring in particular the work activity organization, the level of satisfaction in their professional life, and the level of perceived health. A pilot activity was conducted to validate the questionnaire. Fisher exact test and ordinal logistic regression (ologit) models were used for the univariate and multivariate analysis. The highest level of job dissatisfaction, in both men and women, was found to be in the practice type without any form of association; among women, it reached an even higher level for those who had their own practice at a distance of 20-40 km from their home. Women, compared to men, maintained a lower level of job satisfaction also while working in Pediatric Primary Care Units (PPCUs). In PPCUs, for the same distance, females showed a more similar pattern to males. Men working in PPCUs, regardless of distance, declared a higher degree of job satisfaction. Both men and women, working as a group pediatrician or in PPCUs, did not show a significant difference in the level of job satisfaction. The study contributes to a deeper understanding of the factors that may influence levels of career satisfaction in female and male PCPs. Therefore, research and interventions regarding job satisfaction should foster an organizational network connection among PCPs for their job and individual well-being, from a perspective of enhancing patient care. A major effort to improve work-life balance and career satisfaction among women is important, suggesting that interventions for improving job satisfaction could benefit from a gender-specific approach.


Sex-specific relationships of the infant microbiome and early-childhood behavioral outcomes.
A link between the gut microbiome and behavior is hypothesized, but most previous studies are cross-sectional or in animal models. The modifying role of host sex is poorly characterized. We aimed to identify sex-specific prospective associations between the early-life gut microbiome and preschool-age neurobehavior. In a prospective cohort, gut microbiome diversity and taxa were estimated with 16S rRNA sequencing at 6 weeks, 1 year, and 2 years. Species and gene pathways were inferred from metagenomic sequencing at 6 weeks and 1 year. When subjects were 3 years old, parents completed the Behavioral Assessment System for Children, second edition (BASC-2). A total of 260 children contributed 523 16S rRNA and 234 metagenomics samples to analysis. Models adjusted for sociodemographic characteristics. Higher diversity at 6 weeks was associated with better internalizing problems among boys, but not girls [βBoys = -1.86 points/SD Shannon diversity; 95% CI (-3.29, -0.42), pBoys = 0.01, βGirls = 0.22 (-1.43, 1.87), pGirls = 0.8, pinteraction = 0.06]. Among other taxa-specific associations, Bifidobacterium at 6 weeks was associated with Adaptive Skills scores in a sex-specific manner. We observed relationships between functional features and BASC-2 scores, including vitamin B6 biosynthesis pathways and better Depression scores. This study advances our understanding of microbe-host interactions with implications for childhood behavioral health. This is one of the first studies to examine the early-life microbiome and neurobehavior, and the first to examine prospective sex-specific associations. Infant and early-childhood microbiomes relate to neurobehavior including anxiety, depression, hyperactivity, and social behaviors in a time- and sex-specific manner. Our findings suggest future studies should evaluate whether host sex impacts the relationship between the gut microbiome and behavioral health outcomes.


The long-term outcomes of laparoscopic versus open pancreatoduodenectomy for ampullary carcinoma showed similar survival: a case-matched comparative study.
Few studies have compared the oncological benefit of laparoscopic (LPD) and open pancreatoduodenectomy (OPD) for ampullary carcinoma. The aim of this study was to compare the oncological results of these two approaches. Between 2011 and 2020, 103 patients who underwent PD for ampullary carcinoma, including 31 LPD and 72 OPD, were retrospectively analyzed. Patients were matched on a 1:2 basis for age, sex, body mass index, American Society of Anaesthesiologists score, and preoperative biliary drainage. Short- and long-term outcomes of LPD and OPD were compared. The 31 LPD were matched (1:2) to 62 OPD. LPD was associated with a shorter operative time (298 vs. 341 min, p = 0.02) than OPD and similar blood loss (361 vs. 341 mL, p = 0.747), but with more intra- and post-operative transfusions (29 vs. 8%, p = 0.008). There was no significant difference in postoperative mortality (6 vs. 2%), grades B/C postoperative pancreatic fistula (22 vs. 21%), delayed gastric emptying (23 vs. 35%), bleeding (22 vs. 11%), Clavien ≥ III morbidity (22 vs. 19%), or the length of hospital stay (26 vs. 21 days) between LPD and OPD, respectively, but there were more reinterventions (22 vs. 5%, p = 0.009). Pathological characteristics were similar for tumor size (21 vs. 22 mm), well differentiated tumors (41 vs. 38%), the number of harvested (23 vs. 26) or invaded lymph nodes (48 vs. 52%), R0 resection (84 vs. 90%), and other subtypes (T1/2, T3/4, phenotype). With a comparable mean follow-up (41 vs. 37 months, p = 0.59), there was no difference in 1-, 3-, and 5-year overall (p = 0.725) or recurrence-free survival (p = 0.155) which were (93, 74, 67% vs. 97, 79, 76%) and (85, 58, 58% vs. 90, 73, 73%), respectively. This study showed a similar long-term oncological results between LPD and OPD for ampullary carcinoma. However, the higher morbidity observed with LPD compared to OPD, restricting its use to experienced centers.


