Social communication interventions for preschoolers: targeting peer interactions during peer group entry and cooperative play.
Some preschoolers with language impairment approach and manage peer interactions less effectively than typically developing peers. This article discusses assessment and intervention strategies for targeting preschoolers' social communication skills during peer entry and cooperative play situations. Essential features of effective interventions include identification of appropriate social communication targets, addressing and facilitating children's use of these targets during small group sessions with peers, and supporting generalization of newly acquired social communication behaviors to children's peer interactions within the classroom setting.


Comparison of nasal responsiveness to histamine, methacholine and phentolamine in allergic rhinitis patients and controls.
In a selected group of rhinitis patients with an IgE-mediated allergy to house dust mites the nasal response to insufflation of histamine chloride, methacholine and phentolamine was demonstrated to be higher than in a control group. With the methods used histamine chloride was better at discriminating between healthy subjects and patients than methacholine or phentolamine. This discrimination was shown by assessing the severity of reflex-mediated symptoms such as the number of sneezes and the amount of secretion, and not by differences in nasal airway resistance.


Two sequence-specific binding proteins from the promoter region of the c-Ha-ras-I oncogene.
The role of sequence-specific binding proteins in transcriptional control in higher eukaryotes is unclear. We have investigated the control region of the c-Ha-ras-I protooncogene containing upstream sequences from the transcriptional initiation point. Two proteins, which bind these sequences, with molecular weights of 20 K and 43 K were found. The possible role in the process of transformation is discussed.


Thyroid function reference ranges during pregnancy in a large Chinese population and comparison with current guidelines.
A correct thyroid function reference range is important for the accurate diagnosis of thyroid disease during pregnancy. However, there is no consensus on whether thyroid function reference ranges in Chinese population should follow the America Thyroid Association (ATA) guidelines. This study aimed to establish a thyroid function reference range more suited to the Chinese population by evaluating the current thyroid function reference range in pregnant Chinese women and comparing it to the ATA guidelines. A total of 52,027 pregnant women were enrolled from January 2013 to December 2016. Thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) levels were tested during the first and third trimesters of pregnancy. Reference ranges of TSH and FT4 were established from the 2.5th and 97.5th percentiles of the TPOAb-negative population of women. The Mann-Whitney U test was used to compare thyroid hormones between the TPOAb-positive and TPOAb-negative groups. We obtained that the TSH reference ranges were 0.03 to 3.52 mU/L and 0.39 to 3.67 mU/L, and the FT4 reference ranges were 11.7 to 19.7 pmol/L and 9.1 to 14.4 pmol/L, in the first and third trimester, respectively. If we used the 2011 ATA criteria about 7.0% and 4.0% pregnant women would be over diagnosed in first and third trimester, respectively, compared with local population thyroid hormone reference. When we compared our local criteria with the new 2017 ATA criteria, about 1.2% and 0.8% pregnant women would have a missed diagnosis in first and third trimester, respectively. Based on our data, which is in line with the current ATA guidelines, a population-based thyroid function reference range would be the first choice for diagnosis of thyroid disease during pregnancy in China. In case such population-based thyroid function reference ranges are unavailable in the east of China, our reference ranges can be adopted, if the same assay is used. www.chictr.org.cn (No. ChiCTR1800014394).


[Chemotherapy with cisplatin-bleomycin and subsequent radiotherapy in advanced head and neck tumors].
42 patients with advanced stage III and IV squamous cell carcinoma of the head and neck were treated with initial cisplatin and bleomycin chemotherapy and subsequent radiotherapy. 39 were evaluable for results, and 3 for toxicity only. 8 patients suffered from stage III and 31 from stage IV tumors, of these 10 with distant metastases. 5 patients underwent later a rescue operation. 27 were previously untreated (= group A) including 2 cases with localized relapses beyond the margins of surgical and/or radiotherapeutic treatment fields. 12 patients had a recurrence within pretreated areas (= group B). The induction chemotherapy alone showed the following results: In group A 4 (15%) CR, 10 (37%) PR, 7 (26%) MR; in group B 3 (25%) PR, 2 (17%) MR. The subsequent radiotherapy mostly consisted of a 65 Gy tumor dose given in 61/2 weeks. The results after completion of the combined modality therapy were: In group A 44% CR, 28% PR; in group B 10% CR and 30% PR. No patient resistant to the initial chemotherapy responded to the radiotherapy. The median survival time of stage III patients was 20 months but only 7 months in stage IV patients. 4 of all live with NED now between 30+ and 41+ months; 1 patient is alive with relapse. All the others are dead after a survival time of max. 32 months, included the 5 with rescue operation. In general, hematologic and renal toxicities were not severe, but nausea and vomiting were the worst tolerated side effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Sirolimus and post transplant Cy synergistically maintain mixed chimerism in a mismatched murine model.
Because of the toxicity associated with myeloablative conditioning, nonmyeloablative regimens are increasingly being used in vulnerable patient populations. For patients with sickle cell disease, stable mixed chimerism has proven sufficient to reverse the phenotype. Because the vast majority of patients do not have an HLA-matched sibling, a safe nonmyeloablative regimen that could be applied to the haploidentical setting would be ideal. We employed a mismatched mouse model using BALB/c donors and C57BL/6 recipients. Recipient mice were conditioned with 200 cGy TBI and sirolimus or CSA with or without post transplant Cy (PT-Cy). Our data show that when sirolimus or PT-Cy alone is given to C57BL/6 recipients, donor cells are not detected. However, when sirolimus is administered for 15 or 31 days starting 1 day before or up to 6 days after transplant with PT-Cy, all mice maintain stable mixed chimerism. In contrast, conventional therapy employing CSA with or without PT-Cy does not result in stable mixed chimerism. Lastly, mice with stable mixed chimerism after sirolimus display decreased reactivity to donor Ag both in vitro and in vivo. These data identify a novel strategy for inducing mixed chimerism for the treatment of nonmalignant hematologic diseases.


High-resolution separation of DNA restriction fragments by capillary electrophoresis in cellulose derivative solutions.
The performance and the efficiency of several cellulose derivatives as a molecular sieving agent for the capillary electrophoretic separation of DNA restriction fragments were investigated. All fragments up to 12,000 base pairs (bp) in the 1-kbp DNA ladder were resolved using linear polyacrylamide-coated capillaries filled with a buffer solution containing 0.5% cellulose derivative and the separation was completed within 17 min. High-concentration (0.7%) cellulose derivative solutions are effective for the complete separation of small fragments (50-1000 bp) of a HincII and a HaeIII digest of phi X174 DNA. A plate number of 0.5-1 x 10(6) plates per metre was achieved. The migration time and the resolution of DNA fragments were manipulated by varying several parameters, such as the size (viscosity) and the concentration of cellulose derivatives and the applied field strength. Some guidelines are presented for choosing these parameters, depending on the size of the DNA fragments being separated.


Absence of Chromosome Damage in the bone marrow of rats fed detergent actives for 90 days.
Four detergent actives, sodium lauryl sulphate, DOBS 055, Dobanol 25 sulphate LCU and Dobanol 25 sulphate HCB, were fed to rats in the diet for 90 days at the maximum tolerated dose, 1.13 percent active ingredient in each case. Sodium lauryl sulphate and DOBS 055 were also fed at half this concentration. Chromosome preparations were made from the bone marrow and scored for the presence of rearrangements, chromatid gaps and breaks and isochromatid gaps and breaks. The four detergent actives were found to have no effect on the chromosomes of rat bone marrow cells.


Microbial community composition of food waste before anaerobic digestion.
Anaerobic digestion is widely used to process and recover value from food waste. Commercial food waste anaerobic digestion facilities seek improvements in process efficiency to enable higher throughput. There is limited information on the composition of microbial communities in food waste prior to digestion, limiting rational exploitation of the catalytic potential of microorganisms in pretreatment processes. To address this knowledge gap, bacterial and fungal communities in food waste samples from a commercial anaerobic digestion facility were characterised over 3 months. The abundance of 16S rRNA bacterial genes was approximately five orders of magnitude higher than the abundance of the fungal intergenic spacer (ITS) sequence, suggesting the numerical dominance of bacteria over fungi in food waste before anaerobic digestion. Evidence for the mass proliferation of bacteria in food waste during storage prior to anaerobic digestion is presented. The composition of the bacterial community shows variation over time, but lineages within the Lactobacillaceae family are consistently dominant. Nitrogen content and pH are correlated to community variation. These findings form a foundation for understanding the microbial ecology of food waste and provide opportunities to further improve the throughput of anaerobic digestion.


Rosacea fulminans.
We review rosacea fulminans, a rare condition that may cause facial scarring and disfigurement. All physicians and health care professionals must be aware of this form of rosacea to treat or refer the patient. Early treatment of rosacea fulminans is essential to avoid scarring.


RNA double strand hybridization measured at the single molecule level.
RNA double strand hybridization is a hallmark for gene expression regulation. In this function, single stranded regulatory RNA forms Watson-Crick base pairs with complementary messenger RNA. In the presented work the dissociation constants of complementary equally sized RNA single strands were measured at the single molecule level applying fluorescence correlation spectroscopy (FCS). Dissociation constants of 3.2 nM, 1.4 nM and 1.0 nM were determined for 26 bp, 41 bp and 54 bp dsRNA, respectively. The translational diffusion coefficients of RNA, measured at infinite dilution, could be accurately predicted applying the model D = 4.58 × 10-10 N-0.39 m2s-1.


IgA nephropathy in systemic lupus erythematosus patients: case report and literature review.
Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear fine speckled pattern, and anticardiolipin IgM and 280U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non-SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in both the short and long terms.


Synthesis of α-CF3-substituted carbonyl compounds with relative and absolute stereocontrol using electrophilic CF3-transfer reagents.
Evans-type chiral lithium imide enolates undergo diastereoselective α-trifluoromethylation with a hypervalent iodine-CF(3) reagent with up to 91% combined isolated yield and 97:3 dr. The resulting isolated diastereopure products can be further transformed into valuable products without racemization.


Draft Genome Sequence of Lactobacillus rhamnosus CRL1505, an Immunobiotic Strain Used in Social Food Programs in Argentina.
We report the draft genome sequence of the probiotic Lactobacillus rhamnosus strain CRL1505. This new probiotic strain has been included into official Nutritional Programs in Argentina. The draft genome sequence is composed of 3,417,633 bp with 3,327 coding sequences.


