Who fares worse after liver transplantation? Impact of donor and recipient variables on outcome: data from a prospective study.
Numerous donor and recipient risk factors influence survival after liver transplantation (LT). The aim of this study was to prospectively evaluate the effect of donor and recipient variables on 12-month patient and graft survival after LT. Five hundred forty-six patients underwent LT in a single center (2000-2010). Bilirubin (P=0.006) and cold ischemia time (P=0.002) were predictive of graft loss at 12 months after LT. Model for End-Stage Liver Disease score ≥25 was associated with a lower 12-month graft survival than Model for End-Stage Liver Disease score <15 (P=0.02). Hepatitis C virus (HCV)-positive patients showed a lower survival than HCV-negative patients 12 months after LT (P=0.04), with serum sodium concentration (P=0.01) predictive for graft survival. Donor age demonstrated a trend of prediction (P=0.05) for HCV-positive patient survival. In hepatocellular carcinoma patients, donor age (P=0.02 and 0.02) and use of partial graft (P=0.01 and 0.02) were predictive of patient and graft survival at 12 months after LT. Bilirubin and cold ischemia time are crucial for graft outcome post-LT. Survival in HCV-positive patients is lower than in HCV-negative recipients. Donor age and partial graft use are predictive of patient and graft survival in hepatocellular carcinoma patients.


Fermentation characteristics and protein expression patterns in a recombinant Escherichia coli mutant lacking phosphoglucose isomerase for poly(3-hydroxybutyrate) production.
For the efficient production of poly(3-hydroxybutyrate) (PHB) using recombinant Escherichia coli, it is of primal importance to overproduce NADPH, which is necessary for the PHB synthetic pathway. In order to overproduce NADPH in the pentose phosphate (PP) pathway, a recombinant E. coli was constructed in which the phosphoglucose isomerase ( pgi) gene was knocked out to force the carbon flow into the PP pathway. The fermentation characteristics of the recombinant E. coli mutant lacking pgi were then investigated to determine the effect of overproduction of NADPH on efficient PHB production. It was found that, compared with the parent strain ( E. coli JM109), growth of the E. coli mutant lacking pgi ( E. coli DF11) is repressed due to NADPH overproduction in the PP pathway. Furthermore, repressed cell growth can be recovered to some extent by introducing a NADPH-consuming pathway, such as the PHB synthetic pathway. Efficient PHB production using such recombinant E. coli (DF11/pAeKG1) could be attained by appropriately controlling the glucose concentration in the fermentor. Total gene expression was investigated at the protein level by two-dimensional electrophoresis. Out of 22 differentially expressed proteins, 12 were identified with the aid of MALDI-TOF mass spectrometry. Variations in the accumulation of PHB in the recombinant pgi mutant carrying phb (E. coli DF11/pAeKG1) corresponded to the expression of proteins encoded by rpsA, znuA, fabD, potD, fkpA, gapA, ynaF and ibpA. The unfavorable conditions generated by PHB accumulation in the pgi mutant carrying phb resulted in the highest expression of 30S ribosomal protein S1, which ultimately caused a further increase in soluble protein synthesis.


Clinical Inquiry: Which nonhormonal treatments are effective for hot flashes?
Selective serotonin reuptake inhibitors (SSRIs [fluoxetine, sertraline, paroxetine]) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine, as well as clonidine and gabapentin, reduce hot flashes by about 25% (approximately one per day) in women with and without a history of breast cancer. No studies compare medications against each other to determine a single best option.


Gene expression suggests conserved aspects of Hox gene regulation in arthropods and provides additional support for monophyletic Myriapoda.
Antisense transcripts of Ultrabithorax (aUbx) in the millipede Glomeris and the centipede Lithobius are expressed in patterns complementary to that of the Ubx sense transcripts. A similar complementary expression pattern has been described for non-coding RNAs (ncRNAs) of the bithoraxoid (bxd) locus in Drosophila, in which the transcription of bxd ncRNAs represses Ubx via transcriptional interference. We discuss our findings in the context of possibly conserved mechanisms of Ubx regulation in myriapods and the fly.Bicistronic transcription of Ubx and Antennapedia (Antp) has been reported previously for a myriapod and a number of crustaceans. In this paper, we show that Ubx/Antp bicistronic transcripts also occur in Glomeris and an onychophoran, suggesting further conserved mechanisms of Hox gene regulation in arthropods.Myriapod monophyly is supported by the expression of aUbx in all investigated myriapods, whereas in other arthropod classes, including the Onychophora, aUbx is not expressed. Of the two splice variants of Ubx/Antp only one could be isolated from myriapods, representing a possible further synapomorphy of the Myriapoda.


[Hodgkin's disease variant of Richter's syndrome. Two cases and literature review].
We report the clinical and immunohistological features of two cases of chronic lymphocytic leukaemia (CLL) with Hodgkin's transformation. These cases occurred in a 70-year-old man with a three-year history of CLL and in a 76-year-old man with a few months history of CLL. Microscopic examination showed the presence of large tumor cells with the morphological and immunophenotypic features of classical Hodgkin and Reed-Sternberg (R-S) cells, in a background of otherwise typical B-CLL. The transformation of CLL into large B cell lymphoma (Richter's syndrome) is a well-documented phenomenon. Only rarely does CLL transform into Hodgkin's lymphoma, but this diagnosis is often easy and offers few differential diagnoses. The major points of interest lie in the pathogenetic relationship between CLL and Hodgkin's disease, and in the potential clinical implications of this peculiar condition. Literature on the subject indicates that identical IgH gene rearrangements in micromanipulated R-S and CLL cells have been identified in 7/12 cases. In these patients, the R-S and CLL cells belong to the same clonal population, suggesting a progression from the underlying CLL cells. This group appears to have a poor prognosis, identical to classical Richter's syndrome. In other cases, the R-S cells were often Epstein-Barr virus (EBV) positive and did not share the clonal rearrangements identified in CLL cells, suggesting that Hodgkin's disease in these patients could represent a second malignancy, EBV-related and favored by immunosuppression, associated with a better prognosis.


Alternaria toxins: DNA strand-breaking activity in mammalian cellsin vitro.
Treatment, for 1 h, of cultured Chinese hamster V79 cells, human liver HepG2 cells, and human colon HT-29 cells with theAlternaria toxins alternariol (AOH) and alternariol methyl ether (AME) caused a concentration-dependent induction of DNA strand breaks at concentrations ranging from 5 to 50 micromolar. After treatment for 24 h, DNA strand breaks were observed in HepG2 but not HT-29 cells. Analysis of the 24 h-incubation media of HT-29 cells showed that both toxins were completely conjugated, whereas 75% were still present as unconjugated compounds in the 24 h-media of HepG2 cells. Lysates of both cell types fortified with UDPGA were found to convert both toxins into two glucuronides each, but HT-29 cells exhibited a much high activity than HepG2 cells and gave rise to a different ratio of glucuronides. It is concluded that glucuronidation eliminates the DNA strandbreaking potential of AOH and AME, and that the two glucuronides of eachAlternaria toxin are generated by different UGT isoforms.


Separation of four components of the phosphoenolpyruvate: glucose phosphotransferase system in Vibrio parahaemolyticus.
Four classes of Vibrio parahaemolyticus mutants defective in the phosphoenolpyruvate: glucose phosphotransferase system (PTS) are described. They were phenotypically different, and were defective in different PTS components. The components designated tentatively as II, I, III, and H were separated by gel filtration of a wild-type extract. Component II, which was specific for glucose and found in the particulate fraction, is probably membrane-bound, glucose-specific enzyme II. Both components I and H were soluble proteins, and the latter was relatively heat-stable. Component I was required for phosphorylation of glucose, trehalose, fructose, mannose, and mannitol. Component H was also required for phosphorylating all the above sugars except fructose. These and some additional findings strongly suggest that components I and H correspond to enzyme I and HPr, respectively. Component III, a soluble heat-stable protein, may be equivalent to the sugar-specific factor III found in other organisms, although it seems to participate in phosphorylating two sugars, glucose and trehalose. There were evidences that mutants defective in components I and III were deficient in cyclic adenosine 3',5'-monophosphate synthesis under certain conditions.


Telomerase inhibitor GRN163L inhibits myeloma cell growth in vitro and in vivo.
Human telomerase, the reverse transcriptase which extends the life span of a cell by adding telomeric repeats to chromosome ends, is expressed in most cancer cells but not in the majority of normal somatic cells. Inhibition of telomerase therefore holds great promise as anticancer therapy. We have synthesized a novel telomerase inhibitor GRN163L, a lipid-attached phosphoramidate oligonucleotide complementary to template region of the RNA subunit of telomerase. Here, we report that GRN163L is efficiently taken up by human myeloma cells without any need of transfection and is resistant to nucleolytic degradation. The exposure of myeloma cells to GRN163L led to an effective inhibition of telomerase activity, reduction of telomere length and apoptotic cell death after a lag period of 2-3 weeks. Mismatch control oligonucleotides had no effect on growth of myeloma cells. The in vivo efficacy of GRN163L was confirmed in two murine models of human multiple myeloma. In three independent experiments, significant reduction in tumor cell growth and better survival than control mice was observed. Furthermore, GRN163L-induced myeloma cell death could be significantly enhanced by Hsp90 inhibitor 17AAG. These data provide the preclinical rationale for clinical evaluation of GRN163L in myeloma and in combination with 17AAG.


History of perinatal loss and maternal-fetal attachment behaviors.
Maternal-fetal attachment (MFA) is an important requirement for optimal maternal-infant adaptation. Current studies showed conflicting findings about whether a history of perinatal loss (fetal/neonatal death) affects maternal attachment in pregnancy. "Does a history of perinatal loss affect maternal-fetal attachment behaviors?" One hundred women with and without a history of PL were recruited using a convenience method of sampling, from prenatal care services affiliated to Shahid Behesti University of Medical Sciences. Data collected by questionnaires from a convenience sample of multiparous women in the 3rd trimester of pregnancy with no surviving children were compared with data from a selected cohort of primigravid women. The two groups of women were matched for health and literacy. The data collected included demographic characteristics and responses to 24 questions in five groups of behaviors on the Persian version of Cranly's Maternal-Fetal Attachment Scale. Data were analyzed by SPSS 13 and using t, ANOVA, Chi square, Pearson correlation and Mann-Whitney tests. Finding showed that total score of MFA for women with a history of PL (68.95±9.20%) is not significantly different from this score for women without such a history (71.22±11.75%; p<0.05). Women with a history of PL had a significantly lower score for a subgroup of behaviors "differentiation of self from fetus" compared to women without of a history of PL (78.25 vs. 83.21%; p<0.05). But, there were no statistically significant differences between two groups respecting to other subgroups of behaviors between two groups. In this study, a history of pregnancy loss was found to be associated with disturbances in the group of maternal-fetal attachment behaviors related to "differentiation of self from fetus" in a subsequent pregnancy.


