[Anelloviruses (TTV and variants): state of the art 10years after their discovery].
Ten years after their discovery, anelloviruses combine some characteristics making them particularly intriguing. In support of their extreme genetic diversity and high prevalence in various populations, their natural history is still poorly understood along with their implication in human health. These viruses have been identified in blood and blood-derived products, and are probably remarkable examples of co-existence and co-evolution in their various hosts. This article presents epidemiological and molecular characterizing this new viral family.


Successful booster antibody response up to 54 months after single primary vaccination with virosome-formulated, aluminum-free hepatitis A vaccine.
This study demonstrates that a booster dose of the virosome-formulated, aluminum-free hepatitis A vaccine Epaxal (Berna Biotech) is highly immunogenic in subjects who received a single primary dose of this vaccine 18-54 months earlier. There were no significant differences in geometric mean antibody titers (GMTs) among subjects who received the booster dose 18-29 months (GMT, 2330 mIU/mL), 30-41 months (GMT, 2395 mIU/mL), or 42-54 months (GMT, 2432 mIU/mL) after primary vaccination, indicating that delays in the administration of booster vaccination do not lead to a loss of immunogenicity.


[Angiotensin II type 2 receptors participate in the regulation of inflammatory cytokine secretion in adult rat hypertrophied cardiomyocytes].
To investigate the effect of angiotensin II (AngII) type 2 (AT2) receptors on pressure overload-induced inflammatory cytokine secretion in adult rat hypertrophied cadiomyocytes. Rat models of left ventricular hypertrophy induced by pressure overload was established by placing a band around the abdominal aortic of the rats, from which the hypertrophied cadiomyocytes were isolated and purified 8 weeks later. The isolated cardiomyocytes were treated with AngII plus losartan or AngII plus PD123319, and 36 h after the treatments, the expression levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6 in the supernatant were detected using radioimmunoassay. AngII induced TNF-alpha and IL-1beta secretion from the hypertrophied cardiomyocyets, and pretreatment of the cells with PD123319, but not losartan, decreased their secretion. IL-6 level was not detected in the supernatant. AngII-induced the expression of inflammatory cytokines in adult rat hypertrophied cardiomyocytes is mediated mainly by AT2, not by AT1 receptors.


[Incidence of inflammatory placental changes in threatened premature labor with and without additional antibiotic therapy].
Considering the causal association of silent intrauterine infection and prematurity we investigated the possible effect of adjuvant antibiotic treatment of women with preterm labour on the appearance of inflammatory placental lesions. 140 patients with preterm labour in the 30 + 2 week of gestation (median; range: 17 + 2-34 + 6) without premature rupture of the membranes and detection of facultative-pathogenic micro-organisms in the vagina and/or in the canal of the cervix were enrolled in the study. 74 women were treated vaginally (polyvidone-iodine) in addition to intravenous tocolysis, 66 women were given ampicillin, cefotiam or erythromycin intravenously. After delivery the placentas were examined histologically and the frequency of inflammatory lesions was evaluated by use of 4 scores of classification. For statistical analysis the Fisher Exact- and the Wilcoxon Rank Sum Test were used. We found no differences concerning amnamnestic and perinatal parameters comparing the 2 groups of patients. With only one of the histological scores used (according to Salafia et al. [18]) we found a higher frequency of inflammatory placental lesion in the antibiotic treated group (12/66) in comparison to the vaginal treated group (4/74). Fifty patients of the antibiotics' group received the antibiotic during the last 10 days before birth. No differences in the frequency of inflammatory placental lesions were detectable in these patients when compared with the local treated group. However, we found a lower prolongation of gestation (calculated from the day of admission to the day of delivery, median: 7; range: 1-92 days) and a lower gestational age at delivery (median: 33 + 0; range: 22 + 2-39 + 6 weeks) in the patients receiving antibiotics during the last 10 days before birth in comparison to the local treated women (22; 1-138 days and 35 + 0; 23 + 4-41 + 5 weeks, respectively). There is the same incidence of inflammatory placental lesions in patients with preterm labour and facultative-pathogenic micro-organisms in the vagina and/or in the canal of the cervix who received adjuvant antibiotic treatment during pregnancy compared with patients who were treated vaginally with polyvidone-iodine.


Chromosome region maintenance-1 (CRM1) regulates apoptosis of intestinal epithelial cells via p27kip1 in Crohn's disease.
To investigate the role of chromosome region maintenance-1 (CRM1) in Crohn's disease (CD) and its potential pathological mechanisms. The expression and distribution of CRM1 in mucosal biopsies from patients with active CD and normal controls were detected by immunohistochemistry (IHC). We established a murine model of acute colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Western blot was performed to investigate the expression levels of CRM1, apoptotic markers (active caspase-3 and cleaved PARP), p27kip1 and p-p27ser10. IHC was performed to evaluate the distribution of CRM1, and double immunofluorescence (IF) was performed to evaluate the co-localization of CRM1 and active capase-3. Cells of the human intestinal epithelial cell line HT-29 were incubated with tumor necrosis factor-α (TNF-α) to establish an apoptotic in vitro model. Western blot was performed to determine the expression levels of CRM1, active caspase-3, cleaved PARP and p-p27ser10. Cytoplasmic and nuclear extracts were assessed to examine the translocation of CRM1. The interaction between CRM1 and p27kip1 was assessed by co-immunoprecipitation (co-IP) assays. Furthermore, we used small interfering RNA (siRNA) to knock down the protein expression of CRM1 in HT-29 cells and then measured the expression of active caspase-3, cleaved PARP and p-p27ser10. Flow cytometry was used to determine the effect of CRM1 on intestinal epithelial cell (IEC) apoptosis. We observed up-regulation of CRM1 accompanied by elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and p-p27ser10 in IECs of patients with active CD and in TNBS-induced colitis model cells. However, the expression of p27kip1 was negatively correlated with the expression patterns of CRM1, p-p27ser10 and apoptotic biochemical markers. Co-localization of CRM1 and active caspase-3 in IECs of the TNBS group further indicated the possible involvement of CRM1 in IEC apoptosis. By employing TNF-α-treated HT-29 cells as an in vitro IEC apoptosis model, we found that the expression levels of CRM1 and p-p27ser10 were in accordance with active caspase-3 and cleaved PARP. In addition, immunoprecipitation confirmed the physical interaction between CRM1 and p27kip1. siRNA knockdown of CRM1 significantly inhibited the phosphorylation of p27kip1 and the expression of active caspase-3 and cleaved PARP. In addition, flow cytometry analysis also showed that silencing CRM1 by siRNA inhibited TNF-α-induced cellular apoptosis in HT-29 cells. Up-regulated CRM1 may facilitate IEC apoptosis possibly through p27kip1 in CD, indicating an important role of CRM1 in the pathophysiology of CD.


Affinities of Treponema pallidum for human lactoferrin and transferrin.
The acquisition of lactoferrin and transferrin by live Treponema pallidum organisms was examined. Saturation binding kinetics were obtained for virulent treponemes with increasing amounts of radioiodinated lactoferrin but not with transferrin. Furthermore, lactoferrin bound up to 100 times more effectively than transferrin. Only unlabelled lactoferrin stoichiometrically completed with iodinated lactoferrin binding. Time course kinetics showed maximum lactoferrin acquisition within the first five minutes at 34 degrees C. Optimum iron accumulation, however, was achieved by T pallidum in 30 minutes at 34 degrees C, and amounts of iron were six times greater than the equivalent amount of lactoferrin bound. Interestingly, iron uptake was also detected in the presence of transferrin, despite the minimal amounts of transferrin acquired by live treponemes. These observations reinforce the possibility that the associations of T pallidum with host molecules, such as plasma proteins, are essential for survival of the parasite within host environments.


Is there a fragile(X) negative Martin-Bell syndrome?
During the course of the preventative screening program for the fra(X) syndrome, we identified 32 men with the phenotype but who were fra(X) negative. These were reviewed and none fitted the full criteria, so we were unable to confirm the existence of the fra(X) negative Martin-Bell syndrome. The literature and 4 families previously thought to have the fra(X) negative Martin-Bell syndrome were also reviewed. We were unable to make a concrete diagnosis of the fra(X) negative Martin-Bell syndrome.


Urinary sodium and potassium excretion in idiopathic hypercalciuria of children.
An increased spot urine Na/K ratio (UNa/K) has been found to be related to urinary stone disease in adults with a history of nephrolithiasis and in children with idiopathic hypercalciuria (HC). However, the respective role played by Na and K excretion in the rise of the UNa/K in growing individuals is not well clarified. The urinary excretion of Na and K was evaluated in fasting morning and 24-hour urine samples of 37 consecutive children with HC and of 21 previously HC children who were normocalciuric at the time of the study (ExHC). None of them had received any dietary or specific drug prescription. In the HC and in the ExHC group, respectively, the Na excretion was 4 +/- (SD) 2.4 and 2.9 +/- 1.3 mmol/kg/day (p = 0.009); the K excretion was 1.1 +/- 0.4 and 1.2 +/- 0.7 mmol/kg/day (p = 0.86); the fasting UNa/K was 3 +/- 1.6 and 2.1 +/- 1 mmol/mmol (p = 0.044), and the 24-hour UNa/K was 4.2 +/- 3.9 and 2.8 +/- 1.5 mmol/ mmol (p = 0.045). The 24-hour UNa/K was significantly higher than the fasting UNa/K in both HC (p = 0.002) and ExHC (p = 0.002) subjects. The 24-hour UNa/K significantly increased with age in both HC (p = 0.02) and ExHC (p = 0.015) children. The K excretion significantly decreased with age in HC (p = 0.0001) and ExHC (p = 0.005) subjects, as well as with body weight gain in HC (p = 0.005) and ExHC (p = 0.0001) children and with increasing body height in HC (p = 0.006) and ExHC (p = 0.001) subjects. In neither group was the K excretion significantly related to body mass index Z score nor to height Z score. No significant relation resulted between Na excretion and age, body weight and height, and body mass index Z score and height Z score. HC children have a higher Na excretion as well as a higher fasting and 24-hour UNa/K than ExHC children, but no different K excretion. Meals are accompanied by a significant rise in UNa/K. The rise in UNa/K with age is mostly due to a decrease in K excretion which possibly depends on childhood body growth.