Wound infiltration with ropivacaine as an adjuvant to patient controlled analgesia for transforaminal lumbar interbody fusion: a retrospective study.
Surgical procedure usually causes serious postoperative pain and poor postoperative pain management negatively affects quality of life, function and recovery time. We aimed to investigate the role of wound infiltration with ropivacaine as an adjuvant to patient controlled analgesia (PCA) in postoperative pain control for patients undergoing transforaminal lumbar interbody fusion. One hundred twelve patients undergoing lumbar fusion were retrospectively reviewed and divided into two groups (ropivacaine and control groups) according to whether received wound infiltration with ropivacaine or not. Visual Analogue Scale (VAS) score, analgesics consumption, number of patients requiring rescue analgesic, hospital duration and incidence of complications were recorded. Surgical trauma was assessed using operation time, intraoperative blood loss and incision length. The amount of sufentanil consumption in ropivacaine group at 4 h postoperatively was lower than that of control group (24.5 ± 6.0 μg vs 32.1 ± 7.0 μg, P < 0.001) and similar results were observed at 8, 12, 24, 48 and 72 h postoperatively(P < 0.001). Fewer patients required rescue analgesia within 4 to 8 h postoperatively in ropivacaine group (10/60 vs 19/52, P = 0.017). Length of postoperative hospital durations were shorter in patients receiving ropivacaine infiltration compared to control cohorts (6.9 ± 0.9 days vs 7.4 ± 0.9 days, P = 0.015). The incidence of PONV in ropivacaine group was lower than that in control group (40.4% vs 18.3%, P = 0.01). However, VAS scores were similar in two groups at each follow-up points postoperatively, and no difference was observed(P > 0.05). Wound infiltration with ropivacaine effectively reduces postoperative opioid consumption and PONV and may be a useful adjuvant to PCA to improve recovery for patients undergoing lumbar spine surgery.


Trends in concentrations of nitrate and total dissolved solids in public supply wells of the Bunker Hill, Lytle, Rialto, and Colton groundwater subbasins, San Bernardino County, California: influence of legacy land use.
Concentrations and temporal changes in concentrations of nitrate and total dissolved solids (TDS) in groundwater of the Bunker Hill, Lytle, Rialto, and Colton groundwater subbasins of the Upper Santa Ana Valley Groundwater Basin were evaluated to identify trends and factors that may be affecting trends. One hundred, thirty-one public-supply wells were selected for analysis based on the availability of data spanning at least 11 years between the late 1980s and the 2000s. Forty-one of the 131 wells (31%) had a significant (p<0.10) increase in nitrate and 14 wells (11%) had a significant decrease in nitrate. For TDS, 46 wells (35%) had a significant increase and 8 wells (6%) had a significant decrease. Slopes for the observed significant trends ranged from -0.44 to 0.91 mg/L/yr for nitrate (as N) and -8 to 13 mg/L/yr for TDS. Increasing nitrate trends were associated with greater well depth, higher percentage of agricultural land use, and being closer to the distal end of the flow system. Decreasing nitrate trends were associated with the occurrence of volatile organic compounds (VOCs); VOC occurrence decreases with increasing depth. The relations of nitrate trends to depth, lateral position, and VOCs imply that increasing nitrate concentrations are associated with nitrate loading from historical agricultural land use and that more recent urban land use is generally associated with lower nitrate concentrations and greater VOC occurrence. Increasing TDS trends were associated with relatively greater current nitrate concentrations and relatively greater amounts of urban land. Decreasing TDS trends were associated with relatively greater amounts of natural land use. Trends in TDS concentrations were not related to depth, lateral position, or VOC occurrence, reflecting more complex factors affecting TDS than nitrate in the study area.


Recipient and donor body mass index as important risk factors for delayed kidney graft function.
Obesity is increasingly impacting the overall health status and the global costs for health care. The increase in body mass index (BMI) is also observed in kidney allograft recipients and deceased organ donors. In a retrospective single-center study, we analyzed 1132 deceased donor kidney grafts, transplanted at our institution between 2000 and 2009 for recipient and donor BMI and its correlation with delayed graft function (DGF). Recipients/donors were classified according to their BMI (<18.5, 18.5-24.9, 25-29.9, and >30 kg/m(2)). DGF was defined as requirement for one dialysis within the first week after transplantation. Overall DGF rate was 32.4%, mean recipient BMI was 23.64 ± 3.75 kg/m(2), and mean donor BMI was 24.69 ± 3.44 kg/m(2). DGF rate was 25.2%, 29.8%, 40.9%, and 52.6% in recipients with BMI less than 18.5, 18.5 to 24.9, 25 to 29.9, and more than 30 kg/m, respectively (P<0.0001). Donor BMI less than 18.5, 18.5 to 24.9, 25 to 29.9, more than 30 kg/m(2) resulted in a DGF rate of 22.5%, 31.0%, 37.3%, and 51.2% (P < 0.0001). Multivariate analysis revealed recipient BMI and dialysis duration as independent risk factors for DGF. DGF results in inferior 1- and 5-year graft and patient survival. Recipient and donor BMI correlate with the incidence of DGF. Awareness thereof should have an impact on peri- and posttransplant measures in renal transplant recipients.


Outcome of self-expandable metal stents placement for obstructive colorectal cancer: 7 years' experience from a Swedish tertiary center.
Self expandable metal stents (SEMS) is an alternative to emergency surgery to treat malignant large bowel obstruction. It can be used either for palliation or as a bridge to curative surgery. Our study aims to review the outcomes of SEMS treatment in a tertiary center and to find predictors for the clinical outcome. We retrospectively analyzed data from SEMS insertion at Sahlgrenska University Hospital, a referral center in Western Sweden (1.7 million inhabitants), between 2014 and 2020. Data collected were age, the intent of intervention, tumor localization, complication rate, technical and clinical success, 30- and 90-days mortality as well as long-term survival for the indication bridge to surgery. We identified 265 SEMS insertions (mean age 72, female 49.4%). Most SEMS were used for palliation (90.2%). The malign obstruction was most often located in the left colon (71.7%). Technical success was achieved in 259 (97.7%) cases and clinical success in 244 (92.1%) cases. Post-operative complications occurred in 11 cases (4.2%). The 30-days mortality rate was 11.7% and the 90-day was 31.7%. In our analysis the tumor site was not associated with adverse outcomes and bridge to surgery indication was a positive prognostic factor for the 90-day mortality. We found that SEMS is an effective and safe treatment for patients with acute obstructive colorectal cancer.


MEPE is downregulated as dental pulp stem cells differentiate.
Previous studies on dental pulp cell culture have described heterogenous mixtures of cells that differentiate into odontoblasts and form mineralized dentin. The aim of this study was to characterize the matrix extracellular phosphoglycoprotein (MEPE) expression by dental pulp stem cells (DPSC), related to cell differentiation. DPSC differentiation to form mineralized nodules was characterized by Alizarin red staining and micro-Raman spectroscopy. Osteogenesis SuperArray analysis was used to broadly screen for osteogenesis-related genes altered by DPSC differentiation. Relative levels of expression of MEPE and DSP were determined by semiquantitative RT-PCR and Western blot. Mineral analysis showed that as DPSC differentiated, they formed a carbonated hydroxyapatite mineral. Differentiation was initially marked by upregulation by Runx2, TGFbeta-related genes, EGFR and genes involved in collagen metabolism. ALP activity first increased, as DPSCs reached confluence but later decreased when cells further differentiated three weeks after confluence. MEPE was the only marker that was downregulated as DPSCs differentiated. DPSC differentiation can be characterized by downregulation of MEPE as other markers of DPSC differentiation, such as DSP, are upregulated. Expression of MEPE related to DSP and can be used to monitor DPSC as they are used for studies of odontoblast differentiation, tissue engineering or vital pulp therapy. The downregulation of MEPE as DPSC differentiate, suggests that MEPE is an inhibitor of mineralization.


Synthesis and Tribological Properties of Bio-Inspired Nacre-Like Composites.
Ceramic materials possessing the properties of high-strength and rigidity are widely used in industry. The shell nacre has a layered structure containing both macroscopic and microscopic levels and is equipped with superior qualities regarding hardness and strength. Therefore, the ceramic composites with a nacre-like layered structure have the potential to be utilized as sliding bearings employed in the harsh conditions of wells. For the purpose of this paper, a porous Al₂O₃ ceramics skeleton with nanometer powder is prepared using the freeze-casting method. Then the porous ceramic skeleton is filled with polymer polymethyl methacrylate (PMMA) through mass polymerization to produce a bionic Al₂O₃/PMMA composite with a lamellar structure. The properties of the prepared composite are determined by the analysis of micro-hardness, fracture toughness, friction coefficient, wear scar diameter, and the morphology of the worn surface. Consequent results indicate that elevation in the A1₂O₃ powder, which acts as the initial solid phase content, prompts the ceramic slurry to exhibit an increase in viscosity and a gradual decrease in the pore size of the ceramic skeleton. The prepared layered Al₂O₃/PMMA composite possesses high fracture toughness, which closely resembles that of Al, is approximately four times that of the matrix of the Al₂O₃ ceramics and 16 times that of the PMMA. Three kinds of composites containing different solid phase content are subjected to testing involving lubrication by water-based drilling fluid to determine the friction coefficient of each. The results indicate that an increased load leads to a decreased friction coefficient while the impact of speed is not evident. Under dry conditions, the friction coefficient of three different composites tested, declines with elevated load and speed. With the use of water-based drilling fluid as lubrication, the wear scar diameter increases at higher speed, while dry conditions denote increased load. Abrasive wear is determined to be the principal form of erosion of layered Al₂O₃/PMMA composites.


Identification and characterization of an iron ABC transporter operon in Gluconacetobacter diazotrophicus Pal 5.
Gluconacetobacter diazotrophicus is a nitrogen-fixing bacterium and endophyte of sugarcane. We have cloned and sequenced the genes coding for the components of the iron ABC-type acquisition system of G. diazotrophicus. Sequence analysis revealed three ORFs, (feuA, feuB, and feuC) organized as an operon and encoding polypeptides of 346 (38 kDa), 342 (34.2 kDa), and 240 (26 kDa) amino acids, respectively. The deduced translation products of the feu operon showed similarity with a periplasmic solute-binding protein (FeuA), permease (FeuB), and ATPase (FeuC) involved in Fe transport. The role of FeuB in the survival of G. diazotrophicus under iron depletion was evaluated by comparing the ability of wild-type and FeuB-Km(R) -mutant strains in a medium without iron supplementation and in a medium containing 2, 2'-dipyridyl (DP). Growth of the mutant was affected in the medium containing DP. The operon was expressed at higher levels in cells depleted for iron than in those that contained the metal. A decrease in nitrogenase activity was observed with the FeuB-Km(R) -mutant strain that with the wild-type under iron deficiency conditions, suggesting that the Feu operon play role in Fe nutrition of G. diazotrophicus.