Resequencing of 414 cultivated and wild watermelon accessions identifies selection for fruit quality traits.
Fruit characteristics of sweet watermelon are largely the result of human selection. Here we report an improved watermelon reference genome and whole-genome resequencing of 414 accessions representing all extant species in the Citrullus genus. Population genomic analyses reveal the evolutionary history of Citrullus, suggesting independent evolutions in Citrullus amarus and the lineage containing Citrullus lanatus and Citrullus mucosospermus. Our findings indicate that different loci affecting watermelon fruit size have been under selection during speciation, domestication and improvement. A non-bitter allele, arising in the progenitor of sweet watermelon, is largely fixed in C. lanatus. Selection for flesh sweetness started in the progenitor of C. lanatus and continues through modern breeding on loci controlling raffinose catabolism and sugar transport. Fruit flesh coloration and sugar accumulation might have co-evolved through shared genetic components including a sugar transporter gene. This study provides valuable genomic resources and sheds light on watermelon speciation and breeding history.


A sub-centimeter HCC with bright loop appearance diagnosed by contrast-enhanced ultrasonography.
Detection of a hepatocellular carcinoma (HCC) in the early stage is critical, as clinical stage influences treatment selection and patient prognosis. Carcinogenetic development of an HCC is a multi-step process, and a differential diagnosis between a dysplastic nodule and a well-differentiated HCC is often difficult. A bright loop appearance is a significant finding that indicates disappearance of fatty deposition in the central area of the nodule during the progression toward HCC, however such a finding is rare in cases of sub-centimeter-sized HCCs. We encountered a case of HCC that developed a bright loop appearance on ultrasound (US) without enlargement approximately 2 years after diagnosis as a dysplastic nodule. Moreover, the hypoechoic area in the center of the nodule showed an HCC pattern in contrast enhanced US with Sonazoid™. Vascularity in the nodule could not be observed on dynamic contrast-enhanced CT or Gd-EOB-DTPA-enhanced MRI. When a change in the intranodular echo pattern is observed in sub-centimeter-sized nodules, examination of intranodular vascularity by contrast-enhanced US is important to evaluate borderline lesions.


Use of normal daughters' and sisters' creatine kinase levels in estimating heterozygosity in Duchenne muscular dystrophy.
A modification is given of the original density function formula of EMERY and MORTON for estimating heterozygosity in X-linked Duchenne muscular dystrophy. This modification takes into account SCK levels in both normal sisters and normal daughters of a suspected carrier in families where there is only one affected male.


Effects of chronic ethanol consumption on alpha-adrenergic-induced contractions in rat thoracic aorta.
1. The effects of chronic oral administration of ethanol (EtOH, 80 mM daily during 15-18 days) on the modulation exerted by the endothelium on the contractions induced by phenylephrine (Ph) and clonidine (C) were studied in rat aortic rings with and without endothelium. 2. The maximal contraction induced by a 70 mM KCl depolarizing solution was similar in control and EtOH treated-rings. 3. EtOH pretreatment significantly enhanced the contractile response to Ph in vessels with intact endothelium, but did not significantly affect the response of endothelium-denuded rings. 4. This effect reflects a reduction of the modulation exerted by the endothelial cells on alpha 1-adrenergic vasoconstriction. 5. C did not contract control aortic rings with endothelium, but after EtOH treatment, the response reached about 20% of the maximal KCl-induced contraction. 6. EtOH pretreatment significantly enhanced the contractile response to C both in endothelium-denuded and intact aortic rings. 7. The results indicate that chronic EtOH consumption significantly potentiates alpha-adrenergic-induced contractions in rat aortic rings, probably through interference with the production and/or the release of EDRF.


