[Selective CT mesentericography in the diagnostics of obscure overt intestinal bleeding: preliminary results].
To evaluate intra-arterial CT mesentericography (CTM) in the diagnostics of severe obscure overt intestinal bleeding in comparison with conventional mesentericography (MG) and surgery. In 8 patients (23 - 82 years, mean 59 years), CTM was performed via the catheter left in the superior mesenteric artery after MG to detect the source of bleeding. Early and late-phase spiral CT scans were acquired after administration of contrast medium. Active bleeding was considered to be present if extravasation of contrast medium into the bowel was found. The results of MG and CTM were compared with the results of surgery. With MG active bleeding was found in one patient, with CTM in five patients. In three patients, both MG and CTM were negative. Six patients underwent surgery. Five cases of bleeding detected with CTM were confirmed by surgery. In one case, bleeding found with CTM was not confirmed by surgery. One patient underwent surgery although all imaging procedures were negative. The source of bleeding remained unknown. Surgically, the site of bleeding was located in the jejunum in 3 patients (jejunitis, jejunal ulcers, carcinoid), one patient had a diverticulum in the ascending colon. The colonic bleeding site was correctly localized with CTM, whereas the small bowel bleeding could only roughly be assigned to the proximal or distal jejunum or jejunoileal transition area. Preliminary results indicate that selective CTM is superior to MG in the evaluation of severe obscure overt intestinal bleeding.


GID1-mediated gibberellin signaling in plants.
Gibberellin (GA) perception is mediated by GID1 (GA-INSENSITIVE DWARF1), a receptor that shows similarity to hormone-sensitive lipases. A key event in GA signaling is the degradation of DELLA proteins, which are negative regulators of GA response that interact with GID1 in a GA-dependent manner. This GID1-DELLA GA-perception system is conserved among vascular plants but is not found in the moss Physcomitrella patens. The identification of factors in GA signaling downstream of DELLA and the development of a new concept of DELLA function beyond its role as a repressor of GA signaling are important advances. DELLA proteins appear to have at least two other distinct roles: maintaining GA homeostasis and regulating cross-talk between GA and other plant hormones.


Phagolysosome formation, cyclic adenosine 3':5'-monophosphate and the fate of Salmonella typhimurium within mouse peritoneal macrophages.
Salmonella typhimurium did not inhibit fusion of lysosomes with the phagocytic vacuoles in infected macrophages and caused no increase in cyclic adenosine 3':5'-monophosphate. Glutaraldehyde-killed bacteria showed rapid ultrastructural degeneration within the phagolysosomes. In contrast, untreated bacteria were resistant to digestion by lysosomal enzymes. Intracellular survival of this species appears to depend on resistance to, and not evasion of, lysosomal enzymes.


Plasmid-borne catabolism of methyl parathion and p-nitrophenol in Pseudomonas sp. strain WBC-3.
Pseudomonas sp. strain WBC-3 utilises methyl parathion (MP) or p-nitrophenol (PNP) as the sole source of carbon, nitrogen, and energy. A plasmid designated pZWL0 of approximately 70 kb in this strain was found to be responsible for MP and PNP degradation. This was based on the fact that the plasmid-cured strains showed PNP- MP- phenotype and the PNP+ MP+ phenotype could be conjugally transferred. We have also cloned a 3.4-kb HindIII fragment which exhibited methyl parathion hydrolase activity, which revealed a methyl parathion hydrolase (mph) gene whose DNA sequence is 99.5% identical to the recently identified mpd gene from Plesiomonas sp. M6 [C. Zhongli, L. Shunpeng, F. Guoping, Isolation of methyl parathion-degrading strain M6 and cloning of the methyl parathion hydrolase gene, Appl. Environ. Microbiol. 67 (2001) 4922-4925]. The mph gene was functionally expressed in Escherichia coli and the relative activities of the enzyme against different substrates were determined. The sequence alignment and phylogenetic analysis suggested that MPH and MPD evolved independently from other well-studied organophosphate hydrolases and may be originated from class B beta-lactamase family. Subsequently obtained a 6.5-kb KpnI and BamHI fragment containing the above HindIII fragment revealed that the mph gene was physically located in a typical transposon.


Aluminium complexes containing indolyl-phenolate ligands as catalysts for ring-opening polymerization of cyclic esters.
A family of aluminium complexes supported by mono-anionic indolyl-phenolate ligands are described. Reactions of indolyl-phenolate based ligand precursors, IndHPhROH, with 1.0 or 0.5 equivalents of AlMe2Cl in toluene afforded aluminium indolyl-phenolate complexes 1-4 and aluminium bis-indolyl-phenolate complexes 5-8 respectively. The molecular structure is reported for 5. Based on the NMR spectroscopic and X-ray crystallographic studies, a 1,3-hydrogen shift could happen from nitrogen to carbon on the five-membered ring of the indolyl group upon reacting with aluminium reagents. These novel aluminium complexes demonstrate catalytic activities toward the ring-opening polymerization of cyclic esters in the presence of alcohol.


Prospective evaluation of same day versus next day colon manometry results in children with medical refractory constipation.
We evaluated the change in colon manometry (CM) parameters and interpretation comparing results when the study is performed the same day after the motility catheter is placed under anesthesia or the following day. CM catheter was placed with colonoscopy under anesthesia and recorded on day 1 and repeated on day 2. Study parameters including motility index during fasting, post-prandial and post-Bisacodyl challenge phase; gastrocolonic response; number, presence and propagation of high amplitude propagating contractions (HAPCs); and, study interpretation were compared between both the days. Motility index (fasting, post-Bisacodyl phase, P<.05), HAPC number (10.1 vs 6.6, P=.01) and the proportion of patients having HAPCs (92% vs 70%, P=.002) was significantly higher on day 2 vs day 1. HAPC propagation improved on day 2 vs day 1 (fully propagated, 49% vs 37%; partially propagated, 43% vs 33%; absent 8% vs 30%). Study interpretation changed from day 1 to day 2. On day 1, 37% had a normal study and 63% had an abnormal study. On day 2, all patients with a normal study on day 1 remained normal, and patients with an abnormal study on day 1, 53% remained abnormal and 47% had a normal study. CM parameters are affected the day the catheter is placed with colonoscopy under anesthesia. The number, presence, and propagation of HAPCs were significantly higher/improved on day 2 compared to day 1. Overall, CM interpretation changed from abnormal to normal from day 1 to day 2 in 47% of the patients.


Polymorphisms in the oligoadenylate synthetase gene cluster and its association with clinical outcomes of dengue virus infection.
Oligoadenylate synthetases (OAS) play an important role in the immune response against dengue virus. Single nucleotide polymorphisms (SNPs) in the OAS genes are known to affect OAS activity and are associated with outcome of viral infections. Polymorphisms in the OAS1 (rs1131454 and rs10774671), OAS3 (rs2285932 and rs2072136) and OAS2 (rs15895 and rs1732778) genes were studied using PCR followed by restriction fragment length polymorphism methods in 109 patients hospitalized for dengue (DEN) and 105 healthy controls (HCs) who have no documented evidence of symptomatic dengue. The two locus haplotype of OAS2 G-G was significantly higher in all patient groups [DEN vs. HCs, P=0.0041, P corrected (Pc)=0.012, Odds ratio (OR) 1.73 95% CI 1.16-2.59] while the four locus haplotype of OAS3-OAS2 C-G-A-G was significantly lower in all dengue patient groups [DEN vs. HCs, P=0.0054, Pc=0.0486, OR 0.09, 95% CI 0.00-0.64] compared to controls. When the six locus haplotypes involving OAS1, OAS3 and OAS2 polymorphisms were analyzed and compared, the frequency of the haplotype A-A-C-A-G-G was significantly higher [P=0.0267, Pc=0.486, OR 2.34, 95% CI 1.08-4.91] and the frequency of the haplotype A-A-C-G-G-A was significantly lower in DHF cases [P=0.014, Pc=0.252, OR 0.12, 95% CI 0.01-0.85] compared to healthy controls. The results suggest that OAS1-OAS3-OAS2 haplotypes are associated with differential susceptibility to clinical outcomes of dengue infection.


Soil type regulates carbon and nitrogen stoichiometry and mineralization following biochar or nitrogen addition.
Most studies on the effects of biochar and fertilizer on soil carbon (C) and nitrogen (N) mineralization, and microbial C and N content, are restricted to a single soil type, limiting our understanding of the interactions between these factors and microbial functions. To address this paucity in knowledge, we undertook a 3-year experiment using four contrasting soils to assess the role of peanut shell biochar and fertilizer on C and N mineralization, microbial C and N, and N stoichiometry. Across all four soils, biochar significantly (P < 0.05) increased soil carbon mineralization (Cmin) and nitrogen mineralization (Nmin) over three years compared to fertilizer and the control. Biochar also increased total C (Csoil) across the four soils in year 1, with the Fluvisol recording greater total C in year 2 and Phaeozem having greater total C in year 3. Biochar resulted in a higher microbial biomass C (Cmic), total N (Nsoil) and microbial biomass N (Nmic); the degree of change was closely related to Csoil and Nsoil. There was a positive correlation between Cmic:Nmic and Csoil:Nsoil; while Csoil and Cmic increased following amendment with biochar, which reduced the soil C and N stoichiometric imbalance (Nimb) caused by the increase in the C to N ratio. However, fertilizer exacerbated the imbalance of soil C and N stoichiometry. Fertilizer also reduced the Csoil:Nsoil and Cmic:Nmic ratios. Soil pH had a positive correlation with Csoil, Cmic, Nmic, Cmin, Nmin, Csoil:Nsoil, Cmic:Nmic, and biochar increases this correlation. The soil pH was negatively correlated with Cimb:Nimb and Nsoil. Fertilizer was positively correlated Cimb:Nimb and Nsoil. In contrast, fertilizer N application lowered microbial biomass C:N. We conclude that biochar reduces the imbalance of soil C and N stoichiometry, whereas fertilizer increased this imbalance. Biochar had a greater impact on C and N in soils with a lower pH.