Reduced anticipation of negative emotional events in alexithymia.
Alexithymia is characterized by difficulties in different domains of emotion processing, especially in relation to negative emotions. Nevertheless, its causal mechanisms remain elusive. Reduced anticipation of negative emotional events might be one such mechanism because it enables the individual to prepare to respond effectively to coming events. To test this, changes in skin conductance response (SCR) were recorded during classical fear conditioning in sixty participants with high (HA), medium (MA) and low (LA) levels of alexithymia. Two coloured squares were presented, one was reinforced with a mild electrical stimulation (CS+) while the other was never reinforced (CS-). Critically, despite all groups showing higher SCR to CS+ compared to CS-, SCR to CS+ was lower and extinguished earlier in HA compared to MA and LA. These differences appeared to be attributable neither to differences in the intensity of stimulation received, nor to SCR to the stimulation itself. Groups showed comparable SCR to CS- as well. Therefore, HA exhibited decreased anticipation of the occurrence of a negative emotional event. Disruption of this mechanism may then compromise effective emotion recognition, emotional response and response regulation, which characterise HA, and represent a unifying causal mechanism underlying the difficulties in emotion processing of this group.


Immunocytochemical detection of the microsomal glucose-6-phosphatase in human brain astrocytes.
Using an antibody raised against the catalytic subunit of glucose-6-phosphatase, this enzyme was immunolocalized in many astrocytes in 20 normal human brains. Double immunofluorescence studies showed co-localization of glial fibrillary acidic protein (GFAP) with glucose-6-phosphatase in astrocytes. However, not all GFAP-positive cells were also glucose-6-phosphatase positive, indicating that some astrocytes do not contain demonstrable expression of this enzyme. Reactive astrocytes in a variety of abnormal brains were strongly glucose-6-phosphatase positive, but neoplastic astrocytes were often only weakly positive. Expression of the enzyme could not be demonstrated in radial glia, neurons or oligodendroglia. Astrocytes normally contain glycogen and the demonstration that some astrocytes also contain glucose-6-phosphatase indicates that they are competent for both glycogenolysis and gluconeogenesis, which may be critical for neuronal welfare.


Difference in particle transport between two coastal areas in the Baltic Sea investigated with high-resolution trajectory modeling.
A particle-tracking model based on high-resolution ocean flow data was used to investigate particle residence times and spatial distribution of settling sediment for two geo-morphologically different Swedish coastal areas. The study was a part of a safety assessment for the location of a future nuclear-waste repository, and information about the particle-transport patterns can contribute to predictions of the fate of a possible leakage. It is also, to our knowledge, the first time particle-transport differences between two coastal areas have been quantified in this manner. In Forsmark, a funnel-shaped bay shielded by a number of islands, the average residence time for clay particles was 5 times longer than in the modeled part of Simpevarp, which is open to the Baltic Sea. In Forsmark, <10 % of the released particles left the domain compared to 60-80 % in Simpevarp. These site-specific differences will increase over time with the differences in land uplift between the areas.


Selection system for genes encoding nuclear-targeted proteins.
Nuclear proteins have essential roles in cell proliferation and differentiation. We have developed a yeast selection system-the nuclear transportation trap (NTT)-to identify genes encoding nuclear transport signals. Both unknown and previously identified nuclear localization signals were identified from a human fetal brain cDNA library. The majority (75%) of the unknown proteins examined were exclusively localized to the nucleus in COS-7 cells. We propose that NTT is an efficient method for isolating cDNAs that encode nuclear targeted proteins that can be applied to the retrieval of novel nuclear proteins and to annotate gene function.


Dataset of octocoral assemblages in fore reefs in the northwestern region of Cuba.
This dataset accompanies "Spatio temporal variation in octocoral assemblages along a water quality gradient in the northwestern region of Cuba" [1]. Sampling units were quadrats of 1 m2 (each 1 x 1 m), positioned by a random-systematic design at 10 m depth on the rocky-coral substrate. The number of colonies of octocoral species in thirteen fore reefs was counted to determine the composition, richness and abundance (expressed as density) of octocorals for the period from 2008-2015. Density of six species that most influenced spatial variation of octocoral assemblage structure was compared [1]. Species richness of octocorals was determined in each reef and for the 2008-2015 period. The accumulated species richness was calculated based on 100 randomizations without replacement. This dataset can be used in meta-analysis studies on spatial variations of the structure of octocoral assemblages related to anthropogenic activities and climate variability in the Caribbean Sea, as well as, experimental studies on thresholds to specific pollutants.


Spino-bulbar neurons convey information to the brainstem about different phases of the locomotor cycle in the lamprey.
Lamprey retriculospinal neurons show phasic oscillations of their membrane potential during fictive locomotion. This modulation originates from the spinal cord locomotor networks. The aim of the present study was to elucidate the pattern of discharge of the spino-bulbar axons responsible for this modulation. Experiments were performed on in vitro brainstem/spinal cord preparations. Two baths were formed in the recording chamber. The caudal one was perfused with 150 microM N-methyl-D-aspartate (NMDA) solution to induce fictive locomotion. The rostral bath containing the brain and the first 3-5 segments of the spinal cord was exposed to a 0 Ca2+ + 2.6 mM Mn2+ solution to block synaptic transmission and therefore to abolish any rhythmic descending activity. Spinobulbar axons were recorded intracellularly at the level of the brain/spinal cord junction. They exhibited phasic discharges correlated with the ongoing motor activity in the caudal pool. Some discharged in phase with either the ipsilateral or the contralateral ventral root bursts, others with either of the transition phases between these two bursts. These spinal cells with ascending axons, running in the ventrolateral spinal cord, may be important for modulating the activity of supraspinal neurons to match the ongoing locomotor activity.


Expression and biological function of the cellular communication network factor 5 (CCN5) in primary liver cells.
The cellular (centralized) communication network (CCN) factor protein family contains six small secreted cysteine-rich proteins sharing high structural similarity. These matricellular proteins have vital biological functions in cell adhesion, migration, cell cycle progression, and control of production and degradation of extracellular matrix. However, in liver the biological functions of CCN proteins become most visible during hepatic injury, disease, and remodeling. In particular, most of the hepatic functions of CCN proteins were derived from CCN2/CTGF, which becomes highly expressed in damaged hepatocytes and acts as a profibrogenic molecule. On the contrary, CCN1/CYR61 seems to have opposite effects, while the biological activity during hepatic fibrosis is somewhat controversially discussed for other CCN family members. In the present study, we analyzed the expression of CCN5/WISP2 in cultures of different types of primary liver cells and in an experimental model of hepatic fibrosis. We found that CCN5 is expressed in hepatic stellate cells, myofibroblasts and portal myofibroblasts, while CCN5 expression is virtually absent in hepatocytes. During hepatic fibrogenesis, CCN5 is significantly upregulated. Overexpression of CCN5 in portal myofibroblasts reduced expression of transforming growth factor-β receptor I (ALK5) and concomitant Smad2 activation, whereas JunB expression is upregulated. Moreover, elevated expression of CCN5 induces endoplasmic reticulum stress, unfolded protein response and apoptosis in portal myofibroblasts. We suggest that upregulated expression of CCN5 might be an intrinsic control mechanism that counteracts overshooting fibrotic responses in profibrogenic liver cells.


Groove pancreatitis: a case series and review of the literature.
Groove pancreatitis is a form of chronic pancreatitis affecting the space surrounded by the pancreatic head, duodenum and common bile duct. The clinical findings can conflict with pancreatic cancer causing diagnostic dilemma preoperatively. We describe two patients with a history of alcohol excess, who presented with a few months history of upper abdominal pain associated with weight loss and vomiting. Endoscopic and radiological investigations related duodenal narrowing, biliary dilatation and multiple pseudocysts around the head of the pancreas and duodenum. A Whipple's pancreaticoduodenectomy was carried out in both patients. Histopathology report demonstrated cystic areas in both medial and lateral walls of the duodenum microscopically consistent with groove pancreatitis. The diagnosis of groove pancreatitis should be considered in patients with duodenal stenosis and cystic lesions around the head of the pancreas associated with history of alcohol excess. Differentiation from pancreatic cancer is difficult preoperatively.


Graded Combined Aerobic Resistance Exercise (CARE) to Prevent or Treat the Persistent Post-concussion Syndrome.
To review the growing body of indirect and direct evidence that suggests that exercise can be helpful for children, adolescents, and adults with persistent symptoms following a mild traumatic brain injury (mTBI). The direct evidence shows that graded exercise assessments are safe, and that aerobic exercise interventions are associated with improvement of multiple symptoms and other benefits, including earlier return-to-sport. The indirect evidence supports this approach via studies that reveal the potential mechanisms, and show benefits for related presentations and individual symptoms, including headaches, neck pain, vestibular problems, sleep, stress, anxiety, and depression. We document the forms of exercise used for the post-acute management of mTBI, highlight the knowledge gaps, and provide future research directions. We recommend trialing a new approach that utilizes a graduated program of individually prescribed combined aerobic resistance exercises (CARE) if mTBI symptoms persist. This program has the potential to improve patient outcomes and add to the management options for providers.


Pediatric endoscopic nasal and sinus surgery.
A total of 83 children and teenagers underwent endoscopic nasal and sinus surgery. Six patients had surgery for choanal atresia (4) and adenoid hypertrophy (2) and will only be briefly mentioned. Seventy-seven children and teenagers underwent endoscopic sinus surgery for acute and chronic sinusitis, choanal polyposis, and nasal polyposis with a minimum 2-year follow-up. One hundred thirty-three ethmoidectomies, 37 sphenoidotomies, and 119 maxillary antrostomies were performed. Subjective evaluation of the sinus surgery patients indicated that 38% of patients were cured and 55% improved during an average of 3.5 years of follow-up. The number cured and number improved are lower and higher, respectively, than in other reports of results because of the longer follow-up and patient selection. In addition, objective data were obtained on 34 patients with a second- or third-look procedure 2 weeks to 2 months after surgery. These examinations found significant granulation tissue, and almost 50% of patients had at least one maxillary ostia closed. Long-term objective results, however, are not available to determine whether the ostia remained closed. Problems with healing in children's endoscopic sinus surgery are unpredictable compared those in adult surgery because postoperative debridement and examination are often difficult to perform, thus allowing tissue to heal without control. In this series, other factors such as the increased risks of cystic fibrosis, allergy, and immunodeficiency were also more prevalent and compromised healing.(ABSTRACT TRUNCATED AT 250 WORDS)


Cancer and Aging: General Principles, Biology, and Geriatric Assessment.
Cancer is a disease of aging as older adults are much more likely to develop cancer compared with their younger counterparts. Understanding the biology of cancer and aging remains complex, and numerous theories regarding the relationship between the two have been proposed. Cancer treatment decisions in older patients are particularly challenging, because the evidence is scarce and the risk of toxicity increases with age. Determination of biologic age is essential due to heterogeneity of functional status, comorbidity, and physiologic reserves between patients of the same chronologic age.