Application of cellulose nanocrystals prepared from agricultural wastes for synthesis of starch-based hydrogel nanocomposites: Efficient and selective nanoadsorbent for removal of cationic dyes from water.
A novel and bio-based hydrogel nanocomposite were developed using reinforcement of starch grafted copolymers of 2-acrylamido-2methyl propane sulfonate and acrylic acid (starch-g-(AMPS-co-AA)) hydrogel with magnetite-functionalized cellulose nanocrystals (MCNCs). The MCNCs-hydrogel was utilized as a proficient and environmentally benign nanoadsorbent for removal of cationic dyes with great capacity and selectivity. Sugar-beet pulp (SBP) was exploited for CNCs production through acid hydrolysis of enzymatic-mediated SBP. Fe3O4 nanoparticles were anchored on CNCs to synthesize MCNCs as the nanofiller of MCNCs/starch-g-(AMPS-co-AA) hydrogel. The synthesis of CNCs, MCNCs and hydrogel nanocomposite were confirmed using FESEM, FTIR, VSM and TGA analyses. Hydrogel nanocomposite showed excellent and reusable capacity for specific adsorption of cationic dyes. The effects of nanoadsorbent dosage, time, pH, dye initial concentration, and temperature on the adsorption were scrutinized for two model cationic dyes (crystal violet (CV) and methylene blue (MB). Adsorption capacities for CV and MB were 2500.0 mg/g and 1428.6 mg/g, respectively.


Diagnosis of nontuberculous mycobacterial lymphadenitis: the role of fine-needle aspiration.
Nontuberculous mycobacterial lymphadenitis often presents a diagnostic challenge. This study aimed to evaluate the role of fine-needle aspiration cytology in the diagnosis of nontuberculous mycobacterial lymphadenitis in children. We conducted a retrospective review of fine-needle aspiration cytology performed in patients < 17 year-old with subacute lymphadenitis from 2003 to 2016 in a tertiary hospital in Spain. Confirmed nontuberculous mycobacterial lymphadenitis (isolation of nontuberculous mycobacterial in culture from fine-needle aspiration cytology or biopsy samples) and probable nontuberculous mycobacterial lymphadenitis ("granulomatous inflammation" in cytopathologic examinations from fine-needle aspiration cytology or biopsy and clinical-epidemiological history compatible with nontuberculous mycobacterial) were selected. Forty-one patients with nontuberculous mycobacterial lymphadenitis were included: 14 confirmed and 27 probable. Fine-needle aspiration cytology was done in all of them. For 34 patients with excised lymphadenopathy, cytopathology from fine-needle aspiration cytology was concordant with biopsy in 100% cases. Culture results were available from 78.0% (32/41) of patients with fine-needle aspiration cytology and from 85.3% (29/34) with excisional biopsy. Among 22 patients with microbiological results from fine-needle aspiration cytology and biopsy, fine-needle aspiration cytology allowed advanced results in concordance with biopsy or with positive isolation not found in biopsy in 90.1% (20/22) of patients. Sensitivity of nontuberculous mycobacterial cultures obtained by fine-needle aspiration cytology compared to biopsy was 45.5% vs. 36.4% (p = 0.07). Two patients with previous skin alterations presented fistulas after fine-needle aspiration cytology (4.9%); no other complications were described.Conclusion: Fine-needle aspiration cytology provides quick cytopathologic information and is an accurate and safe technique for the diagnosis of nontuberculous mycobacterial lymphadenitis, especially in cases with challenging work-up. What is Known: • Nontuberculous mycobacterial (NTM) infection is an important cause of subacute lymphadenitis in children. • Fine-needle aspiration cytology (FNAC) is an available technique for the diagnosis of lymphadenitis of unknown etiology. What is New: • FNAC is an accurate and safe technique for the diagnosis of NTM lymphadenitis in children. • FNAC can provide reliable samples for cytopathological studies and even a better sensitivity for microbiological culture than excisional biopsy in the study of suspected NTM lymphadenitis.


Effect of varying X-ray tube voltage and additional filtration on image quality and patient dose in digital radiography system.
This study investigated the effect of varying x-ray tube voltage and additional filtration thicknesses on radiation dose and image quality in digital radiography system. The polymethylmethacrylate (PMMA) phantoms of different thicknesses simulating both the adult chest and abdomen and the pediatric patient's chest examinations were used. X-ray tube voltage range of 70-125 kVp was used for adult patient chest radiography, 70-100 kVp for adult patient abdominal radiography, and 50-70 kVp for pediatric 1-year-old chest examination. 0.1-0.3 mm Cu and 1.0 mm Al filters were used as additional filters. Patient doses were measured with an ionization chamber, considering the irradiation parameters recommended for radiographic examinations performed in radiology clinics in the EUR 16260 protocol. The Entrance Skin Dose (ESD) was calculated from the air kerma value measured at the entrance surface of the PMMA phantoms. Effective dose values were calculated by employing PCXMC 2.0 program. For image quality evaluations, CDRAD, LCD-4, Beam stop and Huttner test object used together with PMMA phantoms and Alderson RS-330 Lung/Chest phantom were used. Figure of Merit (FOM), which allows quantitative assessment in terms of image quality and patient dose, has been calculated. Based on the calculated FOM values were evaluated at the tube voltages and additional filter thicknesses recommended in the EUR 16260 protocol. Entrance Skin Dose and Inverse Image Quality Figure (IQFinv) value obtained from contrast detail analysis decreased with increasing filter thickness and tube voltage. Decrease in ESD and IQFinv with increasing tube voltage without additional filter was 56% and 21% for adult chest radiography, 69% and 39% for adult abdominal radiography and 34% and 6% for 1-year-old pediatric chest radiography. When calculated FOM values are examined, it can be recommended to use a 0.1 mm Cu filter at 90 kVp and a 0.1 mm Cu + 1.0 mm Al filter at 125 kVp for adult chest radiography. For adult abdominal radiography, 0.2 mm Cu filter at 70 and 80 kVp and 0.1 mm Cu filter at 90 and 100 kVp were found to be appropriate. It was determined that the appropriate additional filter at 70 kVp for 1-year-old chest radiography was 1.0 mm Al+0.1 mm Cu.


Impact of renal function on cardiovascular events in elderly hypertensive patients treated with efonidipine.
This study evaluated the impact of renal function on cardiovascular outcomes in elderly hypertensive patients enrolled in the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive patients. The patients were randomly assigned to either a strict-treatment group (target systolic blood pressure (BP) <140 mm Hg, n=2212) or a mild-treatment group (target systolic BP, 140 to <160 mm Hg, n=2206), each with efonidipine (a T/L-type Ca channel blocker)-based regimens. Cardiovascular events (stroke, cardiovascular disease and renal disease) were evaluated during the 2-year follow-up period following the prospective randomized open-blinded end-point method. Estimated glomerular filtration rate (eGFR) was elevated throughout the trial period in both the strict-treatment (59.4-62 ml min⁻¹ per 1.73 m²) and the mild-treatment group (58.8-61.4 ml min⁻¹ per 1.73 m²). This tendency was also observed in diabetic patients and patients aged ≥75 years, with baseline eGFR<60 ml min⁻¹ per 1.73 m². Baseline eGFR (<60 vs. ≥60 ml min⁻¹ per 1.73 m²) had no definite relationship with the incidence of cardiovascular events, nor did the level of BP control. Proteinuria at the time of entry into the study, however, was significantly correlated with cardiovascular event rates (7.1%), an association that was more apparent in patients with eGFR<60 ml min⁻¹ per 1.73 m² (8.2%). Furthermore, the event rate was more elevated in patients with greater declines in eGFR and was amplified when the baseline eGFR was <60 ml min⁻¹ per 1.73 m². In conclusion, the rates of decline of renal function and proteinuria constitute critical risk factors for cardiovascular events in elderly hypertensive patients, trends that are enhanced when baseline eGFR is diminished. Furthermore, the fact that efonidipine-based regimens ameliorate renal function in elderly hypertensive patients with chronic kidney disease may offer novel information on the mechanisms of cardiovascular protection.


Mendelian Randomization Analysis Identifies CpG Sites as Putative Mediators for Genetic Influences on Cardiovascular Disease Risk.
The extent to which genetic influences on cardiovascular disease risk are mediated by changes in DNA methylation levels has not been systematically explored. We developed an analytical framework that integrates genetic fine mapping and Mendelian randomization with epigenome-wide association studies to evaluate the causal relationships between methylation levels and 14 cardiovascular disease traits. We identified ten genetic loci known to influence proximal DNA methylation which were also associated with cardiovascular traits after multiple-testing correction. Bivariate fine mapping provided evidence that the individual variants responsible for the observed effects on cardiovascular traits at the ADCY3 and ADIPOQ loci were potentially mediated through changes in DNA methylation, although we highlight that we are unable to reliably separate causality from horizontal pleiotropy. Estimates of causal effects were replicated with results from large-scale consortia. Genetic variants and CpG sites identified in this study were enriched for histone mark peaks in relevant tissue types and gene promoter regions. Integrating our results with expression quantitative trait loci data, we provide evidence that variation at these regulatory regions is likely to also influence gene expression levels at these loci.