Effect of gliclazide treatment on insulin secretion and beta-cell mass in non-insulin dependent diabetic Goto-Kakisaki rats.
The Goto-Kakisaki rat is a genetic non-overweight model of non-insulin-dependent diabetes mellitus. Adult Goto-Kakisaki rats exhibit a mild basal hyperglycaemia (11 mmol/l) with impaired glucose tolerance, elevated basal plasma insulin level, a failure of insulin release in response to glucose together with a 50% depletion of the total pancreatic beta-cell mass and insulin stores. We have examined the effects of long-term (4 weeks) gliclazide treatment on the severity of diabetes in adult male Goto-Kakisaki rats (10-12 weeks of age). Gliclazide was administered orally (10 mg/kg per day). Gliclazide-treated Goto-Kakisaki rats were evaluated against Wistar and untreated Goto-Kakisaki rats. In the gliclazide-treated Goto-Kakisaki rats, basal plasma glucose levels declined progressively reaching 8 mmol/l as a mean at the end of treatment, and their basal insulin levels decreased to values similar to those in non-diabetic Wistar rats. Despite their total pancreatic beta-cell remaining unaffected, their pancreatic insulin stores were twice increased, with a similar improvement of the insulin content per individual beta-cell. Furthermore, the glucose-stimulated insulin release as evaluated in vivo during an intravenous glucose tolerance-test was significantly improved (twice increased) in the gliclazide-treated Goto-Kakisaki rats. This was correlated with a modest but significant enhancement of the early phase of insulin release in vitro (isolated perfused pancreas), in response to glucose. However, the overall insulin response in vitro remained clearly defective with no reappearance of the late phase of insulin release. The in vitro response to arginine (which was basically amplified in the Goto-Kakisaki model) or to gliclazide were kept unchanged after the gliclazide treatment. In conclusion, chronic gliclazide does not exert any beta-cytotrophic effect, but improves beta-cell function in the adult Goto-Kakisaki rat as far as it lowers basal insulin release, increases beta-cell insulin stores, and increases the glucose-induced insulin release.


Self-help approaches to smoking cessation: a report from the normative aging study.
Self-quitters make up by far the largest proportion of ex-cigarette smokers, yet this population has not been extensively characterized to date. We compared male self-quitters (N = 191) and age-matched recidivists (N = 110) on smoking histories, psychosocial attributes and quitting methods. A number of significant relationships were found, some of which may have clinical implications. those who substituted cigars or pipes for cigarettes were nearly four times more likely to be successful, and those who reported consuming more food/snacks after quitting were 80% more likely to be successful quitters. Subjects who reported using no coping strategies in former smoking settings after cessation because they had no urges to smoke in these settings were also much more likely to be successful quitters. Recidivists were more likely to report using physical activity as a means of coping with temptations to smoke, and were somewhat older at the time of the quit attempt. Withdrawal symptoms and psychosocial stress were reported as reasons for relapse by early relapsers, while late relapsers reported being around other smokers on social occasions, and psychosocial stress.


Caregiver-Reported Presentation of Severe Food-Induced Allergic Reactions in Infants and Toddlers.
Recognizing anaphylaxis in infants and toddlers can be challenging for health care providers and caregivers, and current diagnostic criteria and anaphylaxis action plans do not specifically address this younger population. To describe symptoms and signs observed by primary caregivers of infants and toddlers during severe food-induced allergic reactions. We conducted a national online survey among primary caregivers of children who experienced a severe food-induced allergic reaction when less than 36 months of age. Respondents who were present during the child's most severe reaction were asked to report symptoms and signs observed. The survey asked about infant- and toddler-specific symptoms and signs in lay language for caregivers. Data were compared with patient-reported data from past studies to identify distinct patterns among the younger population. The survey was completed for 374 children (193 infants, 181 toddlers). The most common symptoms and signs reported were skin reactions (90%), facial and extremity swelling (59%), gastrointestinal issues (51%), and coughing/wheezing (45%). Infants (aged <12 months) more frequently experienced skin reactions, skin mottling, and ear pulling/scratching or putting fingers in ears, as compared with toddlers (aged 12-35 months). Toddlers experienced throat itching and coughing/wheezing more frequently than infants. Anaphylaxis presentation demonstrates similarities and differences in infants and toddlers. Modifying the terminology used in the current criteria allowed for reporting of symptoms and signs of anaphylaxis that are more common in infants and toddlers. Diagnostic criteria, clinical guidelines, and anaphylaxis action plans may be enhanced to address this young, often nonverbal, population.


The impact of Climate Change on the Western Pacific Subtropical High and the related ozone pollution in Shanghai, China.
Severe ozone (O3) episodes occur frequently in Shanghai during late-summers. We define geopotential height averaged over the key area region (122.5°E-135°E, 27.5°N -35°N) at 500 hPa as a WPSH_SHO3 index which has high positive correlation with surface O3 concentration in Shanghai. In addition, the index has a significant long-term increasing trend during the recent 60 years. Analysis shows the meteorological conditions under the strong WPSH_SHO3 climate background (compared to the weak background) have several important anomalies: (1) A strong WPSH center occurs over the key area region. (2) The cloud cover is less, resulting in high solar radiation and low humidity, enhancing the photochemical reactions of O3. (3) The near-surface southwesterly winds are more frequent, enhancing the transport of upwind pollutants and O3 precursors from polluted regions to Shanghai and producing higher O3 chemical productions. This study suggests that the global climate change could lead to a stronger WPSH in the key region, enhancing ozone pollution in Shanghai. A global chemical/transport model (MOZART-4) is applied to show that the O3 concentrations can be 30 ppbv higher under a strong WPSH_SHO3 condition than a weak condition, indicating the important effect of the global climate change on local air pollution in Shanghai.


Sleep EEG findings in depressed children and adolescents.
Sleep polysomnographic data on 17 juveniles (age 9 to 14) with major depression revealed abnormalities similar to those in depressed adults.


Understanding Subcutaneous Tissue Pressure for Engineering Injection Devices for Large-Volume Protein Delivery.
Subcutaneous injection allows for self-administration of monoclonal antibodies using prefilled syringes, autoinjectors, and on-body injector devices. However, subcutaneous injections are typically limited to 1 mL due to concerns of injection pain from volume, viscosity, and formulation characteristics. Back pressure can serve as an indicator for changes in subcutaneous mechanical properties leading to pain during injection. The purpose of this study was to investigate subcutaneous pressures and injection site reactions as a function of injection volume and flow rate. A pressure sensor in the fluid path recorded subcutaneous pressures in the abdomen of Yorkshire swine. The subcutaneous tissue accommodates large-volume injections and with little back pressure as long as low flow rates are used. A 1 mL injection in 10 seconds (360 mL/h flow rate) generated a pressure of 24.0 ± 3.4 kPa, whereas 10 mL delivered in 10 minutes (60 mL/h flow rate) generated a pressure of 7.4 ± 7.8 kPa. After the injection, the pressure decays to 0 over several seconds. The subcutaneous pressures and mechanical strain increased with increasing flow rate but not increasing dose volume. These data are useful for the design of injection devices to mitigate back pressure and pain during subcutaneous large-volume injection.


No significant association between stable iodine intake and thyroid dysfunction in children after the Fukushima Nuclear Disaster: an observational study.
Stable iodine prophylaxis helps prevent childhood thyroid cancer in nuclear emergencies; however, there is limited information on its effect on thyroid function. This study aimed to examine thyroid function and autoimmunity among children and adolescents that took stable iodine after the Fukushima Nuclear Disaster. For this observational study, data were obtained from children and adolescents that underwent thyroid cancer screening at Hirata Central Hospital from April 2012 to March 2018. Participant characteristics, including possible hypothyroidism and hyperthyroidism, were compared between the prophylaxis and no-prophylaxis groups. Multivariable logistic regression models were used to assess for possible hypothyroidism, autoantibodies positive, and hyperthyroidism. A total of 1,225 participants with stable iodine prophylaxis and 3,946 without prophylaxis were enrolled. Of those participants, blood samples were available for 144 and 1,201 participants in the prophylaxis and no-prophylaxis groups, respectively. There were 17 (11.8%) and 146 cases (12.2%) of possible hypothyroidism or autoantibodies positive cases in the prophylaxis and no-prophylaxis groups, respectively, and there were no cases and 3 cases (0.2%) of possible hyperthyroidism in those two groups, respectively. Multivariable analysis for possible hypothyroidism revealed no association between stable iodine intake and possible hypothyroidism or autoantibodies positive [odds ratio 0.716 (95% confidence interval 0.399-1.284)] (p = 0.262). We did not perform multivariable analysis for hyperthyroidism due to the limited number of cases. Significant adverse effects of stable iodine intake on thyroid function were not observed among children and adolescents 7 years after the Fukushima Nuclear Disaster.


5-Fluoroindole-3-acetic acid: a prodrug activated by a peroxidase with potential for use in targeted cancer therapy.
Indole-3-acetic acid and some derivatives are oxidized by horseradish peroxidase, forming a radical-cation that rapidly fragments (eliminating CO(2)) to form cytotoxic products. No toxicity is seen when either indole-3-acetic acid or horseradish peroxidase is incubated alone at concentrations that together form potent cytotoxins. Unexpectedly, 5-fluoroindole-3-acetic acid, which is oxidized by horseradish peroxidase compound I 10-fold more slowly than indole-3-acetic acid, is much more cytotoxic towards V79 hamster fibroblasts in the presence of peroxidase than the unsubstituted indole. The fluorinated prodrug/peroxidase combination also shows potent cytotoxic activity in human and rodent tumor cell lines. Cytotoxicity is thought to arise in part from the formation of 3-methylene-2-oxindole (or analogues) that can conjugate with thiols and probably DNA or other biological nucleophiles. Levels of the fluorinated prodrug in the murine carcinoma NT after intraperitoneal administration of 50 mg/kg were about 200 microM. Although these were 4-5-fold lower than plasma levels (which reached 1mM), the integrated area under the concentration/time curve in tumors over 2 hr was approximately 20 mM min, almost double the exposure needed to achieve approximately 90-99% cell kill in human MCF7 breast or HT29 colon tumor cell lines and CaNT murine cells in vitro, although the human bladder T24 carcinoma cell line was more resistant. The high cytotoxicity of 5-fluoroindole-3-acetic acid after oxidative activation suggests its further evaluation as a prodrug for targeted cancer therapy involving antibody-, polymer-, or gene-directed delivery of horseradish peroxidase or similar activating enzymes.


Association of angiotensin-converting enzyme (ACE) I/D variation with biochemical parameters and oxidative stress markers in systemic lupus erythematosus patients in west of Iran.
We aimed to study insertion/deletion (I/D) variation (rs4646994) of ACE gene in a group of SLE patients in west of Iran and its possible relationship with oxidative stress. Genotypes and allele frequencies related to ACE (I/D) variation were determined in 108 SLE patients and 110 gender and age-matched healthy controls using PCR. Neopterin, malondialdehyde (MDA), and serum lipid concentrations were determined by HPLC and enzyme assay respectively. The overall distribution of ACE I/D genotypes in SLE patients was different from that of the control group (P = 0.005). DD genotype compared to ID genotype increased the risk of SLE (OR = 2.57, 95% CI 1.4-4.8, P = 0.003). ID genotype compared to the II genotype decreased the risk of disease (OR = 0.45, 95% CI 0.2-0.99, p = 0.042). SLE patients with DD, ID, and II genotypes had lower paraoxonase (PON) activity and higher serum levels of MDA and neopterin versus control patients. We also detected a significant protective effect against SLE in presence of ACE I alleles and lack of angiotensin II receptor, type 1 (AGTR1) A1166C (NCBI reference SNP id: rs5186), C alleles in this study (OR = 0.31, 95% CI 0.14-0.68, P = 0.002). Carriers of the DD genotype of ACE gene with higher serum concentrations of neopterin and MDA, and lower PON activity had a high risk to develop SLE, while ID genotype decreased the risk of disease development by 2.22 times compared to II genotype.