Cryptocotyle lata (Trematoda: Heterophyidae) Adult from a Korean Raccoon Dog, Nyctereutes procyonoides koreensis.
Total 513 heterophyid flukes were collected from a carcass of wild Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. With morphological and molecular characteristics, the flukes were identified to Cryptocotyle lata. The adult C. lata were minute, transparent, pentagonal, 522 µm long by 425 µm wide. Ceca extended into post-testicular region. Ventrogenital sac elliptical, 79 µm by 87 µm with genital pore and ventral sucker. Two testes semielliptical and slightly lobed, located in the posterior region, right testis 173 µm by 155 µm, left testis 130 µm by 134 µm. In a phylogenetic tree, the fluke specimen of this study was grouped with C. lata divergent from Cryptocotyle lingua. We report here N. procyonoides koreensis first as a natural definitive host of C. lata.


Strepyrazinone, a tricyclic diketopiperazine derivative with cytotoxicity from a marine-derived actinobacterium.
Strepyrazinone (1), a tricyclic diketopiperazine derivative with a carbon skeleton unprecedented in natural products, was isolated from the marine-derived Streptomyces sp. B223. Its structure was elucidated by spectroscopic analyses and electronic circular dichroism calculation. Compound 1 showed cytotoxic activity against HCT-116 cancer cell lines with an IC50 value of 0.34 µM.


Nitric oxide modulation of the growth and differentiation of freshly isolated acute non-lymphocytic leukemia cells.
Freshly isolated acute non-lymphocytic leukemia (ANLL) cells were treated with the nitric oxide (NO)-liberating compounds sodium nitroprusside or S-nitrosoacetyl penicillamine and analyzed for viability, growth, and differentiation at 3-5 days. NO decreased the viability and the growth of freshly isolated ANLL cells in vitro. NO treatment significantly increased expression of CD14 in blast cells from patients with M5 ANLL, and increased at least one differentiation parameter in M4 or M5 cells. It had little or no effect on parameters of differentiation in other ANLL cells. We conclude that in vitro culture with NO decreases the growth and viability of most freshly isolated ANLL cells. NO also induces the differentiation of ANLL cells with a monocytic phenotype.


Detection and removal of contaminating hydroxylamines from the spin trap DEPMPO, and re-evaluation of its use to indicate nitrone radical cation formation and S(N)1 reactions.
A previous report that the spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO) allows DEPMPO radical cation formation to be detected via the production of a carbon-centred radical adduct (assigned as the cis-hydroxyethyl species, formed by an intramolecular process) is shown to be incorrect. Rather, this and other paramagnetic species arise from the facile oxidation of trace hydroxylamine impurities present in commercial DEPMPO samples. As a result, techniques for the detection and elimination of such hydroxylamine impurities from DEPMPO solutions were developed and are described; these should prove to be of general use in EPR spin trapping experiments.


Mechanisms of action of novel skin penetration enhancers: phospholipid versus skin lipid liposomes.
Employing thermal analysis, we investigated the mechanism of action of novel enhancers and probed phospholipid (PL) versus stratum corneum lipid (SCL) liposomes as model membranes. The enhancers included octyl salicylate (OS), padimate O (PADO) and 2-(1-nonyl)-1,3-dioxolane (ND). The negative controls were the empty liposomes. Positive controls employed dimethylsulfoxide (DMSO) and Azone (AZ). For PL liposomes, DMSO sharpened the transitions. AZ abolished the pre-transition, broadened the main transition and linearly reduced its transition temperature (T(m)). OS or PADO reduced T(m) and size of pre-transition, broadened the main transition and decreased its T(m) (non-linearly). ND abolished the pre-transition but increased T(m) of the main endotherm, suggesting retardation rather than enhancement. The results of SCL correlated with PL liposomes except for ND. In SCL liposomes, ND reduced T(m) and broadened the peaks indicating lipid disruption, which indicated its enhancing effects. In conclusion, OS, PADO and ND can enhance drugs by disrupting intercellular lipid domain but they differ from AZ in terms of the relationship between efficacy and concentration. Although PL liposomes are simple model membranes with sharp transitions which give detailed information about the effects of enhancers, they can provide misleading results. Simultaneous use of other models like SCL liposomes is recommended.