A cadaveric study of endoscopic decompression of the cubital tunnel.
A cadaveric study of endoscopic decompression of the cubital tunnel was performed. Four fresh-frozen upper limbs were used for dissection, with a focus on the relationship between the ulnar nerve and Osborne's band. The endoscopic procedure was performed with the Ectra II system (Smith & Nephew, Andover, MA). After the surgical procedure, further dissection was done to evaluate the effectiveness and safety of the endoscopic cut of Osborne's band. Our conclusion is that endoscopic release is not a technically difficult procedure, and may be limited to certain clinical situations.


Diverse acyclic diterpene derivatives from Aphanamixis sinensis.
Fifteen diterpene derivatives including seven new ones, sinensisins A-G (1, 2, 4, 7, 10, 14, 15), were obtained from the leaves and twigs of Aphanamixis sinensis. Their structures were elucidated by NMR spectroscopic and ECD data analyses. These diverse carbon skeletons containing meroditerpenoids, acyclic diterpenes, and norditerpenoids biogenetically were derived from chain-like diterpenes. Compounds 3, 5, and 6 showed inhibitory effects of nitric oxide (NO) production in LPS-induced RAW 264.7 cells.


Characteristics of lactose-free frozen yogurt with κ-carrageenan and corn starch as stabilizers.
Frozen yogurt is a type of dairy product that is considered to be a more healthful alternative to conventional ice cream due to its lower fat content and the presence of viable lactic acid bacteria. Lactose-free products are a growing trend in the dairy industry, and lactose-free yogurts and ice creams can both be found on the market. However, lactose-free frozen yogurt has not yet reached the market. In this study, we aimed to investigate the effect of adding κ-carrageenan (0.05, 0.1, and 0.15%) and corn starch (1, 2, and 3%) on acidity, texture, viscosity, overrun, melting properties, color attributes, and sensory characteristics of lactose-free frozen yogurts. Lactose was reduced by enzymatic hydrolysis during the fermentation process. The effectiveness of the hydrolysis was measured by HPLC, and lactose was reduced to 0.05% after 80 min of incubation with the enzyme. The addition of stabilizers did not change overrun and melting properties of frozen yogurt, but it did affect pH, titratable acidity, and color parameters. The product with 0.15% κ-carrageenan had the highest hardness and stickiness values. Moreover, κ-carrageenan had a positive effect on sensory attractiveness of lactose-free frozen yogurt, and it reduced the coarse texture in comparison with the control without stabilizers. A lactose-free frozen yogurt with good quality and nutritional characteristics was produced, particularly with the use of κ-carrageenan as stabilizer.


Hypomineralised second primary molars: prevalence, pattern and associated co morbidities in 8- to 10-year-old children in Ile-Ife, Nigeria.
This study tries to determine the prevalence and co-morbidities associated with hypomineralised second primary molars (HSPM) in 8- to 10- year-old children in Ile-Ife, Nigeria; and the co-existence of HSPM and Molar Incisor Hypomineralisation (MIH) in the study population. This was a cross sectional study involving 8- to 10- year-old children in schooling in suburban Nigeria. Information was collected on the child's age, sex and socioeconomic status. Intraoral examination was conducted to determine the presence of HSPM, MIH, caries and the oral hygiene status of study participants. The severity of HSPM was also determined. The prevalence of HSPM, the association between HSPM, sex and socioeconomic status of study participants, the difference in the prevalence of caries and poor oral hygiene in children with and without HSPM, and the prevalence of HSPM and MIH co-morbidity were determined. Twenty seven of the 469 children examined (5.8 %) had HSPM. The tooth prevalence of HSPM was 3.9 %. There was no significant sex (p = 0.06), age (p = 0.41), and socioeconomic status (p = 0.67) differences between children with HSPM and without HSPM. More children with HSPM had caries (p ≤ 0.001) and poor oral hygiene (p = 0.01). Children with HSPM have increased odds having dental caries (AOR: 6.34; CI: 2.78-14.46; p = <0.001) and reduced odds of having good oral hygiene (AOR: 0.32; CI: 0.13-0.78; p = 0.01) when compare with children without HSPM. Also 77.8 % of children with HSPM also had MIH. The prevalence of HSPM in the study population is significantly high. The large number of children with HSPM and MIH also suggests that HSPM is a predisposing factor for MIH. The significantly higher proportion of children with HSPM who had caries and poor oral hygiene makes it imperative to institute screening programmes for HSPM/MIH in the study population.


Hydrophobic gold nanoparticles via silane conjugation: chemically and thermally robust nanoparticles as dopants for nematic liquid crystals.
We examine for the first time how chemically and thermally stable gold nanoparticles (NPs), prepared by a silane conjugation approach, affect both the thermal and the electro-optical properties of a nematic liquid crystal (LC), when doped at concentrations ranging from 0.25 to 7.5 wt%. We find that the octadecylsilane-conjugated gold NPs stabilize both the enantiotropic nematic and the monotropic smectic-A phases of the LC host with a maximum stabilization of 2(°)C for the nematic and 3.5(°)C for the smectic-A phases for the mixture containing 1 wt% of the silanized particles. The same mixture shows the lowest values for the Fréedericksz transition threshold voltage and the highest value for the dielectric anisotropy. Generally, all NP-containing mixtures, except mixtures with NP concentrations exceeding 5 wt%, reduce the threshold voltage, increase the dielectric anisotropy and reduce both rise and decay time; the latter particularly at temperatures at least 10(°)C below the isotropic-nematic phase transition on cooling.


Postoperative Morbidity Risks Following Ileocolic Resection for Crohn's Disease Treated With Anti-TNF Alpha Therapy: A Retrospective Study of 360 Patients.
Despite the effectiveness of anti-TNF alpha (ATA) treatment to induce and maintain remission in Crohn's disease, surgical intervention is frequently required. Results of previous studies on the impact of anti-TNF on postoperative course are discordant. The aim of this study was to evaluate the impact of ATA on postoperative morbidity following ileocolic resection for Crohn's disease. A retrospective review of Crohn's disease patients undergoing ileocolic resection was performed. Patients receiving medical treatment ≤8 weeks prior to surgery were included and followed up for postoperative morbidity. The Clavien-Dindo classification was used for grading complications. Risk factors for postoperative morbidity were assessed on multivariable analysis. A total of 360 patients underwent ileocolic resection for Crohn's disease between 2002 and 2013; 15.3% of patients had ATA ≤8 weeks prior to surgery. Laparoscopic resections were performed in 110 cases (31%), of which 6% were converted to an open operation. Primary anastomosis without the formation of a diverting ileostomy was performed in 301 cases. Overall morbidity was 24.2%, with a mortality rate of 0.8%. ATA use prior to surgery was identified as an independent risk factor for overall morbidity (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.08-3.82; P = 0.027) and septic complications (OR, 2.14; 95% CI, 1.03-4.29; P = 0.04). In subgroup analysis of patients with a primary anastomosis, ATA use had no significant impact on septic or overall morbidity. Preoperative ATA use is a risk factor for overall postoperative morbidity and septic complications. However, the formation of a primary anastomosis should not be influenced by preoperative ATA use.


Inhibition of DMBA-croton oil two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate through modulation of cutaneous oxidative stress and inhibition of nitric oxide production.
Selenium, an essential micronutrient, plays important roles against different diseases, including several types of cancer. In the present study, antioxidative and chemopreventive properties of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated with a 7,12-dimethylbenz (a) anthracene - croton oil induced two-stage mouse skin carcinogenesis model. The compound was administered orally to carcinogen-treated mice at two different non-toxic doses, 2mg/kg. b.w. and 3mg/kg. b.w. Significant inhibition in the incidence of papilloma formation (53-80%) as well as in the cumulative numbers of papillomas per papilloma bearing mouse were observed in the treated groups as compared to the carcinogen control group. The compound was also found to upregulate significantly different phase II detoxifying enzymes such as glutathione-S-transferase (p<0.01) and superoxide dismutase (p<0.01) in skin cytosol when measured after 15 days and also after 12 weeks of the first 7,12-dimethylbenz (a) anthracene treatment. Lipid peroxidation measured with reference to thiobarbituric acid reactive substances in skin microsomes was significantly inhibited (p<0.05) in a dose dependent manner by diphenylmethyl selenocyanate. Considerable inhibition of the level of nitric oxide production in peritoneal macrophages was observed after 12 weeks (p<0.05). Thus the compound appears to exert chemopreventive activity in terms of papilloma formation, which may be through modulation of cutaneous lipid peroxidation, the phase II detoxifying enzyme system and nitric oxide production.


Influence of the solvent on the ground- and excited-state buffer-mediated proton-transfer reactions of a xanthenic dye.
The buffer-mediated proton-transfer reactions of the fluorescent xanthenic derivative 9-[1-(2-Methyl-4-methoxyphenyl)]-6-hydroxy-3H-xanthen-3-one (TG-II) have been studied in different aqueous media. We have employed various buffers to investigate the influence of donor/acceptor systems with different anion and/or cation chemical constituents on the kinetic parameters of proton-transfer. The kinetic parameters were recovered both in the ground-state by means of Fluorescence Lifetime Correlation Spectroscopy (FLCS) and in the excited-state by means of Time Correlated Single Photon Counting (TCSPC) and Global Compartmental Analysis (GCA). Both ground- and excited- deprotonation and protonation recovered rate constants in the presence of either phosphate or acetate buffer as donor/acceptor systems were similar. The presence of Tris-HCl buffer does not promote the excited-state proton-transfer (ESPT) reaction. The results indicate the influence of the ions on the ground-state proton-transfer (GSPT) rates and concomitantly on the ESPT reaction. The proton-transfer rate constants recovered here show a trend correlated with the Hofmeister series or the Marcus classification of ions.


Bone marrow cellularity in normal and polycythemic mice estimated by DNA incorporation of 3H-TdR.
Nucleated bone marrow cell numbers in normal and polycythemic mice were determined using 3H-thymidine (3H-TdR). The cellularities were estimated by extrapolating the exponential disappearance of labeled cells after a single injection of 3H-TdR to the time of injection. Dermestid beetles (Anthrenus piceus) were used to prepare tissue-free skeletons labeled with 3H-TdR. The correlation between tritium activity in bone marrow DNA and tritium derived from the combusted skeleton was determined. The total skeletal cellularity determined by isotope dilution analysis in both normal and polycythemic mice was 2.6 x 10(8) cells/mouse or 17.6 x 10(9) cells/kg body weight. Although the red cell component of the marrow was reduced in the polycythemic mouse, the total numbers of nucleated cells in both types of animals were similar. The differential distribution of cells in the polycythemic animal showed a twofold increase in granulocytic cells, which may explain the identical nucleated cell count in normal and in polycythemic mice.