Mining the transcriptome of target tissues of autoimmune and degenerative pancreatic β-cell and brain diseases to discover therapies.
Target tissues of autoimmune and degenerative diseases show signals of inflammation. We used publicly available RNA-seq data to study whether pancreatic β-cells in type 1 and type 2 diabetes and neuronal tissue in multiple sclerosis and Alzheimer's disease share inflammatory gene signatures. We observed concordantly upregulated genes in pairwise diseases, many of them related to signaling by interleukins and interferons. We next mined these signatures to identify therapies that could be re-purposed/shared among the diseases and identified the bromodomain inhibitors as potential perturbagens to revert the transcriptional signatures. We experimentally confirmed in human β-cells that bromodomain inhibitors I-BET151 and GSK046 prevent the deleterious effects of the pro-inflammatory cytokines interleukin-1β and interferon-γ and at least some of the effects of the metabolic stressor palmitate. These results demonstrate that key inflammation-induced molecular mechanisms are shared between β-cells and brain in autoimmune and degenerative diseases and that these signatures can be mined for drug discovery.


Human Acid β-Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease.
A collection of carbohydrate-derived iminosugars belonging to three structurally diversified sub-classes (polyhydroxylated pyrrolidines, piperidines, and pyrrolizidines) was evaluated for inhibition of human acid β-glucosidase (glucocerebrosidase, GCase), the deficient enzyme in Gaucher disease. The synthesis of several new pyrrolidine analogues substituted at the nitrogen or α-carbon atom with alkyl chains of different lengths suggested an interpretation of the inhibition data and led to the discovery of two new GCase inhibitors at sub-micromolar concentration. In the piperidine iminosugar series, two N-alkylated derivatives were found to rescue the residual GCase activity in N370S/RecNcil mutated human fibroblasts (among which one up to 1.5-fold). This study provides the starting point for the identification of new compounds in the treatment of Gaucher disease.


Approximately optimal one-parameter boundaries for group sequential trials.
We present a class of group sequential tests, indexed by a single parameter, that yields approximately optimal results. We also provide tables of key values to help in the design of group sequential tests that meet selected specifications.


Peripheral and central muscarinic receptor affinity of psychotropic drugs.
The muscarinic receptor affinity of 27 psychotropic and 5 anticholinergic substances was examined in 2 in-vivo and 2 in-vitro models. A highly significant correlation was obtained between the effect of all compounds examined on the atropine sensitive binding of 3H-PrBCM and the effect in the conventional guinea-pig ileum preparation. Antagonism of oxotremorine induced tremors in mice by anticholinergics and neuroleptics was also significantly correlated to the corresponding data obtained in the in-vitro tests. Due to very low potency in the physostigmine induced mortality test in mice too few ED50 values were obtained to perform statistical comparisons. It is concluded, that the conventional guinea-pig ileum model and the 3h-prBCM binding model are equally predictive as tests for antimuscarinic properties. When in-vivo anticholinergic data for neuroleptics are used it must be considered that a possible dopamine receptor blockade may diminish the antimuscarinic effect of the substance.


Heterocyclic aromatic amines induce Neuro-2a cells cytotoxicity through oxidative stress-mediated mitochondria-dependent apoptotic signals.
Heterocyclic aromatic amines (HAAs) are a class of hazardous compounds produced in food thermal processing. These compounds raise concerns because they have mutagenic and carcinogenic properties. However, the neurotoxicity of these compounds has received limited attention. Here, the toxic effects of three HAAs, i.e. 9H-pyrido[3,4-b]indole (Norharman), 1-methyl-9H-pyrido[3,4-b]indole (Harman), and 2-amino-3-methylimidazole[4,5-f]quinoline (IQ) were investigated in Neuro-2a cells model. The results showed that the survival rate of cells decreased in a dose-dependent manner and apoptosis occurred after exposure to the three HAAs for 24 h and 48 h. Their neurotoxicity was ranked as Harman > Norharman > IQ. Further, treatment of Harman, Norharman, or IQ at 50 and 100 μM for 48 h led to intracellular REDOX imbalance, which was manifested as increased ROS and malondialdehyde (MDA) levels, decreased GSH/GSSG ratio, and reduced SOD and CAT activities. Moreover, Norharman and Harman up-regulated the expression level of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as the mRNA levels of Heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoredutase1 (NQO1), while IQ had no significant effect on the levels of Nrf2, HO-1, and NQO1. Additionally, Harman, Norharman, or IQ exposure significantly reduced mitochondrial membrane potential and intracellular ATP levels and up-regulated the levels of apoptosis-related genes and proteins. Collectively, our finding suggested that HAAs were neurotoxic, with mechanisms related to induction of oxidative stress and mitochondrial dysfunction.


Reliability and Validity of the Lower Extremity Motor Activity Log for Measuring Real-World Leg Use in Adults With Multiple Sclerosis.
To determine the test-retest reliability and validity of the Lower Extremity Motor Activity Log (LE-MAL) for assessing LE use in the community in adults with multiple sclerosis (MS). Prospective analysis of measures conducted by trained examiners. Participants were evaluated by telephone on several measures of LE use. Adults with MS (N=43). Not applicable. The LE-MAL has 3 subscales (Assistance, Functional Performance, and Confidence). It was administered twice, at least 2 weeks apart. The Multiple Sclerosis Walking Scale (MSWS-12), Patient Determined Disease Steps (PDDS), and Mobility Scale were only administered during the first call. The test-retest reliability of the composite and the 3 subscale LE-MAL scores were high (intraclass correlation, >0.94). The composite and subscale LE-MAL scores were strongly correlated with the MSWS-12, PDDS, and Mobility Scale scores (r=-0.56 to -0.77; P<.001). This initial study suggests that the LE-MAL reliably and validly measures LE use in the community in adults with MS.


[Redescription of d'Apatemon (Apatemon) graciliformis Szidat, 1928 (Trematoda: Strigeidae) with a preliminary note on its life cycle (author's transl)].
Apatemon (Apatemon) graciliformis Szidat, 1928 is redescribed from specimens obtained experimentally in the domestic duck; the larval stages develop in Biomphalaria glabrata in Guadeloupe (French West Indies).


Patient selection for biventricular pacing.
Biventricular pacing improves functional status in the majority of patients with drug-refractory heart failure, dilated cardiomyopathy, and interventricular conduction delay. The aim of this study was to analyze the baseline clinical and functional data of a cohort of patients implanted with a biventricular stimulation system in a single-center experience, to verify if the pathophysiologic characteristics of patients affect outcome, and to determine if preliminary identification of the right candidates for the new therapy is possible with noninvasive parameters. Since March 1999, 52 patients with advanced heart failure (idiopathic cardiomyopathy 50%, ischemic cardiomyopathy 35%, other etiology 15%) and left bundle branch block underwent cardiac resynchronization and were followed prospectively. Paired analysis over mean (+/- SD) follow-up of 348 +/- 154 days showed an overall significant decrease of QRS width (baseline 194 +/- 33.2 msec vs follow-up 159.6 +/- 20.1 msec), New York Heart Association (NYHA) functional class (baseline 3.2 +/- 0.5 vs follow-up 2.3 +/- 0.5), quality-of-life score (baseline 54 +/- 25 vs follow-up 25 +/- 16), and increase of maximal VO2 (baseline 12.6 +/- 2.5 mL/kg/min vs follow-up 15.0 +/- 3.3 mL/kg/min). There were 80% responders (documented, persistent decrease > or = 1 NYHA class) and 20% nonresponders (same NYHA class or decline of status; need for heart transplant; death due to progressive pump failure). No significant differences in baseline clinical and functional variables between the two subgroups were observed. In responders, there was a highly significant global improvement of all variables; in nonresponders, no parameters changed between baseline and follow-up. These data confirm the role of biventricular pacing in improving the functional status of the great majority of a selected patient population having advanced heart failure and left bundle branch block with wide QRS complex. Basal demographic, clinical, and functional characteristics are not helpful in preliminary selection of responders. Simple evaluation of NYHA class confirms favorable outcome (improvement of functional and hemodynamic status).


Associations between nighttime and daytime maximum voided volumes: Relevance for nocturia?
The relationship between maximum voided volumes (MVV) during the night and day is poorly understood. Such measurements are important because they are often used to indicate functional bladder capacity (FBC), a relevant parameter for nocturia. This study examined the association of such nighttime and daytime measurements in men with nocturia. We retrospectively analyzed 356 24-hour voiding diaries showing ≥2 nocturnal voids from 220 men at an outpatient urology clinic. We defined small FBC as MVV ≤ 200 mL. A total of 131 entries demonstrated a nocturnal MVV ≤ 200 mL, of which a majority (98 [74.8%]) also showed a 24-hour MVV ≤ 200 mL (ie, global small FBC), and 33 (25.2%) exceeded the 200 mL threshold during the day (ie, nocturnal-specific small FBC). Correspondingly, among voiding diaries without global small FBC (n = 258), most (225/258 [87.2%]) showed a nocturnal MVV > 200 mL. Data were similar when analyzing only the first complete voiding diary per case, when limiting analyses to those without benign prostatic obstruction, and when limiting analyses to cases with nocturnal polyuria. Nocturia may be attributable to nocturnal-specific small FBC or global small FBC. Although the etiology of nocturnal-specific small FBC remains unclear, it was present in a significant minority of patients with small FBC, thus necessitating more directed research. Conversely, diminished nocturnal MVV was nevertheless relatively uncommon in the absence of global small FBC, such that nocturnal-only voiding diaries may provide a rational alternative for follow-up evaluation in patients with nocturia due to global small bladder capacity.


