Development and in vivo evaluation of therapeutic phytosomes for alleviation of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with progressive articular damage, functional loss and comorbidity. Conventional RA therapy requires frequent dosing and prolonged use, and usually results in poor efficacy and severe toxicity. In the current study, for the first time, we describe a combination strategy using phytosomes co-loaded with curcumin (CUR) and leflunomide (LEF) to improve the clinical outcomes of RA therapy. Exploiting 23 factorial design, various compositions of CUR and LEF co-loaded phytosomes (CUR/LEF-phytosomes) were successfully prepared and were extensively characterized (e.g., particle size, zeta potential, drugs encapsulation efficiency, morphology, DSC, FTIR and release kinetics). The optimal CUR/LEF-loaded phytosomes (F2) demonstrated high stability and spherical morphology with a particle size of ca. 760 nm and negative zeta potential value of - 55.7, high entrapment for both drugs, and sustained release profile of the entrapped medications. In vivo, oral administration of the CUR/LEF-phytosomes (F2) in arthritic rats resulted in significant reduction of paw swelling and inflammatory markers, compared to the free drugs and their physical mixture. Histopathological examination revealed significant improvement in phytosomes-treated animal group with no signs of arthritis. CUR/LEF-loaded phytosomes provide an auspicious strategy for alleviation of RA.


Phonological short-term store and the nature of the recency effect: evidence from neuropsychology.
The recency effect in immediate recall of lists of unrelated words was investigated in P.V., a left hemisphere-damaged patient, who had a grossly reduced auditory verbal span, attributed to a selective impairment of a phonological short-term store. No recency effect was evident in free recall of auditorily presented material. When the patient was instructed to recall the final items of the list first, the recency performance remained defective, even though P.V. was able to adopt a recall from end order. In the case of visual presentation, P.V.'s free recall performance was within the normal range and a clear recency occurred in the recall from end condition. These results are consistent with the view that the standard recency effect in immediate free recall of auditorily presented material represents the output of a phonological short-term store to which ordinal retrieval strategies, in P.V.'s case unimpaired, are applied. Finally, the contributions of the phonological short-term store and the process of rehearsal to the recency effect and to immediate memory span performance are discussed.


High-fat-diet-induced obesity is associated with decreased antiinflammatory Lactobacillus reuteri sensitive to oxidative stress in mouse Peyer's patches.
Diet-induced inflammation in the small intestine may represent an early event that precedes and predisposes to obesity and insulin resistance. This is related to decrease of lactobacilli in Peyer's patches (PP) revealed in our previous study. The present study aimed to clarify specific changes of PP Lactobacillus on the strain level and related biological activity. C57 BL/6 J male mice were fed with either low-fat diet (control [CT]; 10% calories from fat) or high-fat diet (HFD; 50% calories from fat) for 25 wk, and the HFD-fed mice were classified into obesity prone (OP) or obesity resistant (OR) on the basis of their body weight gain. Lactobacillus was isolated from PP using a selective medium. Oxidative resistance and cytokine-inducing effect were analyzed in vitro. We obtained 52, 18, and 22 isolates from CT, OP, and OR mice, respectively. They belonged to 13 different types according to enterobacterial repetitive intergenic consensus sequence-PCR analysis. Lactobacillus reuteri was the most abundant strain, but its abundance in OP mice was much lower than that in CT and OR mice. This strain includes eight subgroups according to genotyping. L. reuteri L3 and L. reuteri L8 were the specific strains found in CT and OP mice, respectively. Oxidative-resistant L. reuteri was much higher in HFD-fed mice. When co-cultured with PP cells, L8 induced higher production of proinflammatory cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor-α, whereas L3 induced higher production of an anti-inflammatory cytokine (IL-10). HFD may induce oxidative stress that drives strain selection of Lactobacillus strains, resulting in decreased anti-inflammatory response in PP.


Macrophages and resistance to tumours: influence of agents affecting macrophages and delayed-type hypersensitivity on resistance to tumours inducing concomitant immunity.
Early, specific concomitant immunity to each of four tumours was inhibited by treatment with silica or carrageenan. Late, non-specific concomitant immunity was, with one exception, not inhibited by these agents. Treatment of non-immune mice with silica at certain critical periods before challenge promoted the growth of four of six syngeneic methylcholanthrene-induced tumours in their feet. Treatment with carrageenan was much less effective. Early and late concomitant immunity were inhibited by one or more agents inhibiting delayed-type hypersensitivity: irradiation, niridazole and reserpine. Irradiation of non-immune mice did not effect the growth of tumours in their feet. Treatment of non-immune mice with niridazole or reserpine actually inhibited the growth of some tumours. It is suggested that (a) mice offer some natural resistance to tumour growth, macrophages perhaps being effectors; (b) some tumour isografts may survive only if an inflammatory reaction occurs; (c) mechanisms akin to those of delayed-type hypersensitivity operate in the expression of concomitant immunity; (d) macrophages are important in early, specific concomitant immunity, but perhaps less so in the late non-specific phase.


Moyamoya disease concurrent with Graves' disease treated by direct bypass: clinical features and treatment strategies.
Moyamoya disease (MMD) concurrent with Graves' disease (GD) is rare. There is no guideline about optimizing thyroid hormones and the appropriate timing of surgical treatment for MMD with GD. We encountered eight patients with MMD and GD presenting with cerebral ischemia who were treated by direct bypass. Thyroid hormones [free thyroxin (fT4) and free triiodothyronine (fT3)], thyroid-stimulating hormone (TSH), and TSH receptor antibody (TRAb) were measured sequentially. After thyrotoxic conditions were medically optimized, revascularization surgery was performed by superficial temporal artery-middle cerebral artery (STA-MCA) double bypass in all cases. Clinical outcomes were estimated by modified Rankin scale (mRS) at discharge and 3 months after surgery. In six patients with thyrotoxicosis, the fT4, fT3, and TRAb (range) at the onset of cerebral ischemia were 4.81-10.30 pg/ml, 13.08-31.90 pg/ml, and 3.5-83.8 IU/l, respectively. At surgery, mean (range) fT3 and fT4 were optimized to 3.02 (1.01-4.87) pg/ml and 1.09 (0.41-1.68) ng/dl, respectively. In the thyrotoxic cases, it took 70-310 days (mean, 142 days) to optimize thyroid hormones before surgery. There was no neurological aggravation after surgery, and outcome was excellent at 3 months with mRS scores ≤2 in all cases. For MMD concurrent with GD, optimizing thyroid hormones followed by STA-MCA double bypass was successful to prevent cerebral ischemic events.


Ovarian torsion: an unusual cause of bilateral pelvic calcifications.
Ovarian calcification in children is rare, usually unilateral, and in most cases implies tumor involvement. A case of bilateral ovarian torsion with calcification that might mimic neoplasm is presented along with a literature review.


Morbidity risk for psychiatric disorders in families of probands with affective disorders divided according to levels of platelet MAO activity.
In a series comprising 166 subjects with affective disorders, the lowest and highest quartiles in the male and female platelet monoamine oxidase (MAO) distribution, respectively, were included. The morbidity risk in the first-degree relatives (parents and siblings) of these low and high platelet MAO subjects was determined. First-degree relatives of low platelet MAO probands were found to have an increased morbidity risk for neurotic-reactive depressions and for alcoholism. The results seem to be in line with the biological high-risk paradigm, indicating that platelet MAO could be a biological marker for increased vulnerability. First-degree relatives of high platelet MAO probands were found to have an increased morbidity risk for bipolar affective disorders.


The effect of physical appearance perfectionism and social comparison to thin-, slim-thick-, and fit-ideal Instagram imagery on young women's body image.
Body image research to date has examined the impact of thin- and fit-ideal media on women's body image, however cultural trends in Western media have recently shifted towards a curvier body type called slim-thick, which is characterized by a large butt and thighs and small waist and flat stomach. We experimentally examined the impact of forced social comparison to slim-thick-, thin-, and fit-ideal imagery on women's body image relative to a control condition, and whether physical appearance perfectionism moderated these findings. Participants were 402 female undergraduate students. Results revealed that comparison to body-ideal imagery resulted in greater weight and appearance dissatisfaction and less overall body satisfaction, relative to the control condition. Those exposed to slim-thick imagery experienced more weight and appearance dissatisfaction and less body satisfaction than those in the thin-ideal condition. Physical appearance perfectionism moderated these results, such that women who reported moderate or high levels of physical appearance perfectionism experienced greater weight and appearance dissatisfaction and lower body satisfaction in the slim-thick condition, than in the thin-ideal, fit-ideal, or control conditions. It was concluded that drive to achieve body ideals is shifting to a slim-thick body, which maybe more detrimental to women's body image than thin-ideal imagery.


The effect of serum supplementation on the cleavage of human embryos.
The effect of serum supplementation was evaluated on 108 oocytes obtained from 29 patients. The oocytes were all mature and randomly distributed in two groups. Each ovum was paired with another ovum within the same patient. The experimental group contained no serum in the insemination and growth medium, but in the control group 10% serum was added to the insemination and growth medium. In the experimental group the cleavage rate was 66.7%, compared to 83.3% in the control group. The embryos from each patient were individually evaluated. The sign test was used for statistical analysis. A significant difference between the two groups (P = 0.01) indicated that in this study the addition of serum to the medium gives better cleavage results. The effect of serum on embryos is discussed, as well as the practical implications of this finding.


Mechanical gastric outlet obstruction after continent urinary diversion.
A number of complications have been associated with complex continent urinary diversions. We report a case of postoperative mechanical gastric outlet obstruction after continent urinary diversion with distal ileum and ascending colon. Following adequate urinary reservoir drainage gastric outlet obstruction resolved. Such mechanical effects from distended urinary reservoirs must be considered in any patient undergoing continent urinary diversion.


Changes in anteroposterior stability following total knee arthroplasty.
This study evaluated the changes in anteroposterior stability at flexion and extension following posterior cruciate ligament (PCL)-retaining and PCL-substituting total knee arthroplasty (TKA), in comparison with normal knees. Altogether, 29 knees of 24 patients underwent either PCL-retaining ( n = 19) or PCL-substituting ( n = 10) TKA. Anteroposterior displacement was measured with a KT-2000 arthrometer preoperatively, 1 month after surgery, and again an average of 3 years after surgery. Anteroposterior stability at flexion and extension did not change following PCL-retaining TKA and was not significantly different from that of normal subjects, whereas anteroposterior stability increased following PCL-substituting TKA and was significantly greater than that of normal subjects an average of 3 years after surgery.