Liquid storage of equine semen: Assessing the effect of d-penicillamine on longevity of ejaculated and epididymal stallion sperm.
Short-term storage of equine sperm at 5°C in an extender containing milk and/or egg yolk components is common practice in the equine breeding industry. Sperm motility, viability, DNA integrity and, consequently, fertilizing ability decline over time, partly due to reactive oxygen species (ROS) generation. We investigated whether adding the anti-oxidant d-penicillamine to a commercial milk/egg yolk extender delayed the decrease in semen quality. Semen was recovered on four consecutive days from eight 3-year old Warmblood stallions. On day 5, seven of the stallions were castrated and sperm recovered from the caudae epididymides. Ejaculated samples were split, and one portion was centrifuged and re-suspended to reduce seminal plasma content. All samples were diluted to 50millionsperm/ml and divided into two portions, one of which was supplemented with 0.5mM d-penicillamine. After 48h, 96h, 144h and 192h storage, sperm motility was assessed by computer-assisted semen analysis (CASA), viability by SYBR14/PI staining, and DNA integrity using the sperm chromatin structure assay (SCSA). d-Penicillamine had no effect on motility of ejaculated sperm (P>0.05) but reduced total and progressive motility of epididymal sperm. Sperm chromatin integrity was not influenced by storage time, seminal plasma or d-penicillamine. In short, adding d-penicillamine to a commercial semen extender was neither beneficial nor detrimental to the maintenance of quality in ejaculated semen stored at 5°C. The negative effect on motility of epididymal sperm may reflect differences in (membrane) physiology of spermatozoa that have not been exposed to seminal plasma.


Lingual orthodontics--its renaissance.
Lingual treatment has obvious advantages over labial treatment for the patient: no damage to labial or buccal surfaces of the teeth, no labial or buccal gingival hypertrophy or gingivitis, and better visualization of tooth alignment and facial contours. By the same token, lingual treatment has inherent disadvantages over labial treatment. Brackets are attached to very irregular and inconsistent lingual surfaces, which are not the surfaces to be aligned. Furthermore, lingual brackets are cantilevered a substantial distance from the labial surfaces, making the vertical height of the brackets vary with the torque angle of the labial surfaces and also making torquing adjustments affect not only the torque of the labial surfaces but also their heights. These factors make direct placement of preangulated, pretorqued brackets very inaccurate, especially on maxillary anterior teeth; mandibular anterior teeth are not so variable. More accurate indirect bracket placement with predictable and accurate indirect bonding procedures is resolving these disadvantages. It has been shown that a lingual appliance can have the same capacity to align the teeth as a labial appliance. The mere lingual placement of labial brackets, tubes, and arch wires with minor modifications has not proved to be a satisfactory solution. Rather, the designing of a completely new appliance system has been necessary to meet the mechanical requirements inherent in the lingual environment. This engineering challenge has basically been met with the Conceal occlusal-slot lingual system. Undoubtedly, refinements in the appliance system will be made as experience in its use expands ultimately to make lingual treatment as common as labial treatment.


The molecular basis of transdifferentiation.
There is now excellent experimental evidence demonstrating the remarkable ability of some differentiated cells to convert to a completely different phenotype. The conversion of one cellular phenotype to another is referred to as 'transdifferentiation' and belongs to a wider class of cell-type switches termed 'metaplasias'. Defining the molecular steps in transdifferentiation will help us to understand the developmental biology of the cells that interconvert, as well as help identify key regulatory transcription factors that may be important for the reprogramming of stem cells. Ultimately, being able to produce cells at will offers a compelling new approach to therapeutic transplantation and therefore the treatment and cure of diseases such as diabetes.


The effect of a spinal orthosis on posture and cardio-respiratory functions in progressive myopathic scoliosis.
Historically, the orthotic treatment in progressive myopathic scoliosis has not been as effective as expected. The purpose of this study was to investigate the effect of a spinal orthosis on scoliotic curve correction, alignment of altered posture and cardio-respiratory functions. An 11 year-old girl diagnosed with myopathy was fitted with a custom molded thoraco-lumbo-sacral orthosis to enhance the sitting ability. The cardio-respiratory tests were performed by a COSMED K4 b(2); metabolic analyzer. The anterior posterior radiographs were analyzed for measuring Cobb angle and Ferguson angle. A plumb line test was used to assess the postural improvements. No significant difference was observed for variables such as O(2) consumption level, PaO(2), tidal volume, heart rate and energy expenditure/min. The improved posture was evident by shifting of the plumb line 18 mm towards the mid line with the use of orthosis. Very minor improvements in both angles were observed with the use of the brace. The brace treatment cannot be expected to have a lasting corrective effect although it can be used as a sitting support and for maintaining posture Clinical relevance This case study provides an objective prescription of thoraco-lumbo-sacral orthosis as a sitting support and for improving posture in progressive myopathic scoliosis if suitably designed and properly fitted.


The role of interpretation biases and safety behaviours in social anxiety: an intensive longitudinal study.
Interpretation bias and safety behaviours (Safe-B) have been proposed as factors perpetuating social anxiety (SA). However, longitudinal research on how they contribute to SA in everyday life is scarce. The aim was to examine whether interpretation bias predicts daily Safe-B and SA. A mediated moderation was hypothesized, where the relationship between daily social stressors and Safe-B would be moderated by interpretation bias, and Safe-B, in turn, would mediate the association between stressors and SA levels. In addition, it was hypothesized that prior levels of SA would predict higher Safe-B use, especially in co-occurrence with stressors. An intensive longitudinal design was employed, with 138 vocational training students (51% men, mean age 20.15 years). They completed initial measures of SA and interpretation bias and 7-day diaries with measures of social stressors, Safe-B, and SA. They reported SA levels two months later. Both stressors and interpretation bias in ambiguous situations predicted Safe-B, which in turn predicted daily SA levels. However, neither interpretation bias nor Safe-B predicted SA levels at the follow-up, and interpretation bias did not moderate the association between stressors and daily SA. In addition, the relationship between stressors and Safe-B was stronger in people with higher initial SA levels. The results suggest that Safe-B are a mechanism through which earlier SA levels and interpretation bias contribute to higher SA levels in daily life.


Cost-effectiveness of combined catheter ablation and left atrial appendage closure for symptomatic atrial fibrillation in patients with high stroke and bleeding risk.
Combined catheter ablation (CA) and left atrial appendage closure (LAAC) have been proposed for management of symptomatic atrial fibrillation (AF) in patients with high stroke and bleeding risk. We assessed the cost-effectiveness of combined CA and LAAC compared with CA and standard oral anticoagulation (OAC) in symptomatic AF. A Markov model was developed to assess total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio among 2 post-CA strategies: (1) standard OAC and (2) LAAC (combined CA and LAAC procedure). The base-case used a 10-year time horizon and consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with high thrombotic (CHA2DS2-VASc = 3) and bleeding risk (HAS-BLED = 3), and planned for AF ablation. Values for transition probabilities, utilities, and costs were derived from the literature. Costs were converted to 2020 US dollars. Half-cycle correction was applied, and costs and QALYs were discounted at 3% annually. Sensitivity analyses were performed for significant variables and scenario analyses for higher embolic risk. In the base-case cohort of 10,000 patients followed for 10 years, total costs for the LAAC strategy were $29,027 and for OAC strategy were $27,896. The LAAC strategy was associated with 122 fewer disabling strokes and 203 fewer intracranial hemorrhages per 10,000 patients compared with the OAC strategy. The LAAC strategy had an incremental cost-effectiveness ratio of $11,072/QALY. In sensitivity analyses, although cost-effectiveness was highly dependent on the risk of intracranial hemorrhage in the LAAC strategy and the cost of the combined procedure, LAAC was superior to OAC under the most circumstances. Scenario analyses demonstrated that the combined procedure was more cost-effective in patients with higher stroke risk. In symptomatic AF patients with high stroke and bleeding risk who are planned for CA, the combined CA and LAAC procedure may be a cost-effective therapeutic option and be more beneficial to patients with CHA2DS2-VASc risk score ≥3.


Female crucian carp, Carassius carassius, lose predator avoidance behavior when getting ready to mate.
In predator-prey interactions, the prey often have to compromise fitness-related behaviors such as feeding, courting, and territorial defense in order to avoid predators. In these trade-off situations, some behaviors have priority over others. These priorities are not rigid, and may be context-dependent; for instance, many animals show increased risk-taking during courtship behavior by paying less attention to potential predators. We investigated whether the fright reaction, a stereotypical avoidance response to olfactory cues from injured conspecifics, may be affected by reproductive status in a teleost fish, the crucian carp. We demonstrate that among individuals not responding to alarm substances with a fright reaction, the majority were ovulated or spermiated. In females, mean plasma concentrations of 17beta-estradiol and testosterone, gonadal steroids known to decrease during the later stages of sexual maturation, were lower in the individuals not responding with a fright reaction compared to those responding. In males, there were no differences between responsive and non-responsive individuals in mean plasma levels of androgens (testosterone and 11-ketotestosterone) involved in spermatogenesis and male sexual behavior. As the fright reaction in crucian carp consists of behavior incompatible with spawning behavior, we hypothesize that this short-term suppression of the alarm response has evolved so that spawning can occur uninterrupted.