Advances in the Acute and Preventive Treatment of Pediatric Migraine.
Headaches are common in children and adolescents. Treatments for debilitating migraine are often not FDA approved or lack evidence of efficacy for children. This narrative review looks at the evidence for acute and preventative pharmacologic and non-pharmacologic treatment of pediatric migraine, as well as reviewing any recent or ongoing clinical trials. Studies have been published on pharmacological treatments for headache, as well as non-pharmacological treatments. Recent findings in pediatric migraine using onabotulinumtoxinA, calcitonin gene related peptide antagonists, interventional procedures, and devices are reviewed. Pharmacologic as well as non-pharmacologic approaches for the prevention and treatment of migraine show safety and efficacy data that is promising. These treatments should be incorporated in a multi-modal approach to the management of pediatric migraine. Continued studies, prospective and randomized, are needed to further assess these newer treatments for migraine in the pediatric setting.


The effects on performance of two antidepressants, alone and in combination with diazepam.
1. Ninety healthy adult men participated in a study of the effects on performance of 60 mg fluoxetine, 50 mg amitriptyline or placebo, alone and in combination with 5 mg diazepam or placebo. 2. In a 2X3 factorial design study, groups of 15 Ss received one of six possible treatment combinations. 3. Ss were tested with a battery of laboratory tests at two post-dosing times. 4. Amitriptyline impaired the performance of all tasks. When diazepam was added to the amitriptyline treatment, the impairment of three tasks increased. Diazepam alone produced impairment on two measures. 5. Fluoxetine alone impaired no task; some impairment occurred with the fluoxetine-diazepam combination.


Rapid development of micronodular cirrhosis following small bowel by-pass for obesity. A form of iatrogenic nutritional cirrhosis?
Two cases of rapidly progressive fatal liver disease in females after by-pass surgery for obesity are reported. Histologically the livers are similar to the florid cirrhosis of the alcoholic described by Popper and Szanto. It is postulated that the nutritional disturbance, including protein deficiency, and large amounts of fatty acids delivered to the liver from the fat depots, results in fatty metamorphosis, the Mallory bodies and finally cirrhosis. Bacterial toxins from the excluded loop of intestine may contribute to this process.


Evaluation of radial peripapillary capillary density in patients with newly diagnosed iron deficiency anemia.
To investigate the effects of iron deficiency anemia (IDA) on radial peripapillary capillary vessel density (RPCvd) and retinal nerve fiber layer (RNFL) thickness. Forty patients with IDA, and 46 healthy participants, were enrolled in this study. Optical coherence tomography angiography was used to determine RNFL thickness and RPCvd measurements. In addition, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and ferritin laboratory values were evaluated. Analysis of retinal regions (whole images, peripapillary, superior-hemi, inferior-hemi, inferior-nasal, inferior-temporal, temporal-inferior, temporal-superior, superior-nasal) showed that RPCvd values were significantly lower in patients with IDA compared to the control group values (p < 0.05 for all). However, there were no significant differences in RNFL thickness values between the IDA patient group and the control group (p > 0.05 for all). In addition, there were significant positive correlations between RPCvd values and hematological values for Hb, HCT, MCV, MCH, MCHC, and ferritin. It is important to identify changes in retinal vascularity to prevent possible ocular problems in patients with IDA. Specifically, the significant positive correlations between RPCvd values and hematological values suggest that anemia treatment is important for optic nerve perfusion.


[Experience in treating patients with microsporosis of the smooth skin with involvement of the lanugo hair].
Seventy-four patients with smooth skin microsporosis with involvement of the lanugo were treated with a 10% quinosol solution in dimexid. The foci were smeared twice a day. Resolution of the clinical manifestations and elimination of the fungi were achieved in 5-14 days, in 9.4 days on an average. This therapeutic method does not involve manual epilation and oral griseofulvin, no side effects were recorded.


Comparative endometrial histology in postmenopausal women with sequential hormone replacement therapy of estradiol and, either chlormadinone acetate or micronized progesterone.
To determine the endometrial response in postmenopausal women treated with a sequential hormone replacement therapy (HRT) of estradiol and, either chlormadinone acetate (CA) or micronized progesterone (MP). Three hundred and thirty-six postmenopausal women with a normal endometrium were randomized in the double-blind study. All patients received percutaneous estradiol 1.5 mg/day from day 1 to day 24 and either CA 10 mg/day or oral MP 200 mg/day from day 10 to day 24. The total duration of treatment was 18 months. Endometrial biopsies were performed before treatment and between day 18 and day 24 of the 18th month of HRT. Of the 336 patients selected, 317 had a biopsy at inclusion. Of them, 244 patients (124 in the CA group and 120 in the P group) were suitable for evaluation for analysis at the 18th month. Insufficient sampling occurred in 33.9% in the CA group and 60% in the MP group (probably atrophic). No case of hyperplasia could be reported in both groups. The endometrium was atrophic in 19.5 versus 27.1%, proliferative in 3.7 versus 8.3% and secretory in 76.8 versus 62.5% in CA and MP groups, respectively. It was possible to see histological differences induced by the two progestins. The CA endometria showed fewer glands lined by a cubo-cylindrical epithelium, with an edematous stroma, compared to the MP endometria which had more glands lined by a cylindrical epithelium, stroma being poorly edematous. These figures varied in intensity due to the length of progestative impregnation, predecidualization occurring later in the CA group, with distended capillaries. These results show that CA 10 mg/day is a powerful progestin compared to MP 200 mg/day, on weakly estradiol-primed endometria, giving a molecule-specific histological aspect with a good endometrial safety.


Assessment of the lacrimal recess of the maxillary sinus on computed tomography scans.
To assess the frequency of the lacrimal recess in the maxillary sinus (MS) in computed tomography (CT) of the paranasal sinuses. CT of the paranasal sinuses (CT PNS) done in a total of 78 patients. According to the discoveries, the MS were classified in two types: anterior or lateral. 41 CT PNS of 41 patients of a total of 78 patients preselected were excluded. 37 CT of the paranasal sinuses from 37 patients, in a total of 68 maxillary sinuses were studied. In the 33 right maxillary sinuses, 10 lacrimal recesses were found, 9 from male patients. Eleven left maxillary sinuses with lacrimal recess were found from a total of 35 left maxillary sinuses. From the analysis of 68 MS, a frequency of 30.9% of lacrimal recesses in the maxillary sinuses in CT was observed.


Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.
Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.


Comparison of acebutolol and propranolol in essential hypertension.
A multicenter, double-blind study compared oral acebutolol (n = 186) with propranolol (n = 190) in the treatment of mild to moderately severe essential hypertension (diastolic greater than or equal to 95 to 129 mm Hg). Both beta blockers produced significant and comparable reductions in diastolic, systolic, and mean arterial blood pressures of 16%, 12%, and 14% on acebutolol and 15%, 12%, and 14% on propranolol (all p less than 0.01). At equipotent, antihypertensive doses, acebutolol induced significantly less reduction in resting heart rate than propranolol (13% on acebutolol, 17% on propranolol, p = 0.02). The mean effective doses of acebutolol and propranolol were 738 mg and 231 mg, respectively. Significantly fewer acebutolol patients experienced central nervous system side effects (acebutolol, n = 50; propranolol, n = 75; p = 0.01) or withdrew from the study prematurely due to side effects (acebutolol, n = 11; propranolol, n = 29; p less than 0.01). No clinically significant trends in abnormalities of laboratory parameters were seen, and there were no statistically significant differences in the development of positive antinuclear antibody titers between the two treatment groups. It is concluded that acebutolol is as effective as propranolol in the treatment of hypertension, and acebutolol was better tolerated on the basis of heart rate and central nervous system side effects.


Copy number alterations detected by whole-exome and whole-genome sequencing of esophageal adenocarcinoma.
Esophageal adenocarcinoma (EA) is among the leading causes of cancer mortality, especially in developed countries. A high level of somatic copy number alterations (CNAs) accumulates over the decades in the progression from Barrett's esophagus, the precursor lesion, to EA. Accurate identification of somatic CNAs is essential to understand cancer development. Many studies have been conducted for the detection of CNA in EA using microarrays. Next-generation sequencing (NGS) technologies are believed to have advantages in sensitivity and accuracy to detect CNA, yet no NGS-based CNA detection in EA has been reported. In this study, we analyzed whole-exome (WES) and whole-genome sequencing (WGS) data for detecting CNA from a published large-scale genomic study of EA. Two specific comparisons were conducted. First, the recurrent CNAs based on WGS and WES data from 145 EA samples were compared to those found in five previous microarray-based studies. We found that the majority of the previously identified regions were also detected in this study. Interestingly, some novel amplifications and deletions were discovered using the NGS data. In particular, SKI and PRKCZ detected in a deletion region are involved in transforming growth factor-β pathway, suggesting the potential utility of novel biomarkers for EA. Second, we compared CNAs detected in WGS and WES data from the same 15 EA samples. No large-scale CNA was identified statistically more frequently by WES or WGS, while more focal-scale CNAs were detected by WGS than by WES. Our results suggest that NGS can replace microarrays to detect CNA in EA. WGS is superior to WES in that it can offer finer resolution for the detection, though if the interest is on recurrent CNAs, WES can be preferable to WGS for its cost-effectiveness.


Association of redox-active iron bound to high molecular weight structures in nuclei with inhibition of cell growth by H2O2.
Perturbations to Fe species contributing to generation of DNA single-strand breaks (SSBs) and inhibition of growth by H2O2 were studied in HL-60 cells made Fe-deficient by 24 h pretreatment with 144 microM bathophenanthroline disulfonic acid and 400 microM ascorbic acid (Free Radic. Biol. Med. 20: 399; 1996). The diffusion distance for SSB generation (d) in Fe-deficient cells, measured via inhibition with the *OH scavenger Me2SO using alkaline elution, was 6.5 nm. This is similar to the d for Fe-normal cells reported previously. After 1 and 3 h in fresh RPMI 1640 medium containing 10% serum, SSB generation increased from 29 to 56 and 93% of control Fe-normal cells, respectively. The d of the major contributor to SSB generation at these two treatment times was 1.9 nm. This d resembled the d for Fe-ATP as determined in isolated Ehrlich cell nuclei. The association of ATP with Fe2+ was further supported by decreased SSB generation in cells in which ATP synthesis was inhibited. In contrast to SSB generation, H2O2-induced inhibition of growth of Fe-deficient cells treated immediately after placing in fresh medium was not appreciably different from Fe-normal cells. However, after 3 h, an approximately 70% greater concentration of H2O2 than for control, Fe-normal cells was required to inhibit growth. This increase in H2O2 concentration was associated with decreased generation of SSBs by H2O2 in isolated HL-60 cell nuclei. Thus, Fe bound to nuclear structures is more closely associated with inhibition of cell growth than apparent Fe-ATP species. In parallel experiments, changes in total cellular Fe assayed by ashing and complexing with ferrozine were consistent with a non-transferrin mode of acquisition. These short-term changes appear due to processes accompanying reestablishment of the Fe content and distribution normally observed during long-term growth.