Long-read Nanopore sequencing identified D4Z4 contractions in patients with facioscapulohumeral muscular dystrophy.
Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disorder caused by abnormal expression of the DUX4 protein, commonly resulting from a contraction of D4Z4 repeat units with the presence of a polyadenylation (polyA) signal. More than 10 units of the D4Z4 repeat, with a length of 3.3 kb per unit, are typically required to silence DUX4 expression. Consequently, molecular diagnosis of FSHD is challenging. We used Oxford Nanopore technology to perform whole-genome sequencing of seven unrelated patients with FSHD, their six unaffected parents, and 10 unaffected controls. All seven patients were successfully identified to harbor one to five D4Z4 repeat units and the polyA signal, whereas none of the 16 unaffected individuals met the molecular diagnostic criteria. Our newly developed method provides a straightforward and powerful molecular diagnostic tool for FSHD.


A new nomogram model for prognosis of hepatocellular carcinoma based on novel gene signature that regulates cross-talk between immune and tumor cells.
The combined application of immune cells and specific biomarkers related to the tumor immune microenvironment has a better predictive value for the prognosis of HCC. The purpose of this study is to construct a new prognostic model based on immune-related genes that regulate cross-talk between immune and tumor cells to assess the prognosis and explore possible mechanisms. The immune cell abundance ratio of 424 cases in the TCGA-LIHC database is obtained through the CIBERSORT algorithm. The differential gene analysis and cox regression analysis is used to screen IRGs. In addition, the function of IRGs was preliminarily explored through the co-culture of M2 macrophages and HCC cell lines. The clinical validation, nomogram establishment and performing tumor microenvironment score were validated. We identified 4 immune cells and 9 hub genes related to the prognosis. Further, we identified S100A9, CD79B, TNFRSF11B as an IRGs signature, which is verified in the ICGC and GSE76427 database. Importantly, IRGs signature is closely related to the prognosis, tumor microenvironment score, clinical characteristics and immunotherapy, and nomogram combined with clinical characteristics is more conducive to clinical promotion. In addition, after co-culture with M2 macrophages, the migration capacity and cell pseudopod of MHCC97H increased significantly. And CD79B and TNFRSF11B were significantly down-regulated in MHCC97H, Huh7 and LM3, while S100A9 was up-regulated. We constructed an IRGs signature and discussed possible mechanisms. The nomogram established based on IRGs can accurately predict the prognosis of HCC patients. These findings may provide a suitable therapeutic target for HCC.


Comparability of four clinical laboratory measurement methods for GGT and commutability of candidate reference materials.
This study was conducted to evaluate the progress in the standardization of the gamma-glutamyl transferase (GGT) to achieve metrological traceability of routine in vitro diagnosis (IVD) medical devices. We collected 25 single fresh frozen serum samples for GGT analysis. Candidate reference materials (RMs), calibrators, internal quality controls (IQC), and external quality assessment (EQA) materials from the National Center for Clinical Laboratory (NCCL), Beijing Center for Clinical Laboratory (BCCL), and College of American Pathologists (CAP) were randomly added to these serum samples. A total of 42 samples were examined using IFCC reference method and four different IVD medical devices to perform the comparability and commutability study. The four IVD medical devices achieved trueness assessment within the measurement range. Linear analysis showed the agreement of Siemens ADVIA 2400, Hitachi 7600-020/BioSino, Beckman AU 5800, and Roche Cobas 501 with the reference method. These assay pairs were comparable at the medical decision levels. The GGT in-house candidate RMs, and Beckmann and Roche calibrators were all within the limits of the 95% prediction intervals, the commutability of BioSino calibrators was indeterminate, and some internal and external quality controls were not commutable for comparisons of certain IVD medical devices vs the reference method. By comparing with the reference method, we found that performance of GGT conventional measurement systems to be traceable to the higher order references was improved. The commutable materials for calibration and trueness controls of routine methods were significant to promote the standardization of GGT analysis.


Rapid identification and monitoring of cooking oil fume-based toxic volatile organic aldehydes in lung tissue for predicting exposure level and cancer risks.
Cooking oil fumes (COFs) comprised of a mixture of cancer-causing volatile organic aldehydes (VOAs), particularly trans, trans-2,4-decadienal (t,t-DDE), 4-hydroxy-hexenal (4-HHE), and 4-hydroxy-nonenal (4-HNE). Monitoring toxic VOAs levels in people exposed to different cooking conditions is vital to predicting the cancer risk. For this purpose, we developed a fast tissue extraction (FaTEx) technique combined with UHPLC-MS/MS to monitor three toxic VOAs in mice lung tissue samples. FaTEx pre-treatment protocol was developed by combining two syringes for extraction and clean-up process. The various procedural steps affecting the FaTEx sample pre-treatment process were optimized to enhance the target VOAs' extraction efficiency from the sample matrix. Under the optimal experimental conditions, results exhibit good correlation coefficient values > 0.99, detection limits were between 0.5-3 ng/g, quantification limits were between 1-10 ng/g, and the matrix effect was <18.1%. Furthermore, the extraction recovery values of the spiked tissue exhibited between 88.9-109.6% with <8.6% of RSD. Cooking oil fume (containing t,t-DDE) treated mice at various time durations were sacrificed to validate the developed technique, and it was found that t,t-DDE concentrations were from 14.8 to 33.8 μg/g. The obtained results were found to be a fast, reliable, and semi-automated sample pre-treatment technique with good extraction efficiency, trace level detection limit, and less matrix effect. Therefore, this method can be applied as a potential analytical method to determine the VOAs in humans exposed to long-term cooking oil fumes.


Ambient PM2.5 and its chemical constituents on lifetime-ever pneumonia in Chinese children: A multi-center study.
The long-term effects of ambient PM2.5 and chemical constituents on childhood pneumonia were still unknown. A cross-sectional study was conducted in 30,315 children in the China Children, Homes, Health (CCHH) project, involving 205 preschools in six cities in China, to investigate the long-term effects of PM2.5 constituents on lifetime-ever diagnosed pneumonia. Information on the lifetime-ever pneumonia and demographics were collected by validated questionnaires. The lifetime annual average ambient PM2.5, ozone and five main PM2.5 constituents, including SO42-, NO3-, NH4+, organic matter (OM) and black carbon (BC), were estimated according to preschool addresses by a combination of satellite remote sensing, chemical transport modeling and ground-based monitors. The prevalence of lifetime-ever diagnosed pneumonia was 34.5% across six cities and differed significantly among cities (p = 0.004). The two-level logistic regression models showed that the adjusted odds ratio for PM2.5 (per 10 µg/m3) and its constituents (per 1 µg/m3)-SO42-, NO3-, NH4+, and OM were 1.12 (95% CI:1.07-1.18), 1.02 (1.00-1.04), 1.06 (1.04-1.09), 1.05 (1.03-1.07) and 1.09 (1.06-1.12), respectively. Children in urban area, aged < 5 years and breastfeeding time < 6 months enhanced the risks of pneumonia. Our study provided robust results that long-term levels of ambient PM2.5 and its constituents increased the risk of childhood pneumonia, especially NH4+, NO3- and OM.


Colorimetric determination of thiram based on formation of gold nanoparticles using ascorbic acid.
A novel optical method for the determination of thiram has been developed using surface plasmon resonance peak of gold nanoparticles (AuNPs). The stable and dispersed AuNPs were directly synthesized by reduction of HAuCl4 with ascorbic acid in micellar media according to a simple approach. The presence of thiram during formation of AuNPs results in the decrease of the intensity of plasmon resonance peak. The variation in the plasmon absorbance allows the colorimetric determination of thiram. The effect of different variables such as pH, ascorbic acid and CTAB concentrations was studied and optimized. The proposed method is capable of determining thiram over a range of 2.0×10(-7)-1.0×10(-5) mol L(-1) with a limit of detection 1.7×10(-7) mol L(-1). The relative standard deviation of the method was <3.7%. The method was successfully applied to the determination of thiram in water and plant seed samples.


On posttraumatic intracavernous false aneurysms and arteriovenous fistulas.
Posttraumatic high-flow communications between the intracavernous internal carotid artery (ICA) and the cavernous sinus may give rise to two different pathological entities. A connection between the ICA and one of the adjacent intracavernous veins will result in a carotico-cavernous fistula (CCF). A false aneurysm will develop if the arterialized rent from the injured ICA flows directly into the bare perivenous spaces within the cavernous sinus, without a shunt with one of the veins. A CCF and a false aneurysm can be present in the same patient. Angiographically these two entities may be demonstrated, and clinically have a somewhat different behaviour. Life-threatening massive epistaxis is the most serious complication, particularly in false intracavernous aneurysms. Most high-flow CCFs are the result of a small side-wall laceration of the ICA, while large ICA injuries or even complete transection of the artery are responsible for the origin or false aneurysms.


Robotic Skull Base Surgery.
Robotic surgery has become more common in otolaryngologic surgery since the introduction of the da Vinci robotic system, but has played a limited role in anterior and central skull base surgery, largely because of technical limitations of existing robots. Current robotic technology has been used in creative ways to access the skull base, but was not designed to navigate these complex anatomic constraints. Novel robots should target many of the limitations of current robotic technology, such as maneuverability, inability to suture, lack of haptic feedback, and absent integration with image guidance.