Long-Term Patient-Reported Quality of Life of Anal Cancer Survivors Treated With Intensity Modulated Radiation Therapy and Concurrent Chemotherapy: Results From a Prospective Phase II Trial.
Intensity modulated radiation therapy (IMRT) has confirmed its superiority in improving acute treatment-related toxicities in anal cancer, without compromising tumor control. However, the effect of IMRT on long-term quality of life (QOL) is poorly documented. The study prospectively evaluated the long-term patient-reported QOL after IMRT-based chemoradiation in anal cancer. Fifty-eight patients treated with IMRT and concurrent 5 fluorouracil/mitomycin-C were enrolled in the study. A prespecified secondary endpoint was prospective evaluation of long-term QOL. Fifty-four patients underwent QOL evaluation at baseline, after treatment, and during follow-up until 60 months, with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) scales and the Colorectal Cancer-Specific Quality Of Life Questionnaire (QLQ-CR29) scales. The QOL scores at baseline and posttreatment periods were compared. For QLQ-C30, at 60 months, the mean scores of global health status, all functional scales, and all symptoms except diarrhea had improved, indicating normalization of QOL. Clinically and statistically significant improvements in the global health status (15.4; P = .003), role functioning (19.3; P = .0017), emotional functioning (18.9; P = .008), and social functioning (29.8; P ≤ .001) were observed. Diarrhea persisted as a concern over the years (P = .172). For European Organization for Research and Treatment of Cancer QLQ-CR29, rectal pain (-38.6; P = .001), mucous or blood discharge per rectum (-22.8; P = .005), and perianal soreness (-37.3; P ≤ .001) were improved both clinically and statistically. Clinically significant fecal leakage was reported by 16% of patients (5.6; P = .421). Volumes receiving 45 and 54 Gy were independent predictors for fecal incontinence. Clinically and statistically significant urinary incontinence occurred in 21% of patients (17.5; P = .014). Deterioration of dyspareunia was clinically significant (26.7; P = .099) at 60 months. Compared with historical data, IMRT is associated with reduced long-term effects on QOL. The majority of patients treated with IMRT experienced clinically significant recovery of function and improvement in QOL over 5 years after completion of treatment. Specific toxicities such as chronic diarrhea, fecal incontinence, and urinary and sexual dysfunction were primarily responsible for deterioration of the long-term QOL. Future research aimed at reducing such toxicities is needed to further improve long-term QOL in anal cancer.


Deep Neural Networks Predict the Need for CT in Pediatric Mild Traumatic Brain Injury: A Corroboration of the PECARN Rule.
Only 10% of CT scans unveil positive findings in mild traumatic brain injury, raising concerns of its overuse in this population. A number of clinical rules have been developed to address this issue, but they still suffer limitations in their specificity. Machine learning models have been applied in limited studies to mimic clinical rules; however, further improvement in terms of balanced sensitivity and specificity is still needed. In this work, the authors applied a deep artificial neural networks (DANN) model and an instance hardness threshold algorithm to reproduce the Pediatric Emergency Care Applied Research Network (PECARN) clinical rule in a pediatric population collected as a part of the PECARN study between 2004 and 2006. The DANN model was applied using 14,983 patients younger than 18 years with Glasgow Coma Scale scores ≥ 14 who had head CT reports. The clinical features of the PECARN rules, PECARN-A (group A, age < 2 years) and PECARN-B (group B, age ≤ 2 years), were used to directly evaluate the model. The average accuracy, sensitivity, precision, and specificity were calculated by comparing the model's prediction outcome to that reported by the PECARN investigators. The instance hardness threshold and DANN model were applied to predict the need for CT in pediatric patients using 5-fold cross-validation. In the first phase, the DANN model resulted in 98.6% sensitivity and 99.7% specificity for predicting the need for CT using the predictors of the two PECARN clinical rules combined to train the model. In the second phase, the DANN model was superior to both the PECARN-A and PECARN-B rules using the predictors for each age group separately to train the model. Compared with the clinical rule, for group A, the model achieved an average sensitivity (93.7% versus 100%) and specificity (97.5% versus 53.6%); for group B, the average sensitivity of the model was 99.2% versus 98.6%, and the specificity was 98.8% versus 58.2%. In this study, a DANN model achieved comparable sensitivity and outstanding specificity for replicating the PECARN clinical rule and predicting the need for CT in pediatric patients after mild traumatic brain injury compared with the original statistically derived clinical rule.


Targeting epigenetics for cancer therapy.
Cancer can be identified as a chaotic cell state, which breaks the rules that govern growth and reproduction, with main characteristics such as uncontrolled division, invading other tissues, usurping resources, and eventually killing its host. It was once believed that cancer is caused by a progressive series of genetic aberrations, and certain mutations of genes, including oncogenes and tumor suppressor genes, have been identified as the cause of cancer. However, piling evidence suggests that epigenetic modifications working in concert with genetic mechanisms to regulate transcriptional activity are dysregulated in many diseases, including cancer. Cancer epigenetics explain a wide range of heritable changes in gene expression, which do not come from any alteration in DNA sequences. Aberrant DNA methylation, histone modifications, and expression of long non-coding RNAs (lncRNAs) are key epigenetic mechanisms associated with tumor initiation, cancer progression, and metastasis. Within the past decade, cancer epigenetics have enabled us to develop novel biomarkers and therapeutic target for many types of cancers. In this review, we will summarize the major epigenetic changes involved in cancer biology along with clinical and preclinical results developed as novel cancer therapeutics.


Endocannabinoid Signaling from 2-Arachidonoylglycerol to CB1 Cannabinoid Receptor Facilitates Reward-based Learning of Motor Sequence.
The endocannabinoid system modulates synaptic transmission, controls neuronal excitability, and is involved in various brain functions including learning and memory. 2-arachidonoylglycerol, a major endocannabinoid produced by diacylglycerol lipase-α (DGLα), is released from postsynaptic neurons, retrogradely activates presynaptic CB1 cannabinoid receptors, and induces short-term or long-term synaptic plasticity. To examine whether and how the endocannabinoid system contributes to reward-based learning of a motor sequence, we subjected male CB1-knockout (KO) and DGLα-KO mice to three types of operant lever-press tasks. First, we trained mice to press one of three levers labeled A, B, and C for a food reward (one-lever task). Second, we trained mice to press the three levers in the order of A, B, and C (three-lever task). Third, the order of the levers was reversed to C, B, and A (reverse three-lever task). We found that CB1-KO mice and DGLα-KO mice exhibited essentially the same deficits in the operant lever-press tasks. In the one-lever task, both strains of knockout mice showed a slower rate of learning to press a lever for food. In the three-lever task, both strains of knockout mice showed a slower rate of learning of the motor sequence. In the reverse three-lever task, both strains of knockout mice needed more lever presses for reversal learning. These results suggest that the endocannabinoid system facilitates reward-based learning of a motor sequence by conferring the flexibility with which animals can switch between strategies.


Randomized Controlled Trial of a MUFA or Fiber-Rich Diet on Hepatic Fat in Prediabetes.
Increased prevalence of type 2 diabetes mellitus and prediabetes worldwide is attributed in part to an unhealthy diet. To evaluate whether 12 weeks of high monounsaturated fatty acid (MUFA) or fiber-rich weight-maintenance diet lowers hepatic fat and improves glucose tolerance in people with prediabetes. Subjects underwent a [6, 6-2H2]-labeled 75-g oral glucose tolerance test to estimate hepatic insulin sensitivity and liver fat fraction (LFF) using magnetic resonance spectroscopy before and after intervention. Mayo Clinic Clinical Research Trials Unit. 43 subjects with prediabetes. Subjects were randomized into three isocaloric weight-maintaining diets containing MUFA (olive oil), extra fiber, and standard US food (control-habitual diet). LFF, glucose tolerance, and indices of insulin action and secretion. Body weight was maintained constant in all groups during the intervention. Glucose and hormonal concentrations were similar in all groups before, and unchanged after, 12 weeks of intervention. LFF was significantly lower after intervention in the MUFA group (P < 0.0003) but remained unchanged in the fiber (P = 0.25) and control groups (P = 0.45). After 12 weeks, LFF was significantly lower in the MUFA than in the control group (P = 0.01), but fiber and control groups did not differ (P = 0.41). Indices of insulin action and secretion were not significantly different between the MUFA and control groups after intervention (P ≥ 0.11), but within-group comparison showed higher hepatic (P = 0.01) and total insulin sensitivity (P < 0.04) with MUFA. Twelve weeks of a MUFA diet decreases hepatic fat and improves both hepatic and total insulin sensitivity.


Complementary and integrative medicine for older adults in palliative care.
Complementary and Integrative Medicine (CIM) encompasses many diverse therapies, including natural products and mind and body practices. Use of CIM is common and can benefit patients in palliative care. However, because patients in palliative care are often frail and elderly, the clinician should consider a patient's comorbidities before recommending certain therapies, such as natural products. In this article, specific examples of CIM are provided for symptoms commonly seen in palliative care.


Pure shift amide detection in conventional and TROSY-type experiments of 13C,15N-labeled proteins.
Large coupling networks in uniformly 13C,15N-labeled biomolecules induce broad multiplets that even in flexible proteins are frequently not recognized as such. The reason is that given multiplets typically consist of a large number of individual resonances that result in a single broad line, in which individual components are no longer resolved. We here introduce a real-time pure shift acquisition scheme for the detection of amide protons which is based on 13C-BIRDr,X. As a result the full homo- and heteronuclear coupling network can be suppressed at low power leading to real singlets at substantially improved resolution and uncompromised sensitivity. The method is tested on a small globular and an intrinsically disordered protein (IDP) where the average spectral resolution is increased by a factor of ~ 2 and higher. Equally important, the approach works without saturation of water magnetization for solvent suppression and exchanging amide protons are not affected by saturation transfer.


Ganglioside headgroup dynamics.
Gangliosides, spin-labelled specifically on N-acetylneuraminic acid residues or on random-headgroup sugars, have been used to extend previous studies of headgroup behaviour. Headgroup sugar mobility is seen to be homogeneous and relatively unrestricted in a range of systems including three lines of cultured cells. The effects of temperature and pH have been considered. Binding of small quantities of the lectin, wheat germ agglutinin, was found to increase average headgroup mobility for gangliosides in lipid bilayers, most likely as a result of a disordering effect on ganglioside clusters.