Laying the foundation for enhancing safety of desmopressin in older people: Validation of capillary blood sodium levels.
We aim to make desmopressin a safe treatment option for (older) patients at risk for hyponatremia, by introducing a new way of sodium monitoring. The goal is to reduce the risk of hyponatremia, enhance patient safety and ultimately introduce self-monitoring of sodium levels. The first step in the aforementioned is to validate capillary sodium. 100 randomly selected patients admitted to the urology department received a single finger prick to collect capillary blood (250 µl) in a lithium-heparin tube. Each patient acted as its own control for the capillary and venous blood sample. Venous and capillary plasma sodium were analyzed by indirect ion-selective electrode measurement. The primary outcome was the agreement between capillary and venous sodium measurements, measured by the intra-class correlation coefficient (ICC). One hundred paired blood samples were obtained of which four were excluded. There was no significant statistical difference observed between venous and capillary sodium (-0.23 mmol/L, p = 0.374). The ICC for single measures between capillary and venous sodium was 0.82 (95% confidence interval 0.75-0.88). Inter-method differences analyzed by a Bland-Altman plot and a Passing-Bablock regression did not reveal a statistically significant difference between both groups. We demonstrated that venous and capillary sodium levels are interchangeable, taken into account the inter- and intravariability between analyses. We provided the first step towards a simple and safe solution for frequent sodium monitoring through a minimal invasive capillary blood collection. The results are of direct clinical relevance to safely use desmopressin in (older) patients at risk.


Exercise increases the plasma antioxidant capacity of adolescent athletes.
The reactive oxygen species produced as a result of exercise might exceed an individual's antioxidant defence system. Various endogenous antioxidants are elevated in adult athletes, resulting in an improved antioxidant capacity. However, little is known about antioxidant defence in adolescents. The purpose of this study was to examine presumed adaptations of antioxidant capacity in exercising adolescents. Trolox-equivalent antioxidant capacity (TEAC), uric acid and nutritional antioxidants were measured in the plasma of 91 male and 98 female athletes (mean age 15.9 +/- 2.0 years) and compared to those of 18 male and 22 female sedentary controls (mean age 16.3 +/- 2.1 years). Antioxidant intake was calculated using 4-day dietary records. Neither male nor female athletes showed differences in alpha-tocopherol, beta-carotene or ascorbate intake compared to controls. Plasma levels of alpha-tocopherol and carotenoids in athletes and controls did not differ either. Nevertheless, athletes of both sexes had higher TEAC values than their respective controls (male athletes 1.48 +/- 0.22 mmol/l vs. male controls 1.23 +/- 0.19 mmol/l, female athletes 1.47 +/- 0.20 mmol/l vs. female controls 1.15 +/- 0.04 mmol/l, p < 0.05). Regular exercise enhances antioxidant capacity in adolescent athletes, independently of their dietary antioxidant intake, which indicates activity-related adaptations.


The nuclear receptor coactivator AIB3 is a modulator of HOMA beta-cell function in nondiabetic children.
The amplified in breast cancer-3 protein (AIB3) is a nuclear coactivator involved in proliferation, apoptosis and development. AIB3 loss of function causes deficient insulin secretion in mice, indicating that AIB3 participates in beta-cell regulation. Our objective was to evaluate genetic variants located on AIB3 associated with beta-cell function in children and to analyse the effect of AIB3 overexpression on gene expression in insulin 1 (INS-1) beta-pancreatic cells. Polymorphisms from AIB3 were genotyped in 148 children with normal or low birthweights for gestational age. The effect of AIB3 overexpression on gene expression was analysed by real-time polymerase chain reaction (PCR) in INS-1 cells. AIB3 variants were associated with homeostasis model assessment of beta-cell function (HOMA-beta-cell) in children with normal or low birthweights for gestational age, but not with HOMA of insulin resistance (HOMA-IR), or with birthweight. AIB3 overexpression increased the expression of genes involved in signalling, such as IRS-1, IRS-2, IGF-II receptor or Foxo1, or of genes that control insulin secretion, such as Cplx2, Glut2 or Kv3.1 in INS-1 cells. Our results suggest that AIB3 contributes to the maintenance of beta-cell function in nondiabetic children and regulates gene expression in INS-1 cells.


An unusual case of cystic fibrosis with pancytopenia due to copper deficiency and blindness caused by vitamin A deficiency: A case-report.
Cystic fibrosis (CF) is a multi-systemic autosomal recessive disease which mostly involves the respiratory, digestive, and reproductive systems, but it can present with various clinical presentations, especially in adulthood. We describe a 19-year-old boy, a known case of CF who presented with less known clinical presentations of CF, blindness, liver cirrhosis, vitamin A deficiency, and pancytopenia.


Molecular insights into the role of amylose/amylopectin ratio on gluten protein organization.
Waxy (WX) and high-amylose (HA) wheat flours have interesting functional and/or nutritional characteristics, but low technological properties compared to regular wheat. Here a set of three wheat lines, having different amylose content but sharing the same varietal background, were compared to shed light on the role of the amylose/amylopectin ratio on the protein conformational changes that lead to gluten formation. Despite the absence of differences in their protein profile, as also confirmed by thiolomic approaches, both WX and HA lines developed a weaker gluten than the control sample. The altered amylose/amylopectin ratio exerts a matrix effect establishing a competition for water with proteins, leading to a different protein structure and three-dimensional organization of the gluten network. These results add a piece to the understanding of the molecular aspects that oversee matrix effects on gluten formation in wheat, which description can be helpful for a rational optimization of the transformation process.


Validation of behavioral phenotypes in the BACHD rat model.
Huntington disease (HD) is a neurodegenerative disorder caused by a polyglutamine expansion in the HTT gene. Various HD animal models have been generated to mimic the motor, cognitive and neuropsychiatric disturbances that affect HD patients. Reproducing disease phenotypes within these models is essential to identify reliable readouts for therapy studies. We validated behavioral phenotypes shown earlier by other research groups in the BACHD rat model, using both previously applied and novel tests for motor, cognitive and anxiety-like behaviors. We first confirmed known BACHD rats' phenotypes in rotarod, open field (OF) and elevated plus maze (EPM) tests. We then assessed the reproducibility of key phenotypes in the model using new tests: cliff hanging, passive avoidance (PA), Morris water maze (MWM), light dark box and light spot tests. We confirmed impaired motor coordination in the rotarod test and reduced activity in the OF. In line with earlier results in BACHD rats using different tests, we showed impaired reversal learning in MWM and decreased anxiety-like behavior with the light spot test supporting the validity of BACHD rats as a model of HD. Results in the EPM, light dark box, cliff hanging and PA tests did not confirm earlier findings. This may depend on phenotype inconsistencies or rather be related to differences in environmental variables, test typology, experimental settings, animal age and chosen behavioral parameters.


Impact of a national hospital evaluation program using clinical performance indicators on the use of surgical antibiotic prophylaxis in Korea.
Clinical performance measurement in surgical antibiotic prophylaxis (SAP) was implemented as part of a national hospital evaluation program (NHEP) in Korea in 2007. This study investigated changes in SAP quality before and after the implementation of clinical performance measurement. The medical records of patients who underwent three types of surgery that were included for assessment in the NHEP (NHEP surgery) - arthroplasty, gastrectomy, and hysterectomy - and two other types of non-NHEP assessment surgery - craniotomy and spine surgery (non-NHEP surgery) - at six hospitals, from August to October in 2006-2008, were retrospectively reviewed. Three clinical indicators of SAP (antibiotic selection, timing of administration of the first dose, and duration) and the development of surgical site infections (SSIs) were compared before and after implementation. A total of 1949 patients were enrolled: 356 arthroplasty, 273 gastrectomy, 615 hysterectomy, 168 craniotomy, and 537 spinal surgery. There were no significant changes in age, gender, wound class, or ASA score for each surgery during the study period. From 2007, SAP quality was significantly improved in NHEP surgery for the three clinical indicators. The timing of administration of the first dose was most markedly improved. SAP quality was also improved in non-NHEP surgery, but not as much as in NHEP surgery. Changes in the SSI rates for each surgery were not significant. Hospital evaluation using clinical performance indicators can considerably improve the use of SAP. Further studies are warranted to investigate whether this hospital evaluation will decrease the development of SSIs.


Comparative Outcomes of Laparoscopic Gastrectomy and Open Gastrectomy for Scirrhous Gastric Cancer: A Multicenter Retrospective Cohort Study.
A multicenter retrospective cohort study was performed to compare the outcomes of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for scirrhous gastric cancer (GC) as a unique subtype also known as type 4 gastric cancer or linitis plastica. Although data on the efficacy and safety of LG as an alternative to OG are emerging, the applicability of LG to scirrhous GC remains unclear. Patients with clinical type 4 GC undergoing gastrectomy at 13 hospitals from 2005 to 2015 were retrospectively reviewed. As the primary endpoint, we compared overall survival (OS) between the LG and OG groups. To adjust for confounding factors, we used multivariate Cox regression analysis for the main analyses and propensity-score matching for sensitivity analysis. Short-term outcomes and recurrence-free survival were also compared. A total of 288 patients (LG, 62; OG, 226) were included in the main analysis. Postoperative complications occurred in 25.8% and 30.1%, respectively (P = 0.44). No significant difference in recurrence-free survival was observed (P = 0.72). The 5-year OS rates were 32.4% and 31.6% in the LG and OG groups, respectively (P = 0.60). The hazard ratio (LG/OG) for OS was 0.98 (95% confidence interval [CI], 0.65-1.43) in the multivariate regression analysis. In the sensitivity analyses after propensity-score matching, the hazard ratio for OS was 0.92 (95% CI, 0.58-1.45). Considering the hazard ratios and 95% CIs for OS, LG for scirrhous GC was not associated with worse survival than that for OG.


Turner syndrome patients with a ring X chromosome.
A patient with clinical features of Turner syndrome and a 45,X karyotype in repeated blood cultures was re-evaluated when she spontaneously entered puberty. A ring X cell line was found in a small proportion of fibroblasts. A review of 35 previously published ring X cases is presented. All are mosaic, the major cell line in most cases being 45,X. There is wide variation in the frequency with which the abnormalities associated with Turner syndrome are found in these patients. All have short stature. Some are sexually developed and fertile. Cardiovascular anomalies are uncommon. This phenotypic variation may have at least two causes: the size of the deleted portion at each end of the X chromosome, and the relative frequency and distribution of 45,X and 46,X,r(X) cell lines in various body tissues.


Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.
The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.


Cadmium-tolerant bacteria: current trends and applications in agriculture.
Cadmium (Cd) is considered a toxic heavy metal; nevertheless, its toxicity fluctuates for different organisms. Cadmium-tolerant bacteria (CdtB) are diverse and non-phylogenetically related. Because of their ecological importance these bacteria become particularly relevant when pollution occurs and where human health is impacted. The aim of this review is to show the significance, culturable diversity, metabolic detoxification mechanisms of CdtB and their current uses in several bioremediation processes applied to agricultural soils. Further discussion addressed the technological devices and the possible advantages of genetically modified CdtB for diagnostic purposes in the future.