Amazon forests green-up during 2005 drought.
Coupled climate-carbon cycle models suggest that Amazon forests are vulnerable to both long- and short-term droughts, but satellite observations showed a large-scale photosynthetic green-up in intact evergreen forests of the Amazon in response to a short, intense drought in 2005. These findings suggest that Amazon forests, although threatened by human-caused deforestation and fire and possibly by more severe long-term droughts, may be more resilient to climate changes than ecosystem models assume.


Alcoholics Anonymous and hazardously drinking women returning to the community after incarceration: predictors of attendance and outcome.
The number of women incarcerated within the United States has risen dramatically in recent decades, and high rates of alcohol problems are evident among this population. Although little is known about the patterns of help utilization and efficacy for alcohol problems, preliminary evidence suggests that Alcoholics Anonymous (AA) is a widely available resource for this population. Data were collected as part of a study evaluating the effect of a brief intervention to reduce alcohol use among hazardously drinking (i.e., score of 8 or above on the Alcohol Use Disorders Identification Test or 4 or more drinks at a time on at least 3 days in prior 3 months) incarcerated women. The current study characterized demographic, clinical, and previous AA attendance variables associated with AA attendance in the 6 months following incarceration. Associations between frequency of AA attendance and drinking outcomes following incarceration were also evaluated. Among the 224 participants who provided data about AA attendance, 54% reported some AA attendance during the follow-up assessment period. AA attendance in the year prior to study entry (OR = 4.02; 95% CI: 3.32 to 4.71) and greater baseline consequences of alcohol use (OR = 2.09; 95% CI: 1.73 to 2.44) were associated with increased odds of higher frequency of AA attendance following incarceration. Weekly or greater AA attendance was associated with reductions in negative drinking consequences (B = -0.45; p < 0.01) and frequency of drinking days (B = -0.28; p < 0.01) following incarceration. Findings from this study suggest that AA is frequently utilized by hazardously drinking women following incarceration. Alcohol outcomes may be enhanced by AA attendance at a weekly or greater frequency is associated with better alcohol outcomes relative to lower levels of AA attendance. Evaluation of clinical guidelines for prescribing AA attendance for incarcerated women remains a task for future research.


Predictors of delayed Antenatal Care (ANC) visits in Nigeria: secondary analysis of 2013 Nigeria Demographic and Health Survey (NDHS).
Antenatal Care (ANC) is an important component of maternal health and covers a wide range of activities with huge potential benefits for positive pregnancy out comes. However, large proportions of women do initiate ANC early resulting in adverse consequences. The study utilized the nationally-representative sample of women of reproductive age interviewed during the 2013 Nigeria DHS. Analysis was restricted to 20, 467 women aged 15-49 years who had a live birth in the five-year period prior to the survey. Multinomial logistic regression was performed using Stata v13 to determine significant factors related to timing of initiation of ANC. Relative risk ratio (RRR) was used to assess the strength of association between independent and dependent variables. Overall, 27%, 62% and 12% of women initiated ANC in the first, second and third trimesters respectively. In both the two model, the findings reveal that maternal education, level of media exposure, region and place of residence are the uniform predictors of initiation of ANC; having health insurance is a significant predictor of third trimester ANC initiation relative to first to first trimester only. Within the categories of household wealth, levels of participation in household decision-making and region some categories are significant predictors while others are not. Maternal education, level of media exposure, region and place of residence are the uniform and consistent predictors of delay in ANC initiation. This suggests that girl-child education, universal health coverage and universal health insurance could be the interventions required to improve service utilization and maternal health.


Astrocytic Responses to Binge Alcohol Intake in the Mouse Hindbrain.
Ethanol is the most commonly used toxic chemical in human cultures. Ethanol predominantly damages the brain causing various neurological disorders. Astrocytes are important cellular targets of ethanol in the brain and are involved in alcoholic symptoms. Recent studies have revealed the diversity of astrocyte populations in the brain. However, it is unclear how the different astrocyte populations respond to an excess of ethanol. Here we examined the effect of binge ethanol levels on astrocytes in the mouse brainstem and cerebellum. Ethanol administration for four consecutive days increased the glial fibrillary acidic protein (GFAP)-immunoreactive signals in the spinal tract of the trigeminal nerve (stTN) and reticular nucleus (RN). Another astrocyte marker, aquaporin 4 (AQP4), was also increased in the stTN with a pattern similar to that of GFAP. However, in the RN, the immunoreactive signals of AQP4 were different from that of GFAP and were not changed by ethanol administration. In the cerebellum, GFAP-positive signals were found in all four astrocytic populations, and those in the Bergmann glia were selectively eliminated by ethanol administration. We next examined the effect of estradiol on the ethanol-induced changes in astrocytic immunoreactive signals. The administration of estradiol alone increased the AQP4-immunoreactivity in the stTN with a pattern similar to that of ethanol, whereas the co-administration of estradiol and ethanol suppressed the intensity of the AQP4-positive signals. Thus, binge levels of ethanol intake selectively affect astrocyte populations in the brainstem and cerebellum. Sex hormones can affect the ethanol-induced neurotoxicity via modulation of astrocyte reactivity.


[Computer modeling the cytochrome P450 three-dimensional structure: problems and prospects].
The review is devoted to the description of basic approaches, problems and prospects of computer modelling of 3D structures of cytochromes P450 (P450s). The following questions have been are considered in the review: (1) the role of computer molecular modelling in P450s research; (2) basic stages of homology modelling of protein 3D structures; (3) purposes and tasks of molecular modelling; (4) problems of P450s homology modelling; (5) criteria for successful P450s homology modelling; (6) methods of P450s models refinement, verification of correctness and reliability.


[3-unit complex for proton therapy].
Since 1969 proton beam therapy of patients with different types of diseases using the ITEP synchrotron proton beam with the energy up to 200 MeV has been conducted in a number of Moscow medical centers. These irradiations employing a specially formed beam are used on a routine basis and are performed in parallel with the program of physical research. Two additional channels as well as two new procedure rooms have been in operation since 1982. A special setup of equipment including clinical dosimetry devices, equipment for patients' irradiation (4 special units), and computer-controlled systems have been installed at the facility. By the present time over 1300 patients have been irradiated. The authors describe physical and dosimetric equipment and irradiation techniques. A summary table containing data on the patients is provided.


Integrative analyses of the RNA modification machinery reveal tissue- and cancer-specific signatures.
RNA modifications play central roles in cellular fate and differentiation. However, the machinery responsible for placing, removing, and recognizing more than 170 RNA modifications remains largely uncharacterized and poorly annotated, and we currently lack integrative studies that identify which RNA modification-related proteins (RMPs) may be dysregulated in each cancer type. Here, we perform a comprehensive annotation and evolutionary analysis of human RMPs, as well as an integrative analysis of their expression patterns across 32 tissues, 10 species, and 13,358 paired tumor-normal human samples. Our analysis reveals an unanticipated heterogeneity of RMP expression patterns across mammalian tissues, with a vast proportion of duplicated enzymes displaying testis-specific expression, suggesting a key role for RNA modifications in sperm formation and possibly intergenerational inheritance. We uncover many RMPs that are dysregulated in various types of cancer, and whose expression levels are predictive of cancer progression. Surprisingly, we find that several commonly studied RNA modification enzymes such as METTL3 or FTO are not significantly upregulated in most cancer types, whereas several less-characterized RMPs, such as LAGE3 and HENMT1, are dysregulated in many cancers. Our analyses reveal an unanticipated heterogeneity in the expression patterns of RMPs across mammalian tissues and uncover a large proportion of dysregulated RMPs in multiple cancer types. We provide novel targets for future cancer research studies targeting the human epitranscriptome, as well as foundations to understand cell type-specific behaviors that are orchestrated by RNA modifications.


Cardiovascular phenotype in extremely low birth weight infants: long-term consequences.
Low birth weight, a possible consequence of prematurity at birth or intrauterine growth restriction, has been recently recognized as an emerging risk factor to develop cardiovascular (CV) future adverse events. Our aim was to perform a short review about the studies conducted in order to evaluate the CV risk profile of a specific subpopulation of infants suffering from low birth weight, that is those having a birth weight less than 1,000 g, called extremely low birth weight.


[Chemical constituents from lipophilic parts of stems of Celastrus monospermus].
The chemical constituents from lipophilic parts of the stems of Celastrus monospermus were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods including silica gel, ODS and Sephadex LH-20, and the structures of compounds were determined by spectral data analyses. Twenty six compounds were obtained and identified as 3-oxofriedelane(1), 3-oxofriedelan-28-al(2), 3,12-dioxofriedelane(3), 3β-hydroxyolean-12-en(4), 3-oxo-28-hydroxyfriedelane(5), 3-oxo-29-hydroxyfriedelane(6), 3-oxo-11β-hydroxyfriedel-ane(7), 3-oxo-16α-hydroxyfriedelane(8), 3,12-dioxo-28-hydroxyfriedelane(9), 1,3-dioxo-15α-hydroxyfriedelane(10), 3β,6α-dihydroxyolean-12-en(11), 3-oxo-7α,26-dihydroxyfriedel-ane(12), oleanolic acid(13), 3,15-dioxofriedelane(14), 3α-friedelinol(15), 3,12-dioxofriedelan-28-al(16), 3-oxo-12α-hydroxyfriedelane(17), 3,15-dioxo-12α-hydroxyfriedelane(18), 3β,11β-dihydroxyolean-12-en(19), 1β,3β-dihydroxylupan-20(29)-en(20), 3-oxo-12α,28-dihydroxyfriedelane(21), 3β,23-epoxyfriedelan-28-oic acid(22), salaquinone A(23), 2α,3β-dihydroxyfriedelan-28-oic acid(24), 23-nor-6-oxodemethylpristimerol(25) and 3-oxo-friedelan-27,28-dioic acid(26). Among them, compounds 8, 10-15, 18-20, 22-26 were obtained from this plant for the first time, and compounds 8, 10, 12, 14-15, 18, 22-24, 26 were separated from the genus Celastrus for the first time.


Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications.
Thiamine (vitamin B1) is an essential cofactor in most organisms and is required at several stages of anabolic and catabolic intermediary metabolism, such as intracellular glucose metabolism, and is also a modulator of neuronal and neuro-muscular transmission. Lack of thiamine or defects in its intracellular transport can cause a number of severe disorders. Thiamine acts as a coenzyme for transketolase (TK) and for the pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism. In particular, TK is able to shift excess fructose-6-phosphate and glycerhaldeyde-3-phosphate from glycolysis into the pentose-phosphate shunt, thus eliminating these potentially damaging metabolites from the cytosol. Diabetes might be considered a thiamine-deficient state, if not in absolute terms at least relative to the increased requirements deriving from accelerated and amplified glucose metabolism in non-insulin dependent tissues that, like the vessel wall, are prone to complications. A thiamine/TK activity deficiency has been described in diabetic patients, the correction of which by thiamine and/or its lipophilic derivative, benfotiamine, has been demonstrated in vitro to counteract the damaging effects of hyperglycaemia on vascular cells. Little is known, however, on the positive effects of thiamine/benfotiamine administration in diabetic patients, apart from the possible amelioration of neuropathic symptoms. Clinical trials on diabetic patients would be necessary to test this vitamin as a potential and inexpensive approach to the prevention and/or treatment of diabetic vascular complications.


[Molecular mechanism of the replication of several DNA viruses].
Study of the replicative mechanism of viruses is extremely important, since the knowledge of the events taking place at a molecular level can contribute to new antiviral product elaboration. A unique pattern of the DNA virus replication cannot be given, because every virus family has its own mechanism of replication. Investigations were conducted on the replication of two groups of viruses of major importance in human pathology: the hepadnaviruses and the herpesviruses, which are involved not only in acute infections, but also in some cellular transformations and even in cancerogenesis. It was shown that the replication mechanism of the hepadnaviruses has several points in common with retroviruses, fact which places them in a rather peculiar position among the DNA viruses. On the other hand, the herpes viruses have their own characteristics such as the four genome isomeres, whose significance is yet unclear. The viral message transcription and translation stages, as well as the mechanism of replication of the genome are described.


Long-term stability of osseointegrated implants in augmented bone: a 5-year prospective study in partially edentulous patients.
This prospective clinical study evaluated the 5-year survival and success rates of 66 titanium implants placed in bone that had been previously augmented with autografts and nonresorbable barrier membranes. During the observation period, three patients with five implants dropped out of the study. None of the remaining 61 implants were lost during the follow-up period (implant survival rate of 100%). One implant exhibited a periimplant infection, whereas 60 implants were considered clinically successful at the 5-year examination, resulting in a 5-year success rate of 98.3%. It can be concluded that the clinical results of implants in regenerated bone are comparable to those of implants in nonregenerated bone.


Vitamin nutritional status in Italy.
In almost all countries, the critical point for defining the nutritional status of a population is represented by the poor source of representative data of the whole population or of the main subgroups of the population. Also, in Italy, the sources of data on the nutritional status of biochemically evaluated macro- and micronutrients are scant in relation to specific groups of the population, mainly children and the elderly. In this short review, only the nutritional status for vitamins is considered. The existing limited data, however, indicate that clinical signs of severe deficiency are not observed in Italy and the incidence of vitamin malnutrition is moderate. This is probably due to the large availability and variety of food and to Italian eating habits which reflect the typical Mediterranean diet: rich, for example, in cereals, fresh fruit and vegetables, and olive oil. However, there are particular conditions, linked to lifestyle, in which the risk of a mild or moderate vitamin malnutrition increases. These include a monotonous diet, drug interactions, smoking habits and alcohol consumption.


Late onset leflunomide-induced cutaneous ulcers in a seronegative arthritis patient: A case report.
The differential diagnosis for chronic cutaneous ulcers is wide. Once the common causes have been excluded, infrequent ones, including drugs, should be considered. We report the case of a 67 year old woman with multiple ulcers not responding to conventional treatment. Multiple investigations including laboratory testing, skin biopsies and tissue cultures were negative. A few cases of leflunomide-induced cutaneous ulcers are reported in the literature. Our patient was on this drug for 12 years. Discontinuation of leflunomide led to ulcers resolution. This is the longest reported time interval between leflunomide initiation and ulceration onset.


[The effect of rosiglitazone on plasma adiponectin and resistin levels in obese PCO woman--preliminary report].
to determine the effect of rosiglitazone on plasma adiponectin and resistin levels in obese, non-diabetic polycystic ovary (PCO) subjects and relationship between circulating adipocytokines, insulin resistance and lipid profile. PCOS women were treated 6 months with 4mg rosiglitazone daily (the blood was tested before and 3; 6 months after treatment). Plasma resistin, adiponectin, total-cholesterol, triglycerides, HDL- and LDL-cholesterol levels were examined in 12 obese PCO women (age 18-45) with BMI >30. Twelve healthy, obese individuals with BMI >30 were controls. We measured peripheral insulin resistance using FIRI and Quicki indexes derived from fasting insulin and glucose levels, and insulin area under the curve during an oral glucose challenge. BMI, WHR, % of total fat, FIRI, Quicki and fasting insulin were comparable in both groups. We observed significantly lower adiponectin and resistin plasma levels in PCO woman. Fasting plasma insulin level was similar in both groups and didn't change after treatment. We noticed decrease in insulin area under the curve after 3 and 6 months of rosiglitazon (respectively p = 0.029 and 0.03). There were decreases after treatment in BMI and WHR and beneficial changes in lipid profile--but not significant. Plasma adiponectin level increased after 6 months of treatment (p = 0.03) but plasma resistin level didn't change. We revealed negative correlation between adiponectin, BMI and fasting glucose. Our data confirm that in obese, hyperinsulinemic PCO women adiponectin and resistin levels were decreased. After therapy we observed increase in adiponectin level and no change in resistin level.


Influence of polyethylene glycol chain length on the physicochemical and biological properties of poly(ethylene imine)-graft-poly(ethylene glycol) block copolymer/SiRNA polyplexes.
Polyplexes between siRNA and poly(ethylene imine) (PEI) derivatives are promising nonviral carriers for siRNA. The polyplex stability is of critical importance for efficient siRNA delivery to the cytoplasm. Here, we investigate the effect of PEGylation at a constant ratio ( approximately 50%) on the biophysical properties of the polyplexes. Particle size, zeta potential, and stability against heparin as well as RNase digestion and reporter gene knockdown under in vitro conditions of different siRNA polyplexes were characterized. Stability and size of siRNA polyplexes were clearly influenced by PEI-PEG structure, and high degrees of substitution such as PEI(25k)-g-PEG(550)(30) resulted in large (300-400 nm), diffuse complexes (AFM) which showed condensation behavior only at high N/P ratios. All other polyplexes and the PEI control showed similar sizes (150 nm) and compact structures in AFM, with complete condensation reached at N/P ratio of 3. Stability of siRNA polyplexes against heparin displacement and RNase digestion could be modified by PEGylation. Protection against RNase digestion was highest for PEI(25k)-g-PEG(5k)(4) and PEI(25k)-g-PEG(20k)(1), while siRNA/PEI provided insufficient protection. In knockdown experiments using NIH/3T3 fibroblasts stably expressing beta-galactosidase, it was shown that PEG chain length had a significant influence on biological activity of siRNA. Polyplexes with siRNA containing PEI(25k)-g-PEG(5k)(4) and PEI(25k)-g-PEG(20k)(1) yielded similar efficiencies of ca. 70% knockdown as lipofectamine controls. Confocal microscopy demonstrated enhanced cellular uptake of siRNA into cytosol by polyplexes formation with PEI copolymers. In conclusion, both the chain length and graft density of PEG were found to strongly influence siRNA condensation and stability and hence affect the knockdown efficiency of PEI-PEG/siRNA polyplexes.


Polymer-supported stereoselective synthesis of benzimidazolinopiperazinones.
We describe the efficient synthesis of 4,7,8,10-tetrasubstituted-(((4S,10aS)-3-oxo-3,4,10,10a-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-2(1H)-yl)alkyl)amides on solid phase via tandem N-acyliminium ion cyclization-nucleophilic addition reactions. The synthesis proceeded with complete stereocontrol of a newly formed stereogenic center, provided crude material of high purity, and used commercially available building blocks under mild reaction conditions.


[Long-term results of arthrodesis of the upper ankle joint].
From 1985 to 1987 a total of 95 ankle arthrodesis were performed. The retrospective study showed in most cases a bony healing within 14 weeks with a complication rate of 20%, due to reduced conditions of the soft tissue. The follow up examination of 52 patients showed a good to very good result in 48 cases. Nearly 70% of the patients did not use orthopaedic made-to-measure shoes at the time of follow up. Only 4% were dissatisfied with this procedure. Therefore the arthrodesis of the ankle should be preferred in comparison to the arthroplastik.


5-Hydroxytryptamine type 7 receptor neuroprotection against NMDA-induced excitotoxicity is PDGFβ receptor dependent.
The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the hippocampus. Long-term (2-24 h) activation of 5-HT7 receptors regulates growth factor receptor expression, including the expression of platelet-derived growth factor (PDGF) β receptors. Direct activation of PDGFβ receptors in primary hippocampal and cortical neurons inhibits NMDA receptor activity and attenuates NMDA receptor-induced neurotoxicity. Our objective was to investigate whether the 5-HT7 receptor-induced increase in PDGFβ receptor expression would be similarly neuroprotective. We demonstrate that 5-HT7 receptor agonist treatment in primary hippocampal neurons also increases the expression of phospholipase C (PLC) γ, a downstream effector of PDGFβ receptors associated with the inhibition of NMDA receptor activity. To determine if the up-regulation of PDGFβ receptors is neuroprotective, primary hippocampal neurons were incubated with the 5-HT7 receptor agonist, LP 12, for 24 h. Indeed, LP 12 treatment prevented NMDA-induced neurotoxicity and this effect was dependent on PDGFβ receptor kinase activity. Treatment of primary neurons with LP 12 also differentially altered NMDA receptor subunit expression, reducing the expression of NR1 and NR2B, but not NR2A. These findings demonstrate the potential for providing growth factor receptor-dependent neuroprotective effects using small-molecule ligands of G protein-coupled receptors.