Resistance of alfalfa and Indian mustard to Cd and the correlation of plant Cd uptake and soil Cd form.
Phytoremediation of heavy metal-contaminated soil is considered to be one ecological environmental protection way that is effective and economical. The selection of suitable hyperaccumulators is a key issue for phytoremediation of heavy metal-contaminated soil. Pot experiments were conducted to study the effects of different Cd levels (0, 75, 150, 300, and 600 mg kg-1 Cd) on the dry weight, antioxidant enzyme activities, malondialdehyde (MDA) contents, Cd concentration, Cd accumulation, and soil Cd form distribution ratio (FDC) of alfalfa (Medicago sativa L.) and Indian mustard (Brassica juncea L.). The correlations between Cd concentration in shoots and roots of alfalfa and Indian mustard and soil Cd form were also investigated. The results showed that with the increase of soil Cd levels, dry weight of shoot and root of alfalfa and Indian mustard significantly decreased, which decreased by 50.0-71.8% and 29.6-59.3% (alfalfa), 59.6-89.0% and 64.3-74.8% (India mustard), respectively, compared with the control. With the increase of soil Cd level, superoxide dismutase (SOD) activity in shoot of alfalfa significantly increased. Catalase (CAT) activity and malondialdehyde contents in shoots and roots of alfalfa and Indian mustard, as well as superoxide dismutase activity in the roots of alfalfa and Indian mustard increased first and then decreased with the increase of soil Cd level. With increasing Cd stress, Cd concentration in shoots and roots of alfalfa and Indian mustard significantly increased. At soil Cd level of 75 mg kg-1, Cd concentrations in shoots of alfalfa and Indian mustard exceeded the critical value of Cd-hyperaccumulator (100 mg kg-1), which was 356.46 mg kg-1 and 308.74 mg kg-1, respectively. Cadmium concentrations in shoots and roots of plants were in the order of that of alfalfa > Indian mustard; total Cd accumulation in the aboveground tissues and roots of the plants was in the order of that of Indian mustard > alfalfa at the same Cd level. With increasing soil Cd level, Cd concentrations of exchangeable form (EXC-Cd), carbonate-bound form (CAB-Cd), iron-manganese oxide-bound form (FeMn-Cd), organic-bound form (OM-Cd), and residual form (RES-Cd) showed an increasing trend. The form distribution ratio of soil Cd forms in alfalfa's rhizosphere was in the order of that of exchangeable form Cd > carbonate-bound form Cd > iron-manganese oxide-bound form Cd > residual form Cd > organic-bound form Cd. Except for organic-bound form Cd, soil Cd forms were significantly positively correlated with Cd concentration in shoot and root (P < 0.01). Comprehensively considering the biomass and Cd accumulation, Indian mustard is more suitable as remediation material for soil Cd pollution.


Plant competition, abiotic, and long- and short-term effects of large herbivores on demography of opportunistic species in a semiarid grassland.
The emergence and subsequent survival and growth of five opportunistic "weeds" were monitored after seed additions to long-term grazing treatments with or without current-year grazing, long-term ungrazed treatments, and removal treatments designed to eliminate plant competition from existing perennials while either leaving vegetation and soil structure unaltered or disturbed. The treatments were applied on both uplands and lowlands to assess the relative influence of macroabiotic environment versus plant competition. The long-term effects of large herbivores on the initial emergence of seedlings were greater than the effects of removing competition. Very few individuals emerged on the long-term grazed treatments that were either grazed or ungrazed during the experiment. Numbers of individuals emerging on the long-term ungrazed treatments were greater or equal to those emerging on the no-competition-undisturbed treatments, but numbers were greatest on no-competition-disturbed treatments. None of the seeded individuals on the long-term grazed, currently grazed treatments survived to the end of the growing season. There was a slightly greater end-of-season biomass of seeded species and percentage of the total population reaching reproductive status on the long-term ungrazed compared with grazed-nondefoliated treatments, and very high survival, biomass, and proportions of reproductives on both no-competition treatments. Cover types in the immediate vicinity of seedlings influenced both germination and survival, but the effects differed between species and treatments. Equal compensation to current-year herbivory occurred on long-term heavily grazed treatments even though above-ground production was much greater on long-term protected sites. Productivity varied with topography, but very few topographic main effects or interactions occurred with demographic variables of seeded species, suggesting that macroabiotic effects were of minor importance compared with grazing and plant competition.


Growth and laboratory maintenance of Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a common, free-living, Gram-negative bacterium that can cause significant disease as an opportunistic pathogen. Rapid growth, facile genetics, and a large suite of virulence-related phenotypes make P. aeruginosa a common model organism to study Gram-negative opportunistic pathogens and basic microbiology. This unit describes the basic laboratory growth and maintenance of P. aeruginosa.


Joint effects of Chlamydia pneumoniae infection and classic coronary risk factors on risk of acute myocardial infarction.
Although not in itself strongly predictive of coronary heart disease, Chlamydia pneumoniae infection could interact with classic risk factors in determining risk of acute myocardial infarction (AMI). We assessed C pneumoniae immunoglobulin (Ig) G and IgA titers and classic risk factors in 618 patients with AMI and in 967 controls. IgG titers were not related to AMI, but a significant association was seen between IgA titers and AMI. Excess risk of AMI was noted mainly among patients with the highest IgA titers, such as those beyond 2.88 (the 95th percentile cutoff point in control subjects), showing a 1.8-fold increase in risk (odds ratio 1.75, 95% CI 1.04-2.92). Classic risk factors did not differ between subjects with IgA titers above and below the 95th percentile cutoff. However, in multivariate analyses, models incorporating both IgA titers and a classic risk factor such as obesity, hypercholesterolemia, or smoking predicted risk more effectively than single-parameter models. For example, the odds ratio for AMI among subjects with the highest IgA titers plus hypercholesterolemia was greater than the product of individual risks associated with these high IgA titers and with hypercholesterolemia. Interactions with classic risk factors (ie, obesity, hypercholesterolemia, and smoking), increased the predictive value of C pneumoniae IgA antibody titers in determining risk of AMI.


Proliferative activity and steroid hormone receptor status in male breast carcinoma.
Hormonal factors have been implicated in the development of both female and male breast cancers (MBC). However, MBCs are rare and seem to have different biological behavior than those of females. The aim of this study was to evaluate proliferative activity and to establish an association with steroid hormone receptor concentration and clinicopathological parameters in MBC. Proliferative activity was assessed in 18 MBC by mitotic figure counts and immunohistochemical evaluation of MIB-1 and proliferating cell nuclear antigen (PCNA). Estrogen (ER), progesterone (PR) and androgen (AR) receptors were evaluated in serial section from the same tumor by immunohistochemistry. PCNA (range 17-73%; mean, 51.6%) and MIB-1 (range 18.5-58%; mean 38.4%) were positive correlated with the mitotic rate. High proliferative activity assessed either by mitotic index or MIB-1 expression was associated with more poorly differentiated tumors. Sixty one percent (11/18) of the tumors were ER+, 72% (13/18) PR+ and 38.5% (5/13) AR+. Proliferative activity in tumors displaying ER+/PR+ phenotype showed a tendency to be higher than in ER-/PR- tumors. This difference was statistically significant when MIB-1 expression was used as proliferation marker. An association between AR concentration and age at diagnosis was found; in the AR negative group (8/13) mean age at diagnosis was 54.4 +/- 7.3 which was significantly lower than the age of patients with AR+ tumors, 63.2 +/- 11.1 (5/13). Results presented here show that decreased androgen action (AR-) within the breast might contribute to an earlier development of MBC. Besides that, the presence of ER and PR in carcinoma cells is considered to provide a growth advantage as shown by the positive association between the phenotype (ER+/PR+) and high proliferative activity. These results add information for a better understanding of hormonal control of MBC growth and development.


Potential of chemotherapy-herb interactions in adult cancer patients.
The purpose of this study was to examine the specific herbs or vitamins (HV) used by patients receiving chemotherapy. Specifically, the following aspects were investigated: (1) HV use among adult cancer patients receiving chemotherapy, (2) the frequency of potential chemotherapy-HV interactions, (3) communication patterns between oncologists and their cancer patients taking HV, and (4) patients' reactions to two hypothetical scenarios of chemotherapy-HV interactions. Adult cancer patients receiving chemotherapy at a university-based outpatient clinic over a 1-month period were sent a validated eight-page questionnaire regarding the use of complementary/alternative medicine, focusing on HV use. A total of 76 patients participated; relevant medical information was obtained from study participants' charts. The chemotherapy received was compared with HV use to assess for potentially detrimental chemotherapy-HV interactions. HV use in patients receiving chemotherapy was common (78%), with 27% of the study participants being at risk of a detrimental chemotherapy-HV interaction. Most patients (>85%) would discontinue their HV or ask their medical oncologist for advice if a detrimental chemotherapy-HV interaction was suspected. Although most patients discussed HV use with their oncologist, the majority also relied on their friends and naturopathic physician for information regarding HV. Considerable potential exists for detrimental chemotherapy-HV interactions. Methods to improve communication of HV use between cancer patients receiving chemotherapy and health-care practitioners are necessary to identify and minimize the risk of these interactions.


Interaction of myosin subfragment-1 with actin. II. Location of the actin binding site in a fragment of subfragment-1 heavy chain.
The heavy chain of subfragment-1 prepared by chymotrypsin treatment had a molecular weight of about 96K. The heavy chain was split into 26 K, 50 K, and 21 K fragments by trypsin. When the trypsin-treated subfragment-1 was cross-linked with dimethyl suberimidate, cross-linked products of 26 K, 50 K, and 21 K fragments and of 50 K and 21 K fragments appeared, but there was little cross-linked product of 26 K and 50 K fragments or of 26 K and 21 K fragments. When the cross-linking experiments were carried out in the presence of actin, a new band appeared and the amount of cross-linked product of 26 K, 50 K, and 21 K fragments decreased by about 50%. The molecular weight of the new band was lower than that of the cross-linked product of 26 K, 50 K, and 21 K fragments, and higher than that of the dimer of actin. Based on this and some other results, we suggest that this band represented a cross-linked product of actin and the 50 K fragment. We also suggest that the decrease in the amount of cross-linked product of 26 K, 50 K, and 21 K fragments reflected the conformational change in subfragment-1 due to the binding of actin.


Caring for an aging society: cohort values and eldercare services.
Understanding the impact of cohort values is important in trying to project future aging service needs. The cultural characteristics of cohorts yet to reach the age of 65 are compared with those already "old," with specific focus on the Baby Boomers. Aging policies (and available services) reflect the cultural notions of age and aging held as normative during the historical era in which they are enacted. Previous research into lifestyle preferences, consumer practices, and key characteristics is drawn upon to investigate the values of Baby Boomers in light of their projected needs for eldercare services. Cohort research and generational marketing practices offer a promising foundation for exploring how best to develop, target, and deliver aging services that most effectively utilize our social resources.


Extraintestinal Clostridioides difficile infection.
Clostridioides (Clostridium) difficile is the major cause of healthcare antibiotic-associated diarrhoea. However, extra-intestinal manifestations of Clostridioides (Clostridium) difficile infection (CDI) (including bacteremia and tissue infection) are extremely rare. We report a case of extraintestinal CDI after surgery. The isolate of C. difficile was not the PCR ribotype 027. However, this isolate produced toxins A and B. The patient underwent a follow-up examination 30 days after discharge, which showed complete recovery. This case report adds to existing knowledge of CDI.