Immobilization of diastase α-amylase on nano zinc oxide.
Diastase α-amylase extracted from malt, catalyses break down of starch into maltose. It is commonly used in food and fermentation industry. In the present study nano zinc oxide is used as support for this starch hydrolyzing enzyme. IR study revealed that the enzyme got adsorbed via electrostatic interaction with the functional groups on the support. The immobilized enzyme possessed a better heat-resistance than free enzyme. The kinetic parameters were determined using Lineweaver-Burk plot. The immobilized enzyme showed higher Km 2.08mg/ml than the free enzyme whose Km is 0.45±.05mg/ml. The Vmax of immobilized enzyme was about 2.92±.02mg/ml/min and that of free enzyme was 7.14±.02mg/ml/min, showing decrease in activity after immobilization. The immobilized enzyme showed 70% activity after 30days of storage while free enzyme lost its activity within 7days. About 80% of enzyme retained activity after 4 cycles of reuse.


Role of leukotrienes and platelet activating factor in acute gastric mucosal lesions in rats.
Leukotriene C4 (LTC4) and platelet activating-factor (PAF) were found to affect gastric microcirculation and mucosal integrity but their role in acute gastric damage has not been established. The present study with rats confirms that exogenous LTC4 (10 micrograms/kg.h s.c.) or PAF (10 micrograms/kg i.p.) alone caused only mild gastric mucosal injury but greatly augmented mucosal lesions produced by other irritants such as absolute ethanol, taurocholate, aspirin or stress. These acute lesions were accompanied by a significant increase in mucosal generation of LTC4, and the addition of PAF further increased it. Pretreatment with BN 52021, a PAF receptor antagonist, abolished PAF-induced gastric lesions and reduced LTC4 generation in tests with PAF plus ethanol. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, and FPL 55712, an LTC receptor-antagonist, reduced dose dependently the extent of gastric damage in various models of gastric lesions. Again, these protective effects were accompanied by a reduction in mucosal LTC4 formation. In addition, the protection induced by nordihydroguaiaretic acid was reversed in part by the pretreatment with indomethacin, suggesting that it could be attributed to increased biosynthesis of protective PG. The results indicated that LTC4 biosynthesis is increased in various forms of gastric damage and that LTC4 may be involved in the pathogenesis of this damage.


A sequential study of viral DNA in serum in experimental transmission of duck hepatitis B virus.
To understand the relationship among the time of infection, infection patterns, and liver diseases, experimental transmission of duck hepatitis B virus (DHBV) utilizing 165 Japanese white domestic ducklings was performed. Twenty to 25 ducklings were each inoculated with DHBV-positive serum intravenously at day one, 3, 5, 7, 10, and 14 posthatch and were sacrificed during the 1st, 2nd, 3rd, and 4th (and 24th in those inoculated on day one and day 3 posthatch) week after inoculation to obtain sera and the liver. The sera served for the measurement of DHBV DNA by spot hybridization test and DNA polymerase activity, and the liver was subjected to morphological examination including immunostaining for DHBV. The ducklings inoculated with DHBV on 1 day and 3 days posthatch always revealed persistent viremia, whereas those on and after 5 days posthatch showed persistent or transient viremia. The hepatitis activity in the liver was seen in ducklings inoculated with DHBV on and after 3 days posthatch and was very weak consistent with the diagnosis of mild acute hepatitis of humans. The serum transaminase activity was not significantly elevated at the time of occurrence of histological hepatitis activity. Since host immune mechanism establish at 3 to 5 days posthatch in birds, the host immune response seemed to determine whether DHBV infection was persistent or transient and the occurrence of hepatitis activity as seen in human hepatitis B virus (HBV) infection.


Treatment of hypertension in renal disease.
Experimental and clinical evidence are summarized that support the hypothesis that enhanced transmission of systemic hypertension to the adapted glomerulus in the setting of reduced nephron mass may be responsible for accelerated vascular and glomerular damage in the hypertensive stage of parenchymal renal disease in man. In experimental models of hypertension associated with reduced renal mass, the kidney appears to be damaged directly by transmission of pressure rather than primarily through vasoconstriction and ischemia. When hypertension is combined with models of glomerular disease, vascular and glomerular injury are aggravated. It is proposed that adaptive glomerular hemodynamic alterations which occur in parenchymal renal disease magnify the transmission of increased pressure and flows when hypertension supervenes. Accelerated vascular and glomerular damage and functional deterioration result. According to this hypothesis, control of systemic hypertension and minimization of hydraulic stress on the diseased glomerulus become critical to the management of chronic renal disease and the prevention of progressive renal insufficiency.