Familial occurrence of testicular cancer.
A case of testicular cancer in 2 brothers is reported and a review of the literature about testicular malignancies and etiologic factors in closely related family members is given. The familial incidence of testicular tumor is found to be 3% in twins and 0.6-2.1% in less closely related men. Tumors were of the same histology in 70-77% of the twins, whereas in brothers and in other degrees of relationship tumors of different histology mostly occur. Following the diagnosis of the tumor in the first man, the average interval to presentation of the tumor in the relative was 3.7 years in twins, 7.7 years in nontwin brothers and 13.5 years for less closely related men. The need for a thorough checkup of other family members is advised.


Nanoparticles Composed of Zn and ZnO Inhibit Peronospora tabacina Spore Germination in vitro and P. tabacina Infectivity on Tobacco Leaves.
Manufactured nanoparticles (NPs) are increasingly being used for commercial purposes and certain NP types have been shown to have broad spectrum antibacterial activity. In contrast, their activities against fungi and fungi-like oomycetes are less studied. Here, we examined the potential of two types of commercially available Zn NPs (Zn NPs and ZnO NPs) to inhibit spore germination and infectivity on tobacco leaves resulting from exposure to the fungi-like oomycete pathogen Peronospora tabacina (P. tabacina). Both types of NPs, as well as ZnCl₂ and bulk ZnO control treatments, inhibited spore germination compared to a blank control. ZnO ENMs were shown to be a much more powerful suppressor of spore germination and infectivity than bulk ZnO. ZnO and Zn NPs significantly inhibited leaf infection at 8 and 10 mg·L-1, respectively. Both types of NPs were found to provide substantially higher concentration dependent inhibition of spore germination and infectivity than could be readily explained by the presence of dissolved Zn. These results suggest that both NP types have potential for use as economic, low-dose, potentially non-persistent anti-microbial agents against the oomycete P. tabacina.


Molecular design in drug discovery: a comprehensive review of deep generative models.
Deep generative models have been an upsurge in the deep learning community since they were proposed. These models are designed for generating new synthetic data including images, videos and texts by fitting the data approximate distributions. In the last few years, deep generative models have shown superior performance in drug discovery especially de novo molecular design. In this study, deep generative models are reviewed to witness the recent advances of de novo molecular design for drug discovery. In addition, we divide those models into two categories based on molecular representations in silico. Then these two classical types of models are reported in detail and discussed about both pros and cons. We also indicate the current challenges in deep generative models for de novo molecular design. De novo molecular design automatically is promising but a long road to be explored.


High fever. Experience in private practice.
Experience with confirmed high fever, 40 C (104 F) or more, in a private practice during 14 years is presented. The records of 1,500 patients covering 8,000 patient years disclosed only 108 confirmed episodes of high fever. Eleven diagnostic categories included 149 diagnoses. Fourteen of 43 roentgenographic examinations yielded positive findings, including two cases of pneumonia not detected on physical examination. Two of six stool cultures yielded specific enteric pathogens. Convulsions occurred in 12 of the 108 episodes of high fever, and recurred only once in one child. There were no deaths in this series of children with high fevers. Only one diagnosis, pneumonia, was significantly more frequent in confirmed high fever than in unconfirmed high fever. Lastly, the ability of a group of mothers to read thermometers set at three different temperatures proved to be surprisingly good.


Tolerance induction by veto CTLs in the TCR transgenic 2C mouse model. II. Deletion of effector cells by Fas-Fas ligand apoptosis.
The direct assay of veto CTLs in the 2C mouse model enables monitoring, by FACS, the fate of the TCR transgenic effector CD8(+) T cells, the transgene of which can be stained with clonotypic Ab 1B2. After the addition of veto cells, CD8(+)1B2(+) effector cells increasingly express annexin V, and maximal apoptosis is attained 72 h after initiation of MLR. This veto activity can be partially blocked by anti-CD8 Abs directed against the allele expressed by the veto CTLs, but not by the effector cells. When effector CD8(+) T cells were from 2C mice, which lack Fas expression ((2CX lpr)F(2)), deletion of effector cells was not exhibited by veto cells. The protein levels of the apoptosis inhibitors FLIP and Bcl2 in purified CD8(+)1B2(+) effector cells at different time points after MLR showed an initial up-regulation of these inhibitors, with marked reduction of FLIP, but not of Bcl2, by 48 h after initiation of culture. Taken together, these results are in accordance with a Fas-FasL-based mechanism in which prolonged binding between the effector cell and the veto cell might be required to allow FLIP to be down-regulated. Such prolonged interaction might be afforded through the interaction of CD8 molecules on the veto cell with the alpha3 domain of H2 class 1 on the effector cell.


A survey of the parasites of coyotes (Canis latrans) in New York based on fecal analysis.
Coyotes (Canis latrans) have colonized northeastern North America only within the past 10-80 yr. We examined feces of coyotes in 2000-01 at three sites in New York (USA) to survey parasites in the region. Two cestodes, nine nematodes, five protozoa, one trematode, and two arthropods were identified from 145 coyote fecal samples. Parasite component community diversity was higher (n = 16 species) in southern New York than in middle and northern sites (nine species each) and infracommunity species richness was greater in southern New York than at the other sites. These differences may reflect the variable diets of coyotes, as well as recent colonization of the region and the mixing of component communities from expanding coyote populations.


A toxicity profile of osteoprotegerin in the cynomolgus monkey.
Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.


Adult-Onset Atopic Dermatitis: Fact or Fancy?
Atopic dermatitis therapy can be a challenge in many cases. Persistence into adulthood often reflects the more severe cases and such patients have the added problems of hand eczema and thick nummular lesions that resist topical medications. Within this group are patients labeled as having adult-onset atopic dermatitis, a designation that is hard to define and probably represents those whose childhood eczema was simply forgotten. Management is difficult for most adult cases and should not be diverted by questionable labels.


The reactions of a series of terpenoids with H(3) O(+) , NO(+) and O 2+ studied using selected ion flow tube mass spectrometry.
The reactions of H(3) O(+) , NO(+) and O 2+ with twelve terpenoids and one terpene, all of which occur naturally in plants and which possess important smell and flavourant properties, were characterized using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS). The H(3) O(+) reactions resulted primarily in the formation of the proton transfer product and occasionally in a water elimination product. The NO(+) reactions instead generated the charge transfer product or NO(+) adducts, and occasionally alkyl fragments, or resulted in hydride abstraction. Reaction with O 2+ caused a higher fragmentation of the terpenoids with the molecular ion being the minor product of most reactions. Identification and quantification of each compound in complex mixtures are probably possible in most cases using the H(3) O(+) and/or NO(+) precursors while O 2+ may be useful for isomer discrimination. Our data suggests that SIFT-MS may be a useful tool for the rapid analysis of these compounds in plants and derived foodstuffs.


Botulinum toxin treatment in patients with focal dystonia and hemifacial spasm. A multicenter study of the Italian Movement Disorder Group.
In six Centers belonging to the Italian Movement Disorder Study Group, the efficacy of botulinum toxin treatment was evaluated in an open collaborative study in 251 patients with focal dystonia and hemifacial spasm. The percentage of functional improvement ranged from 66% to 81% in patients with blepharospasm, from 40% to 51% in patients with spasmodic torticollis and from 73% to 81% in those with hemifacial spasm. Good results were also obtained in patients with oromandibular dystonia, laryngeal dystonia and writer's cramp. Side effects were mild and transient. Local botulinum toxin injection is the first choice symptomatic treatment in focal dystonia and hemifacial spasm.


Beta 2 adrenergic receptor polymorphisms in cystic fibrosis.
There has been a recent emphasis on identifying modifier genes that influence the severity of cystic fibrosis (CF) lung disease. The beta-2-adrenergic receptor is expressed on airway smooth muscle, is the target for inhaled beta agonists, and has several common polymorphisms in its gene, ADRB2. Polymorphisms changing glycine to arginine or glutamate to glutamine in codons 16 and 27, respectively, were associated with differences in clinical response to inhaled beta agonists in individuals with asthma. We compared acute airway responsiveness and 5-year decline in pulmonary function in CF patients with different ADRB2 genotypes. One hundred and six subjects performed spirometry before and after the administration of an inhaled bronchodilator, and had ADRB2 genotype determined for codons 16 and 27. Comparing the percent change in FEV(1) and FEF(25-75) continuously revealed differences in the degree of airway responsiveness to bronchodilator between ADRB2-genotyped groups. However, there was no significant relationship between the ADRB2 genotype at positions 16 and 27 and bronchodilator response when defined as 12% improvement in FEV(1). Five-year decline in percent predicted FEV(1) showed no association with ADRB2 genotype. These data are consistent with variants of the ADRB2 gene having different responses to bronchodilator, but the long-term effects, if any, are not apparent over a 5-year period.


Communicating an evolutionary diagnosis of disability to parents.
Communicating a diagnosis of disability to parents, when the diagnosis and prognosis are unclear, is problematic. This is discussed in the light of information received from mothers of such children who attended a counselling and support group. It is concluded that dissatisfaction with diagnosis is not inevitable, if similar guidelines to those suggested for children with Down's syndrome are used. It is essential that parents are involved in management and feel they have something practical to do to help their children. Clinics must organize themselves to avoid swamping parents with information and to provide regular ongoing support.


Performance of Verigene Rapid Diagnostic Testing for Detection of Inpatient Pediatric Bacteremia.
Verigene blood culture panels comprise rapid diagnostic testing, which aids in early bacteremia species identification. This study determined the concordance of Verigene rapid diagnostic results compared with the Vitek reference standard in patients admitted to a children's hospital. This was a 3-year retrospective observational study of neonatal and pediatric patients ≤18 years admitted to a children's hospital with confirmed bacteremia for whom Verigene testing was performed. Verigene testing was conducted on cultures with reported growth on Gram stain and final organism speciation confirmed via Vitek. Percent concordance and positive percent agreement with 95% CIs were calculated for Verigene panel-identifiable organisms. Negative percent agreement with 95% CIs was calculated for non-panel organisms. Time-to-result was calculated from Gram stain reporting to both Verigene and Vitek final organism susceptibility. One hundred thirty-five Gram-positive (GP) and 51 Gram-negative (GN) isolates were identified through Vitek. Verigene GP panel-detectable organisms were correctly identified 96.9% (125/129) at the genus level and 95.3% (123/129) at the species level. Overall positive percent agreement was 95.3 (CI: 90.2-98.3). Negative percent agreement was 83.3 (CI: 35.9-99.6) for the 6 non-panel GP organisms. All GN isolates were correctly identified on Verigene. Median time-to-result was 2.9 hours (IQR 2.6, 3.2) and 44.4 hours (IQR: 35.4, 52.5) for Verigene and final susceptibilities, respectively. There was a statistically significant time savings of 41.5 hours (CI: 29.8-53.2) for identification and detection of resistance markers (p < 0.0001). Verigene concordance at our institution aligns with results from previously published studies and can be considered a reliable clinical decision-support tool.