Follicular fluid estradiol and progesterone are markers of preovulatory oocyte quality.
Follicular fluid estradiol (FF E2) and progesterone (P) have previously been shown to vary with the maturation of the follicle. A profile of follicular fluid E2 and P was obtained from follicles of 19 preovulatory oocytes, which resulted in normal term pregnancies from single embryo transfers. A narrow band was defined around the linear regression line E2/P = 1.2 X 10(-2) + 1.57 X 10(-4) E2, r = 0.806, P less than 0.01, when E2/P was plotted versus E2 that included 84.2% of these oocytes. Eleven of the 19 pregnancies were clustered between an E2 of 240 to 460 ng/ml and an E2/P ratio of 0.044 to 0.084. Sixty-eight patients undergoing in vitro fertilization and embryo transfer were studied. A significantly greater number of preovulatory follicles from the fertilized, cleaved, and pregnant group (10 of 40) was found in the cluster than from the fertilized, cleaved, but not pregnant group (4 of 46; P = 0.04) and fertilized but not cleaved group (0 of 13; P = 0.04). Significantly more pregnant patients (14 of 20) had a preovulatory follicle within the band than nonpregnant patients (11 of 36) (P less than .02), as well as in the cluster (10 of 20), compared with 4 of 36, respectively (P less than 0.01). It may be concluded that a range of FF E2 and E2/P values define a stage of maturation that is compatible with successful pregnancies.


Synthesis and characterization of 3D CoPt nanostructures.
Cobalt platinum polypod-like nanostructures were synthesized by thermolytic reduction of Pt(acac)2 and Co(CH3COO)2 in oleylamine at 250 degrees C. The as-made CoPt nanopolypods are ferromagnetic, are soluble in nonpolar organic solvents, and reveal a coercive field of 525 and 1200 Oe at room temperature and 5 K, respectively.


Beads phantom for evaluating heterogeneity of SUV on 18F-FDG PET images.
This study aimed to develop a dedicated phantom using acrylic beads for texture analysis and to represent heterogeneous 18F-fluorodeoxyglucose (FDG) distributions in various acquisition periods. Images of acrylic spherical beads with or without diameters of 5- and 10-mm representing heterogeneous and homogeneous 18F-FDG distribution in phantoms, respectively, were collected for 20 min in list mode. Phantom data were reconstructed using three-dimensional ordered subset expectation maximization with attenuation and scatter corrections, and the time-of-flight algorithm. The beads phantom images were acquired twice to evaluate the robustness of texture features. Thirty-one texture features were extracted, and the robustness of texture feature values was evaluated by calculating the percentage of coefficient of variation (%COV) and intraclass coefficient of correlation (ICC). Cross-correlation coefficients among texture feature values were clustered to classify the characteristics of these features. Heterogeneous 18F-FDG distribution was represented by the beads phantom images. The agreements of %COV between two measurements were acceptable (ICC ≥ 0.71). All texture features were classified into four groups. Among 31 texture features, 24 exhibited significant different values between phantoms with and without beads in 1-, 2-, 3-, 4-, 5-, 20-min image acquisitions. Whereas, the homogeneous and heterogeneous 18F-FDG distribution could not be discriminated by seven texture features: low gray-level run emphasis, high gray-level run emphasis, short-run low gray-level emphasis, low gray-level zone emphasis, high gray-level zone emphasis, short-zone low gray-level emphasis, and coarseness. We have developed the acrylic beads phantom for texture analysis that could represent heterogeneous 18F-FDG distributions in various acquisition periods. Most texture features could discriminate homogeneous and heterogeneous 18F-FDG distributions in the beads phantom images.


Moving targets in drug discovery.
Drug Discovery is a lengthy and costly process and has faced a period of declining productivity within the last two decades resulting in increasing importance of integrative data-driven approaches. In this paper, data mining and integration is leveraged to inspect target innovation trends in drug discovery. The study highlights protein families and classes that have received more attention and those that have just emerged in the scientific literature, thus highlighting novel opportunities for drug intervention. In order to delineate the evolution of target-driven research interest from a biological perspective, trends in biological process annotations from Gene Ontology and disease annotations from DisGeNET are captured. The analysis reveals an increasing interest in targets related to immune system processes, and a recurrent trend for targets involved in circulatory system processes. At the level of diseases, targets associated with cancer-related pathologies, intellectual disability, and schizophrenia are increasingly investigated in recent years. The methodology enables researchers to capture trends in research attention in target space at an early stage during the drug discovery process. Workflows, scripts, and data used in this study are publicly available from https://github.com/BZdrazil/Moving_Targets . An interactive web application allows the customized exploration of target, biological process, and disease trends (available at https://rguha.shinyapps.io/MovingTargets/ ).


Clinical profile and outcome of isolated pulmonary embolism: a systematic review and meta-analysis.
Isolated pulmonary embolism (PE) appears to be associated with a specific clinical profile and sequelae compared to deep vein thrombosis (DVT)-associated PE. The objective of this study was to identify clinical characteristics that discriminate both phenotypes, and to characterize their differences in clinical outcome. We performed a systematic review and meta-analysis of studies comparing PE phenotypes. A systematic search of the electronic databases PubMed and CENTRAL was conducted, from inception until January 27, 2023. Exclusion criteria were irrelevant content, inability to retrieve the article, language other than English or German, the article comprising a review or case study/series, and inappropriate study design. Data on risk factors, clinical characteristics and clinical endpoints were pooled using random-effects meta-analyses. Fifty studies with 435,768 PE patients were included. In low risk of bias studies, 30% [95% CI 19-42%, I 2 = 97%] of PE were isolated. The Factor V Leiden [OR: 0.47, 95% CI 0.37-0.58, I 2 = 0%] and prothrombin G20210A mutations [OR: 0.55, 95% CI 0.41-0.75, I 2 = 0%] were significantly less prevalent among patients with isolated PE. Female sex [OR: 1.30, 95% CI 1.17-1.45, I 2 = 79%], recent invasive surgery [OR: 1.31, 95% CI 1.23-1.41, I 2 = 65%], a history of myocardial infarction [OR: 2.07, 95% CI 1.85-2.32, I 2 = 0%], left-sided heart failure [OR: 1.70, 95% CI 1.37-2.10, I 2 = 76%], peripheral artery disease [OR: 1.36, 95% CI 1.31-1.42, I 2 = 0%] and diabetes mellitus [OR: 1.23, 95% CI 1.21-1.25, I 2 = 0%] were significantly more frequently represented among isolated PE patients. In a synthesis of clinical outcome data, the risk of recurrent VTE in isolated PE was half that of DVT-associated PE [RR: 0.55, 95% CI 0.44-0.69, I 2 = 0%], while the risk of arterial thrombosis was nearly 3-fold higher [RR: 2.93, 95% CI 1.43-6.02, I 2 = 0%]. Our findings suggest that isolated PE appears to be a specific entity that may signal a long-term risk of arterial thrombosis. Randomised controlled trials are necessary to establish whether alternative treatment regimens are beneficial for this patient subgroup. None.


Difference in prevalence of gestational diabetes and perinatal outcome in an innercity multiethnic London population.
In order to establish the prevalence of gestational diabetes mellitus (GDM) among ethnic groups residing in the catchment area of one hospital in central London and to assess both the mode of delivery and the baby outcome, we studied retrospectively 703 women selected for screening for GDM during the years 1991 and 1992. While the prevalence of GDM was approximately 2% overall, within the ethnic groups a significant difference was found with Asians and Africans/Afrocaribbeans being four and two times more likely to have GDM, respectively, than Caucasians (P < 0.001). Both maternal obesity and the diagnosis of GDM influenced the time and the mode of delivery, but perinatal mortality and morbidity did not differ significantly between women with GDM and women with normal glucose tolerance. An association between the GTT glucose area and the gestational age and ethnicity adjusted birth weight was observed in women with normal glucose tolerance test, but was absent in the GDM pregnancies, providing indirect evidence that dietary treatment, with or without insulin treatment, altered the maternal milieu in the latter sufficiently to modify fetal growth.


The influence of maternal hypnosis on fetal movements in anxious pregnant women.
The influence of maternal hypnotherapy on fetal body movements in anxious parturients was studied in 25 patients at 35-37 weeks of gestation. There were two groups of patients. Group A consisted of 16 parturients who performed self-hypnosis. Group B consisted of 9 parturients in whom hypnosis was induced by a physician. When compared to a control period of 30 min there was a significant increase in the duration of fetal body movements recorded by ultrasound during 30 min of maternal hypnosis, p less than 0.005 for group A and p less than 0.01 for group B. It is suggested that in anxious parturients fetuses move into a more active state when maternal relaxation is achieved by hypnotherapy.


Immunization coverage of children in a semi-urban village panchayat in Nepal, 1985.
This research project, funded by the Yale International Committee and in cooperation with UNICEF, Nepal, used a questionnaire to survey and assess the immunization status of children 3 years or younger in a semi-urban panchayat. Mothers of children ranging in age from less than 1 month to 3 years were questioned both about immunization status of their children and their own use of health care and specific sources of information. 54% (124/228) of the children had received at least one vaccine and only 4% (10/228) had full coverage with the recommended vaccines (3 doses of DPT and TOPV, one dose of measles and BCG). The mean number of vaccinations for males was significantly greater than that for females (2.12 vs 1.39, P = 0.007, t = 2.80). Male children were twice as likely to have received vaccines as females (76/122, 62% vs 48/106, 45%; Odds Ratio = 2.00). Children born at a hospital were more likely than those born at home to have been vaccinated (23/34, 68% vs 101/194, 52%; P = 0.05, chi 2 = 12.52, d.f. = 2). Most mothers obtained health information from neighbors (38%), radio (22%), or health workers (18%), and 85% of the children were born at home; the majority (164/228, 72%) of the women received assistance during childbirth, 28% of the total reported self delivery. More than 70% of the women felt that vaccinations were good preventive measures. The study results suggest that health education about immunization efforts should be focused on women and these efforts should be intensified.


The effect of manipulation of basal pulsatile insulin on insulin action in Type 2 diabetes.
Disordered insulin pulsatility is associated with insulin resistant states including Type 2 diabetes. However, whether abnormal basal insulin pulses play a role in the pathogenesis of insulin resistance or are simply an associated feature remains undetermined. We investigated this relationship further by studying the effect of overnight (10 h) pulsatile insulin infusion on subsequent insulin sensitivity. We studied 17 Type 2 diabetic patients who underwent one of two protocols. In protocol A (10 patients) on two separate nights we infused insulin 0.1 mU/kg/min either in a constant infusion or in pulses every 13 min. Octreotide (0.43 microg/kg/h) was given to suppress endogenous insulin secretion and physiological replacement of glucagon (30 ng/kg/h) administered. Insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp (2 mU/kg/min) next morning. In protocol B (seven patients), we employed the same experimental procedure but used a basal insulin infusion rate of 0.09 mU/kg/min in 7-min or 13-min pulses. Appropriate pulse patterns were confirmed in each protocol. In protocol A, after overnight infusions, glucose infusion rates required to maintain euglycaemia at steady state hyperinsulinaemia were similar (33.9 +/- 5.2 vs. 31.2 +/- 4.1 micromol/kg/min; P = NS). In protocol B, after overnight infusions the glucose infusion rates required during hyperinsulinaemia were significantly lower during 7-min pulses (39.9 +/- 5.7 vs. 44.7 +/- 5.6 micromol/kg/min; P < 0.05). There was no demonstrable priming effect derived from overnight pulsatile insulin compared with constant insulin infusion on subsequent insulin sensitivity in Type 2 diabetic subjects. The failure of 7-min pulses to exhibit an advantageous effect over 13-min pulses raises questions about the natural frequency of basal insulin pulses and their biological effect.