Efficient and targeted chemo-gene delivery with self-assembled fluoro-nanoparticles for liver fibrosis therapy and recurrence.
The treatment options of liver fibrosis remain limited except for liver transplantation due to the complexity and slow development in its progression. Besides, liver fibrosis recurrence and intervention time have not been reported as significant indicators to affect the anti-fibrotic efficacy of tested drugs/strategies. Herein, a novel fluoropolymer is developed to achieve high drug loading of sorafenib and efficient delivery of miR155 inhibitor (anti-miR155) for dual-targeting of hepatic stellate cells (HSCs) and kupffer cells (KCs), and we report a detailed plan on the design of treatment regimen to reveal the relationship between chemogene therapy, intervention time and fibrosis recurrence. Such a combined chemo-gene therapy of sorafenib and anti-miR155 can achieve superior therapeutic efficiency by polarizing the pro-inflammatory M1 to anti-inflammatory M2 of KCs and inhibiting the proliferation of HSCs. Importantly, efficacy and recurrence prevention of chemogene therapy earlier in the liver fibrosis will be more effective than the treatment at later stage. In conclusion, this work proposes a novel strategy to improve the efficacy and prevent recurrence of liver fibrosis by dual-regulating of KCs and HSCs, and emphasizes the importance of therapy earlier in the treatment of liver fibrosis.


Rhabdoid meningioma: analysis of one case.
Rhabdoid meningioma (RM) is rare, and it occurs mainly in children. We report the clinical and pathological features of rhabdoid meningioma in a 9-year-old child. A 9-year-old child with RM presented to our hospital with headache that had persisted for 3 days. Magnetic resonance imaging of his brain demonstrated supratentorial lesions of the right temporal petrous bone and cisterna magna cyst. He underwent surgery on January 13, 2010. The pathological diagnosis was rhabdoid meningioma (grade III). The patient underwent radiotherapy with 30 Gy/16 fractions delivered to the recurrent tumor after surgery. The patient died in December as a result of complications of recurrent meningioma. The accumulated data, including this current case, demonstrate the difficulties in reaching the diagnosis and providing treatment for this disease as a consequence of its low incidence, aggressive nature, and poor treatment options for children with rhabdoid meningioma.


TriPer, an optical probe tuned to the endoplasmic reticulum tracks changes in luminal H2O2.
The fate of hydrogen peroxide (H2O2) in the endoplasmic reticulum (ER) has been inferred indirectly from the activity of ER-localized thiol oxidases and peroxiredoxins, in vitro, and the consequences of their genetic manipulation, in vivo. Over the years hints have suggested that glutathione, puzzlingly abundant in the ER lumen, might have a role in reducing the heavy burden of H2O2 produced by the luminal enzymatic machinery for disulfide bond formation. However, limitations in existing organelle-targeted H2O2 probes have rendered them inert in the thiol-oxidizing ER, precluding experimental follow-up of glutathione's role in ER H2O2 metabolism. Here we report on the development of TriPer, a vital optical probe sensitive to changes in the concentration of H2O2 in the thiol-oxidizing environment of the ER. Consistent with the hypothesized contribution of oxidative protein folding to H2O2 production, ER-localized TriPer detected an increase in the luminal H2O2 signal upon induction of pro-insulin (a disulfide-bonded protein of pancreatic β-cells), which was attenuated by the ectopic expression of catalase in the ER lumen. Interfering with glutathione production in the cytosol by buthionine sulfoximine (BSO) or enhancing its localized destruction by expression of the glutathione-degrading enzyme ChaC1 in the lumen of the ER further enhanced the luminal H2O2 signal and eroded β-cell viability. A tri-cysteine system with a single peroxidatic thiol enables H2O2 detection in oxidizing milieux such as that of the ER. Tracking ER H2O2 in live pancreatic β-cells points to a role for glutathione in H2O2 turnover.


Revalidation and expansion of an adolescent substance abuse screening measure.
The perceived-benefit-of-drinking scale has been developed to assess reasons for drinking in an adolescent population. In this study, the self-administered questionnaire, which has been expanded to include a reason-for-drug-use scale, was completed by 1363 junior and senior high school students. A comprehensive battery of analytic techniques was used to investigate the performance of these perceived-benefit scales on this larger and wider age-range sample. The results confirmed the reliability and validity of the instrument. The findings showed the two scales to perform well across a range of sociodemographic and age groups. These data reassert the strength of the approach and support the instrument's potential as a tool for clinically assessing adolescent substance use.