Post-translational dysfunctions in channelopathies of the nervous system.
Channelopathies comprise various diseases caused by defects of ion channels. Modifications of their biophysical properties are common and have been widely studied. However, ion channels are heterogeneous multi-molecular complexes that are extensively modulated and undergo a maturation process comprising numerous steps of structural modifications and intracellular trafficking. Perturbations of these processes can give rise to aberrant channels that cause pathologies. Here we review channelopathies of the nervous system associated with dysfunctions at the post-translational level (folding, trafficking, degradation, subcellular localization, interactions with associated proteins and structural post-translational modifications). We briefly outline the physiology of ion channels' maturation and discuss examples of defective mechanisms, focusing in particular on voltage-gated sodium channels, which are implicated in numerous neurological disorders. We also shortly introduce possible strategies to develop therapeutic approaches that target these processes. This article is part of the Special Issue entitled 'Channelopathies.'


Consecutive oxygen-for-sulfur exchange reactions between vanadium oxide cluster anions and hydrogen sulfide.
Vanadium oxide cluster anions Vm(16)On(-) and Vm(18)On(-) were prepared by laser ablation and reacted with hydrogen sulfide (H2S) in a fast flow reactor under thermal collision conditions. A time-of-flight mass spectrometer was used to detect the cluster distributions before and after the interactions with H2S. The experiments suggest that the oxygen-for-sulfur (O/S) exchange reaction to release water was evidenced in the reactor for most of the cluster anions: VmOn(-) + H2S → VmOn-1S(-) + H2O. For reactions of clusters VO3(-) and VO4(-) with H2S, consecutive O/S exchange reactions led to the generation of sulfur containing vanadium oxide cluster anions VO3-kSk(-) (k = 1-3) and VO4-kSk(-) (k = 1-4). Density functional theory calculations were performed for the reactions of VO3-4(-) with H2S, and the results indicate that the O/S exchange reactions are both thermodynamically and kinetically favorable, which supports the experimental observations. The reactions of VmOn(+) cluster cations with H2S have been reported previously (Jia, M.-Y.; Xu, B.; Ding, X.-L.; Zhao, Y.-X.; He, S.-G.; Ge, M.-F. J. Phys. Chem. C 2012, 116, 9043), and this study of cluster anions provides further new insights into the transformations of H2S over vanadium oxides at the molecular level.


Application of Bronchoscopic TransParenchymal Nodule Access in tuberculous bronchial occlusion.
Bronchoscopic TransParenchymal Nodule Access (BTPNA) technology is mainly used for sampling or ablative treatment of lung parenchymal lesions that cannot be reached by bronchoscopy and its appendages, generally for palliative treatment of some lung tumors. We used BTPNA to treat a 32-year-old young woman with pulmonary tuberculosis and successfully perforated her occluded left main bronchus. Her left atelectasis was recovered, and a silicone stent was inserted to preserve the shape of the left main bronchus.


[Karyometric studies of the pancreas and adrenal glands of the albino-rat fed an unbalanced glucose diet or a glucose diet supplemented with thiamine].
Karyometric measurements in rats which for 30 days had received a glucose diet or a glucose diet supplemented with thiamine showed the following decrease in nuclear size in contrast to no treated controls. (see article) In both experimental groups there was a 30% loss of weight during the course of the experiment. The different decreases in nuclear volume in the examined organs cannot be explained only by a relative state of hunger. The very large decrease in activity in the fasciculated zone of the adrenal cortex is explained as an adaptation mechanism favouring glucose oxidation by insulin, and the relative increase in activity in the adrenal medulla as an adaptation mechanism to accomplish an elevated lipolysis.


Circulating endothelin-1 levels in patients with bronchial asthma.
We attempted to clarify the relationship between circulating endothelin-1 levels and bronchial hyperreactivity in asthmatic patients. Sixty-two asthmatic patients were studied for plasma endothelin-1 levels during acute asthma. The relationship between plasma endothelin-1 levels and pulmonary function (FEV1/FVC) was examined in 17 patients. Twelve patients were studied for changes in plasma endothelin-1 levels during methacholine inhalation tests. Plasma endothelin-1 levels during acute asthma correlated with the severity of acute asthma defined with the Clinical Asthma Evaluation Score, and those during the methacholine challenge test correlated with the grade of bronchoconstriction (P < .01). A significant negative correlation was observed between plasma endothelin-1 levels and FEV1/FVC ratio (P < .01). These results suggest that circulating endothelin-1 levels may reflect the severity of acute asthma.


Turns with multiple and single head cast mediate Drosophila larval light avoidance.
Drosophila larvae exhibit klinotaxis when placed in a gradient of temperature, chemicals, or light. The larva samples environmental stimuli by casting its head from side to side. By comparing the results of two consecutive samples, it decides the direction of movement, appearing as a turn proceeded by one or more head casts. Here by analyzing larval behavior in a light-spot-based phototaxis assay, we showed that, in addition to turns with a single cast (1-cast), turns with multiple head casts (n-cast) helped to improve the success of light avoidance. Upon entering the light spot, the probability of escape from light after the first head cast was only ~30%. As the number of head casts increased, the chance of successful light avoidance increased and the overall chance of escaping from light increased to >70%. The amplitudes of first head casts that failed in light avoidance were significantly smaller in n-cast turns than those in 1-cast events, indicating that n-cast turns might be planned before completion of the first head cast. In n-casts, the amplitude of the second head cast was generally larger than that of the first head cast, suggesting that larvae tried harder in later attempts to improve the efficacy of light avoidance. We propose that both 1-cast turns and n-cast turns contribute to successful larval light avoidance, and both can be initiated at the first head cast.


A comparison of the energy costs with use of different types of manual wheelchair in disabled persons.
The energy cost of physical activity is a well-documented field of research both in non-disabled subjects and in subjects with physical disabilities, in particular spinal cord lesions. The aim of this study was, therefore, to investigate the energy cost and subjective fatigue in disabled persons who make daily use of a manual wheelchair by comparing three different types of wheelchair (standard, lightweight and ultra-light) in order to obtain indices useful for prescribing the most effective and appropriate wheelchairaid for the individual patient. The study was carried out on 18 patients affected by paraplegia or paraparesis due to spinal cord injury at different levels. Result revealed a significant difference across the three types of wheelchair, with the energy expenditure to cover 100 m increasing from the ultra-light (lowest expenditure) to the lightweight to the standard type (highest expenditure). The differences observed in the average energy consumed to cover a distance of 100 meters with the three types of wheelchair confirm the hypothesis that it is the weight of the wheelchair chosen by the rehabilitation team together with the patient that constitutes the fundamental criterion in making such a prescription. Obviously, in making the final choice, other factors as well need to be taken into account, such as the person's age and anthropometric characteristics, the nature of the disability and prognosis, the achievable degree of autonomy, functional capacities, personal preferences, the type of use (domestic or external), accessibility, reliability and durability, esthetic features, eventual accessories available, etc.


Dream-associated behaviors affecting pregnant and postpartum women.
Evaluate the prevalence and phenomenology of dream-associated behaviors affecting pregnant and postpartum mothers. Episodes consist of anxious dreams and nightmares about the new infant that are accompanied by complex behaviors (motor activity, speaking, expressing emotion). Three-group design (postpartum, pregnant, null gravida), self-report, and repeated measures. Pregnancy and postpartum groups: completion of questionnaires in hospital room within 48 hours of giving birth and home telephone interviews; null gravida group: completion of questionnaires and interview in person or by telephone. Two hundred seventy-three women in 3 groups: postpartum: n = 202 (mean age = 29.7 +/- 4.94 years; 95 primiparas, 107 multiparas); pregnant: n = 50 (mean age = 31.1 +/- 5.44 years); null gravida: n = 21 (mean age = 28.5 +/- 6.34 years). Subjects completed questionnaires about pregnancy and birth factors, personality, and sleep and participated in interviews concerning the prevalence of recent infant dreams and nightmares, associated behaviors, anxiety, depression, and other psychopathologic factors. Most women in all groups recalled dreams (88%-91%). Postpartum and pregnant women recalled infant dreams and nightmares with equal prevalence, but more postpartum women reported they contained anxiety (75%) and the infant in peril (73%) than did pregnant women (59%, P < 0.05 and 42%, P < 0.0001). More postpartum (63%) than pregnant (40%) women reported dream-associated behaviors (P < 0.01), but neither group differed from null gravida women (56%). This was due to different distributions over groups of the behavior subtypes. Motor activity was present in twice as many postpartum (57%) as pregnant (24%) or null gravida (25%) women (all P < 0.0001). Expressing emotion was more prevalent among null gravida (56%) than postpartum women (27%) (P < 0.05) but was not different from pregnant women (37%). Speaking was equally prevalent among the 3 groups (12%-19%). Behaviors were associated with nightmares, dream anxiety and, among postpartum women, post-awakening anxiety (41%), confusion (51%), and a need to check on the infant (60%). Primiparas and multiparas differed in dream and nightmare recall but not in prevalence of dream-associated behaviors. The prevalent occurrence of pregnancy and postpartum infant dreams and associated behaviors may reflect the pervasive emotional influence of maternal concerns or changes instigated by severe sleep disruption, rapid eye movement sleep deprivation, and altered hormone levels.