Unraveling the reaction mechanism of selective C9 monomeric phenols formation from lignin using Pd-Al2O3-activated biochar catalyst.
The conversion of biomass-derived lignin to valuable monomeric phenols at high selectivity is of paramount importance for sustainable biorefineries. In this study, a novel Pd-Al2O3 supported on activated biochar catalyst is developed for lignin hydrogenolysis. The catalyst characterization revealed that the (111) planes of both of Pd0 and Al2O3 were exposed to the surface. The maximum lignin conversion of 70.4% along with high liquid yield (∼57 wt%) was obtained at 240 °C, 3 h and 3 MPa H2 pressure. The total monomeric phenols yield in the liquid was 51.6 wt%, out of which C9 monomeric guaiacols constituted ∼ 30.0 wt% with 38.0% selectivity to 4-propyl guaiacol. Using the reaction intermediate, coniferyl alcohol, chemoselective hydrogenation of Cα=Cβ is proved to occur over the Pd site, while dehydroxylation of Cγ-OH is shown to occur over the alumina site. An impressive carbon atom economy of 60% was achieved for the production of monomeric phenols.


Cytokine-induced expression of an inducible type of nitric oxide synthase gene in cultured vascular smooth muscle cells.
In unstimulated cultured vascular smooth muscle cells (VSMC), mRNA of an inducible macrophage-type of nitric oxide synthase (iNOS) was barely detectable. Interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha) markedly increased iNOS mRNA levels in time- and dose-dependent manners. The induction of iNOS mRNA paralleled the cytokine-induced nitrite production. Actinomycin D abolished the IFN gamma- and TNF alpha-induced increases in iNOS mRNA and nitrite production. Cycloheximide, which abolished both the IFN gamma- and TNF alpha-induced increases in nitrite production, had no effect on the IFN gamma-induced increase in iNOS mRNA but markedly inhibited the TNF alpha-induced one. These results suggest that IFN gamma directly induces the expression of the iNOS gene whereas TNF alpha mainly induces it via the induction of an intermediary protein in cultured VSMC.


Myelin proteolipid protein--the first 50 years.
Myelin proteolipid protein (PLP), the most abundant protein of central nervous system (CNS) myelin, is a hydrophobic integral membrane protein. Because of its physical properties, which make it difficult to work with, progress towards determining the exact function(s) and disease associations of myelin PLP has been slow. However, recent molecular biology advances have given new life to investigations of PLP, and suggest that it has multiple functions within myelin and is of importance in several neurological disorders.


The effect of dexmedetomidine on electrocorticography in patients with temporal lobe epilepsy under sevoflurane anesthesia.
Although dexmedetomidine is often used in neuroanesthesia and neuronal critical care practice, its effect on cerebral electrical activity in those with an abnormal electroencephalogram is not known. The electrocorticogram (ECoG), a sensitive method for examining the effect of drugs on cerebral electrical activity and surgical treatment for epilepsy, is usually guided by monitoring of the ECoG. We investigated the effect of dexmedetomidine on ECoG in patients with epilepsy undergoing surgery with sevoflurane. Patients with medically intractable temporal lobe epilepsy undergoing resection of the epileptic foci (n = 11) were enrolled. Under general anesthesia with 2.5% sevoflurane and end-tidal carbon dioxide tension at 30 mm Hg, ECoG was recorded by strip electrodes with eight contacts placed on the mesial temporal lobe ipsilateral to the epilepsy foci. Dexmedetomidine was given as a computer-controlled infusion to achieve target plasma concentrations of 0.5 and 1.5 ng/mL. Each concentration was maintained for 20 min and ECoG was recorded before infusion of dexmedetomidine and between the 10th and 20th min after starting infusion. The median frequency of ECoG, spectral power density of each spectral band, and number of spikes at each concentration of dexmedetomidine were compared by Kruskal-Wallis test, followed by Student-Newman-Keuls test. The median frequency of ECoG in 88 leads from all leads from all patients was significantly decreased by 1.5 ng/mL of dexmedetomidine compared with those at baseline and 0.5 ng/mL (P = 0.003 and 0.03, respectively); however, spectral power densities in the frequency bands: delta (<4 Hz), theta (> or =4 and <8 Hz), alpha (> or =8 and <13 Hz), and beta (> or =13 Hz), were not changed. Neither the number of leads with spikes nor the number of spikes in all leads and in the lead with highest number of spikes at baseline was affected by dexmedetomidine. Dexmedetomidine at plasma concentrations of 0.48 and 1.60 ng/mL decreased the median frequency of ECoG, but did not affect spike activity in patients with temporal lobe epilepsy anesthetized with 2.5% sevoflurane.


Estimated salt intake and risk of atrial fibrillation in a prospective community-based cohort.
Hypertension predisposes to atrial fibrillation (AF) - a major risk factor for ischaemic stroke. Since a high dietary salt consumption is associated with hypertension, we investigated the association between urinary sodium excretion as a marker for dietary sodium intake and risk of new-onset AF in community-dwelling adults. The UK Biobank includes 40- to 69-year-old British residents recruited 2006-2010. Participants were divided into sex-specific quintiles according to 24-hour sodium excretion estimated based on spot samples with the Kawasaki equation. We excluded participants with AF at baseline. Cox regression adjusted for cardiovascular risk factors was used to assess associations with risk of AF, using the third quintile as reference. A total of 257 545 women and 215 535 men were included. During up to 10 years' follow-up, 2221 women and 3751 men were diagnosed with AF. There was a tendency for an increased risk of AF in the lowest and highest quintiles of estimated daily salt intake in both women and men. In the fully adjusted model, significant associations were seen amongst men in the lowest and highest quintiles of sodium excretion (hazard ratio, HRQv1 , 1.20; 95% CI, 1.08-1.32, P < 0.001, and HRQv5 1.15, 95% CI, 1.03-1.27, P = 0.011). We found evidence for a U-shaped association between estimated daily salt intake and AF risk amongst men. A suggestive J-shaped association in women was not statistically confirmed, but analyses were likely underpowered. Our results suggest that above a certain physiological minimum level progressively higher salt intake is associated with increasing risk of AF.


The effects of projection geometry and trabecular texture on estimated fractal dimensions in two alveolar bone models.
To study the effects of trabecular texture and projection geometry on estimates of fractal dimensions from simulated alveolar bone. Two models, one scale-variant and the other relatively scale-invariant, were used. Projections of 2-D slices through both the models were calculated, a uniform series of projections computed for the angular orientations between (0 degree and 180 degrees). Results of the 128 stacked projections are the projection of the 3-D object from different angles. Power spectra were produced by calculating the squared magnitude from the data and plotted as the logarithm of the power against the logarithm of the frequency, to give the fractal dimension. In the scale-variant model, the alveolar trabecular texture produced with a relatively thicker cylindrical diameter yielded a smaller fractal dimension (t = 8.44, P = 0.00). Linear regression analysis showed that the correlation between projection angle and the resulting fractal dimension was low for both the thicker cylinder (r = 0.02, P = 0.82), and for thinner cylinder (r = 0.02, P = 0.84). The scale-invariant model, also yielded a relatively smaller estimated fractal dimension (t = 7.23, P = 0.00). However, the correlation between projection angle and the resulting estimate of the fractal dimension was found to be low for both trabecular configurations (r = 0.10, P = 0.29 and r = 0.07, P = 0.45 respectively). Fractal dimensions increased when the diameter of the simulated cylindrical trabeculae decreased irrespective of the differences in self-similarity. The degree to which they varied with projection angle was relatively less for the scale-invariant (self-similar) model. However, fractal dimensions changed significantly with projection geometry.


Assessment of satisfaction with antiretroviral drugs and the need for long-acting injectable medicines among people living with HIV in Japan and its associated factors: a prospective multicenter cross-sectional observational study.
Long-acting injectable formulations for HIV infection have been approved and are now available in Japan. Although not currently recommended as first-line drugs in Japanese or overseas guidelines, use of such formulations may increase, in accordance with patient conditions and preference. We determine the level of satisfaction with current anti-HIV drugs and analyzed the preferences of patients who favor long-acting injectable drugs based on their satisfaction level with the present anti-HIV drugs. People living with HIV (PLWH) who had received antiretroviral therapy (ART) for at least one month and consented to the study between 1 April and 31 December 2021 were included in a survey conducted using a self-administered questionnaire. The content of the survey included satisfaction with seven items (tablet size, ease and feeling when taking the medicine, color, taste, portability, daily oral therapy, and co-payment) related to the anti-HIV drugs they were taking and their need for future drugs (dosage form, frequency of dosing, long-acting injectable, etc.). In addition, factors related to the need for long-acting injectable medications were analyzed with regard to the relationship with satisfaction with anti-HIV drugs. Overall, 667 patients available for analysis were included in this study. Satisfaction with anti-HIV drugs was highest with regard to "co-payment" and lowest with "daily oral therapy". Regarding the need for long-acting injectable medications, logistic regression analysis indicated that tablet size and daily oral therapy were significant predictors of patient preference for a once-every-eight-weeks intramuscular formulation in terms of their requirement for long-acting injectable medications (tablet size, OR = 2.14, 95%CI 1.030-4.430, p = 0.042; and daily oral therapy, OR = 1.75, 95%CI 1.010-3.030, p = 0.044). Patients currently receiving anti-HIV drugs who express dissatisfaction with tablet size and daily oral therapy may prefer a long-acting injectable formulation, taking into consideration patient age, employment status, ART history, frequency of daily dosage and concomitant medications other than ART.