Aerobic ferrisiderophore reductase assay and activity stain for native polyacrylamide gels.
The reduction of ferric iron from microbial iron-binding compounds (siderophores) releases the iron from the siderophore so that it may be utilized by the microorganism. A method to detect aerobic ferrisiderophore reductase activity using ferrozine as a ferrous iron trap is shown to be applicable to cytoplasmic fractions from Rhodopseudomonas sphaeroides and four other different species of bacteria. The ferrisiderophore reductase uses reduced nicotinamide cofactors as reducing agents, and activity is stimulated by flavins. This assay has been adapted as a staining method to locate ferrisiderophore reductase activity in native polyacrylamide gels.


MiR-338-3p inhibits the proliferation and migration of gastric cancer cells by targeting ADAM17.
MicroRNAs (miRNA) have been documented playing a critical role in cancer progression. Although miR-338-3p has been implicated in several cancers, its role in gastric cancer is still unknown. The aim of our study was to investigate the role of miR-338-3p in gastric cancer progression. Expression levels of miR-338-3p in gastric cancer cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR). The effect of miR-338-3p on proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays. Furthermore, luciferase reporter assay was conducted to confirm the target gene of miR-338-3p, and the results were validated in gastric cancer cells. In the present study, we found that miR-338-3p was down-regulated in both gastric cancer cell lines and tissues. Enforced expression of miR-338-3p inhibited proliferation, migration and invasion of gastric cancer cells in vitro. Moreover, we identified A disintegrin and metalloproteinase 17 (ADAM17) gene as potential target of miR-338-3p. Importantly, ADAM17 rescued the miR-338-3p mediated inhibition of cell proliferation, migration and invasion. Our study suggested that miR-338-3p is significantly decreased in gastric cancer, and inhibits cell proliferation, migration and invasion partially via the downregulation of ADAM17. Thus, miR-338-3p may represent a potential therapeutic target for gastric cancer intervention.


The syndromes of primary hormone resistance.
The clinical features, genetics, pathophysiology, and management of endocrine diseases in which primary hormone resistance is the fundamental defect have been reviewed. Primary hormone resistance has been documented for nearly all hormones--vasopressin, parathyroid hormone, growth hormone, adrenocroticotropin, thyrotropin, gonadotropins, insulin, androgens, cortisol, aldosterone, progesterone, thyroid hormones, and vitamin D. A striking exception is estradiol, a steroid that may be vital for early embryonic development. Most of the hormone unresponsiveness syndromes represent only partial defects, and it is likely that most such patients go unrecognized. Therefore, hormone resistance should be suspected not only when a patient presents with hypofunction of particular endocrine system combined with high endogenous hormone levels but also whenever apparently normal function of an endocrine system is associated with inappropriately elevated levels of the corresponding hormone. The value of these defects in hormone responsiveness as a natural laboratory for the study of the normal mechanisms of hormone action is discussed.


Platelet‑rich fibrin exudate promotes the proliferation and osteogenic differentiation of human periodontal ligament cells in vitro.
The purpose of the present study was to evaluate the effects of platelet‑rich fibrin (PRF) exudate on the proliferation, osteogenic differentiation and mineralization of human periodontal ligament cells (hPDLCs) in vitro. In the present study PRF was obtained with permission, from the peripheral blood of healthy donors and PRF exudates were collected on the 7th day of incubation. hPDLCs were obtained from healthy premolars, cultured by a tissue explant method and identified with anti‑vimentin and anti‑cytokeratin antibodies. PRF exudates were added to hPDLCs in different concentrations to evaluate cell proliferation and osteogenic differentiation. The proliferation of hPDLCs was measured using a colorimetric assay. Osteogenic differentiation and mineralization were determined by Alizarin red staining, alkaline phosphatase activity (ALP), western blotting and reverse transcription‑quantitative polymerase chain reaction. Cell proliferation was enhanced by addition of the PRF exudate, which also promoted the formation of mineralized matrix nodules and upregulated ALP activity and osteoblast‑associated levels of osteocalcin, runt‑related transcription factor and osterix gene expression. As these stimulatory effects occurred in a dose‑dependent manner, it was concluded that high concentrations of the PRF exudate served an essential role in the proliferation, osteogenic differentiation and mineralization of hPDLCs in vitro. The present study demonstrated that PRF exudate enhanced hPDLC proliferation, induced the osteoblastic differentiation of hPDLCs into mineralized tissue‑formation cells in vitro, and may therefore provide potential benefits for periodontal tissue engineering; contributing to the primary processes of periodontal tissue regeneration. From the perspective of both economics and biology, PRF has greater clinical benefits than analogous growth factors.


Pro-subtilisin E: purification and characterization of its autoprocessing to active subtilisin E in vitro.
The formation of active subtilisin E from pro-subtilisin E requires the removal of the N-terminal pro-sequence of 77 residues. Pro-subtilisin E produced in Escherichia coli using a pINIII-ompA vector was first extracted with 6 M guanidine-HCl and 5 M urea and purified to homogeneity in the presence of 5 M urea. Upon drop dialysis against 0.2 M sodium phosphate buffer (pH 6.2), the purified pro-subtilisin in 5 M urea was processed to active subtilisin of which the N-terminal sequence and migration in SDS-polyacrylamide gel electrophoresis were identical to those of authentic active subtilisin E. This process was found to be very sensitive to the ionic strengths and anions used. Under the optimum conditions (dialysis against 0.5 M (NH4)2SO4 and 1 mM CaCl2 in 10 mM Tris-HCl buffer (pH 7.0) at 4 degrees C for 1 h), approximately 20% of pro-subtilisin E was converted to active subtilisin E. The activation process was not inhibited by Streptomyces subtilisin inhibitor, and pro-subtilisin E in which the active site was mutated (Asp32 to Asn) was unable to be processed under the optimum conditions. These results confirmed the previous hypothesis that the processing of pro-subtilisin occurs by an intramolecular, autoprocessing mechanism.


Nitric oxide production in murine spleen cells: role of interferons and prostaglandin E(2) in the generation of cytotoxic activity.
The production of nitric oxide (NO) was measured in cultures of spleen cells stimulated by lipopolysaccharide (LPS), IL-2 or LPS + IL-2. We observed that NO synthesis is increased by IFN-gamma but inhibited by IFN-alpha/beta. This is not the case when IL-2 is present in the cultures, since interferons play a minor role in the regulation of the NO production. When IL-2 and LPS were associated in the cultures, the IFN-alpha/beta role seems more important than that of IFN-gamma. PGE(2) inhibits NO production in LPS supplemented cultures but has a slight effect in the presence of IL-2 and no effect with IL-2 + LPS. 3-isoButyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases, induces a decrease of IFN production. In the presence of H-7, an inhibitor of protein kinase C (PKC), NO production is reduced when the cultures are supplemented by LPS or IL-2 but not when IL-2 and LPS are both added. H-7 also reduced IFN production. In the presence of N(G)-monomethyl-L-arginine (N-MMA), an inhibitor of NO synthesis, IFN production was increased, with no change in the cytotoxic activity. Hence, interferons regulate NO production by mouse spleen cells and, in return, NO modulates the generation of IFN.


Reduced Vascular Practice and Increased Cardiovascular Mortality for COVID-19-Negative Patients.
The aim of our study was to compare COVID-19- and not-COVID-19-related mortality rates in two Italian regions during the pandemic period when the same isolation rules and therapeutic approaches were introduced for all hospitals in Italy. Risk factors for not-COVID-19-related deaths during the pandemic were analyzed; we tried to assess a possible correlation between reducing hospital visits and "deferrable" vascular operations and the increased cardiovascular mortality not related to COVID-19 infection. We analyzed COVID-19- and not-COVID-19-related mortality rates in two Italian regions in the period January 2020-January 2021. We compared mortality rates during the pandemic period with those of the previous five years. We tried to determine the factors involved in increased mortality rates during the pandemic period. Despite the same isolation rules for people and the same therapeutic approaches for hospitals, mortality rates did not increase in the region Lazio, where the pandemic was not severe. In the region Lombardy, the mortality rate was doubled in comparison with the previous years, and 50% of the increase was related to not-COVID-19 deaths. The increase in mortality rates for not-COVID-19-related deaths in the region Lombardy was connected to the generalized turmoil in the acute phase of an overwhelming pandemic, including diffuse stress, inadequate communications, reluctance to ask for medical help unless symptoms were severe, and unexpected inadequate number of health workers, hospital beds, and intensive care unit beds. Reduced hospital visits may have had a fundamental role.


Establishing cancer units.
The creation of effective cancer units is central to the implementation of the report A Policy Framework for Commissioning Cancer Services, produced by the Chief Medical Officers of England and Wales, recently issued by the Department of Health in April 1995. While cancer units are described in this report a range of important questions remain about their nature and how they should be developed. This paper addresses these issues in three ways. A definition of the cancer unit is suggested and its main implications spelt out. The problems of establishing cancer units are covered under three headings. Where should cancer units be? Which cancer sites should the unit cover? What is needed to establish the cancer unit? Finally two checklists are presented, describing the task from the perspectives of the district health authority and hospital(s) concerned. The underlying theme is that real changes in clinical practice and organisation are the goal, and these can only be achieved where there is extensive local dialogue in which the relevant issues are addressed in a structured and rigorous manner. Cosmetic changes in hospital designation will not achieve the consistent quality of cancer service that is the cornerstone of the 'Calman' policy.


Developmental switches in reiterated genes may reduce the rate of age changes in DNA.
The possible role of the redundancy of genetic information in the regulation of the ageing rate has been discussed in several works. However, it was shown recently that the gene reiteration in most cases is represented by families of similar, but not identical genes. Their expression usually related to the different stages of development and when "early" embryonic or fetal genes are active, the "late" or adult genes are repressed. It is known that the DNA repair needs double stranded structure of DNA which is usual for inactive genes. Genes which are being transcribed and active are repressed by unwound, relaxed DNA which is less protected by the DNA repair enzymes. Aging of genetic information in somatic cells can be, therefore, considered as stage specific and alterations of "early" embryonic and fetal genes do not constitute the genetic load which influences the ageing rate of differentiated cells.