Graves' disease presenting as pyrexia of unknown origin.
Fever is a common clinical manifestation of inflammatory processes of the thyroid and thyroid crisis. On the other hand, fever alone as a presenting symptom of thyrotoxicosis, without other manifestations, is extremely rare. A female patient is described in whom fever persisted for two months prior to hospitalization, but without clinical symptoms or signs to lead to suspicion of thyroid disease. After exhaustive investigation it was found that the patient was suffering from hyperthyroidism. Fever disappeared gradually on antithyroid therapy, recurred when the drugs were withdrawn for a rechallenge trial, and cleared up again after renewal. Four other cases of persistent fever as a presenting symptom of hyperthyroidism were found on a review of previous publications. Thyrotoxicosis should, therefore, be included in the differential diagnosis of pyrexia of unknown origin.


Cognitive impairment in multiple sclerosis: a forgotten disability remembered.
Physicians first noted the presence of cognitive impairment in patients with multiple sclerosis (MS) more than 160 years ago, yet it took clinicians until 2001 to codify a standard test to measure cognitive function. We now know that cognitive impairment occurs in up to 65 percent of people with MS and usually lessens their ability to remember previously learned information. So far, trials of drugs formulated to treat cognitive impairment have failed, but the authors remain optimistic that new approaches to diagnosis and drug development could lead to effective therapies in the future.


Assessment of Intravenous Antibiotics to Peroral Antibiotics Conversion Practice and Its Associated Factor at University of Gondar Comprehensive Specialized Hospital: Prospective Observational Study.
Improper utilization of antibiotics harms the patient, the public, and the economy. The overuse of injections is one of the key factors in the irrational use of medicines. However, little is known about intravenous (IV) to peroral (PO) conversion practice in the Ethiopian healthcare setting, specifically in the Northwest part of Ethiopia. To assess antibiotics IV to PO conversion practice and its associated factors at the internal medicine ward of the University of Gondar Comprehensive and Specialized Hospital (UOGCSH). A prospective observational study was conducted on 324 study participants who were admitted to the University of Gondar Specialized Hospital from October 3 to November 14, 2021. A systematic random sampling technique was employed to select the study participants. Stata version 14.2 was used for the analysis. Descriptive statistics result was presented using mean and standard deviation. Logistic regression analysis was done to determine the association between independent variables and dependent variables. The association between independent variables and dependent variables was tested at 95% CI and P value≤ 0.05 was considered statistical significance. A total of 324 study participants were included in the study, and the mean age of the patients was 41.4 ± 18.6. Of the 324 study participants, 63.3% were male. The most frequently prescribed antibiotics used for empiric treatment were ceftriaxone (45.4%), followed by metronidazole (33.2%), and cloxacillin (11.4%). A total of 34.5.57% of patients who took antibiotics were converted to PO antibiotics. The most frequently converted type of conversion practice was sequential (23.1%), followed by the switch type of conversion (7.4%). Tachypnea, unavailability of medication, higher temperature, hospital stay greater than 10.78-days, and the presence of comorbidity were predictors of IV medications not being converted to PO medications. Intravenous to peroral conversion practice was infrequent. The most frequently applied conversion practice was sequential type conversion practice, followed by switch type of conversion practice. IV to PO conversion practice was significantly associated with tachypnea, unavailability of medication, higher temperature, hospital stay greater than 10.78-days, and comorbidity. Awareness of IV to PO conversion practice and short-term training for healthcare teams is vital for better antibiotic conversion practice.


On becoming a confederation.
This paper was presented as the keynote speech at the Seventh International Congress of the World Confederation for Physical Therapy. The question of what it will take to strengthen physical therapy as a world force for the health of mankind is examined. The past and present status of physical therapy and the Confederation are assessed as background for looking at ways to help the Confederation become truly a World Confederation for Physical Therapy.


Survival benefit of repeat resection of successive recurrences after the initial hepatic resection for colorectal liver metastases.
Relapse is common after the resection of colorectal liver metastases (CLM); however, the optimal treatment for such recurrent disease remains uncertain. We investigated whether repeat resections for successive recurrences of CLM provide survival benefit on the postrecurrence survival. We reviewed patients who underwent upfront, curative resection for CLM at our center during a 15-year period. Of these, 263 patients who had not received any other perioperative treatment for the metastases were eligible for our analysis. The recurrence-free survival (RFS0) after the initial hepatic resection and after the first (n = 108), second (n = 43), and third (n = 15) repeat resections for recurrent disease were assessed (RFS1-3). The overall survival after the initial hepatic resection and the postrecurrence survival (n = 198) also was assessed. The median RFS0 was 0.8 years, and RFS1, RFS2, and RFS3 were 1.3, 1.1, and 2.0 years, respectively. The hazard ratio for RFS for the first, second, and third resections versus the initial hepatic resection was 0.9 (95% confidence interval [95% CI] 0.7-1.1; P = .34), 1.00 (95% CI 0.7-1.4; P = .97), and 0.7 (95% CI 0.4-1.3; P = .29). The 5-year and 10-year OS rates were 54.6% and 42.2%, and the 5-year and 10-year postrecurrence survival was 34.3% and 28.6%, respectively. Repeat resection in patients with recurrent disease after CLM resection is beneficial, offering the potential for cure in a small proportion of patients with recurrent disease.


A Novel Dual-Band (38/60 GHz) Patch Antenna for 5G Mobile Handsets.
A compact dual-frequency ( 38 / 60   GHz ) microstrip patch antenna with novel design is proposed for 5G mobile handsets to combine complicated radiation mechanisms for dual-band operation. The proposed antenna is composed of two electromagnetically coupled patches. The first patch is directly fed by a microstrip line and is mainly responsible for radiation in the lower band ( 38   GHz ). The second patch is fed through both capacitive and inductive coupling to the first patch and is mainly responsible for radiation in the upper frequency band ( 60   GHz ). Numerical and experimental results show good performance regarding return loss, bandwidth, radiation patterns, radiation efficiency, and gain. The impedance matching bandwidths achieved in the 38   GHz and 60   GHz bands are about 2   GHz and 3.2   GHz , respectively. The minimum value of the return loss is - 42 dB for the 38   GHz band and - 47 for the 60   GHz band. Radiation patterns are omnidirectional with a balloon-like shape for both bands, which makes the proposed single antenna an excellent candidate for a multiple-input multiple-output (MIMO) system constructed from a number of properly allocated elements for 5G mobile communications with excellent diversity schemes. Numerical comparisons show that the proposed antenna is superior to other published designs.


Temozolomide for the treatment of metastatic melanoma: a systematic review.
This systematic review examines the role of temozolomide in patients with metastatic melanoma. Outcomes of interest include response rate, progression-free survival, overall survival, quality of life, and adverse effects. The MEDLINE, EMBASE, and Cochrane Library databases were searched from 1980 through to 2005 using variations on the search terms: melanoma, clinical trial, random, temozolomide, temodal, and temodar. The American Society of Clinical Oncology Annual Meeting proceedings were searched from 1996 to 2005. Relevant articles and abstracts were selected and reviewed by two reviewers, and the reference lists from these sources were searched for additional trials. Two randomized phase III trials and three randomized phase II trials were located. In addition, 21 phase I or II trials investigating single-agent temozolomide, temozolomide plus interferon-alpha, and temozolomide plus thalidomide were reviewed. A direct comparison of temozolomide and dacarbazine demonstrated equal efficacy for response rates and overall survival; however, no significant difference was reported. A second phase III study comparing single-agent temozolomide with temozolomide combined with interferon-alpha indicated a significantly higher response rate for the combination treatment arm, but no difference in overall survival was noted. Further phase III studies are required to confirm whether there is a benefit associated with the combination of temozolomide and interferon-alpha or thalidomide. Our review of the available literature suggests that temozolomide demonstrates comparable activity to the current standard treatment, dacarbazine, with the additional benefit of being a convenient oral treatment that penetrates the blood-brain barrier.


Suppressed phagocytosis but promoted bacterial growth upon the effect of virus free supernatants of infected lymphocytes.
The pathomechanism of suppressed phagocytosis and bacterial superinfections which follow viral diseases is not completely understood. Both polymorphonuclear leukocytes (PMNL) and mononuclear phagocytes (MNPh) as well as bacterial growth are controlled by several cytokines produced by other immune cells. The effect of disturbed production of cytokines on phagocytes and microbes have not been studied yet. Peripheral T lymphocytes were infected with human adenoviruses (Ad) and herpes simplex virus type 1 (HSV-1) or were activated by phytohaemagglutinin (PHA), then culture supernatants containing no infectious virus were mixed to phagocytes swallowing viable Staphylococcus aureus. Influence of supernatants on eukaryotic and bacterial cell growth was compared to cytokine assays. Supernatant mediators, different from interferon (IFN) and tumour necrosis factor (TNF), induced by oncogenic Ad-12 or HSV-1 diminished phagocytosis of both PMNL and MNPh in a dose dependent manner, promoted bacterial growth free and inside MNPh, while those of latent Ad-5 and nononcogenic Ad-8 exerted moderate effects. Plating efficiency of HEp-2 cells was decreased by all of them. Supernatants of PHA treated lymphocytes containing IFN-gamma enhanced both phagocytosis and bacterial replication free and inside MNPh, while it suppressed HEp-2 plating. Neither viruses nor PHA affected phagocytic process directly. Staphylococci inside PMNL were not affected. Presumably, production of a single mediator by infected T lymphocytes is responsible for the multiple effects. Relationship with another soluble factors is discussed.


Managing maxillary proclination with novel designed angulated implants.
Implant-supported removable dental prostheses may be supported by a variety of splinted (bar and clip) attachment systems or nonsplinted abutment-based attachments (ball, magnets, and resilient stud attachments such as locators [Zest Anchors], ERA [Sterngold], and nonresilient-stud attachments such as ANKYLOS SynCone [Dentsply Implants]). Nonsplinted attachments are preferred as they are more economical, less technique sensitive, easier to clean, repair, and maintain than splinted (bar and clip) attachment systems, but they work favorably only when implants in the arch are placed parallel to each other. Often implants in the anterior maxilla have to be placed with a labial inclination (due to the proclination of the premaxilla), resulting in lack of parallelism between the anterior and posterior implants, making it challenging to fabricate a removable dental prostheses supported by nonsplinted attachments, and necessitating the use of angled abutments. Recently, a novel implant design with a 12° restorative platform angulation has been introduced by Southern Implants (Co-axis, Keystone Dental, Inc., Burlington, MA, USA). These new angulated implants aid in minimizing the divergence between the anterior and posterior maxillary implants without using angled abutments. The purpose of this article was to report a case utilizing the novel angulated implants (Co-axis, Keystone Dental, Inc., Burlington, MA, USA) in the premaxilla for fabrication of maxillary removable dental prostheses supported and retained by nonsplinted attachments.