1H-NMR of human saliva. An application of NMR spectroscopy in forensic science.
1H-NMR was applied to the study of metabolites in human saliva specimens. Acetate, lactate, ethanol, glucose and some other substances were simultaneously identified and quantitated from the 1H-NMR spectra of saliva specimens treated with D2O. These experiments demonstrated the value of 1H-NMR as an analytical method in the field of forensic science and clinical pathology and toxicology.


Design, synthesis, and bioavailability evaluation of coumarin-based prodrug of meptazinol.
Based on the known coumarin-based prodrug system, a new meptazinol (Z)-3-[2-(propionyloxy) phenyl]-2-propenoic ester (3) was designed and synthesized as prodrug to minimize the first-pass effect of meptazinol (1) and improve the oral bioavailability. The prodrug (3) showed a 4-fold increase in oral bioavailability over the parent drug meptazinol in rats.


Asp83, Glu113 and Glu134 are not specifically involved in Schiff base protonation or wavelength regulation in bovine rhodopsin.
Site-specific mutagenesis was employed to investigate the proposed contribution of proton-donating residues (Glu, Asp) in the membrane domains of bovine rhodopsin to protonation of the Schiff base-linking protein and chromophore or to wavelength modulation of this visual pigment. Three point-mutations were introduced to replace the highly conserved residues Asp83 by Asn (D83N), Glu113 by Gln (E113 Q) or Glu134 by Asp (E134D), respectively. All 3 substitutions had only marginal effects on the spectral properties of the final pigment (less than or equal to 3 nm blue-shift relative to native rhodopsin). Hence, none of these residues by itself is specifically involved in Schiff base protonation or wavelength modulation of bovine rhodopsin.


[The diagnostic value of urethral sphincter electromyography in patients with multiple system atrophy].
To analyze diagnostic evaluation of urethral sphincter electromyography (US-EMGs) for patients with multiple system atrophy (MSA). Totally 15 patients who were diagnosed as MSA were examined as treatment group while 17 non-MSA patients were examined as controls. US-EMGs were performed in the both groups. Spontaneous activities when relax, parameters of motor unit potentials (MUPs) mean duration and amplitude, percentage of polyphasic ware, satellite potential, recruitment potentials and amplitude when strong contraction were recorded and analyzed. US-EMGs changes of various abnormalities were found in 13 cases (86.7%) in MSA group. There were significant differences of electromyographic findings between the MSA group and control group including MUPs mean duration [(12.79 ± 3.18) ms vs (9.49 ± 1.51) ms] and amplitude [(828.53 ± 459.89) µV vs (378.76 ± 152.26) µV] as well as recruitment potentials [(11.47 ± 21.55)% vs (8.23 ± 10.74)%] and amplitude [(2.19 ± 1.24) mV vs (0.75 ± 0.42) mV] when strong contraction (all P values < 0.05). There is certain value of US-EMGs for the diagnosis of MSA. It could be used as a routine electrophysiological method for the patients who are suspected of MSA. It could be a supplement of external anal sphincter electromyography.


An overview of synthetic strategies and current applications of gold nanorods in cancer treatment.
Photothermal therapy, also referred to as optical hyperthermia or photothermal ablation, is an emerging strategy for treating solid tumours. Colloidal gold converts the absorbed light into localized heat via a non-radiative mechanism, surface plasmon resonance, which ablates the solid tumours. Several plasmon resonating nanostructures, including gold nanoparticles (AuNPs), gold nanorods (AuNRs), gold nanoshells, gold nanocages, copper sulphide and carbon nanotubes, have shown potential for photo-activated cancer therapy. Generally, spherical AuNPs display absorption maxima between 500-550 nm, making them inefficient due to low tissue penetration. On the other hand, AuNRs absorb light in the near-infrared (NIR) region that penetrates deeper with higher spatial precision, and causes no damage to the surrounding healthy tissues due to the low energy absorption of NIR light by normal tissue. Moreover, the absorption range of light can be fine-tuned to the NIR region by adjusting the aspect ratios of AuNRs. However, large-scale synthesis and stability of this colloidal system still poses challenges for clinical translation. In this review, we discuss various strategies applied up to now for the synthesis of AuNRs. Current trends in the pre-clinical development of multifunctional AuNRs with emphasis on preparation and application strategies in cancer therapy have been delineated.


Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma.
In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery. This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests. Only CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining. Among patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future.