Angiogenesis of glioma: evaluation of ultrastructural characteristics of microvessels and tubular bodies (Weibel-Palade) in endothelial cells and immunohistochemical findings with VEGF and p53 protein.
Capillary endothelial proliferation is often a prominent feature of malignant gliomas. The understanding of structural and functional characteristics of the vascular microenvironment in gliomas is essential for the design of future therapeutic strategies against this tumor. Electron microscopic analysis of the capillary endothelial proliferation in malignant gliomas indicated that the complex vascular structures within the tumor were composed essentially of immature capillaries. Immature capillaries had a narrow slitlike lumen composed of endothelial cells with their high nuclear : cytoplasmic ratio and the relative paucity of organelles. They resembled capillary buds seen in normal repair tissue. Immature microvessels caused by angiogenesis were found more frequently in marginal zone of the tumors with increased microvessels. The tubular body was an organelle observed in vascular endothelial cells and was used frequently as a marker of the endothelial cell. Tubular bodies were evaluated by quantitative measurement of the mean percent (%) ratio of the number of endothelial cells with tubular bodies to all endothelial cells in microvessels of tumors. In glioblastomas it yielded a value of 32.4% in the margin, about two times as high as that in the center of the tumors. However, it was lower in all locations of astrocytomas. Tubular bodies in endothelial cells could be increased in proportion to neovascularization, and they might serve as a marker for increasing microvessels in astrocytic tumors. Tumor angiogenesis may be regulated by growth factors with angiogenic activities that are secreted by tumor cells. Vascular endothelial growth factor (VEGF) may play a critical role in the regulation of vascular endothelial proliferation. We found that 86% of 29 glioblastomas and 79% of 14 anaplastic astrocytomas demonstrated immunoreactivity for VEGF in their tumor cells. There tended to be a correlation between VEGF and vascularity. A correlation existed between the grade of immunoreactivity for VEGF and the grade of p53 protein expression in the malignant gliomas. However, the MIB-1 indices did not increase in correlation with increase in the extent of immunoreactivity for VEGF.


Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date.
The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning, and memory processes. As such, there is increasing interest in oxytocin as a potential treatment for addictions. The endogenous oxytocin system is itself altered by short- or long-term exposure to drugs of abuse. A large number of preclinical studies in rodents have investigated the effect of oxytocin administration on various drug-induced behaviors to determine whether oxytocin can reverse the neuroadaptations occurring with repeated drug and alcohol use. In addition, the mechanisms by which oxytocin acts to modify the behavioral response to drugs of abuse are beginning to be understood. More recently, a few small clinical studies have been conducted in cocaine, cannabis, and alcohol dependence. This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction.


An insertional mutation in the BTF3 transcription factor gene leads to an early postimplantation lethality in mice.
The gene that encodes the general transcription factor known as BTF3 was disrupted in mouse embryonic stem cells in a random mutagenesis screen for developmental genes with the ROSA beta-geo (Friedrich and Soriano, 1991) retroviral gene trap vector. The BTF3 mutation was transmitted through the germline of chimaeric mice. While the endogenous BTF3 gene is ubiquitously expressed, the expression pattern of the beta-galactosidase reporter gene present in the gene trap vector in BTF3 heterozygotes was restricted. Mice homozygous for the mutant allele died soon after implantation, around embryonic day 6.5. Thus, BTF3 is essential for postimplantation development. The isolation of the BTF3 sequences in this ROSA beta-geo insertion was facilitated by a relatively simple single lacZ primer reverse transcription PCR strategy.


Laser: a review.
Lasers and light-based treatments are extremely useful and now standardized techniques in the management of different stages of photoaging. To obtain the most successful results, protocols involving single or combination systems can be used, depending on skin photodamage. In the last years, the trend is to choose noninvasive or minimally invasive treatments, with the aim of reducing the risk of side effects, complications, and downtime. Selective photothermolysis obtained with lasers and with intense pulse light, which is presently considered the most suitable technique by a growing number of authors, is an extremely valid procedure, in particular in types I and II, according to the Glogau classification. Photodynamic therapy is another effective tool in photoaging treatment, especially in the presence of precancerous conditions. In mild and severe photoaging, ablative laser resurfacing is a particularly successful technique, although requiring a very skilled hand. The new systems, such as fractional photothermolysis, seem to be the very next future to face up to resurfacing procedure with high efficacy and less risks. Obviously, lasers and light-based treatments alone might not be sufficient to control all aging symptoms. For this reason, any another treatment (botulinum toxin, filling agents, chemical peels, systemic and topic antioxidants) can be used in combination to improve the final clinical outcome.


The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.


The impact of the physical environment on the psychological well-being of office workers.
This paper examines the relationship between the physical office environment and the psychological well-being of office workers. The results indicate that adverse environmental conditions, especially poor air quality, noise, ergonomic conditions, and lack of privacy, may effect worker satisfaction and mental health. The data also provide substantial evidence that worker assessments of the physical environment are distinct from their assessments of general working conditions, such as work load, decision-making latitude and relationships with other people at work. Stated another way, people who reported problems with the physical environment could not simply be characterized as dissatisfied workers exhibiting a tendency to 'complain' about every aspect of their working conditions. Taken together, these findings lend support to the position that the stress people experience at work may be due to a combination of factors, including the physical conditions under which they labor. Both theoretical and practical considerations arise from these data, including the need for work site based health promotion and stress reduction programs to consider both the physical and psychological design of jobs.


Acute Coronary Syndrome Requiring Coronary Artery Bypass Grafting in a Patient With Sotos Syndrome.
Sotos syndrome, characterized by cerebral gigantism with neurologic disorders, is an overgrowth syndrome caused by mutations of the NSD1 gene, with an estimated prevalence of 1:10,000-1:50,000. We herein describe the first case of Sotos syndrome complicated by acute coronary syndrome, for which emergency coronary artery bypass grafting was performed. (Level of Difficulty: Intermediate.).


Neutrophil/lymphocyte ratio is associated with survival in synovial sarcoma.
Synovial sarcoma is a rare malignant soft tissue tumor, more common in adolescents and young adults and entails a poor prognosis. Several good prognostic factors have been well established such as age less than 25, size less than 5 cm and absence of a poorly differentiated component. Inflammation has a well-established role in tumor proliferation and survival. The aim of this study was to investigate the prognostic significance of the neutrophil/lymphocyte ratio (NLR) in a large cohort of synovial sarcoma patients. Retrospective study of 169 consecutive patients. We analyzed the relation of preoperative NLR on disease-free survival (DFS) and overall survival (OS) using Kaplan-Meier curves and Cox proportional models. Of the 169 patients included, there were 90(53.3%) females and 79(46.7%) males. Median age was 32yo (11-73). Median survival was 34.1 and mean disease-free survival was 21.4 months. Mean tumor size was 12.5 cm (1.2-77 cm). Applying receiver operating curve analysis, we determined a cut-off value of 3.5. In univariate and multivariate analysis, increased NLR was significantly associated with poor OS. A <3.5 NLR was an independent prognostic factor in all stages (p = 0.002). NLR >3.5 was found to be a reliable prognostic factor in this cohort. Given its widespread availability, we believe it's use in clinical practice and further clinical trials should be considered.


Androgen receptor distribution in the social decision-making network of eusocial naked mole-rats.
Naked mole-rats are highly social rodents that live in large groups and exhibit a strict reproductive and social hierarchy. Only a few animals in each colony breed; the remainder are non-reproductive and are socially subordinate to breeders. We have examined androgen receptor immunoreactive (AR+) cells in brain regions comprising the recently described social decision-making network in subordinate and breeder naked mole-rats of both sexes. We find that subordinates have a significantly higher percentage of AR+ cells in all brain regions expressing this protein. By contrast, there were no significant effects of sex and no sex-by-status interactions on the percentage of AR+ cells. Taken together with previous findings, the present data complete a systematic assessment of the distribution of AR protein in the social decision-making network of the eusocial mammalian brain and demonstrate a significant role for social status in the regulation of this protein throughout many nodes of this network.


Frequent Versus Infrequent Bathing in Pediatric Atopic Dermatitis: A Randomized Clinical Trial.
Studies evaluating bathing frequency in pediatric atopic dermatitis (AD) are limited. Parents of children with AD often receive conflicting information, leading to frustration and confusion. To evaluate efficacy of twice-daily soaking baths, followed by immediate application of an occlusive moisturizer (ie, soak-and-seal [SS]), versus twice-weekly SS baths, in the acute management of pediatric AD. We conducted a randomized, single-blind, crossover-controlled trial comparing frequent versus infrequent SS baths, in children 6 months to 11 years of age with moderate-to-severe AD. Children were randomized 1:1 into 2 groups: group 1 underwent twice-weekly SS baths, for 10 minutes or less, over 2 weeks ("dry method" [DM]) followed by twice-daily SS baths, for 15 to 20 minutes, over 2 weeks ("wet method" [WM]). Group 2 did the inverse. Patients received the same moisturizer, cleanser, and low-potency topical corticosteroid (TCS). Primary outcome was AD severity evaluated using the SCORing Atopic Dermatitis (SCORAD) index. Caregiver assessment of AD severity (Atopic Dermatitis Quickscore [ADQ]), quality of life, Staphylococcal aureus colonization, skin hydration, moisturizer, and TCS usage were assessed. Of the 63 children screened, 42 fulfilled inclusion criteria and were randomized. Forty (95%) completed the study. WM decreased SCORAD by 21.2 compared with DM (95% confidence interval [CI], 14.9-27.6; P < .0001). Secondary analysis showed a greater than 30% SCORAD improvement for WM versus DM (McNemar's χ2 = 8.83, df = 1, P = .0030). SCORAD correlated with ADQ (r = 0.66), and ADQ also showed significant improvement with WM decreasing ADQ by 5.8 (95% CI, 1.8-9.7). No other secondary endpoints showed significance. As an acute treatment intervention, WM is superior to DM at improving disease severity in moderate-to-severe pediatric AD.