Biomechanical properties of titanium elastic nail applied to a cadaveric clavicle model.
The goal of this study was to examine biomechanical properties of titanium elastic nail fixation method that was applied to cadaveric clavicles with different thicknesses and lengths. To test stiffness and failure load of clavicle with titanium elastic nail fixation, 12 pairs of clavicles were obtained. A short oblique fracture line (AO/OTA classification: 15-B1.2) was created at midpoint of the cadaveric bones. They were divided into four groups according to the nails with different thickness and length/diameter ratios. The fixated bones were situated on a jig that allows 3-point bending to measure stiffness and load failure. The stiffness was measured to be mean 3.49 ± 1.49 N/mm in group 1. The stiffness for group 2 was mean 10.41 ± 2.18 N/mm, and for groups 3 and 4, the stiffness was mean 11.89 ± 2.99 N/mm and mean 24.44 ± 4.86 N/mm, respectively. When analyzed with statistics, group 1 had significant differences from groups 2 (P < 0.006), 3 (P < 0.001), and 4 (P < 0.000), and group 4 also had statistical significances from rest of the groups (P < 0.000). For 2.5 mm titanium elastic nail, it is necessary to make fixation with a titanium elastic nail that is longer than 3 diameter lengths, and length that is longer than and equal to 3 diameter length titanium elastic nail was required for 3.5 mm titanium elastic nail to provide appropriate stiffness for firm fixation. Also, variances in both thickness and length have shown a similar effect. Cadaveric study.


Health services utilisation and barriers for settlers from the Horn of Africa.
To examine health services use and barriers for recently arrived immigrants from the Horn of Africa. A cross-sectional study conducted in Melbourne, Australia, with a convenience sample of newly arrived immigrants (n=126) from Somalia (n=67), Ethiopia (n=24), Eritrea (n=26) and Sudan (n=6). GPs were the major health providers for participants, yet 22 (17%) respondents had not yet accessed health services in Australia. Thirty-three (26%) participants reported having had an unmet health concern for which they would have liked to seek advice. The most commonly identified barriers to health care and recommendations for improving services were associated with communication. This study illustrates unmet health needs among new arrivals and a need for linguistically appropriate information about the use of Australia's health system. The findings support increased use of professional interpreting services and support for new arrivals in making initial contact with the health system.


Characterization of a new Saccharomyces cerevisiae isolated from banana stems and its mutant with l-leucine accumulation for awamori brewing.
We isolated a new strain of the yeast Saccharomyces cerevisiae, 35a14, from banana stems in Okinawa. This strain did not belong to any industrial yeast groups in a phylogenetic tree and produced high levels of alcohol. Furthermore, awamori, an Okinawa's traditional distilled alcoholic beverage, brewed with an l-leucine overproducing mutant derived from 35a14 showed a high concentration of isoamyl acetate.


Alterations of lateral temporal cortical gray matter and facial memory as vulnerability indicators for schizophrenia: An MRI study in youth at familial high-risk for schizophrenia.
Structural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness. Subjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal pole. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale - Third Edition and the Children's Memory Scale - Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory. Compared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives. These results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs.


Robust folding of a de novo designed ideal protein even with most of the core mutated to valine.
Protein design provides a stringent test for our understanding of protein folding. We previously described principles for designing ideal protein structures stabilized by consistent local and nonlocal interactions, based on a set of rules relating local backbone structures to tertiary packing motifs. The principles have made possible the design of protein structures having various topologies with high thermal stability. Whereas nonlocal interactions such as tight hydrophobic core packing have traditionally been considered to be crucial for protein folding and stability, the rules proposed by our previous studies suggest the importance of local backbone structures to protein folding. In this study, we investigated the robustness of folding of de novo designed proteins to the reduction of the hydrophobic core, by extensive mutation of large hydrophobic residues (Leu, Ile) to smaller ones (Val) for one of the designs. Surprisingly, even after 10 Leu and Ile residues were mutated to Val, this mutant with the core mostly filled with Val was found to not be in a molten globule state and fold into the same backbone structure as the original design, with high stability. These results indicate the importance of local backbone structures to the folding ability and high thermal stability of designed proteins and suggest a method for engineering thermally stabilized natural proteins.


Hydrocortisone-induced hypertension in humans: pressor responsiveness and sympathetic function.
Oral hydrocortisone increases blood pressure and enhances pressor responsiveness in normal human subjects. We studied the effects of 1 week of oral hydrocortisone (200 mg/day) on blood pressure, cardiac output, total peripheral resistance, forearm vascular resistance, and norepinephrine spillover to plasma in eight healthy male volunteers. Although diastolic blood pressure remained unchanged, systolic blood pressure increased from 119 to 135 mm Hg (SED +/- 3.4, p less than 0.01), associated with an increased cardiac output (5.85-7.73 l/min, SED +/- 0.46, p less than 0.01). Total peripheral vascular resistance fell from 15.1 to 12.2 mm Hg/l/min (SED +/- 1.03, p less than 0.05). Resting forearm vascular resistance remained unchanged, but the reflex response to the cold pressor test was accentuated, the rise in resistance increasing from 10.5 mm Hg/ml/100 ml/min (R units) before treatment to 32.6 R units after treatment (SED +/- 6.4, p less than 0.025). The rise in forearm vascular resistance accompanying intra-arterial norepinephrine (25, 50, and 100 ng/min) was also significantly greater after hydrocortisone, increasing from an average of 14.9 +/- 2.4 R units before treatment to 35.1 +/- 5.5 R units after hydrocortisone (SED +/- 6.0, p less than 0.05). A shift to the left in the dose-response relation and fall in threshold suggested increased sensitivity to norepinephrine after treatment. Measurement of resting norepinephrine spillover rate to plasma and norepinephrine uptake indicated that overall resting sympathetic nervous system activity was not increased. The rise in resting blood pressure with hydrocortisone is associated with an increased cardiac output (presumably due to increased blood volume).(ABSTRACT TRUNCATED AT 250 WORDS)


Shionone alleviates NLRP3 inflammasome mediated pyroptosis in interstitial cystitis injury.
Shionone is a triterpenoid component derived from the herbal medicine Aster tataricus, and it has been reported to possess marked anti-inflammatory properties. The activation of NLRP3 inflammasome plays an important role in cystitis, and the effect of Shionone on NLRP3 inflammasome-dependent pyroptosis remains unclear. In this study, we established an interstitial cystitis (IC) rat model and SV-HUC-1 cell model with CYP or LPS + ATP treatment to mimic inflammation response and induce NLRP3 inflammasome activation. Shionone treatment significantly attenuated the bladder wet weight, score of edema and hemorrhage, enhanced the viability of SV-HUC-1 cell, decreased the rate of pyroptosis. Moreover, Shionone reduced the expression of NF-κB, NLRP3, ASC, Pro-caspase-1, Caspase-1, GSDMD, GSDMD-N at the mRNA and protein levels both in rat and SV-HUC-1 cell model, demonstrating NLRP3 inflammasome pathway was blocked and pyroptosis degree was reduced. These results indicated that Shionone could alleviate interstitial cystitis in Rat model and enhancing the viability of SV-HUC-1 cells via NF-κB/NLRP3/GSDMD-N pathway, which illustrated that Shionone could be used as a drug candidate for the treatment of interstitial cystitis.


Characterization of a protein in mid-term human amniotic fluid which reacts in the somatomedin-C radioreceptor assay.
Amniotic fluid contains materials other than insulin which react in a somatomedin C radioreceptor assay using human placental membranes. The material in mid-gestational amniotic fluid which reacted with the somatomedin C radioreceptor assay eluted slightly after albumin from a Sephadex G-150 column equilibrated with 0.1M NH4HCO3. Neither boiling nor treatment of this fraction with 1% formic acid yielded small molecular weight somatomedin-like peptides. Separation of the somatomedin reactive material (Sm RM) from albumin was achieved by gel filtration through Ultrogel AcA44 in 3.1M NH4HCO3. The active product had an apparent molecular weight of 33,000 to 35,000 Daltons; its isoelectric point determined by focusing was between 4.1 and 5.1. The purified amniotic fluid protein displaced somatomedin C in the somatomedin C radioreceptor assay but did not compete with insulin in the insulin radioreceptor assay. Sm RM produced only a slight stimulation of thymidine uptake in human fibroblasts but was inactive in stimulating sulfate uptake in hypox rat costal cartilage. In human fibroblast cultures Sm RM inhibited the stimulation of thymidine uptake induced by human serum and by purified rat somatomedin. When Sm RM was added to the 125I somatomedin C, some of the radioactivity eluted from gel filtration at pH 8.6 was converted to a molecular weight complex of about 43,000. We conclude that the material which we have isolated from mid-gestational amniotic fluid is a protein which may bind somatomedin and make it unavailable to the somatomedin receptor of human placenta and human fibroblasts.


ADP-ribosylation of membrane proteins of Streptomyces griseus strain 52-1.
Membranes purified from cells of Streptomyces griseus strain 52-1 possess an ADP-ribosyltransferase activity. The enzyme transfers the ADP-ribose moiety of NAD to one major membrane protein of Mr 32,000 and 2-3 minor proteins of larger molecular weights. The effects of inhibitors on the ADP-ribosyltransferase activity proves that the reaction is enzymatic and suggests that the enzyme ADP-ribosylates the guanidine group of arginine. The kinetics of liberation of ADP-ribose during alkaline hydrolysis of the modified proteins is consistent with the arginine-ADP-ribose bond. This is the first report of ADP-ribosylation of proteins in a Gram-positive bacterium.


The RhoA- and CDC42-specific exchange factor Dbs promotes expansion of immature thymocytes and deletion of double-positive and single-positive thymocytes.
Specific members of the Rho family of GTPases exert unique influences on thymocyte proliferation, differentiation and deletion. Dbs is a guanine nucleotide exchange factor which is expressed throughout thymocyte development and is able to activate the Rho family GTPases CDC42, RhoA and RhoG. Transgenic mice expressing an activated form of Dbs had increased numbers of double-negative thymocytes. The Dbs transgene promoted expansion of double-negative thymocytes in the absence of pre-TCR, but had no effect on pre-TCR-dependent differentiation of double-negative thymocytes into double-positive thymocytes. Transgenic double-positive thymocytes were proliferative in vivo, but were also susceptible to apoptosis in vivo and in vitro. The transgenic single-positive thymocytes had attenuated proliferative responses following TCR ligation, and were depleted rather than expanded during culture in the presence of anti-CD3. When expressing a positively selectable TCR, transgenic double-positive thymocytes were increased in number and activated, but the output of single-positive thymocytes was reduced. Transgenic double-positive thymocytes were acutely sensitive to deletion by TCR ligation in vivo. These results indicate that activation of Dbs has the potential to promote proliferation throughout thymocyte development, but also sensitizes double-positive and single-positive thymocytes to deletion.