Carvacrol enhances anti-tumor activity and mitigates cardiotoxicity of sorafenib in thioacetamide-induced hepatocellular carcinoma model through inhibiting TRPM7.
Sorafenib (Sora) represents one of the few effective drugs for the treatment of advanced hepatocellular carcinoma (HCC), while resistance and cardiotoxicity limit its therapeutic efficacy. This study investigated the effect of transient receptor potential melastatin 7 (TRPM7) inhibitor, carvacrol (CARV), on overcoming Sora resistance and cardiotoxicity in thioacetamide (TAA) induced HCC in rats. TAA (200 mg/kg/twice weekly, intraperitoneal) was administered for 16 weeks to induce HCC. Rats were treated with Sora (10 mg/Kg/day; orally) and CARV (15 mg/kg/day; orally) alone or in combination, for six weeks after HCC induction. Liver and heart functions, antioxidant capacity, and histopathology were performed. Apoptosis, proliferation, angiogenesis, metastasis, and drug resistance were assessed by quantitative real time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. CARV/Sora combination significantly improved survival rate, and liver functions, reduced Alpha-Fetoprotein level, and attenuated HCC progression compared with Sora group. CARV coadministration almost obviated Sora-induced changes in cardiac and hepatic tissues. The CARV/Sora combination suppressed drug resistance and stemness by downregulating ATP-binding cassette subfamily G member 2, NOTCH1, Spalt like transcription factor 4, and CD133. CARV boosted Sora antiproliferative and apoptotic activities by decreasing cyclin D1 and B-cell leukemia/lymphoma 2 and increasing BCL2-Associated X and caspase-3. CARV/Sora is a promising combination for tumor suppression and overcoming Sora resistance and cardiotoxicity in HCC by modulating TRPM7. To our best knowledge, this study represents the first study to investigate the efficiency of CARV/ Sora on the HCC rat model. Moreover, no previous studies have reported the effect of inhibiting TRPM7 on HCC.


The effects of temperature and inter-individual variation on the locomotor performance of juvenile turtles.
The effects of temperature on aquatic and terrestrial locomotor performance, including measures of burst speed, endurance, and righting response, the inter-individual correlation between measures of locomotor performance, and the temporal repeatability of performance were assessed in juvenile western painted turtles, Chrysemys picta bellii. Locomotor performance increased as temperature increased, with Q(10) values ranging from 1.33 to 1.98 for burst speed and 2.28 to 2.76 for endurance measures. Righting response performance also increased with temperature. Aquatic and terrestrial measures of locomotor performance were highly correlated; however, righting response was not correlated with any other measure of performance. Measures of terrestrial locomotor performance were highly repeatable over the entire 30-week study period, whereas aquatic locomotor performance was only repeatable through week 12. The righting response was repeatable over a 6-week study period. Both the interindividual variation and temperature effects on locomotor performance likely influences the survival of turtles, especially juveniles, by affecting the length of time turtles are exposed to potential predators and their ability to escape.


Shikimate dehydrogenase structure reveals novel fold.
The structure of shikimate 5-dehydrogenase, the fourth enzyme in the shikimate biosynthesis pathway and a member of a large enzyme family without clear structural peer, reveals a novel topological fold for the substrate binding domain and, through homology modeling, expands the possibilities for antimicrobial and herbicide design.


Patient Characteristics and Treatment Outcomes of Symptomatic Catheter-Related Arterial Thrombosis in Infants: A Retrospective Cohort Study.
To describe the clinical characteristics, outcomes, and adverse events of treatment for symptomatic infant catheter-related arterial thrombosis. Single-center retrospective medical record review of 99 infants (age <365 days) with catheter-related arterial thrombosis, either following indwelling arterial catheter placement or cardiac catheterization, who were treated with anticoagulation over an 8-year span at a pediatric tertiary care center. Outcomes measured include thrombosis progression, bleeding events, and thrombus resolution following the treatment period. Thromboses were secondary to indwelling arterial catheter placement in 51 (51.5%) and cardiac catheterization in 48 (48.5%). The median age at diagnosis of catheter-related arterial thrombosis was 52 days. All patients received therapeutic anticoagulation with either unfractionated heparin or low molecular weight heparin for a maximum of 28 days. Progression of catheter-related arterial thrombosis occurred in 8 (8.1%) patients. One (1%) major and 3 (3%) minor bleeding events occurred within the cohort. Complete thrombus resolution was observed in 60 (60.6%), partial resolution in 33 (33.3%), and no resolution in 6 (6.1%) following the treatment period. Factors associated with complete thrombus resolution included time from intervention to catheter-related arterial thrombosis diagnosis (median of 1 day vs 5 days in those who experienced thrombus resolution vs those who did not, P = .035), and iliac and/or femoral artery involvement (P = .015). Our treatment approach to infant catheter-related arterial thrombosis is safe and effective. Limitations of the study are its retrospective nature with a limited number of patients from a single institution. Additional prospective studies are needed to determine the optimal treatment approach to catheter-related arterial thrombosis in infants.


Dual-Depletion of Intratumoral Lactate and ATP with Radicals Generation for Cascade Metabolic-Chemodynamic Therapy.
Increasing evidence has demonstrated that lactate and adenosine triphosphate (ATP) both play important roles in regulating abnormal metabolism in the tumor microenvironment. Herein, an O2 self-supplying catalytic nanoagent, based on tannic acid (TA)-Fe(III) coordination complexes-coated perfluorooctyl bromide (PFOB) nanodroplets with lactate oxidases (LOX) loading (PFOB@TA-Fe(III)-LOX, PTFL), is designed for cascade metabolic-chemodynamic therapy (CDT) by dual-depletion of lactate and ATP with hydroxyl • OH radicals generation. Benefiting from the catalytic property of loaded LOX and O2 self-supplying of PFOB nanodroplets, PTFL nanoparticles (NPs) efficiently deplete tumoral lactate for down-regulation of vascular endothelial growth factor expression and supplement the insufficient endogenous H2 O2 . Simultaneously, TA-Fe(III) complexes release Fe(III) ions and TA in response to intracellular up-regulated ATP in tumor cells followed by TA-mediated Fe(III)/Fe(II) conversion, leading to the depletion of energy source ATP and the generation of cytotoxic • OH radicals from H2 O2 . Moreover, TA-Fe(III) complexes provide photoacoustic contrast as imaging guidance to enhance therapeutic accuracy. As a result, PTFL NPs efficiently accumulate in tumors for suppression of tumor growth and show evidence of anti-angiogenesis and anti-metastasis effects. This multifunctional nanoagent may provide new insight for targeting abnormal tumor metabolism with the combination of CDT to achieve a synergistic therapeutic effect.


The Swedish version of the attitude towards pressure ulcer prevention instrument for use in an operating room context (APUP-OR): A nationwide psychometric evaluation.
To assess operating room (OR) nurses' attitudes towards pressure ulcer prevention, the Attitude towards Pressure Ulcer Prevention (APuP) instrument was developed. The aim of this study was to psychometrically evaluate the Attitude towards Pressure Ulcer Prevention (APuP) instrument in a Swedish OR context. A psychometric evaluation study was conducted, using a convenience sample, between February and August 2020. Validity (content, construct, discriminatory power) and reliability (stability and internal consistency) were evaluated. The first survey (test) was completed by 284 Swedish OR nurses, of whom n = 50 (17.6%) completed the second survey (retest). A Principal Component Analysis was conducted for the 13-item instrument. The KMO value for this model was 0.62. Bartlett's test for sphericity was statistically significant (p 0.001). Five factors were identified which accounted for 56% of the variance in responses related to attitudes toward pressure ulcer prevention. The Cronbach's α for the instrument "attitude towards Pressure Ulcer Prevention" was 0.66. The intraclass correlation coefficient was 0.49 (95% CI = 0.25-0.67). This Swedish version of the APuP- OR is the first step in the development of an instrument to measure OR nurses' attitudes towards PU prevention in a Swedish OR context. The reliability of the instrument was low and the validity moderate. A larger sample and the revision or addition of items related to the context of the operating room should be considered in order to confirm aspects of the psychometric properties.


Subcutaneous transposition of the spleen enhances the survival rate following 90% hepatectomy in rats.
The effects of subcutaneous transposition of the spleen (STS) on the survival rate following 90% hepatectomy were investigated in rats. The survival rate was significantly higher in the STS group than in the non-STS group. Light microscopy enabled us to note that congestion in the terminal portal veins and sinusoids occurred either slightly earlier or to a higher degree in the non-STS group.


Centrally administered orexin-A activates corticotropin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus and central amygdaloid nucleus of rats: possible involvement of central orexins on stress-activated central CRF neurons.
We examined the effects of centrally administered orexin-A on corticotropin-releasing factor (CRF)-containing neurons in the hypothalamic paraventricular nucleus (PVN) and the central amygdaloid nucleus (CeA) of rats, using dual immunostaining for CRF and Fos. Ninety minutes after intracerebroventricular administration of orexin-A, approximately 96% and 45% of CRF-containing neurons expressed Fos-like immunoreactivity (LI) in the PVN and the CeA, respectively. We also examined the effects of immobilized stress and cold exposure on orexin-A-containing neurons in the rat hypothalamus using dual immunostaining for orexin-A and Fos. After immobilized stress for 20 min and cold exposure at 4 degrees C for 30 min, approximately 24% and 15% of orexin-A-containing neurons expressed Fos-LI, respectively. These results suggest that orexins in the central nervous system may be involved in the activation of central CRF neurons induced by stress.