Effect of Sodium Selenite on Pathological Changes and Renal Functions in Broilers Fed a Diet Containing Aflatoxin B₁.
To evaluate the renal toxicity of dietary aflatoxin B₁ (AFB₁) and ameliorating effects of added dietary sodium selenite in broiler, renal histopathological changes, ultrastructural changes, and renal function parameters were monitored at 7, 14, and 21 days of age. Two hundred one-day-old healthy male Avian broilers were divided into four groups, namely control group, AFB₁ group (0.3 mg/kg AFB₁), +Se group (0.4 mg/kg Se), and AFB₁+Se group (0.3 mg/kg AFB₁+0.4 mg/kg Se). Compared with that of the control group, the relative weight of kidney was increased in the AFB₁ group. There were no significant differences between the AFB₁+Se group and the control group. By histopathological observation, the renal epithelia were swelling and necrosis at 7 and 21 days of age. Ultrastructurally, the lipid droplets and expanded endoplasmic reticulum appeared in the plasma of epithelia cells in the AFB₁ group. Enlarged mitochondria with degenerated cristae were observed in the +Se group. Compared with the control group, the contents of serum creatinine and serum uric acid in the AFB₁ group were increased, while the activity of renal Na⁺-K⁺ ATPase was decreased. When 0.4 mg/kg selenium was added into the diet containing 0.3 mg/kg AFB₁, there were no obvious histological changes in the AFB₁+Se group, and the contents of the serum creatinine and serum uric acid contents and the activity of renal Na⁺-K⁺ ATPase were close to those in the control group. In conclusion, sodium selenite exhibited protective effects on AFB₁-induced kidney toxicity in broilers.


Fibrin affinity and clearance of t-PA deletion and substitution analogues.
To investigate structure-function relationships in tissue-type plasminogen activator (t-PA) we deleted the following domains in the heavy chain: a) The epidermal growth factor domain (t-PA del. G), b) the finger domain, and the epidermal growth factor domain (t-PA del. FG), and c) the finger, the epidermal growth factor and Kringle 1 (t-PA del. FGK1). To study specifically the function of the growth factor domain we made two substitutions of d) 8 amino acids (consensus sequence) in the growth factor domain (t-PA G-CS) and e) the whole domain with factor IX growth factor domain (t-PA G-IX). Finally, f) an analogue with substitution in the finger domain (fibronectin consensus sequence) was constructed (t-PA F-CS). A reduced fibrin binding of all the analogues was found. The fibrin stimulated activity of all analogues was also reduced and correlated to the fibrin binding. In contrast, the activity of the analogues in the clot lysis assay and the plate assay were only slightly reduced as compared to authentic t-PA. This suggested that at high fibrin concentrations the decreased fibrin affinity was less critical for obtaining a high fibrinolytic activity. All analogues had a prolonged half-life in vivo as compared to authentic t-PA. The assumption of clearance mechanism involving mainly the growth factor region (or Kringle 1) was not challenged by the observation of a prolonged half-life for the substitution analogue t-PA F-CS.2+off


Immunogenicity of recombinant BCG vaccine strains overexpressing components of the antigen 85 complex of Mycobacterium tuberculosis.
The components of antigen 85 complex of Mycobacterium tuberculosis (Ag 85A, Ag 85B and Ag 85C), due to their immunodominant and secretory nature, represent promising protective antigen candidates and have been used in numerous vaccine preparations. We have used recombinant Bacille Calmette Guerin (BCG) strains overexpressing Ag 85A and Ag 85C to immunize BALB/c mice to investigate the immunogenicity of these strains. Mice immunized with recombinant BCG strains exhibited an increased humoral immune response when compared to mice immunized with wild-type BCG. The recombinant BCG strain overexpressing Ag 85A also induced an increased Th1-like response, characterized by elevated levels of IFN-gamma in antigen stimulated splenocyte cultures and a strong IgG2a antibody response, when compared to wild-type BCG. Immunization with recombinant BCG strain overexpressing Ag 85C, on the other hand did not elicit increased IFN-gamma secretion on restimulation of splenocytes in vitro.


Using a modified Delphi process to explore international surgeon-reported benefits of robotic-assisted surgery to perform abdominal rectopexy.
Robotic-assisted surgery (RAS) offers improved visualisation and dexterity compared to laparoscopy. As a result, RAS is considered an attractive option for performing rectopexy, particularly in the confines of the lower pelvis. The aim of this study was to explore the benefits of RAS in rectopexy by analysing the views of a group of surgeons will have published on robotic rectopexy. A three-round Delphi process was performed. Combined qualitative, Likert scale and binary responses were utilised in rounds one and two with binary responses seeking overall consensus in round two and three. Particular areas that were studied included: clinical aspects of patient selection, technical aspects of using RAS to perform rectopexy, ergonomic factors, training, and consideration of the 'learning-curve'. Consensus was defined as agreement > 80% among participants. Potential experienced RAS rectopexy surgeons were identified using PubMed where authors of studies reporting outcomes from RAS rectopexy were searched and invited. Twenty surgeons participated from the following countries: France, Germany, Ireland, Italy, Netherlands, Switzerland, UK, and USA. Participants had median operative experience of 75 (range 20-450) rectopexies (all techniques) and 11(range 0-300) robotic-rectopexies for all indications. All participants agreed that patient-reported functional outcomes and improved quality-of-life were the most important outcomes following rectopexy. Participants agreed the most significant benefits offered by RAS for rectopexy were improved precision due to better visualisation (80%), improved dexterity (90%) and improved overall accuracy e.g., for suture placement (90%). Ninety percent agreed that the superior ergonomics of RAS rectopexy improved their performance on several steps of the operation, in particular: mesh fixation (85%) and rectovaginal dissection (80%). Consensus on the learning curve for RAS abdominal rectopexy was not achieved: forty-five percent (n = 9) reported the learning curve as 11-20 cases and 55% (n = 11) as 21-30 cases. A panel of surgeons who had published on RAS view that it positively improves performance of rectopexy in terms of technical skills, improved dexterity and visualisation and ergonomics.


Codon usage and mistranslation. In vivo basal level misreading of the MS2 coat protein message.
The coat protein of the small RNA virus MS2 shows charge heterogeneity in vivo. In most strains there is a basic satellite of the native protein. We have shown that this basic satellite is greatly diminished or absent in strains with the streptomycin-resistant allele, rpsL, a mutation which leads to increased translational accuracy. Further, the satellite is present in cells where the coat protein is encoded by duplex DNA. Tryptic digests of the satellite show that it contains new lysine-containing peptides which appear to be the same as those found in derivatives of coat protein which have a lysine for asparagine substitution. Sequencing of the NH2-terminal 19 amino acids of the satellite protein shows that the asparagine codon AAU at amino acid 12 is misread approximately 8 times more frequently than the AAC at amino acid 3. We conclude that the satellite species is the result of basal level lysine for asparagine substitution. These substitutions are most likely caused by preferential misreading of AAU codons at a frequency of approximately 5 X 10(-3), 10-fold higher than the average error frequency.


The "STARS" study: advanced preoperative rehearsal and intraoperative navigation in neurosurgical oncology.
Neurosurgical 3D visualizers and simulators are innovative devices capable of defining a surgical strategy in advance and possibly making neurosurgery safer by rehearsing the phases of the operation beforehand. The aim of this study is to evaluate Surgical Theater™ (Surgical Theater LLC, Mayfield, OH, USA), a new 3D neurosurgical planning, simulation, and navigation system, and qualitatively assess its use in the operating room. Clinical data were collected from 30 patients harboring various types of brain tumors; Surgical Theater™ was used for the preoperative planning and intraoperative 3D navigation. Preoperative and postoperative questionnaires were completed by first and second operators to get qualitative feedback on the system's functionality. Furthermore, we measured and compared the impact of this technology on surgery duration. Neurosurgeons were overall satisfied when using this rehearsal and navigation tool and found it efficient and easy to use; interestingly, residents considered this device more useful as compared to their more senior colleagues (with significantly higher scores, P<0.05), possibly because of their limited anatomical experience and spatial/surgical rehearsal ability. The length of the surgical procedure was not affected by this technology (P>0.05). Surgical Theater™ system was found to be clinically useful in improving anatomical understanding, surgical planning, and intraoperative navigation, especially for younger and less experienced neurosurgeons.


Obsessive-compulsive disorder in popular magazines.
To examine what the general public is learning about Obsessive-Compulsive Disorder (OCD) through popular magazines, all articles listed in the Reader's Guide to Periodical Literature under the topic headings of "obsessive-compulsive behavior" or "obsessive-compulsive disorder" between 1983 and 1997 were read and rated. Only 31 of the 107 articles under these headings dealt explicitly with OCD, and these were found to be reasonably accurate in their presentations of symptoms, causes, and treatments. Many of the other articles under the target headings, however, focused on incidents of "stalking" of famous people by "obsessed" fans. The implications of the content patterns of these articles for understanding and misunderstanding of OCD are discussed.


Thymidine as an anticancer agent, alone or in combination. A biochemical appraisal.
The value of thymidine as a cytotoxic drug alone or in combination with other pyrimidine antimetabolites has received considerable attention in recent years. In this paper, the biochemical basis for the cytotoxicity of thymidine and its interaction with other pyrimidine antimetabolites is described. It is indicated that early clinical trials have largely failed to substantiate data from experimental studies that have shown thymidine to be an effective antimetabolite and capable of potentiating the antineoplastic effect of several other agents. It is suggested that tumours likely to respond to thymidine alone or in combination may be identified by measuring in clinical tumour specimens known biochemical determinants of thymidine efficacy.