Pharmacological reflection of plants traditionally used to manage diabetes mellitus in Tanzania.
The increasing national prevalence of diabetes mellitus (DM) and its complications have overstretched the health care system in Tanzania and influenced patients to use herbal medicines as alternative therapeutic strategies. Therefore, an urgent need exists to validate the safety and efficacy of plants used locally. To identify plants used for the management of DM in Tanzania and analyses their pharmacological, phytochemistry, and safety evidence with a special focus on the mechanism of action. Researchers searched Medline, web of science, and Scopus for published articles. Also, specialized herbarium documents of Muhimbili Institute of traditional medicine were reviewed. Articles were assessed for relevance, quality, and taxonomical accuracy before being critically reviewed. We identified 62 plant species used locally for DM management. Moringa oleifera Lam. and Cymbopogon citratus (D.C) stapf were the most mentioned. Fifty-four phytochemicals from 13 species had DM activities. These were mainly; polyphenolics, phytosterols, and triterpenoids. Extracts, fractions, and pure compounds from 18 species had in vitro antidiabetic activities of which 14 had α-glucosidase and α-amylase inhibition effects. The most studied -Momordica charantia L. increased; glucose uptake and adiponectin release in 3T3-L1 adipocytes, insulin secretion, insulin receptor substrate-1 (IRS-1), GLUT-4 translocation, and GLP-1 secretion; and inhibited protein tyrosine phosphatase 1 B (PTP1B). Preclinical studies reported 30 species that lower plasma glucose with molecular targets in the liver, skeletal muscles, adipose tissues, pancreases, and stomach. While three species; Aspilia mossambiscensis (Oliv.) Willd, Caesalpinia bonduc (L.) Roxb, and Phyllanthus amarus Schumach. & Thonn. had mild toxicity in animals, 33 had no report of their efficacy in DM management or toxicity. Local communities in Tanzania use herbal medicine for the management of DM. However, only a fraction of such species has scientific evidence. A. mossambiscensis, C. bonduc., and P. amarus had mild toxicity in animals. Together, our findings call for future researches to focus on in vitro, in vivo, and phytochemical investigation of plant species for which their use in DM among the local communities in Tanzania have not been validated.


Slow active/inactive transition of the mitochondrial NADH-ubiquinone reductase.
NADH-ubiquinone reductase of bovine heart submitochondrial particles as prepared is unable to catalyze either the direct or reverse electron transfer from NADH to ubiquinone. The deactivated state of the enzyme in coupled particles was revealed as: (i) the absence of the rotenone-sensitive, delta mu H(+)-dependent succinate-ferricyanide reductase activity; (ii) a prominent lag in the aerobic succinate-supported, delta mu H(+)-dependent NAD+ reduction; and (iii) a lag in the rotenone-sensitive NADH-ubiquinone reductase or NADH oxidase activities. Being inactive as NADH-ubiquinone reductase (direct or reverse), the enzyme is fully active as rotenone-insensitive NADH-ferricyanide reductase. The enzyme can be activated by preincubation with substrates (NADH or NADPH) only under the conditions where the turnover of the NADH-ubiquinone reductase reaction (but not in the NADH-ferricyanide reductase) occurs. Partial activation of the enzyme was observed when the particles were preincubated with rotenone. Neither NADH under the conditions when the ubiquinone pool was reduced nor succinate plus delta mu H+ or dithionite were able to activate the enzyme. Once activated, the enzyme remains in the active state for quite a long time (more than 5 h at 0 degree C). The deactivation rate is extremely temperature-dependent, being insensitive to NAD+, ferricyanide or succinate. A comparison of the enzyme activation/deactivation kinetics showed that the same mechanism is involved in the slow activation of the direct and reverse electron transfer from NADH to ubiquinone. Activated particles catalyze the aerobic delta mu H(+)-dependent succinate-supported reverse electron transfer in the absence of ATP at a rate comparable with that of NADH-ubiquinone reductase.


Acute acalculous cholecystitis after radical cystectomy.
We report 2 cases of acute acalculous cholecystitis after radical cystectomy and continent urinary diversion with a Kock reservoir and ileocecal bladder replacement, respectively. Early diagnosis is essential since the mortality is high with conservative treatment. Isotopic cholescintigraphy is an effective diagnostic test and cholecystectomy is the treatment of choice.


Localization of centromere function in a Drosophila minichromosome.
The DNA elements responsible for centromere activity in a metazoan have been localized using the Drosophila minichromosome Dp1187. Deleted minichromosomes were generated by irradiation mutagenesis, and their molecular structures were determined by pulsed-field Southern blot analysis. Analyses of the transmission behavior of Dp1187 derivatives localized sequences necessary for chromosome inheritance within the centric heterochromatin. The essential core of the centromere is contained within a 220 kb region that includes significant amounts of complex DNA. Completely normal inheritance also requires approximately 200 kb on either side of the essential core. This flanking DNA predominantly contains highly repeated sequences, and the amount required for normal transmission differs among division types and between the sexes. We propose that the essential core is the site of kinetochore formation and that flanking DNA provides two functions: sister chromatid cohesion and indirect assistance in kinetochore formation or function.


Goals and Reasons for Entering Inpatient Withdrawal Treatment, and Perceptions of Help Received.
Abstinence has been the primary treatment goal for alcohol and other drug (AOD) users attending withdrawal treatment. However, other outcomes including harm reduction have also been identified. This observational study aimed to describe participants' goals and reasons for seeking inpatient withdrawal treatment and compare the needs of clients with comorbid mental health problems and those without. Participants completed questionnaires at intake and discharge. Questionnaires assessed reasons for entering withdrawal treatment, goals, comorbidity, and perceived help received. The sample comprised 1746 participants (69.4% male). Participants endorsed diverse reasons for entering withdrawal treatment. The most and least endorsed reasons were "stop using" (97.9%) and "legal reasons" (43.1%). Comorbidity groups varied significantly in their endorsement of reasons for mental health, physical health, harm reduction, financial, and legal. AOD users enter withdrawal treatment with a variety of reasons and goals including harm reduction. Variations in rates of endorsement highlight the importance of identifying individual needs dependent on mental health comorbidity.


Design of amino acid-based self-assembled nano-drugs for therapeutic applications.
Amino acids have attracted considerable attention in drug development because they play important roles in many physiological and pathological processes. In the past several decades, various amino acid supplementations have been reported to have potential therapeutic efficacy for the treatment of many disorders in clinical trials. However, their effectiveness is controversially reported, which may be explained by poor pharmacokinetic properties of such low-molecular-weight agents. Amino acid-based self-assembled macromolecules could overcome the aforementioned drawbacks by improving the pharmacokinetic profile and accumulation of specific molecules at target sites to enhance the therapeutic effect. In this review, we have discussed the current therapeutic applications of certain amino acids, and have introduced our approach of using amino acid-based self-assembled nanostructures as novel therapeutic agents.


Diet enriched in saturated fatty acids induces liver oxidative stress and elicits inflammatory pathways prior to metabolic disruption in perinatal protein undernutrition.
The impact of diets high in saturated fatty acids in individuals who have undergone maternal protein restriction is not clear. Here, we tested the hypothesis that a saturated fatty acid-enriched hyperlipidic diet (HL) affects liver expression of genes of the redox balance and inflammatory pathway in postweaning rat offspring subjected to maternal protein restriction. Pregnant Wistar rats received either a control (C; 19% protein) or low protein (LP; 8% protein) diet during gestation and lactation. At weaning, pups received either C or HL diets up to 90 days of life. The LP+HL group showed an upregulation of transcription of peroxisome proliferator-activated receptor γ (+48%) and peroxisome proliferator-activated receptor γ coactivator α (+96%) compared with the LP+C group (P < .05), respectively. Similarly, gene expression of the markers of inflammation, nuclear factor-kappa B1 (+194%) and tumor necrosis factor-α (+192%), was enhanced (P < .05). Although other antioxidant enzymes were not modified in gene expression, catalase (CAT) was 66% higher in LP+HL compared with LP+C. In contrast, CAT protein content in the liver was 50% lower in LP groups compared with C, and superoxide dismutase 2 (SOD2) was twice as high in LP groups compared with C. Postweaning HL after maternal protein restriction induces hepatic metabolic adaptation characterized by enhanced oxidative stress, unbalanced expression in the antioxidant enzymes SOD1, SOD2 and CAT, and activation of inflammatory pathways but does not impact circulating markers of lipid metabolism and liver function.


An electron paramagnetic resonance method for quantification of copper isotopes in proteins: application to a mixed-isotope derivative of laccase.
We have developed a method of denaturing a copper-containing protein and sequestering the copper in the form of the bis(acetylacetonato)copper(II) complex. Because of the excellent resolution of the hyperfine structure in the resulting EPR spectrum, the method is useful for determining the 65Cu/63Cu isotope ratio in proteins such as tree laccase. Here we analyzed a mixed isotope sample prepared by reconstituting 63Cu-enriched type 2-depleted laccase with 65Cu(I) and found that it contained only 25% 65Cu. This proves that reconstitution of the type 2 copper is possible under conditions that permit little or no exchange between resident copper and the external pool. However, exchange does occur under reducing conditions when we expose the holoprotein to a large excess of exogenous copper.


Longitudinal profiles of neighborhood socioeconomic vulnerability influence blood pressure changes across the female midlife period.
To examine whether longitudinal exposure to neighborhood socioeconomic vulnerability influences blood pressure changes throughout midlife in a racially, ethnically, and geographically-diverse cohort of women transitioning through menopause. We used longitudinal data on 2738 women (age 42-52 at baseline) living in six United States cities from The Study of Women's Health Across the Nation. Residential histories, systolic blood pressures (SBP), and diastolic blood pressures (DBP) were collected annually for ten years. We used longitudinal latent profile analysis to identify patterns of neighborhood socioeconomic vulnerability occurring from 1996 to 2007 in participant neighborhoods. We used linear mixed-effect models to determine if a woman's neighborhood profile throughout midlife was associated with blood pressure changes. We identified four unique profiles of neighborhood socioeconomic vulnerability - differentiated by residential socioeconomic status, population density, and vacant housing conditions - which remained stable across time. Women residing in the most socioeconomically vulnerable neighborhoods experienced the steepest increase in annual SBP growth by 0.93 mmHg/year (95% CI: 0.65-1.21) across ten-year follow-up. Neighborhood socioeconomic vulnerability was significantly associated with accelerated SBP increases throughout midlife among women.