Promoting oral mucosal wound healing using a DCS-RuB2A2 hydrogel based on a photoreactive antibacterial and sustained release of BMSCs.
The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals. Following the development of oral mucosal lesions, the oral microenvironment changes, immunity declines, and continuous bacterial stimulation causes wound infection. Traditional antibacterial drugs are ineffective for oral mucosal lesions. To overcome this problem, a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity, which is different from that on the body surface since it mostly remains under dark conditions. In the absence of light, the hydrogel seals the wound to form a barrier, exerts a natural bacteriostatic effect, and prevents invasion by foreign bacteria. Simultaneously, mesenchymal stem cells are presented, and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects, which result in rapid repair of the damaged site. Under light conditions, after photo-induced shedding of the hydrogel, RuB2A exerts an antibacterial effect accompanied by degradation of the hydrogel. Results in a rat oral mucosal repair model demonstrate that DCS-RuB2A2-BMSCs could rapidly repair the oral mucosa within 4 days. Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways. Taken together, our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.


Relation of glycated hemoglobin with carotid atherosclerosis in ischemic stroke patients: An observational study in Indian population.
Glycated hemoglobin A1c(HbA1c) indicates long-term uncontrolled hyperglycemia in the body, which in diabetic patients leads to various vascular complications as a part of generalized atherosclerosis culminating ultimately into ischemic stroke. Study aims to show the association between marker of uncontrolled long-term hyperglycemia HbA1c and marker of atherosclerosis (Carotid intima media thickness [CIMT] and carotid plaque) in ischemic stroke patients. Carotid sonography using high resolution 7.5 MHz sonography technique was done in each patient to find the occurrence of increased CIMT and presence of plaque according to Mannheim CIMT Consensus (2004-2006). Levels of HbA1c measured in blood in both diabetic and non-diabetic patients and a comparison made between them. Finally an association sought between HbA1c levels with CIMT and plaque. The average value of HbA1c of this cohort was 7.51 ± 1.75% with higher values in diabetic patients (9.29 ± 1.73%). The patients with high CIMT (>0.8 mm) had higher values of HbA1c then that of normal CIMT patients and this was nearly significantly (P = 0.06). However, HbA1c levels of blood were significantly associated with stroke patients with presence of carotid arteries plaque (P = 0.008). Prediction of future risk and prevention strategies for ischemic stroke could be formulated by utilizing HbA1c levels in both diabetic and non-diabetic population.


Stroke rehabilitation in China: a systematic review and meta-analysis.
Stroke rehabilitation is regarded as an essential component of organized care, therefore withholding treatment is considered unethical in Western trials. Poststroke rehabilitation is not standard in China, and trials with no treatment controls have been possible. We believed aggregation of these data represented a unique opportunity to examine the 'effect size' of this intervention. The aim of this study was to systematically review randomized controlled trials that compare rehabilitation to standard care after stroke in China. We searched 24 databases including Wanfangdata (China), MEDLINE, EMBASE, CENTRAL, Cochrane Stroke Group Register, and Cochrane Central Register of Controlled trials. The primary outcome of interest was activities of daily living (Barthel Index), and the secondary outcome was disability (Fugl-Meyer Score). Random-effect meta-analysis was performed. Thirty-seven randomized controlled trials consisting of 5916 patients met inclusion criteria. Mean age reported in each study range from 47.2 to 72.5 years, 52.6% were male and 23.8% had a haemorrhagic stroke. Rehabilitation interventions varied between studies, but all included additional exercise therapy. Control patients had no formal rehabilitation. Patients who received rehabilitation showed marked improvements in Barthel Index (standardized mean difference: 1.04, 95% confidence interval: 0.88-1.21, P < 0.001, I(2) = 85.9%) and Fugl-Meyer Score (standardized mean difference: 1.10, 95% confidence interval: 0.82-1.38, P < 0.001, I(2) = 94.3%) compared with controls. However, reporting quality was low, and time to start of rehabilitation was often unclear. These data provide some evidence that rehabilitation poststroke is more effective than no rehabilitation, improving activities of daily living and reducing disability. Although results are limited by low reporting quality and study heterogeneity, conducting research in countries in which rehabilitation is not standard care provides an opportunity to advance our understanding and should be encouraged.


Neuropsychological performance in OCD: a study in medication-naïve patients.
Obsessive-compulsive disorder (OCD) is associated with impairments in multiple neuropsychological domains but the findings are rather inconsistent across studies. One potential reason for poor replication is the confounding influence of medications. There is limited research on neuropsychological performance in medication-naïve, never treated OCD patients. In this study, we assessed 31 medication-naïve, never-treated, DSM-IV OCD patients free of comorbid major depression and 31 healthy controls individually matched for age, gender and years of education, with tests of attention, executive function, memory reasoning and visuo-spatial function. Medication-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Patients performed somewhat poorly only on the highest goal hierarchy of the Tower of London (TOL) test (p=0.001, effect size=0.68). It is intriguing to find that symptomatic, drug-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Our finding of medium effect size on TOL highest goal hierarchy test suggests that brain regions outside the affective orbitofrontal loop may also be perhaps involved in OCD. This finding however needs replication because of modest effect size. Future studies should focus on studying medication-naïve, co-morbidity-free patients and relatives using symptom dimensions for consistent and robust findings.


Phasic gain control of reflexes from the dorsum of the paw during spinal locomotion.
In chronic spinal cats walking with their hindlimbs on a treadmill belt, tactile stimuli were applied to the dorsum of the paw during various phases of the step cycle. A stimulation during the swing phase evoked a flexion response with a concomitant crossed extension, whereas in stance it induced an increased ipsilateral extension. EMG-recordings show short latency reflex responses in flexors and extensors, respectively. The responses are organized such that latencies of knee muscles are shorter than those of ankle and hip muscles. The movements induced by the stimulations appear to be very meaningful during normal conditions in compensating for any unpredicted obstacle disturbing the movement of the paw during locomotion. Responses during forward flexion and during the support phase are well adapted to the ongoing locomotor activity and do not influence the interlimb coordination whereas a stimulation when the foot approaches the ground after the end of flexion disturbs the regular alternating pattern. Different possible mechanisms underlying this phase-dependent reflex reversal are discussed.


Evolutionary changes in left and right ventricular function in acute myocardial infarction.
To determine the evolutionary changes in right and left ventricular function in acute myocardial infarction, 3 serial gated blood pool scans were performed in 76 patients within 24 hours (24 H), at 10 days (10 D) and 3 months (3 M) following the onset of myocardial infarction. The patients were divided into 3 groups: ANT (anterior MI), INF (inferior MI without right ventricular dysfunction) and RVF (inferior MI with right ventricular dysfunction). LVEF in ANT was significantly lower than that of INF and RVF at 24 H, 10 D and 3 M. The ratio of right ventricular volume to LV volume (RVV/LVV) was compared among 3 groups. The mean values of RVV/LVV in RVF were 1.3 through 24 H and 3 M and they were significantly higher than the other two groups. The RVV/LVV in ANT and INF were around 1.0. LVEDVI in RVF was rather smaller than that of ANT and INF. LVESVI in ANT at 24 H was significantly larger than that of INF and RVF and the mean value of LVESVI in ANT were around 60 ml/M2 from 24 H to 3 M. LVEF in ANT, RVF and INF did not increase significantly during peak exercise at 3 M. However, quantitative regional wall motion analysis revealed that regional wall motion of R2 (posterolateral wall motion) in ANT and R5 (septal wall motion) in INF decreased significantly during peak exercise. These impairments in regional wall motion might be due to the exacerbation of ischemia of non-infarcted area.


Successful treatment of acute inferior vena cava and unilateral renal vein thrombosis by local infusion of recombinant tissue plasminogen activator.
Renal vein thrombosis can occur as a complication of nephrotic syndrome. We present the case of a young man with nephrotic syndrome caused by minimal change disease who developed acute inferior vena cava and left renal vein thrombosis. He was treated initially with intravenous heparin. Because of the persistence of severe left flank pain and gross hematuria, local infusion of recombinant tissue plasminogen activator was tried, with resolution of thrombi and subsidence of symptoms. Functional preservation of the involved kidney is good, as indicated by Tc-99m DMSA scan (involved kidney, 47.4%; uninvolved kidney, 52.6%). Anticoagulation is usually recommended as the treatment of choice in renal vein thrombosis. We believe that in cases with critical presentations, such as bilateral involvement, extension into inferior vena cava, acute renal failure, pulmonary embolism or severe flank pain, thrombolytic therapy should be considered as a second-line treatment if good response is not obtained with heparin.


Gonadal effects on plasma ACE activity in mice.
Angiotensin-converting enzyme (ACE) regulates blood pressure and is an important target in the management of hypertension. Hypertension is a gender biased disease. Plasma ACE activity is significantly higher in male mice (309 U/l) than female mice (237 U/l) and is reduced significantly upon gonadectomy to 224 and 209 U/l, respectively. Although, the gonads influence plasma ACE activity in both male and female mice, the effect is more pronounced in male mice. Plasma ACE is derived from the cleavage of tissue ACE and lung has the highest concentration of tissue ACE. However, lung ACE activity is not gender dimorphic but increases significantly upon gonadectomy in both male and female. ACE mRNA level in the lung is not influenced by gender or gondaectomy. Therefore, the gonads affect plasma ACE activity by influencing cleavage of tissue ACE to plasma ACE and/or decrease stability of plasma ACE in gonadectomized mice is mediated.