Underpinning miRNA-miRNA co-functional interaction patterns in the metabolism of Oryza sativa by genome-scale network analysis.
MicroRNA (miRNA) is a class of non-coding small RNAs, which post-transcriptionally regulate a large number of genes and are now known to be important regulators in a wide variety of biological processes including metabolism. Thus, for better understanding these complex biological networks, and to derive their significance and inter-dependency, a systems biology approach enables us to explore and draw vital insights into these molecular network architectures. In this study, we aimed to understand the significance of synergistic miRNA-miRNA interactions in rice by constructing and analysing metabolic networks. The construction of the network involves target gene prediction of experimentally verified miRNAs of rice and then appending associated metabolic pathways to the network. A genome-scale miRNA-miRNA co-functional network (MFSN) is constructed based on co-regulatory interactions among the miRNAs and common target genes by applying transformational procedures. The analysis of the extracted MFSN modules identifies co-regulated target genes that are associated with corresponding interconnected metabolic pathways such as VALDEG-PWY (L-valine degradation I pathway was found to be targeted by multiple miRNA families, such as osa-miR812, osa-miR818, osa-miR821, and osa-miR5799 families while another pathway that was found to be associated with multiple miRNA families was PWY-6952 (glycerophosphodiester degradation pathway), PWY-6952 was found to be targeted by osa-miR812, osa-miR11344 and osa-miR5801 families. Such extensive study will help in systematically elucidating the regulatory networks in metabolism of rice, which in turn can be utilised to devise strategies for crop improvement and novel cultivar development.


Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice.
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, young children, and high-risk adults. Currently, there is no vaccine to prevent RSV infection, and the available therapeutic agents are of limited utility. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are a class of antisense agents that can enter cells readily and interfere with viral protein expression through steric blocking of complementary RNA. Two antisense PPMOs, designed to target sequence that includes the 5'-terminal region and translation start-site region of RSV L mRNA, were tested for anti-RSV activity in cultures of two human-airway cell lines. Both PPMOs showed minimal cytotoxicity and one of them, (AUG-2), reduced viral titers by >2.0 log(10). Intranasal (i.n.) treatment of BALB/c mice with AUG-2 PPMO before the RSV inoculation produced a reduction in viral titer of 1.2 log(10) in lung tissue at day 5 postinfection (p.i.), and attenuated pulmonary inflammation at day 7 postinfection. These data show that the AUG-2 PPMO possesses potent anti-RSV activity and is worthy of further investigation as a candidate for potential therapeutic application.


Chemoarchitectonics of axonal and perikaryal acetylcholinesterase along information processing systems of the human cerebral cortex.
The distribution of axonal and perikaryal acetylcholinesterase (AChE) was studied in whole-brain sections. All cytoarchitectonic sectors and cortical layers of the human cerebral cortex contained AChE-rich axons. These axons displayed multiple varicosities which appeared to come in contact with AChE-rich and AChE-poor cortical perikarya. The upper layers of cortex tended to contain the highest density of AChE-rich axons. The AChE-rich axons were more dense in limbic-paralimbic areas of cortex than in primary sensory-motor and association areas. Within unimodal sensory association areas, the parasensory (upstream) sectors had a slightly lesser density of AChE-rich axons than the downstream sectors. Within paralimbic areas, the nonisocortical sectors displayed a distinctly higher density of AChE-rich axons than the more differentiated isocortical sectors. These observations indicate that the distribution of AChE-rich axons displays orderly variations that obey the organization of information processing systems in the cerebral cortex.


Oxidation of dimethylamine and trimethylamine in methazotrophic yeasts by microsomal mono-oxygenases sensitive to carbon monoxide.
Whole cells of Candida boidinii grown on di- or tri-methylamine as sole nitrogen source readily oxidized both amines. The oxidation was potently inhibited by carbon monoxide. Cell-free extracts required the presence of 20 microM FAD before mono-oxygenase activity with both amines could be demonstrated. NADH was a better electron donor than NADPH. Activity was present in cells grown on secondary and tertiary amines but not on primary amines, and was detected in a number of different yeasts. Enzyme activity could be sedimented at 187 000 x g, and was associated with NADPH-cytochrome c reductase activity. It is thus probably microsomal. Activity was inhibited by cyanide, mercaptoethanol, carbon monoxide and proadifen hydrochloride (SKF 525-A).


Synthesis of allene triazole through iron catalyzed regioselective addition to propargyl alcohols.
Allene triazole derivatives were successfully synthesized for the first time through iron catalyzed regioselective triazole addition to tertiary propargyl alcohols. The reaction proceeds under mild conditions, giving the desired allene-triazoles in good to excellent yields (up to 96%). The resulting allene-triazoles were confirmed by X-ray crystallography and indicated improved stability.


Clinical and pathological analysis of giant cell tumor of bone with denosumab treatment and local recurrence.
Giant cell tumor of bone (GCTB) is a primary bone tumor which comprises giant cells and two types of stromal cells. Recent studies have suggested therapeutic risks of denosumab. No previous studies have reported changes in serum TRACP-5b and SUVmax of 18F-FDG-PET/CT in recurred GCTB after denosumab treatment. Therefore, we assessed the relationship between clinical and pathological features of GCTB which recurred after denosumab treatment. We retrospectively reviewed the medical records of 26 patients with GCTB who underwent curettage between 2010 and 2018. Fourteen patients treated with denosumab were defined as the denosumab group. We evaluated TRACP-5b and SUVmax values in the denosumab group. H&E staining and immunohistochemistry for H3.3 G34W were performed for pathological assessment. Twelve patients treated without denosumab were defined as the non-denosumab group and compared with denosumab group. The local recurrence rate in the denosumab group was 57.4%. The mean TRACP-5b and SUVmax values were significantly decreased after denosumab therapy (P < 0.001, 1077 ± 161 to 74 ± 9 mU/dL and 8.88 ± 0.40 to 3.79 ± 0.56, respectively). Both parameters significantly increased with local recurrence. H&E staining after denosumab treatment revealed the disappearance of giant cells and histological changes in stromal cells. Specimens of local recurrence subjected to H&E staining and immunohistochemistry for H3.3 G34W demonstrated almost identical features to those in the first biopsy. Although denosumab can prevent GCTB from osteolysis, local recurrence cannot be reduced by denosumab treatment. The clinical and pathological results were almost the same as those before denosumab treatment, suggesting that the changes of GCTB by denosumab are reversible.


Verbal memory compensation: application to left and right temporal lobe epileptic patients.
This study investigates the compensatory impact of cognitive aids on left and right temporal lobe epileptic patients suffering from verbal memory disorders, who were candidates for surgery. Cognitive aids are defined in the levels-of-processing framework and deal with the depth of encoding, the elaboration of information, and the use of retrieval cues. Results indicate differential compensatory impact for left and right epileptic patients and are discussed according to the HERA model and the compensation framework.


Utility of CT-cisternogram for radiosurgery in trigeminal neuralgia: A not-to-be forgotten technique.
Radiosurgery (RS) is a well-established ablative therapy for trigeminal neuralgia (TGN). Successful RS requires the delivery of an extremely high dose of radiation to a small cisternal portion of the nerve, which lies amidst critical structures. This study describes the utility of CT-cisternogram in RS targeting for TGN. We report on patients with TGN who required CT-cisternogram for target identification for CyberKnife (CK) RS at our institution between September 2010 and April 2015. CT-cisternogram is a well-tolerated procedure that adds useful information to RS planning. Illustrative cases with complex anatomy and MRI artifacts related to postoperative changes and Teflon implant are described. CT-cisternogram is a complementary imaging modality that is useful in some patients, for RS target delineation.


Genetic diversity among late blight resistant and susceptible potato genotypes.
RAPD polymerase chain reaction analysis was used to study the genetic diversity among a wild potato variety Solanum demissum (very resistant to late blight) and six potato cultivars (Hanna, Lady-Olympia, Lady-Rosetta, Spunta, Diamant and Cara) varied in their resistance to Phytophthora infestans. Cluster analysis of six potato genotypes showed that, all tested genotypes were separated into two clusters (1 and 2). Cluster 1, included only the wild potato variety (S. demissum), whereas cluster 2 divided into two groups (G1 and G2). Late blight high resistant cultivars Hanna and Cara were grouped in G1. Group 2 included the moderate resistant cultivar Spunta and the susceptible cultivars Diamant, Lady-Rosetta and Lady-Olympia. The potato cultivars that showed highest genetic similarity to the wild potato variety were the resistant cultivars Hanna and Cara. Lowest genetic similarity was obtained with the susceptible cultivars Lady-Rosetta, Diamant and Lady-Olympia. RAPD primer K17 yielded a band with molecular weight of 936 bp found in all susceptible potato cultivars (Lady-Rosetta, Lady-Olympia and Diamant). On the other hand, band with molecular weight of 765 bp were detected in the wild potato and the resistant cultivars Hanna and Cara. Results of this study suggested that, the RAPD marker technique could be beneficial for revealing the genetic variability of different genotypes of potato varied in their resistibility to late blight.


Risk factors for medical complication after spine surgery: a multivariate analysis of 1,591 patients.
Several studies have examined the occurrence of medical complication after spine surgery. However, many of these studies have been done using large national databases. Although these allow for analysis of thousands of patients, potentially influential covariates are not accounted for in these retrospective studies. Furthermore, the accuracy of these retrospective data collection in these databases has been called into question. Using multivariate analysis on a prospectively collected data registry to determine significant risk factors for medical complication after spine surgery. Retrospective multivariate analysis of prospectively collected registry data. The registry is a prospectively collected database of all patients who underwent spine surgery in our two institutions from January 1, 2003 to December 31, 2004. Extensive demographic and medical information were prospectively recorded as described previously by Mirza et al. Complications were defined in detail a priori, and they were prospectively recorded for at least 2 years after surgery. We analyzed risk factors for medical complication after spine surgery using univariate and multivariate analyses. We analyzed data from 1,591 patients who met out inclusion criteria. The cumulative incidences of complication after spine surgery per organ system are as follows: cardiac, 8.4%; pulmonary, 13%; gastrointestinal, 3.9%; neurological, 7.35%; hematological, 10.75%; and urological complications, 9.18%. The occurrence of cardiac or respiratory complication after spine surgery was significantly associated with death within 2 years (relative risk, 4.11 and 10.76, respectively). Surgical invasiveness and age were significant risk factors for complications in five of the six organ systems evaluated. Individual organ system-specific elative risk values with 95% confidence intervals and p values are listed in Tables 3 and 4. Risk factors identified in this study can be beneficial to clinicians and patients alike when considering surgical treatment of the spine. Future analyses and models that predict the occurrence of medical complication after spine surgery may be of further benefit for surgical decision making.