Quantification of histone modifications by parallel-reaction monitoring: a method validation.
Abnormal epigenetic reprogramming is one of the major causes leading to irregular gene expression and regulatory pathway perturbations, in the cells, resulting in unhealthy cell development or diseases. Accurate measurements of these changes of epigenetic modifications, especially the complex histone modifications, are very important, and the methods for these measurements are not trivial. By following our previous introduction of PRM to targeting histone modifications (Tang, H.; Fang, H.; Yin, E.; Brasier, A. R.; Sowers, L. C.; Zhang, K. Multiplexed parallel reaction monitoring targeting histone modifications on the QExactive mass spectrometer. Anal. Chem. 2014, 86 (11), 5526-34), herein we validated this method by varying the protein/trypsin ratios via serial dilutions. Our data demonstrated that PRM with SILAC histones as the internal standards allowed reproducible measurements of histone H3/H4 acetylation and methylation in the samples whose histone contents differ at least one-order of magnitude. The method was further validated by histones isolated from histone H3 K36 trimethyltransferase SETD2 knockout mouse embryonic fibroblasts (MEF) cells. Furthermore, histone acetylation and methylation in human neural stem cells (hNSC) treated with ascorbic acid phosphate (AAP) were measured by this method, revealing that H3 K36 trimethylation was significantly down-regulated by 6 days of treatment with vitamin C.


Is percutaneous nephrolithotomy in solitary kidneys safe?
To review our experience from a high volume stone center with a focus on efficacy, safety, and renal function. Stones requiring percutaneous nephrolithotomy (PCNL) in patients with solitary kidneys can pose significant anxiety to the urologist. Limited data are available in published reports in this setting. A comprehensive retrospective review of medical records was performed on patients who underwent PCNL and had a solitary kidney or a single functioning renal unit. Data were collected on patient demographics, stone burden, outcomes, complications, and renal function. Of 378 PCNLs performed between January 2003 and September 2011, 22 were performed in 17 patients with a single functioning kidney. Three procedures were performed in a transplanted kidney. In those with solitary calculus, the longest mean length and stone surface area were 37 mm and 825 mm(2), respectively. Stone-free rate was 59%. Auxiliary procedures were required in 6 cases, resulting in a stone-free rate of 77%. Median inpatient stay was 4 days. Serum creatinine values improved from 144 to 126 umol/L before and after the procedure and mean estimated glomerular filtration rate improved similarly from 51 to 59 mls/minute, respectively. Blood transfusion was required in 1 patient, sepsis developed in 3, and 2 patients required a stent for obstruction. PCNL in solitary kidneys is safe with an acceptable complication rate if performed in a high volume center. Outcomes are good, although auxiliary procedures may be necessary. Renal function remains stable or improves after procedure.


Complicated adult right-sided Bochdalek hernia with Chilaiditi's syndrome: a case report.
An extremely rare adult case that underwent surgery for ileus caused by Bochdalek hernia associated with Chilaiditi's syndrome is presented. A 65-year-old woman complaining of upper abdominal pain presented to our hospital. Abdominal plain radiography showed increased intestinal gas, and computed tomography (CT) showed the transverse colon located above the right lobe of the liver, representing Chilaiditi's sign. She was diagnosed as having ileus and treated with decompression therapy by a nasoenteric tube. After hospitalization, the patient developed dyspnea, and CT showed intestinal herniation into the right thoracic cavity. She was diagnosed as having strangulated ileus caused by Bochdalek hernia. An emergent laparotomy was performed, and it showed a hole of 5 cm in diameter at the right hemi-diaphragm. The transverse colon was incarcerated through the hole, it was pulled back to the abdominal cavity, and a right hemicolectomy was performed because of necrotic changes. A small part of the liver was also herniated into the right thoracic cavity, and it was returned to the abdominal cavity. The defect in the diaphragm was closed by direct suture. Although the patient developed an abscess in the thoracic cavity postoperatively, she improved with antibiotic therapy and was discharged 2 months after the operation.


Analysis of the most important features of obstructive sleep apnoea
Introduction and objective: Obstructive sleep apnoea results in metabolic and cardiovascular disorders due to inter- mittent hypoxia. The main aim of the present study was to analyze the most important features of obstructive sleep apnoea, using anthropometric measurements and blood tests. Material and method: In this prospective investigation, 100 patients (74 male and 26 female patients, mean age +/- SD years, 42.15 +/- 12.7) were enrolled. These patients were divided into control (n = 36) and obstructive sleep apnoea (n = 64) groups regarding the results of polysomnography. The examination of the patients consisted of detailed anamnestic data, anthropometric measurements, laboratory test and the use of apnoea questionnaires. Results: In the obstructive sleep apnoea group, significantly higher neck (p<0.015), hip and abdomen circumfer- ences and BMI values (p<0.000) were observed. Significantly higher ratio of male patients in the case of obstructive sleep apnoea was detected (p<0.000). In the control group, only the neck circumferences differed significantly be- tween the two genders (p<0.000), but in the obstructive sleep apnoea group the neck (p = 0.001) and abdominal circumferences (p = 0.028) have also differed. Hypertension (64% and 21%) and type 2 diabetes mellitus (6.4% and 0%) were more frequent in the obstructive sleep apnoea group, while cardiovascular disorders (1% and 2.7 %) and gastroesophageal reflux disease (4.71% and 5.42%) in the control group. BMI values were significantly positively cor- related with the neck, abdominal and hip circumferences, both in the control and obstructive sleep apnoea groups. Moreover, in the control group, a significant negative correlation between HDL-cholesterol and BMI, neck and abdominal circumferences was observed. Conclusion: Obesity, as one of the most important risk factors for obstructive sleep apnoea and the intermittent hypo- xia contribute to the development of comorbidities. The diagnosis and therapy of the comorbidities is of great im- portance due to their effects on the patients' quality of life.


Physical activity is associated with less comorbidity, better treatment tolerance and improved response in patients with multiple myeloma undergoing stem cell transplantation.
Multiple myeloma (MM) is the second most common hematological malignancy. Progression free survival (PFS) and overall survival (OS) have substantially improved, nonetheless MM usually remains incurable. Patients with active disease may be affected by numerous comorbidities, including fatigue, depression and osteolytic lesions, which influence their quality of life (QoL). Albeit, it is known that exercising is beneficial for patients' QoL, few clinical trials are available in patients with MM. We therefore aimed to compare comorbidities and clinical outcome in physically active and inactive patients with MM. We defined physical activity according to WHO criteria (150 min of moderate activity and two sessions of resistance training/week). We matched 53 physically active patients with 53 controls (for age, gender, cytogenetics, disease stage, and therapy) and compared the cohorts for incidence of comorbidities/MM symptoms (osteolytic lesions, anemia, infections, fatigue, depression, Revised-Myeloma Comorbidity Index [R-MCI]) and clinical outcome (treatment tolerance, responses to therapy, PFS and OS) in a retrospective audit. All patients were newly diagnosed with MM and received autologous stem cell transplantations (ASCT) between 2001 and 2017. Physically active patients showed superior outcomes in R-MCI (p = 0.0005), fatigue (p = 0.0063), treatment tolerance (p = 0.0258) and hospital stays (p = 0.0072). Furthermore, they showed better treatment responses (p = 0.0366), especially complete remission (CR; p = 0.0018) as well as better OS and PFS. Physical activity in patients with MM undergoing ASCT seemed associated with better overall clinical outcome. Randomized clinical trials are required to understand the benefits and devise strategies for improving exercising among patients with MM.


Effect of age on the efficacy of tranexamic acid: An analysis of heterogeneity of treatment effect within the CRASH-2 dataset.
Trauma is a major cause of morbidity and mortality in older adults and will become more common as the population ages. Tranexamic acid (TXA) is a lysine analogue frequently used in the setting of significant trauma with hemorrhage. The aim of this study is to investigate the heterogeneity of treatment effect of TXA as it relates to patient age during trauma care. We included patients from the CRASH-2 trial who were randomized within 3 h of injury. Patients were stratified into age groups <26 years, 26 to 35 years, 36 to 45 years, 46 to 55 years, and >55 years. Multiple logistic regression models were utilized to evaluate adjusted odds ratios (OR) with 95% confidence intervals (CI) for mortality. Heterogeneity of treatment effect was evaluated using Akaike and Bayesian information criteria to determine the optimum logistic regression model after which a Wald Chi-square test was utilized to evaluate statistical significance. On univariate analysis, TXA administration decreased mortality within the <26 years cohort (decrease of 2.1%, 95% CI 0.2 to 4.0), 46 to 55 years cohort (decrease 6.7%, 95% CI 2.7 to 10.7), and >55 years cohort (decrease of 5.3%, 95% CI 0.4 to 10.3). On adjusted analysis, when compared to the 36 to 45 years cohort, the <26 year cohort experienced a decreased mortality (OR 0.72, 95% CI 0.62 to 0.85) whereas the >55 year cohort experienced increased mortality (OR 1.8, 95% CI 1.5 to 2.2). Assessment for heterogeneity of treatment effect of TXA administration between groups approached but did not reach statistical significance (p = 0.11). Mortality related to trauma increases with age, however, there does not appear to be heterogeneity of treatment effect for TXA administration among different age groups.


Obesity Treatment: Environment and Behavior Modification.
Obesity is commonly encountered in veterinary patients. Although there are various published dietary approaches to achieving weight loss, successful long-term prevention of weight regain has proven elusive. Adding environmental and behavioral treatment strategies to a weight loss plan may help the veterinary team, the pet, and the pet owner maximize the effectiveness of the program. Because the owner directly affects the environment and behavior of the pet undergoing a weight loss plan, treatment strategies with an emphasis on owner involvement is the focus of this review. Veterinary use of the 5 A's behavioral counseling approach with the pet owner is discussed.


Functional Outcome After Spinal Meningioma Surgery. A Nationwide Population-Based Study.
To describe and analysed the functional outcome (FO) after spinal meningioma (SM) surgery. We processed the système national des données de santé (SNDS) i.e. , the French national administrative medical database to retrieve appropriate cases. We analysed the International Classification of Diseases 10 codes to assess the FO. Logistic models were implemented to search for variables associated with a favourable FO i.e. , a patient being independent at home without disabling symptom. A total of 2,844 patients were identified of which 79.1% were female. Median age at surgery was 66 years, interquartile range (IQR) (56-75). Ninety-five point nine percent of the SMs were removed through a posterior ± lateral approach and 0.7% need an associated stabilisation. Benign meningioma represented 92.9% and malignant 2.1%. Median follow-up was 5.5 years, IQR (2.1-8), and at data collection 9% had died. The FO was good and increased along the follow-up: 84.3% of the patients were alive and had not associated symptoms at one year, 85.9% at 2 and 86.8% at 3 years. Nonetheless, 3 years after the surgery 9.8% of the alive patients still presented at least one disabling symptom of which 2.7% motor deficit, 3.3% bladder control problem, and 2.5% gait disturbance. One point seven percent were care-provider dependent and 2.1% chair or bedfast. In the multivariable logistic regression an older age at surgery (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.29-0.47, p < 0.001), a high level of comorbidities (OR, 0.71; 95% CI, 0.66-0.75, p < 0.001), and an aggressive tumor (OR, 0.49; 95% CI, 0.33-0.73; p < 0.001) were associated with a worse FO. FO after meningioma surgery is favourable but, may be impaired for older patients with a high level of comorbidities and aggressive tumor.