Does Bienertia cycloptera with the single-cell system of C(4) photosynthesis exhibit a seasonal pattern of delta (13)C values in nature similar to co-existing C (4) Chenopodiaceae having the dual-cell (Kranz) system?
Family Chenopodiaceae is an intriguing lineage, having the largest number of C(4) species among dicots, including a number of anatomical variants of Kranz anatomy and three single-cell C(4) functioning species. In some previous studies, during the culture of Bienertia cycloptera Bunge ex Boiss., carbon isotope values (delta(13)C values) of leaves deviated from C(4) to C(3)-C(4) intermediate type, raising questions as to its mode of photosynthesis during growth in natural environments. This species usually co-occurs with several Kranz type C(4) annuals. The development of B. cycloptera morphologically and delta(13)C values derived from plant samples (cotyledons, leaves, bracts, shoots) were analyzed over a complete growing season in a salt flat in north central Iran, along with eight Kranz type C(4) species and one C(3) species. For a number of species, plants were greenhouse-grown from seeds collected from the site, in order to examine leaf anatomy and C(4) biochemical subtype. Among the nine C(4) species, the cotyledons of B. cycloptera, and of the Suaeda spp. have the same respective forms of C(4) anatomy occurring in leaves, while cotyledons of members of tribe Caroxyloneae lack Kranz anatomy, which is reflected in the delta(13)C values found in plants grown in the natural habitat. The nine C(4) species had average seasonal delta(13)C values of -13.9 per thousand (with a range between species from -11.3 to -15.9 per thousand). The measurements of delta(13)C values over a complete growing season show that B. cycloptera performs C(4) photosynthesis during its life cycle in nature, similar to Kranz type species, with a seasonal average delta(13)C value of -15.2 per thousand.


Dosimetric Predictors of Radiation-Induced Vaginal Stenosis After Pelvic Radiation Therapy for Rectal and Anal Cancer.
Although vaginal stenosis (VS) is a recognized toxicity in women who receive pelvic radiation therapy (RT), the relationship between RT dose and the volume and extent of toxicity has not been analyzed. We modeled this relationship to identify predictors of VS. We evaluated 54 women, aged 29 to 78 years, who underwent pelvic RT for rectal or anal cancer during 2008 to 2011 and were enrolled in a prospective study evaluating vaginal dilator use. Maximum dilator size was measured before RT (baseline) and 1 month and 12 months after RT. Dilator use was initiated at 1 month. The difference (D) in dilator size before and after RT was recorded. Those with D ≤-1 were classified as having VS (n=35); those with D ≥0 were classified as having no VS (n=19 at 1 month). Dose-volume parameters were extracted, and the generalized equivalent uniform dose (gEUD) was used to build a predictive model. The mean vaginal doses were 50.0 Gy and 36.8 Gy for anal and rectal cancer patients, respectively. One month after RT, a gEUD model using a wide range of a values suggests that sparing of vaginal volume to a low dose may be important. When gEUD (a = -1) was <35 Gy and the mean vaginal dose was <43 Gy, severe VS was reduced (P=.02). A 1-year analysis suggests increasingly negative D values with increasing mean dose. However, patients with compliance <40% were more likely to have toxicity. Vaginal stenosis is influenced by multiple RT dose-volume characteristics. Mean dose and gEUD constraints together may reduce the risk of severe VS. Patients receiving higher mean vaginal doses should have greater compliance with dilator therapy to minimize risk of toxicity. Further validation with independent datasets is needed.


MiR-29a-3p negatively regulates circulating Tfh memory cells in patients with Graves' disease by targeting ICOS.
MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate genome expression posttranscriptionally and are involved in autoimmune diseases. Previous studies have indicated that follicular helper T (Tfh) cells play a critical role in the pathogenesis of Graves' disease (GD). However, the molecular mechanisms that contribute to circulating Tfh memory cell response in GD patients remain incompletely understood. This study aimed to investigate the role of miRNAs on circulating Tfh memory cells in GD patients. Herein, our data showed that the proportion of circulating Tfh memory cells, the transcript levels of IL-21, and the plasma concentrations of IL-21 were increased in the peripheral blood from GD patients. We also found that inducible co-stimulator (ICOS) expression, an important molecule expressed on Tfh cells, were significantly augmented in the peripheral blood mononuclear cells (PBMCs) from GD patients and positively correlated with the percentage of circulating Tfh memory cells and the transcript levels of IL-21 in GD. Intriguingly, miRNA sequencing screened miR-29a-3p expression was downregulated and inversely correlated with ICOS expression and the frequency of circulating Tfh memory cells in patients with GD. Luciferase assay demonstrated that ICOS was the direct target gene of miR-29a-3p, and miR-29a-3p could inhibit ICOS at both transcriptional and translational levels. Overexpression of miR-29a-3p reduced the proportion of circulating Tfh memory cells. Moreover, miR-29a-3p expression negatively correlated with serum concentrations of TSH receptor antibody (TRAb) in GD patients. Collectively, our results demonstrate that miR-29a-3p emerges as a post-transcriptional brake to limit circulating Tfh memory cell response in GD patients and may be involved in the pathogenesis of GD.


Establishment of Bisegmented and Trisegmented Reverse Genetics Systems to Generate Recombinant Pichindé Viruses.
Pichindé virus (PICV), isolated from rice rats in Colombia, South America, is an enveloped arenavirus with a bisegmented RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein (GPC). This article describes the successful development of reverse genetics systems to generate recombinant PICV with either a bisegmented or trisegmented genome. We have successfully demonstrated that these systems can generate high-titered and genetically stable replication-competent viruses from plasmid transfection into appropriate cell lines. These systems demonstrate the power and versatility of reverse genetic technology to generate recombinant arenaviruses for use in pathogenesis studies and as new viral vaccine vectors.


Idiopathic retroperitoneal fibrosis.
We treated a patient with idiopathic retroperitoneal fibrosis accompanied by right ureteral constriction. Pyelography, ureterography, and abdominal CT scan were pertinent diagnostics. Close collaboration between the surgeon and the urologist is required when attempting to treat such patients.


Neuropeptide Y suppresses glucose utilization in the dorsal optic tectum towards visual stimulation in the toad Bombina orientalis: a [14C]2DG study.
Neuropeptide Y (NPY) experimentally administered to the surface of the optic tectum in visually stimulated fire bellied toads diminishes local glucose utilization in the retinorecipient tectal laminae. Strong NPY-induced suppression of tectal glucose utilization was found even when visual retinal input to the tectum was boosted pharmacologically under systemic apomorphine treatment. These novel results on the local cerebral energy metabolism contribute to the concept that NPY controls retinotectal visual processing via an inhibitory mechanism.


Contralateral Inferior Alveolar Nerve Transposition for Simultaneous Dental Implant Placement on a Unilateral Reconstructed Mandible: A Case Report With a 7-Year Follow-Up.
This case report describes an unusual case of implant treatment after contralateral inferior alveolar nerve transposition (IANT) on a unilateral reconstructed mandible due to gunshot trauma with a 7-year follow-up. The patient had an edentulous atrophic mandible and underwent large bone reconstruction on the left side. The irregular passage of the right inferior alveolar nerve was within 1-2 mm of the superior aspect of the mandible, passed through the midline, and was nearly exposed under the oral mucosa at the left anterior part of the mandible, which prevented the placement of conventional implants. Consequently, right IANT followed by iliac onlay bone grafting was undertaken under general anesthesia to create a sufficient bone volume for implant placement. Four implants were installed simultaneously on the augmented bone. After a 2-month waiting period, soft tissue graft placement and vestibuloplasty were performed. The patient was scheduled for a continuous follow-up for the next 7 years. After 3 years, the bar-retained supporting system was replaced with the new CAD/CAM milled bar system on the same 4 implants. The 4 implants presented good initial stability (>35 N/cm), and radiographic evaluation showed osseointegration around all 4 implants. The patient experienced lip numbness in the first 5 days postoperatively but recovered by 97% after 2 months. After a 7-year follow-up, the result remained satisfactory with no sign of bone loss around any of the 4 implants, and the prosthesis functioned well and was stable and esthetically satisfactory. In conclusion, an immediate implant placement procedure after a complex surgery involving unilateral IANT and iliac onlay bone grafting remains challenging, especially when the patient has extensive bone defects or an atrophic mandible. However, a successful long-term outcome can be achieved with appropriate perioperative and postoperative care.


Deletion of iscR stimulates recombinant clostridial Fe-Fe hydrogenase activity and H2-accumulation in Escherichia coli BL21(DE3).
Proteins that catalyze H2-pathways often contain iron-sulfur (Fe-S) clusters and are sensitive to O2. We tested whether deletion of the gene encoding the transcriptional negative regulator, IscR, could enhance the ability of Escherichia coli BL21 to synthesize active recombinant H2-pathway components and stimulate ferredoxin-dependent H2-accumulation in the presence or absence of oxygen. Under anoxic conditions, deletion of iscR stimulated recombinant Fe-Fe hydrogenase activity threefold, whilst plasmid-based overexpression of the isc operon had no effect on hydrogenase activity. After cultivation with 21% (v/v) O2 in the headspace, no recombinant hydrogenase activity was observed in soluble extracts of wild-type BL21, although low levels of activity could be observed in the DeltaiscR strain (700-fold lower than anoxic conditions, 180-fold greater than the limit of detection). Under closed batch conditions starting with 5% (v/v) O2, DeltaiscR strains displayed fivefold greater levels of total hydrogenase activity and recombinant ferredoxin-dependent H2-accumulation relative to the control strain. In cultures starting with 10% (v/v) O2, H2-accumulation was stimulated 35-fold relative to the control. DeltaiscR strains displayed enhanced synthesis and activity of integral H2-pathway components under all tested conditions and enhanced H2-accumulation under partially oxic conditions. Deletion of iscR is, therefore, a useful strategy to stimulate H2-production, particularly if the hydrogenase catalyzes the rate-limiting reaction.


National trends in hospital readmission following transsphenoidal surgery for pituitary lesions.
Several institutions recently published their experiences with unplanned readmissions rates after transsphenoidal surgery for pituitary lesions. Readmission rates on a national level, however, have not been explored in depth. We investigated nationwide trends in this procedure and associated independent predictors, costs, and causes of 30-day readmission. The Nationwide Readmissions Database was queried to identify patients 18 and older who underwent transsphenoidal surgery for pituitary lesion resection (2010-2015). National trends and statistical variances were calculated based on weighted, clustered, and stratified sample means. Of the weighted total of 44,759 patients treated over the 6-year period, 4658 (10.4%) were readmitted within 30 days. Readmission rates did not change across the survey period (P = 0.71). Patients readmitted had a higher prevalence of comorbidities than those not readmitted (82.5% vs. 78.4%, respectively, P < 0.001), experienced more postoperative complications (47.2% vs. 31.8%, P < 0.001), and had a longer length of stay (6.59 vs. 4.23 days, P < 0.001) during index admission. The most common causes for readmission were SIADH (17.5%) and other hyponatremia (16.4%). Average total readmission cost was $12,080 with no significant trend across the study period (P = 0.25). Predictors for readmission identified included diabetes mellitus, psychological disorders, renal failure, and experiencing diabetes insipidus during the index admission. Unplanned readmission is an important quality metric. While transsphenoidal pituitary surgery is a relatively safe procedure, 30-day readmission rates and costs have not declined. Future studies on institutional protocols targeting these identified predictors to prevent readmission are necessary to decrease readmission rates on a national scale.