Antidepressant-like actions of the mGlu2/3 receptor antagonist TP0178894 in the chronic social defeat stress model: Comparison with escitalopram.
The metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists are reported to produce ketamine-like rapid-acting and sustained antidepressant-like effects in rodents. In this study, we compared the effects of single administration of the new mGlu2/3 receptor antagonist TP0178894 and the selective serotonin reuptake inhibitor (SSRI) escitalopram in the chronic social defeat stress (CSDS) model of depression, a model which has been shown to be resistant to treatment with a single dose of SSRI. In the tail suspension test and forced swimming test, high dose (3.0 mg/kg) of TP0178894 significantly attenuated the increased immobility time of these tests in CSDS susceptible mice, compared with vehicle-treated mice. In contrast, low doses (0.3 and 1.0 mg/kg) of TP0178894 and escitalopram (10 mg/kg) did not alter the increased immobility time of these two tests. In the sucrose preference test, TP0178894 (3.0 mg/kg) significantly improved the reduced sucrose preference of CSDS susceptible mice, three and seven days after a single dose. In addition, Western blot analyses showed that TP0178894 (3.0 mg/kg), but not low doses of TP0178894 and escitalopram, significantly attenuated the reduced expression of synaptic proteins [α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (GluA1) and postsynaptic density protein 95 (PSD-95)] in the prefrontal cortex from CSDS susceptible mice. This study suggests that TP0178894 shows rapid-acting and sustained antidepressant-like effects in CSDS model, as ketamine does.


Minocycline induced discoloration of the aortic intima and valve: A case report.
Ochronosis refers to the blue-black discoloration of connective tissue. While cardiovascular ochronosis has been described resulting from alkaptonuria, it may also result from chronic minocycline use which is exceedingly rare. Cardiovascular ochronosis often presents with insidious development, often identified incidentally during aortic valve replacement (AVR). Herein, we describe the case of a 71-year-old male undergoing AVR and coronary artery bypass grafting found to have minocycline-induced ochronosis of the aortic valve and aorta. Given the rarity of this case, descriptions of cardiovascular ochronosis cases secondary to minocycline use are imperative in ensuring that it is on the differential diagnosis when identified by others in future cases. Additional care must be taken intraoperatively to ensure that the correct anatomy is identified as discoloration hinders visualization of the anatomy potentially resulting in unintentional consequences such as heart block or perivalvular leak as traditional visual cues for suture placement are distorted.


Chronic kidney disease after nonmyeloablative stem cell transplantation in adults.
Chronic kidney disease (CKD) after myeloablative stem cell transplantation (SCT) is a well-established problem. Little is known about CKD after nonmyeloablative SCT. We performed a retrospective cohort study of 108 adults who received nonmyeloablative SCT with fludarabine and/or total-body irradiation (TBT) conditioning. Renal function was assessed by estimating glomerular filtration rate (GFR) with the MDRD equation. CKD was defined as GFR <60 mL/min/1.73 m(2). CKD developed in 15% of patients after a median of 15 months. None of the patients required dialysis. Cumulative incidence of CKD was 7% at 12 months, 14% at 24 months, and 22% at 48 months. Risk factors for CKD were female sex (P = .021), older age (P = .040), and lower GFR pretransplant (P < .001). Complications after SCT were not associated with CKD. SCT nephropathy, a cause of CKD after myeloablative SCT, did not occur. Overall survival (OS) was 66%. There was no difference in survival between patients with or without CKD. In conclusion, CKD is a frequent complication after nonmyeloablative SCT and is not related to SCT nephropathy. Women, patients above 50 years of age, and patients with slightly decreased kidney function pretransplant have the greatest risk of development of CKD.


Epidemiology of Pediatric Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD), including subtypes Crohn disease and ulcerative colitis is a chronic inflammatory disorder most often diagnosed in young adulthood. The incidence and prevalence of pediatric-onset IBD is increasing globally. IBD is likely caused by an interplay of multiple environmental factors resulting in a dysregulated mucosal response to the commensal intestinal microbiota in genetically predisposed individuals. This article provides an overview of pediatric IBD epidemiology and environmental risk factors associated with its development, such as the Hygiene Hypothesis, air pollution, greenspace and blue space, neonatal factors, antibiotics, and diet.


Dental caries status of students from migrant primary schools in Shanghai Pudong New Area.
In China, there is a large migrant population. A significant proportion of children of the migrant population in China are not able to attend public schools due to the lack of local household registration (HuKou). They turn to privately-operated migrant schools, which are usually under-funded, have bad environmental facilities and are inadequately staffed compared to public schools. This study aims to describe the dental caries status of students from migrant primary schools in Shanghai Pudong New Area and factors that influence their caries status. Children (7-12 years old) from migrant primary schools in Shanghai Pudong New Area were randomly selected through a multi-stage cluster sampling method. Following the recommendation of the World Health Organization, caries experiences were recorded using the dmft index. A questionnaire to survey the children's socio-demographic characteristics and oral health-related behaviours was completed by the children's parents or guardians. A total of 1385 children in migrant primary schools were invited, of which 1323 joined the survey (95.5 %). Among all the surveyed subjects, the prevalence rate of dental caries was 74.7 % (65.7 % for primary teeth and 28.1 % for permanent teeth). The mean (SD) dmft scores were 3.17 (3.12), 2.74 (3.02) for the primary teeth and 0.44 (0.84) for the permanent teeth, and 99.5 % of the carious teeth received no treatment. Students from migrant primary schools in Shanghai Pudong New Area had bad conditions of dental caries and most of the carious teeth were left untreated. The caries experience was associated with tooth brushing habits, snacking habits, dental visit and gender.


Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis.
Benign and precancerous endometrial hyperplasias (EH) are differentiated thorough two possible histomorphologic classifications: WHO (adopting the subjective evaluation of cytologic atypia) and EIN (adopting several histomorphologic parameters, evaluable subjectively, or objectively with a computerized analysis calculating a prognostic score, the D score). ACOG recommends the use of EIN system although no distinction was made between objective assessment (not widely available), and subjective assessment (more applicable in the common practice). Moreover, it is still unclear if subjective EIN system is actually preferable to WHO classification. We aimed to assess the reliability of WHO system, D score and subjective EIN system in stratifying the risk of progression to cancer in EH. MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, Cochrane Library and Google Scholar were searched for relevant articles from the inception to August 2018. All studies assessing the rates of progression of EH to cancer were included. Twelve cohort studies and one case-control study, assessing 3629 EH, were included. Relative risk (RR) for cancer progression was calculated with 95% confidence interval (CI), and results were compared using Chi-square test (significant p value < 0.05). WHO system showed a RR of 8.74 (95% CI 6.66-11.47). Objective D score showed a RR of 29.22 (95% CI 13.24-64.51), significantly higher than WHO (p = 0.005). Subjective EIN system showed a RR of 19.37 (95% CI 5.86-64.01), intermediate between WHO and D score, without significant differences (p = 0.20 and p = 0.57, respectively). Objective EIN criteria with D score are significantly more reliable than WHO criteria in stratifying the risk of progression of EH to cancer. Subjective EIN criteria did not show significant superiority over WHO instead. Further studies are necessary to determine if subjective EIN system should replace WHO system in the routine diagnosis of EH.


Overexpression of CmSOS1 confers waterlogging tolerance in Chrysanthemum.
The Na+ /H+ antiporter SOS1 enhances the salinity tolerance of a number of plant species, but its involvement in the response to hypoxia is less well known. We presented chrysanthemum homologs CmSOS1 and CmRCD1 coordinately mediate waterlogging tolerance by maintaining membrane integrity and minimizing the level of reactive oxygen species.


Distinctive tunable photophysical properties of versatile environmentally-sensitive tribranched cyanopyridine fluorophores.
In the present work, twenty-four environmentally-sensitive cyanopyridine fluorophores bearing pyrene and/ or fluorene with different para-substituted-phenyl moieties that have been previously designed and synthesized by us are studied in depth for their photophysical properties. Initially, the optical performances of the compounds were investigated by employing UV-visible and fluorescence spectroscopic tools in various aprotic and protic solvents. All the compounds exhibited absorption bands between 310 and 452 nm, and emission bands between 454 and 633 nm. High sensitivity emission spectra with solvents of different polarities were recorded and studied. The fluorescence quantum yield (ϕf) increased in solvents of low polarity and decreased on increasing the polarity of solvents. On the other hand, in case of strong electron donating (-NMe2) and strong electron attracting (-CN) substitution, a pronounced increase in Stokes shifts (up to 252 nm, 14250 cm-1) were recorded. Lippert-Mataga and Reichardts correlations, applied for estimating the variation in dipole moments (Δμ), suggested that the emissive state of designed fluorescence 3-cyanopyridine derivatives is of strong ICT character. The aprotic and protic solvents gave a linear plot for the Stokes shifts in a Lippert-Mataga plot, which appeared as two distinct domains in ET(30) scales indicating the presence of hydrogen bondings. It was observed that for compounds 5b - 8b, with (-NMe2) group on the skeleton of phenyl ring, the Lippert-Mataga and Reichardt-Dimroth's plots deviated from linearity signifying that 5b - 8b molecules were involved in specific interaction with protic solvents.


Decreased cell-mediated cytotoxicity against virus-infected cells in systemic lupus erythematosus.
Cell-mediated cytotoxicity, directed against virus-infected tissue culture cells, was studied with peripheral blood mononuclear cells from 11 patients with systemic lupus erythematosus (SLE) and 12 matched, normal subjects in a 51Cr release assay. Baseline (preimmunization) levels of cytotoxicity against target cells infected with influenza A/Victoria, influenza B/Hong Kong, Newcastle disease virus, and herpes simplex virus were significantly decreased in patients with SLE compared to normal subjects (P less than 0.001), although serum antibody levels to the respective viruses were similar in both groups. After intramuscular administration of inactivated influenza A/Victoria vaccine, SLE patients failed to generate elevated levels of cytotoxicity against A/Victoria-infected cells, in contrast to normal subjects. SLE patients responded with levels of serum hemagglutination-inhibition antibody which were similar to those of normal subjects. Thus, SLE patients manifest decreased cell-mediated cytotoxicity against virus-infected target cells, although humoral antibody responses appeared to be intact. Studies of SLE patients with influenza may help to define the role of cell-mediated immunity in the pathogenesis of certain viral infections.