Potency and characterization of estrogen-receptor agonists in United Kingdom estuarine sediments.
The activity of estrogen-receptor (ER) agonists in sediments collected from the United Kingdom (UK) estuaries was assessed using the in vitro recombinant yeast estrogen screen (YES assay). The YES assay was successfully used to determine the in vitro ER agonist potency of pore waters and solvent extracts of sediments collected from UK estuaries. Estrogen-receptor agonists were detected in 66% of the pore water samples and in 91% of the sediment solvent extracts tested. The pore waters tested had ER agonist potencies from less than 2 to 68 ng 17beta-estradiol (E2) L(-1), whereas sediment extracts had potencies from less than 0.2 to 13 microg E2 kg(-1). A toxicity identification evaluation approach using bioassay-directed fractionation was used in an attempt to identify the ER agonists in extracts of sediments collected from the Tyne and Tees estuaries (UK). Gas chromatography-mass spectrometry was used to provide lists of compounds in the fractions obtained that were evaluated for known ER agonist activity using published data and an ER quantitative structure-activity relationship model. Toxicity identification evaluation characterization failed to identify any ER agonists in pore water extracts; however, three compounds in sediment solvent extracts were identified as ER agonists. Nonylphenol, cinnarizine, and cholesta-4,6-dien-3-one were identified in the sample collected from the Tyne estuary. Important ER agonist substances that contaminate marine sediments remain unidentified. The present study as well as previous work on effluents point toward the involvement of natural products in the estrogenic burdens of marine sediments. Further work is required to establish the relative contribution of natural products and anthropogenic chemicals to current environmental impacts in the context of the Oslo and Paris Commission strategy to eliminate hazardous substances by 2020.


Understanding the measurement relationship between EQ-5D-5L, PROMIS-29 and PROPr.
Many generic patient-reported instruments are available for the measurement of health outcomes, including EQ-5D-5L, and the Patient-Reported Outcome Measurement Information System (PROMIS). Assessing their measurement characteristics informs users about the consistency between, and limits of, evidence produced. The aim was to assess the measurement relationship between the EQ-5D-5L descriptive system and value sets, the PROMIS-29 and PROPr (PROMIS value set). Data were extracted from a cross-sectional survey administering measures of quality of life online in Australia. Descriptive analysis, agreement and construct validity assessment methods were used to compare instruments at the item, domain and value set level. In total, 794 Australians completed the survey. Convergent validity analysis found that similar dimensions across instruments were highly correlated (> 0.50), but the PROMIS-29 assesses additional health concepts not explicitly covered by EQ-5D (sleep and fatigue). Known-group assessment found that EQ-5D-5L and PROPr were able to detect those with and without a condition (ES range 0.78-0.83) but PROPr could more precisely detect differing levels of self-reported health. Both instruments were sensitive to differences in levels of pain. There is some consistency in what the EQ-5D-5L, PROMIS-29 and PROPr measure. Differences between value set characteristics can be linked to differences what is measured and the valuation approaches used. This has implications for the use of each in assessing health outcomes, and the results can inform decisions about which instrument should be used in which context.


Study of the effect of a liquid nutrition supplement on the nutritional status of psycho-geriatric nursing home patients.
To evaluate the acceptance of a multinutrient liquid nutrition supplement in psycho-geriatric nursing home patients and the effect on weight, plasma nutrients and activities of daily life. Double-blind, placebo-controlled 12-week intervention study. Two nursing homes in Boxtel, The Netherlands. Forty-two (body mass index (BMI) <23 kg/m2 for men or <25 kg/m2 for women) psycho-geriatric nursing home patients aged 60 y or over. Provision with a complete micronutrient-enriched liquid nutrition supplement of 125 ml and 0.6 MJ (135 kcal) or placebo twice daily during daytime between main meals. Study parameters were assessed at 0, 6 and 12 weeks. MAIN OUTCOME FOR MEASURES: Weight, Barthel index of daily activities, several plasma values (albumin, C-reactive protein (CRP), homocysteine, thiamine, thiamine diphosphate (TDF), vitamin B6, vitamin B12, folic acid, vitamin D), bowel function. The supplement was well accepted. Thirty-five patients completed the intervention period (16 control group; 19 supplement group). Baseline daily nutrient intake was low. A statistically significant improvement was observed for body weight (difference between groups 2.2 kg, P=0.03), and homocysteine, vitamin B1, TDF, vitamin B6, vitamin B12, folate and vitamin D in the supplement group compared to the placebo group. No significant difference was observed in the Barthel index (mean difference -0.3+/-1.1 for both groups). No difference in occurrence of diarrhoea was observed. The study shows that nutritional supplementation is well accepted and can improve the nutritional status of psycho-geriatric nursing home patients. Numico Research BV.


Formyl migration product of chanoclavine-I aldehyde in the presence of the old yellow enzyme FgaOx3 from Aspergillus fumigatus: a NMR structure elucidation.
A previous study showed that together with the festuclavine synthase FgaFS, the old yellow enzyme FgaOx3 from Aspergillus fumigatus catalyzed the conversion of chanoclavine-I aldehyde to festuclavine in the biosynthesis of ergot alkaloids. In the absence of FgaFS, a mixture containing two compounds with a ratio of 7:3 was detected in the enzyme assay of FgaOx3. NMR experiments including (DQF)-COSY, HSQC, HMBC and NOESY identified their structures as E/Z isomers of N-methyl-N-[(5R,10R)-10-(2-oxo-propyl)-2,4,5,10-tetrahydrobenzo[cd]indol-5-yl]formamide and proved the migration of the formyl group at C-8 in chanoclavine I-aldehyde to N-6 in the identified products.


Redundant CAMTA Transcription Factors Negatively Regulate the Biosynthesis of Salicylic Acid and N-Hydroxypipecolic Acid by Modulating the Expression of SARD1 and CBP60g.
Two signal molecules, salicylic acid (SA) and N-hydroxypipecolic acid (NHP), play critical roles in plant immunity. The biosynthetic genes of both compounds are positively regulated by master immune-regulating transcription factors SARD1 and CBP60g. However, the relationship between the SA and NHP pathways is unclear. CALMODULIN-BINDING TRANSCRIPTION FACTOR 1 (CAMTA1), CAMTA2, and CAMTA3 are known redundant negative regulators of plant immunity, but the underlying mechanism also remains largely unknown. In this study, through chromatin immunoprecipitation and electrophoretic mobility shift assays, we uncovered that CBP60g is a direct target of CAMTA3, which also negatively regulates the expression of SARD1, presumably via an indirect effect. The autoimmunity of camta3-1 is suppressed by sard1 cbp60g double mutant as well as ald1 and fmo1, two single mutants defective in NHP biosynthesis. Interestingly, a suppressor screen conducted in the camta1/2/3 triple mutant background yielded various mutants blocking biosynthesis or signaling of either SA or NHP, leading to nearly complete suppression of the extreme autoimmunity of camta1/2/3, suggesting that the SA and NHP pathways can mutually amplify each other. Together, these results reveal that CAMTAs repress the biosynthesis of SA and NHP by modulating the expression of SARD1 and CBP60g, and that the SA and NHP pathways are coordinated to optimize plant immune response.


A Randomized Study of Safety and Efficacy of Two Doses of Ambrisentan to Treat Pulmonary Arterial Hypertension in Pediatric Patients Aged 8 Years up to 18 Years.
To assess the safety and efficacy of the endothelin receptor antagonist ambrisentan in pediatric pulmonary arterial hypertension (PAH). In this open-label, phase IIb study, patients with PAH aged 8 to <18 years were randomized to low- or high-dose ambrisentan for 24 weeks. Most patients were receiving other PAH medication(s) that could not be changed during the trial. The primary outcome was safety (treatment-emergent adverse events [TEAEs]); secondary outcome was efficacy (including change from baseline to week 24 in 6-minute walking distance and World Health Organization functional class). Study staff were blinded to treatment. No statistical testing was performed. Most of the 41 patients randomized (80%) experienced ≥1 TEAE; most were mild (22%) or moderate (49%) in severity (no difference between dose groups). Most common TEAEs were headache (24%), nausea (17%), abdominal pain (12%), and nasopharyngitis (12%). Eight patients had serious TEAEs; 2 were fatal (unrelated to study treatment). Improved 6-minute walking distance was observed from baseline to week 24: total mean (SD) change, +40.69 (84.58) meters; World Health Organization functional class was maintained or improved in 70% and 27% patients, respectively. Ambrisentan was well tolerated; TEAEs were consistent with the adult safety profile. Efficacy was similar to previous findings in adult PAH; however, interpretation is limited by small sample size. Findings support a potentially similar benefit:risk profile in pediatric (8 to <18 years) and adult patients with PAH. ClinicalTrials.gov: NCT01332331.


Peripheral Retinal Nonperfusion in Pediatric Patients With Morning Glory Syndrome.
To report the association of morning glory syndrome (MGS) with peripheral retinal nonperfusion in pediatric patients with MGS. The authors retrospectively analyzed the records of pediatric patients with MGS using fundus fluorescein angiography. The peripheral retinal vascular architecture was recorded and graded according to the severity of peripheral retinal nonperfusion. Eighty-six eyes of 74 patients were enrolled. Seventy-three of 86 eyes (84.88%) had peripheral retinal nonperfusion, in which mild severity was found in 31 of 86 eyes (36.05%), moderate in 17 of 86 eyes (19.77%), severe in 18 of 86 eyes (20.93%), and extreme in seven of 86 eyes (8.14%). Secondary complications of nonperfusion included leakage in six of 73 eyes (8.22%), fibrovascular proliferation in two of 73 eyes (2.74%), and tractional retinal detachment in one of 73 eyes (1.34%). There is a high prevalence of peripheral retinal nonperfusion in pediatric MGS eyes, with secondary complications in some, suggesting that more attention should be paid to the peripheral retina in MGS. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:674-679.].


[Assessment of the check-list in the operating room: perceptions of caregivers and physicians (level II assessment)].
To assess, a year after the deployment of the check-list in the centre hospitalier Lyon Sud (CHLS - HCL), the perception of medical and nursing staff regarding the advantages of the check-list and its level of integration within the overall organization of the operating room. Descriptive study, questionnaires and audits. Distribution of individual questionnaires to the entire operating room staff, and observational audits in the operating room, to objectively assess the quality of implementation of the check-list (level II of the HAS - French National Autority of Health). The medical and nursing staff participated equally in using the check-list. This was derived from the individual questionnaires and reinforced by the observational audit; they also revealed an uneven implementation of the three phases, with phase 3 almost never performed. In two-third of the cases, the time-out requirements did not comply with HAS instructions. Nurses and physicians perceived the check-list differently. Even though they agreed that the check-list should be a team effort and is useful, nurses noted a lack of investment and leadership from doctors, in addition to communication problems, which led to a feeling of disrespect towards them when they play the role of the check-list coordinator. The questionnaire and the audit of practice showed strong adherence to the concept in that the surgical check-list was considered useful by all staff. However, it was also considered to be an added formality and its full implementation was rare in practice. There was a problem of distribution and acceptance of roles with nurses often observing that they were the only ones strictly following the check-list due to a lack of medical investment.