The role of maturation and visual experience in the development of eye alignment in cats.
In the developing kitten, the alignment of the pupils changes from strongly divergent to almost parallel. The visual axes, however, seem to stay almost parallel throughout this period. The infeluence of early visual experience on this development is examined in the present study. The results suggest that the develpment of eye alignment is not controlled by visual experience, but depends on maturational processes, and that normal visual input serves only to halt these processes at the appropriate time.


A lily membrane-associated NAC transcription factor LlNAC014 is involved in thermotolerance via activation of the DREB2-HSFA3 module.
The NTL (NAC with transmembrane motif 1-like) transcription factors with a conserved transmembrane motif are members of the NAC family and are important in plant development and in response to stress. However, knowledge of their regulatory pathways is scarce, especially under heat stress. Here, we cloned and identified a novel lily (Lilium longiflorum) NTL gene, LlNAC014, that increases thermotolerance. High temperature repressed LlNAC014 expression but activated its protein. LlNAC014 contained a typical transmembrane motif at its far C-terminus and was normally located on membranes, but under heat stress it entered the nucleus as a transcription factor. LlNAC014 also has a transactivation domain at its C-terminus, and its active form, LlNAC014ΔC, could function as a trans-activator in both yeast and plant cells. LlNAC014ΔC overexpression in lily and Arabidopsis increased thermotolerance, and also caused growth defects; silencing LlNAC014 in lily decreased thermotolerance. LlNAC014ΔC could constitutively activate the heat stress response by inducing the expression of heat-responsive genes, some of which were dependent on the HSF (heat stress transcription factor) pathway. Further analysis showed that LlNAC014 was a direct regulator of the DREB2-HSFA3 module, and bound to the CTT(N7)AAG element in the promoters of LlHSFA3A, LlHSFA3B, and LlDREB2B to activate their expression. Thus, LlNAC014 increased thermotolerance by sensing high temperature and translocating to the nucleus to activate the DREB2-HSFA3 module.


EMT-Related Gene Signature Predicts the Prognosis in Uveal Melanoma Patients.
Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults. Epithelial-mesenchymal transition (EMT) is an essential regulator of the UVM's immune microenvironment. However, the precise role of EMT in UVM remains to be explored and the development of a related treatment strategy is urgently needed. Multiomics data and clinical information for TCGA-UVM were used to identify the EMT subtypes and analyze their regulatory role in the immune microenvironment in UVM. A machine-learning method based on the identified subtypes was utilized to construct the EMT feature-based prognostic model. External validation cohorts GSE84976 and GSE22138 were employed to validate the model's robustness. Immunotherapy cohort IMvigor210 was used to explore the model's potential to predict immunotherapy responsiveness. Two EMT subtypes were identified in UVM. The role of EMT in shaping the immune microenvironment and regulating cancer-immunity circle of UVM was analyzed. A robust prognostic model was presented and validated to predict patient prognosis. The model also predicted patient's immune features and immunotherapy responsiveness. The EMT-mediated immune features in UVM were illustrated, providing a reliable model to facilitate precise UVM treatment. This research may assist in decision-making during clinical UVM therapy.


Mother-child communication and maternal depressive symptoms in families of children with cancer: integrating macro and micro levels of analysis.
This study examines associations between maternal depressive symptoms and macro- and micro-level aspects of mothers' communication about their children's cancer. Mothers reported depressive symptoms after diagnosis or relapse (child mean age = 10.4 years; 53% male). Mother-child dyads (N = 94) were subsequently observed discussing the child's cancer and maternal communication was coded. Macro-level indicators (positive and negative communication) were associated with certain micro-level indicators of communication (topic maintenance, reflections, reframes, and imperatives). Higher depressive symptoms predicted lower positive communication and higher negative communication. Maternal reflections and imperatives predicted positive communication, and topic maintenance and reframes predicted negative communication, beyond child age, family income, and depressive symptoms. Findings suggest concrete targets for improving communication in families after diagnosis or relapse.


A new technique in Asian nasal tip plasty: Non-incisional double-layered conchal cartilage graft.
The columellar strut graft based on the use of back-to-back autogenous conchal cartilage is one of the most commonly employed invisible grafts used for nasal tip projection. This graft provides an effective means of achieving nasal tip projection but is limited by its flexibility, especially with respect to cephalic rotation. We designed an effective technique that addresses these limitations. A total of 38 patients received augmentation rhinoplasty with non-incisionally bent double-layered conchal cartilage columellar strut graft with nasal tip onlay graft. Projection and location of the nasal tip, nasal length, and nasolabial angle were measured using lateral view photographs. Pre- and postoperative results were compared. Pre- and postoperative nasal tip projection ratios and nasal tip location ratios were significantly different. Revision surgery was not required in any case and no direct graft-associated complication occurred. We performed tip plasty with a modified columellar strut graft, that is, a non-incisionally bent double-layered conchal cartilage columellar strut graft. In most cases, this method resulted in a significant tip projection increase.


Differential perseverations in verbal retrieval related to anterior and posterior left hemisphere lesions.
Sixty-two patients with focal cerebral lesions and 11 control patients were examined using alternating tasks of learning, generation, and recall of words beginning with "K." The results supported the hypothesis that "recurrent" and "stuck-in-set" varieties of perserveration are related to posterior and anterior left hemisphere lesions, respectively. Patients with left posterior lesions usually failed to suppress the expression of previously generated words in the subsequent generation task, whereas patients with left anterior lesions stated a greater number of new (incorrect) words in the recall of previously learned words, presumed to indicate stuck-in-set perseveration of the previous generation performance.


A meta-analysis on small intestinal bacterial overgrowth in patients with different subtypes of irritable bowel syndrome.
Enteric microbiota is increasingly being recognized as an important factor in the pathogenesis of irritable bowel syndrome (IBS). The reported prevalence of small intestinal bacterial overgrowth (SIBO) in subjects with IBS is highly variable, and there is no consensus on the role of SIBO in different subtypes of IBS, and indications and methods of testing. A comprehensive literature search was performed for studies applying tests for SIBO in subjects with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of SIBO in subjects with IBS using different tests. The odds ratios of SIBO among subjects with IBS as compared with healthy controls using different tests were calculated. Of the available studies (22, 17, 5, and 3 using lactulose and glucose hydrogen breath tests [LHBT and GHBT], jejunal aspirate culture, and more than one tests, respectively) meeting the inclusion criteria, 36.7% (95% confidence interval [CI] 24.2-44.6) had a positive test for SIBO. Patients with IBS were 2.6 (95% CI 1.3-6.9) and 8.3 (95% CI 3.0-5.9) times more likely to have a positive test for SIBO as compared with healthy controls using GHBT and jejunal aspirate culture, respectively. Patients with diarrhea-predominant IBS were more likely to have positive GHBT as compared with the other subtypes. Patients with IBS were more likely to have SIBO as compared with healthy subjects using GHBT and jejunal aspirate culture but not using LHBT. Patients with diarrhea-predominant IBS more often have SIBO.


The structure of the major anthocyanin in Arabidopsis thaliana.
The major anthocyanin in the leaves and stems of Arabidopsis thaliana has been isolated and shown to be cyanidin 3-O-[2-O(2-O-(sinapoyl)-beta-D-xylopyranosyl)-6-O-(4-O-(beta-D-glucopyranosyl)-p-coumaroyl-beta-D-glucopyranoside] 5-O-[6-O-(malonyl) beta-D-glucopyranoside]. This anthocyanin is a glucosylated version of one of the anthocyanins found in the flowers of the closely related Matthiola incana.


Risk of post-polypectomy bleeding after endoscopic mucosal resection in patients receiving antiplatelet medication: comparison between the continue and hold groups.
Current guidelines recommend continuing aspirin and discontinuing clopidogrel for colon polypectomy, but evidence for endoscopic mucosal resection (EMR) is insufficient. We aimed to assess post-polypectomy bleeding (PPB) in patients receiving antiplatelet agents and underwent EMR for various polyp sizes. A single-center, prospective observational study was performed. Patients who underwent at least one EMR for polypectomy and those who received aspirin or clopidogrel were included. We compared PPB between the antiplatelet hold group (stopped antiplatelet therapy at least 5 days before the procedure) and continue group (antiplatelet therapy was maintained or stopped within 5 days before the procedure). Among patients who underwent EMR, 305 took aspirin (hold group 257, continue group 48) and 77 took clopidogrel (hold group 66, continue group 11). The mean number of polyps was four, and the mean size was 8.6 mm. There was no difference in the major PPB rate between the hold and continue groups among aspirin users (2.0% vs. 4.2%, P = 0.30), but it was significantly higher in the continue group than in the hold group among clopidogrel users (18.2% vs. 0%, P = 0.02). In patient- and polyp-based logistic regression analysis of clopidogrel users, the number of EMRs (OR 2.12, 95% CI 1.16-3.88), polyp size (OR 1.26, 95% CI 1.06-1.49), and continuing clopidogrel (OR 9.75, 95% CI 1.99-47.64) were independent risk factors for PPB. Continuous administration of antiplatelet agents was significantly associated with higher PPB in clopidogrel users, but not in aspirin users. Endoscopists should consider holding clopidogrel if the EMR includes polypectomy.


Mal de Meleda: A Focused Review.
Mal de Meleda is a rare autosomal recessive palmoplantar keratoderma (PPK) disease with an estimated prevalence of 1:100,000. Clinically, the onset of the disease is typically soon after birth and features a transgrediens (plantar surface progressing to dorsal surface) and progrediens (worsening with age) pattern of hyperkeratosis of the palms and soles. The disease can feature other potentially disfiguring effects on the hands and feet that can severely impact function. Histologically, the lesions show hyperkeratosis and acanthosis without epidermolysis in the epidermis, accompanied by perivascular lymphocytic infiltrate in the dermis. Secreted LY6/urokinase-type plasminogen activator receptor (uPAR)-related protein-1 (SLURP-1) genetic mutations are implicated in Mal de Meleda. SLURP-1 is involved in mediation of inflammation as well as keratinocyte apoptosis regulation. Because the disease is so rare, there are no set guidelines for management, but the accepted approach tends to include oral acitretin plus topical keratolytic therapy. Genetic counseling should also be offered. This focused review highlights the clinical and histological features, differential diagnoses, genetic background, and the current thoughts on management of Mal de Meleda.