First records of the subfamilies Ecliminae and Lomatiinae (Diptera, Bombyliidae) from China with description of two new species.
Two subfamilies of bee flies, Ecliminae and Lomatiinae, are first reported from China with the description of the following two new species: Lomatia shanguii sp. nov. and Thevenetimyia cingulata sp. nov. A key to the Chinese subfamilies of Bombyliidae and a key to the Palaearctic species of Thevenetimyia Bigot are also presented.


Cloning and characterization of phospholipase D from olive flounder (Paralichthys olivaceus).
The phospholipase D1 (PLD1) cDNA, designated PoPLD, encoding a predicted protein of 1053 amino acids in olive flounder (Paralichthys olivaceus) has been cloned. The deduced amino acid sequence shares high identity with that of PLD1s and PLD2 in human, rat and mouse. The phylogenic analysis and sequence comparison of PoPLD with other PLD isozymes were found to be closely related to the PLD1 isozyme in primary structure. The tissue expression analysis of PoPLD showed that the mRNA of PoPLD was predominantly expressed in the brain, gullet, muscle, stomach, head kidney, pyloric caeca, intestine and gill. The expression of the PoPLD gene was examined in various tissues of flounder by RT-PCR following stimulation with LPS and compared also with that of the inflammatory cytokines IL-1beta and IL-8 in various tissues of the stimulated flounder. This provides indirect evidence that PLD1 might have a relevant role in immune responses against pathogens and in inflammation. In addition, the recombinant protein of PoPLD (GFP-PoPLD), which demonstrated a phosphatidylcholine (PC)-hydrolyzing activity, was partially localized as a distinct ring-shaped form surrounding the rim of the nucleus in EPC cells. Together, our results suggest that PoPLD is similar to the mammalian PLD1 isoform, is generally widespread within olive flounder tissue, might have a relevant role in the fish immune system against pathogens and specifically may be localized in the subcellular membranes of the nuclear rim in EPC cells.


Transcriptome, metabolome and suppressor analysis reveal an essential role for the ubiquitin-proteasome system in seedling chloroplast development.
Many regulatory circuits in plants contain steps of targeted proteolysis, with the ubiquitin proteasome system (UPS) as the mediator of these proteolytic events. In order to decrease ubiquitin-dependent proteolysis, we inducibly expressed a ubiquitin variant with Arg at position 48 instead of Lys (ubK48R). This variant acts as an inhibitor of proteolysis via the UPS, and allowed us to uncover processes that are particularly sensitive to UPS perturbation. Expression of ubK48R during germination leads to seedling death. We analyzed the seedling transcriptome, proteome and metabolome 24 h post ubK48R induction and confirmed defects in chloroplast development. We found that mutations in single genes can suppress seedling lethality, indicating that a single process in seedlings is critically sensitive to decreased performance of the UPS. Suppressor mutations in phototropin 2 (PHOT2) suggest that a contribution of PHOT2 to chloroplast protection is compromised by proteolysis inhibition. Overall, the results reveal protein turnover as an integral part of a signal transduction chain that protects chloroplasts during development.


The impact of Rhizopus oryzae cultivation on rice bran: Gamma-oryzanol recovery and its antioxidant properties.
This study evaluated the effect of the solid state cultivation (SSC) time of rice bran by Rhizopus oryzae on γ-oryzanol recovery and its antioxidant properties. Gamma-oryzanol was extracted with organic solvents and its extracts were characterized by GC-FID and HPLC-UV. The antioxidant capacity was assessed by DPPH and ABTS+ assays, β-carotene/linoleic acid system, and reduction of oxidation in lipid system. The biomass showed the γ-oryzanol recovery increased by 51.5% (20.52mg/g), and 5.7% in polyunsaturated fatty acids. The γ-oryzanol major components changing in their profile. The γ-oryzanol extract from biomass (72h) showed the greatest DPPH inhibition (59.0%), while 90.5% inhibition of oxidation of β-carotene/linoleic acid system, and 30% reduction of the indicators of oxidation in olive oil was observed in the one cultivated at 96h, these behaviors were confirmed by PCA analyses. SSC provides an increase in the γ-oryzanol recovery followed by improving of the functional properties of rice bran.


Sucrose modifies ribosomal stability and conformation.
High concentrations of sucrose have a strong protective effect on heat-induced modifications of rat liver ribosomal subunits. They prevent to a large extent subunit inactivation, measured by poly (U)-dependent [14C] Phe tRNA binding (40S subunits) and puromycin reaction (60S subunits), subunit unfolding into light forms, and the release of both free and protein-complexed 5S RNA. They also increase the temperature at which subunits start to melt. Our data indicate that sucrose affects subunit conformation.


Radiation therapy.
RT is an indispensable part of current treatment approaches of locally advanced and metastatic NSCLC. It can be used alone or in combination with surgery or CHT. Because RT can potentially cure some patients, prolong the life of others, and reduce symptoms in the majority of them, it is a unique treatment modality in this disease. Radiation oncologists have learned how to deal with RT-induced toxicities and how to improve quality of life of lung cancer patients. Although recent technologic advances made sophisticated RT somewhat more expensive than before (demanding more manpower and being more time-consuming), it is still an inexpensive treatment modality, which is important in the era of focusing on cost-effectiveness. Although newer RT technologies are used to enable effective dose-escalation-a clear must for the community of radiation oncologists--optimization of RT must also include clear identification of various pretreatment, patient, and tumor-related characteristics that may influence treatment outcome. Regardless of the current therapeutic/technologic potential, we still lack some basic knowledge to better understand the process of, for example, combining RT and CHT. There is recognized need for better translational research that ultimately should be seen as a "two-way road," from laboratory to clinic and vice versa, preferably in a continuous way. The National Cancer Institute in the United States recently organized a workshop on translational research in radiation oncology, which has identified RT-CHT interactions as one of its major areas of research. Research topics include development of the methods of imaging the results of RT/ CHT interactions (confirmed by biopsy), development of new radiation modifiers, and identification of factors other than genetic ones that may influence the response of tumors to RT/CHT interactions. Tumor microenvironment was also clearly addressed as one of the targets for research, indicating as special tasks the development of new, microenvironmentally activated cytotoxic or cytostatic drugs, development and validation of more user-friendly methods for determining tumor oxygenation, and answering whether hypoxia predicts for radioresistance to CHT in treatment and whether it causes increased tumor aggression and metastasis. The future may, therefore, be quite simple: technology meets biology.


Day-to-day variation of 24-hour intragastric acidity.
Twenty-four-hour intragastric acidity was measured continuously using an intragastric electrode in 13 normal volunteers studied four times. Subjects were studied twice in the hospital and twice as outpatients. The dietary conditions were strictly controlled and the replicate studies were compared to assess the variability of such recordings of acidity. The accuracy of the technique was assessed, and a detection limit for differences was calculated for commonly used time periods. Over 24 h, during the night, during the day, and during the evening the technique is able to detect consistent changes of pH of greater than 0.1 units. During separate 5-min periods the limits of detection were considerably greater. This study demonstrates the variability of 24-h intragastric acidity and confirms that continuous monitoring is able to detect important changes of acidity under both hospitalized and ambulant conditions.


The effect of bradykinin on the electrical activity of rat jejunum.
Bradykinin increased the potential difference across both the jejunum and colon of the rat. This effect was significantly reduced by indomethacin, suggesting that it was mediated by prostaglandins. The possibility that bradykinin may contribute to the diarrhoea of the carcinoid syndrome by inducing a net secretory state in the intestine is discussed.


Association between plasma homocysteine levels and coronary artery disease: a population-based study in northern Greece.
Elevated plasma total homocysteine (tHcy) levels constitute a risk factor for coronary artery disease (CAD). We prospectively examined the association of fasting tHcy levels in patients in Northern Greece who had established CAD. Plasma fasting tHcy levels were measured in 42 patients with angiographically documented CAD and compared to 42 age-, sex-, BMI- and smoking habit-matched control subjects. We also determined the plasma vitamin B(12), folic acid and lipoprotein levels in all patients and controls. Conventional risk factors for CAD were also estimated. In a univariate analysis, tHcy (micromol/l) levels were higher in patients compared to controls almost reaching statistical significance (13 (7-41) vs 11.3 (4-39); p= 0.07). Multivariate analysis of conventional risk factors showed that tHcy levels were not an independent risk factor for CAD. However, tHcy levels were significantly higher in patients with a previous history of myocardial infarction compared to patients without such a history and to controls (15 (8.8-29) vs 11.7 (7-41); p = 0.007 and 15 (8.8-29) vs 11.3 (4-39); p = 0.002, respectively). Hyperhomocysteinaemia (> 15 micromol/l) was detected in 35.7% of patients and 11.9% of controls (p < 0.05). In Northern Greece, plasma tHcy levels may not be an independent risk factor for CAD in patients with angiographically documented CAD. However, patients with CAD have a trend towards higher tHcy levels. Additionally, plasma tHcy levels may be associated with the development of myocardial infarction.


Synthesis and structure design of new bio-based elastomers via Thiol-ene-Click Reactions.
The additions of 2-mercaptoethanol to (S)-(-)-limonene via click reaction is described as an adaptable and efficient way to obtain alcohol functionalized renewable monomer for the synthesis of new cross-linkable bio-based elastomers. Thiol first reacted with the limonene endocyclic double bond and then reacted with the exocyclics double bond to form the difunctional monomer. The structure of the monomer was determined by using FTIR, (1)H NMR and mass spectrometry. Thermal Gravimetric Analysis (TGA) and Differential Scanning Calorimetrys (DSC) characterization exposed that this monomer could be used to synthesize elastomers with excellent and adaptable thermal properties. The molecular weight of the synthesized elastomer could reach 186kDaa via melting polycondensation route and the structure-properties relationship was deliberated. Finally, these elastomers were mixed with dicumyl peroxide (DCP) to form cross-linked elastomers with certain mechanical property, and the gel contents of the elastomers were confirmed by using Soxhlet extraction method.