Blunted peripheral tissue responsiveness to thyroid hormone in uremic patients.
To understand the biologic significance of the low triiodothyronine (T3) syndrome in patients with chronic renal failure (CRF), we examined thyroid hormone profile, basal O2 uptake (VO2), and peripheral blood mononuclear leukocyte (PBL) ouabain binding in these patients and in the control subjects before and after L-triiodothyronine (T3) and sodium ipodate treatment. In the controls (N = 8), T3 administration increased serum total T3 from 136 +/- 15 to 232 +/- 11 ng/dl, and reduced total thyroxine (T4) from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, free T4 from 1.59 +/- 0.12 to 1.03 +/- 0.05 ng/dl and thyroid-stimulating hormone (TSH) from 1.74 +/- 0.24 to 0.41 +/- 0.09 microU/ml. VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg/min. Ipodate treatment, on the other hand, resulted in a reduction of serum total T3 to 102 +/- 21 ng/dl, an increase in total T4 to 9.59 +/- 0.50 micrograms/dl, free T4 to 1.91 +/- 0.13 ng/dl and TSH to 3.64 +/- 1.14 microU/ml. VO2 decreased to 2.43 +/- 0.06 ml/kg/min. P values ranged from less than 0.05 to less than 0.001. In the CRF patients (N = 14), T3 treatment also resulted in a rise in serum total T3 from 75 +/- 5 to 185 +/- 8 ng/dl. Total T4 declined from 6.68 +/- 0.34 to 5.18 +/- 0.48 micrograms/dl, free T4 from 0.85 +/- 0.1 to 0.67 +/- 0.08 ng/dl and TSH from 3.67 +/- 0.86 to 0.94 +/- 0.3 microU/ml. VO2, however, did not change (from 2.91 +/- 0.12 to 2.99 +/- 0.17 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)


Pre-hospital provider recognition of intimate partner violence.
The leading risk factor of morbidity and mortality in Victorian women aged between 15 and 45 years is intimate partner violence (IPV) (approximately 8 times than that of smoking). Paramedics are frequently the first point of contact for victims of IPV. Due to this unique viewpoint, paramedics have the advantage of potentially identifying and reporting IPV, which can then result in early intervention. This article will summarise the literature regarding pre-hospital provider knowledge of IPV.


Corrigendum: Positive Effects of Nature on Cognitive Performance Across Multiple Experiments: Test Order but Not Affect Modulates the Cognitive Effects.
[This corrects the article DOI: 10.3389/fpsyg.2019.01413.].


Knowledge Translation and WIC Food Package Regulation Change.
Knowledge Translation (KT) is the exchange, synthesis, and ethically-sound application of knowledge. A case study methodology is used to examine KT at the organizational level of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program. The study used purposeful sampling to select WIC informants from state WIC agencies to participate in semi-structured interviews about their individual experiences during the 2009 WIC regulation change process. Thematic coding of retrospective semi-structured interviews with key informants from WIC state agencies revealed key components of the state-level WIC regulation implementation process, and key constructs of Organizational Readiness for Knowledge Translation in the WIC program. WIC informants highlight that decisions made by WIC state agencies regarding how to appraise, synthesize, and adapt evidence or regulation change are constrained by the KT decisions made by federal agencies. WIC state agencies should assess their level of readiness for KT in terms of 1) innovation readiness; 2) personal readiness; and 3) institutional readiness. This WIC case study can help decision-makers to understand the KT process of implementing evidence-informed regulation changes, identify factors that could influence states' ability to be prepared for implementing changes, and gauge "practicality" of future WIC regulation changes.


The Incidence of Trilateral Retinoblastoma: A Systematic Review and Meta-Analysis.
To estimate the incidence of trilateral retinoblastoma in patients with retinoblastoma. Systematic review and meta-analysis. We searched Medline and Embase for scientific literature published between January 1966 and July 2015 that assessed trilateral retinoblastoma incidence. We used a random-effects model for the statistical analyses. We included 23 retinoblastoma cohorts from 26 studies. For patients with bilateral retinoblastoma the unadjusted chance of developing trilateral retinoblastoma across all cohorts was 5.3% (95% confidence interval [CI]: 3.3%-7.7%); the chance of pineal trilateral retinoblastoma was 4.2% (95% CI: 2.6%-6.2%) and the chance of nonpineal trilateral retinoblastoma was 0.8% (95% CI: 0.4%-1.3%). In patients with hereditary retinoblastoma (all bilateral cases, and the unilateral cases with a family history or germline RB1 mutation) we found a trilateral retinoblastoma incidence of 4.1% (95% CI: 1.9%-7.1%) and a pineal trilateral retinoblastoma incidence of 3.7% (95% CI: 1.8%-6.2%). To reduce the risk of overestimation bias we restricted analysis to retinoblastoma cohorts with a minimum size of 100 patients, resulting in adjusted incidences of 3.8% (95% CI: 2.4%-5.4%), 2.9% (95% CI: 1.9%-4.2%), and 0.7% (95% CI: 0.3%-1.2%) for any, pineal, and nonpineal trilateral retinoblastoma, respectively, among patients with bilateral retinoblastoma. Among hereditary retinoblastoma we found an adjusted trilateral retinoblastoma incidence of 3.5% (95% CI: 1.2%-6.7%) and a pineal trilateral retinoblastoma incidence of 3.2% (95% CI: 1.4%-5.6%). The estimated incidence of trilateral retinoblastoma is lower than what is reported in previous literature, especially after exclusion of small cohorts that were subject to overestimation bias in this context.


Evidence for antinociceptive activity of botulinum toxin type A in pain management.
The neurotoxin, botulinum toxin type A, has been used successfully, in some patients, as an analgesic for myofascial pain syndromes, migraine, and other headache types. The toxin inhibits the release of the neurotransmitter, acetylcholine, at the neuromuscular junction thereby inhibiting striated muscle contractions. In the majority of pain syndromes where botulinum toxin type A is effective, inhibiting muscle spasms is an important component of its activity. Even so, the reduction of pain often occurs before the decrease in muscle contractions suggesting that botulinum toxin type A has a more complex mechanism of action than initially hypothesized. Current data points to an antinociceptive effect of botulinum toxin type A that is separate from its neuromuscular activity. The common biochemical mechanism, however, remains the same between botulinum toxin type A's effect on the motor nerve or the sensory nerve: enzymatic blockade of neurotransmitter release. The antinociceptive effect of the toxin was reported to block substance P release using in vitro culture systems. The current investigation evaluated the in vivo mechanism of action for the antinociceptive action of botulinum toxin type A. In these studies, botulinum toxin type A was found to block the release of glutamate. Furthermore, Fos, a product of the immediate early gene, c-fos, expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin. These findings suggest that botulinum toxin type A blocks peripheral sensitization and, indirectly, reduces central sensitization. The recent hypothesis that migraine involves both peripheral and central sensitization may help explain how botulinum toxin type A inhibits migraine pain by acting on these two pathways. Further research is needed to determine whether the antinociceptive mechanism mediated by botulinum toxin type A affects the neuronal signaling pathways that are activated during migraine.


Plant Hormone Modularity and the Survival-Reproduction Trade-Off.
Biological modularity refers to the organization of living systems into separate functional units that interact in different combinations to promote individual well-being and species survival. Modularity provides a framework for generating and selecting variations that can lead to adaptive evolution. While the exact mechanisms underlying the evolution of modularity are still being explored, it is believed that the pressure of conflicting demands on limited resources is a primary selection force. One prominent example of conflicting demands is the trade-off between survival and reproduction. In this review, we explore the available evidence regarding the modularity of plant hormones within the context of the survival-reproduction trade-off. Our findings reveal that the cytokinin module is dedicated to maximizing reproduction, while the remaining hormone modules function to ensure reproduction. The signaling mechanisms of these hormone modules reflect their roles in this survival-reproduction trade-off. While the cytokinin response pathway exhibits a sequence of activation events that aligns with the developmental robustness expected from a hormone focused on reproduction, the remaining hormone modules employ double-negative signaling mechanisms, which reflects the necessity to prevent the excessive allocation of resources to survival.


The induction of salt stress tolerance by propyl gallate treatment in green microalga Dunaliella bardawil, through enhancing ascorbate pool and antioxidant enzymes activity.
The effect of propyl gallate (PG), a synthetic antioxidant, on antioxidant responses and salinity tolerance was investigated in the cells of the green microalga, Dunaliella bardawil. Algal suspensions grown at three salinity levels of 1, 2, and 3 M NaCl were incubated with 1 mM of PG. The number of cells was significantly lower in all PG-treated cells compared to untreated controls. Despite PG-induced cell death, the fresh weight of all PG-treated cells was considerably higher than controls. PG-treated cells had enhanced antioxidant capacity because of increased levels of Chlorophyll a, β-carotene, reduced ascorbate, protein, and enzymatic activities, but accumulated lower levels of malonyldialdehyde and hydrogen peroxide compared to untreated cells. The results suggest that PG acts as a signal molecule both directly by reducing of free radical oxidants and indirectly by augmenting ascorbate pool levels, β-carotene production, and antioxidant enzymes activity to boost the capacity of antioxidant systems and radical oxygen species scavenging. Therefore, induction of salt stress tolerance by PG in D. bardawil is associated with metabolic adjustments through activation or synthesis of both enzymatic and non-enzymatic molecules involved in antioxidant systems.


The role of transferrin in atherosclerosis.
Transferrin is a plasma protein with the primary role of transporting iron through the body and delivering it to the cells that utilize it. Because free ionic iron is very toxic by creating free radicals, the importance of transferrin lies in its antioxidant properties. Atherosclerosis, a pathological process affecting arterial walls, is a chronic inflammatory response in which oxidative stress caused by free radicals is a key factor in its pathogenesis. We postulate therefore that the plasma protein transferrin acts protectively in these events, by holding iron in containment and reducing oxidative stress. Furthermore, it is possible that a disturbance in transferrin function and homeostasis is a direct factor triggering and exacerbating atherosclerosis. Decreased transferrin levels, increased transferrin saturation, defective transferrin binding of iron, or other disorders may lead to increased oxidative stress and lipid peroxidation involved in the pathology of atherosclerosis. Some oxidative stress-related diseases have been linked to such systemic transferrin abnormalities, and we hypothesize that similar disruptions could account for an unfavorable microenviroment in the evolvement of atherosclerotic plaques. If confirmed, this proposed mechanism would significantly improve our understanding of the disease.