Estimations of Inpatient and Ambulatory Pediatric Tonsillectomy in the United States: A Cross-sectional Analysis.
To estimate the incidence of inpatient and ambulatory pediatric tonsillectomies in the United States in 2019. Cross-sectional analysis. Healthcare Cost and Utilization Project databases. We determined national incidences of hospital-based ambulatory procedures, inpatient admissions, and readmissions among pediatric tonsillectomy patients, ages 0 to 20 years, using the Kids Inpatient Database, Nationwide Ambulatory Surgery Sample, and Nationwide Readmission Database. We described the demographics, commonly associated conditions, complications, and predictors of readmission. An estimated 559,900 ambulatory and 7100 inpatient tonsillectomies were performed in 2019. Among inpatients, the majority were male (59%) and the largest ethnic group was white (37%). Adenotonsillar hypertrophy (ATH), 79%, and obstructive sleep apnea (OSA), 74%, were the most frequent diagnosis and Medicaid (61%) was the most frequent primary payer. The majority of ambulatory tonsillectomy patients were female (52%) and white (65%); ATH, OSA, and Medicaid accounted for 62%, 29%, and 45% of cases, respectively, (all p < .001 when compared to inpatient cases). Common inpatient complications were bleeding (2%), pain/nausea/vomiting (5.6%), and postprocedural respiratory failure (1.7%). On the other hand, ambulatory complications occurred in less than 1% of patients. The readmission rate was 5.2%, with pain/nausea/vomiting and bleeding accounting for 35% and 23% of overall readmissions. All Patient Refined Diagnosis Related Groups severity of illness subclass predicted readmission (odds ratio = 2.18, 95% confidence interval = 1.73-2.73, p < .001). A total of 567,000 pediatric ambulatory and inpatient tonsillectomies were performed in 2019; the majority were performed in ambulatory settings. The index admission severity of illness was associated with readmission risk.


Tissue-engineered blood vessel mimics in complex geometries for intravascular device testing.
Intravascular stents are commonly used to treat occluded arteries during coronary heart disease. After coronary stent implantation, endothelial cells grow over the stent, which is referred to as re-endothelialization. Re-endothelialization prevents blood from clotting on the stent surface and is a good predictor of stent success. Blood vessel mimics (BVMs) are in vitro tissue-engineered models of human blood vessels that may be used to preclinically test stents for re-endothelialization. BVMs have been developed in straight geometries. However, the United States Food and Drug Administration recommends that devices intended to treat coronary occlusions be preclinically tested in bent and bifurcated vessels due to the complex geometries of native coronary arteries. The main objectives of this study were to develop and characterize BVMs in complex geometries. Bioreactors were designed and constructed so that BVMs could be cultivated in bent (>45°) and bifurcated geometries. Human umbilical vein endothelial cells were sodded onto complex-shaped scaffolds, and the resulting BVMs were characterized for cell deposition. For a final proof of concept, a coronary stent was deployed in a severely angulated BVM. The new bioreactors were easy to use and mounting scaffolds in complex geometries in the bioreactors was successful. After sodding scaffolds with cells, there were no statistically significant differences between the cell densities along the length of the BVMs, on the top and bottom halves of the BVMs, or on the inner and outer halves of the BVMs. This suggests cells deposited evenly throughout the scaffolds, resulting in consistent complex-geometry BVMs. Also, a coronary stent was successfully deployed in a severely angulated BVM. Bioreactors can be constructed for housing complex-shaped vessels. BVMs can be developed in the complex geometries observed in native coronary arteries with endothelial cells evenly dispersed throughout BVM lumens.


Nitrene Insertion into C-C and C-H Bonds of Diamide Diimine Ligands Ligated to Chromium and Iron.
The impact of redox non-innocence (RNI) on chemical reactivity is a forefront theme in coordination chemistry. A diamide diimine ligand, [{-CH=N(1,2-C6H4)NH(2,6-iPr2C6H3)}2](n) (n = 0 to -4), (dadi)(n), chelates Cr and Fe to give [(dadi)M] ([1Cr(thf)] and [1Fe]). Calculations show [1Cr(thf)] (and [1Cr]) to have a d(4) Cr configuration antiferromagnetically coupled to (dadi)(2-)*, and [1Fe] to be S = 2. Treatment with RN3 provides products where RN is formally inserted into the C-C bond of the diimine or into a C-H bond of the diimine. Calculations on the process support a mechanism in which a transient imide (imidyl) aziridinates the diimine, which subsequently ring opens.


DNA interactions with a Methylene Blue redox indicator depend on the DNA length and are sequence specific.
A DNA molecular beacon approach was used for the analysis of interactions between DNA and Methylene Blue (MB) as a redox indicator of a hybridization event. DNA hairpin structures of different length and guanine (G) content were immobilized onto gold electrodes in their folded states through the alkanethiol linker at the 5'-end. Binding of MB to the folded hairpin DNA was electrochemically studied and compared with binding to the duplex structure formed by hybridization of the hairpin DNA to a complementary DNA strand. Variation of the electrochemical signal from the DNA-MB complex was shown to depend primarily on the DNA length and sequence used: the G-C base pairs were the preferential sites of MB binding in the duplex. For short 20 nts long DNA sequences, the increased electrochemical response from MB bound to the duplex structure was consistent with the increased amount of bound and electrochemically readable MB molecules (i.e. MB molecules that are available for the electron transfer (ET) reaction with the electrode). With longer DNA sequences, the balance between the amounts of the electrochemically readable MB molecules bound to the hairpin DNA and to the hybrid was opposite: a part of the MB molecules bound to the long-sequence DNA duplex seem to be electrochemically mute due to long ET distance. The increasing electrochemical response from MB bound to the short-length DNA hybrid contrasts with the decreasing signal from MB bound to the long-length DNA hybrid and allows an "off"-"on" genosensor development.


[Pathogenesis and immunologic findings in AIDS].
As the numbers of children suffering from AIDS are slowly increasing in West Germany it is essential for pediatricians to be aware of events leading to clinically overt disease. This review summarizes events involved in viral attachment to CD4-bearing cells, intracellular replication, and destruction of both HIV-infected and non-infected cells. As a consequence of HIV-infection a profound and complex immunodeficiency is observed which is only partially explained by the loss of circulating CD4-bearing cells. Functions of antibodies, cytotoxic T-cells, natural killer cells, killer cells, as well as non-specific immune functions are discussed not only with respect to defense mechanisms in general but also with respect to the control of HIV-infection itself. Detailed understanding of these events seems to be a prerequisite for understanding the occurrence of infections and tumours in AIDS.


Effect of brain irradiation on blood-CSF barrier permeability of chemotherapeutic agents.
Effect of irradiation on blood-cerebrospinal fluid (CSF) barrier (BCB) was studied quantitatively by observing the effect of methotrexate (MTX) permeation into the CSF before, during, and after brain irradiation after i.v. injection of MTX. Observation of 15 brain tumor patients indicated that in large brain tumors, the BCB was seriously damaged; in small tumors, the BCB would gradually open. Compared with the findings before irradiation, the increase of permeability of MTX was zero to threefold. It is thus advisable to give chemotherapy only after 20 Gy of irradiation.


Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages.
Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylcer-amide macrophages, the accumulation of glucosylceramide in lysosomes and the secretion of inflammatory cytokines. However, the connection between this lysosomal storage and inflammation is not clear. Studying macrophages derived from peripheral monocytes from patients with type 1 Gaucher disease with genotype N370S/N370S, we confirmed an increased secretion of interleukins IL-1β and IL-6. In addition, we found that activation of the inflammasome, a multiprotein complex that activates caspase-1, led to the maturation of IL-1β in Gaucher macrophages. We show that inflammasome activation in these cells is the result of impaired autophagy. Treatment with the small-molecule glucocerebrosidase chaperone NCGC758 reversed these defects, inducing autophagy and reducing IL-1β secretion, confirming the role of the deficiency of lysosomal glucocerebrosidase in these processes. We found that in Gaucher macrophages elevated levels of the autophagic adaptor p62 prevented the delivery of inflammasomes to autophagosomes. This increase in p62 led to activation of p65-NF-kB in the nucleus, promoting the expression of inflammatory cytokines and the secretion of IL-1β. This newly elucidated mechanism ties lysosomal dysfunction to inflammasome activation, and may contribute to the massive organomegaly, bone involvement and increased susceptibility to certain malignancies seen in Gaucher disease. Moreover, this link between lysosomal storage, impaired autophagy, and inflammation may have implications relevant to both Parkinson disease and the aging process. Defects in these basic cellular processes may also provide new therapeutic targets.


Potassium secretion in the guinea pig distal colon.
Active K+ secretion in guinea pig distal colon was studied in vitro in Ussing chambers. Changes in short-circuit current (Isc), transepithelial conductance (Gt), and the unidirectional flux of 42K from serosa to mucosa (JKsm) were determined under a variety of physiological and pharmacological conditions. Mucosal tetraethylammonium (TEA) (10 or 30 mM) increased Isc, while it decreased Gt and JKsm. Seroal bumetanide (10(-4) M) also caused an increase in Isc and decreases in Gt and JKsm. The effects produced by TEA were abolished in the presence of bumetanide. The increase in Isc caused by bumetanide was greatly reduced by mucosal high-K+ conditions. Isoproterenol (10(-6) M), a beta-adrenergic agonist, elicited a decrease in Isc and an increase in Gt. Responses to isoproterenol (10(-6) M) were reduced or abolished by mucosal TEA, serosal bumetanide, serosal ouabain (10(-4) M), and serosal Na+- or Cl(-)-free conditions. Mucosal high K+ also reduced the isoproterenol-induced decrease in Isc. These results suggest that K+ secretion is electrogenic and dependent on the bumetanide-sensitive cotransport in the basolateral membrane. K+ exit across the apical membrane might be conductive and sensitive to TEA. In addition, beta-adrenergic agonists might stimulate K+ secretion.


New insights into the pathogenesis and treatment of rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic multisystemic inflammatory disease with autoimmune features, and of unknown cause, associated with characteristic joint deformities and increased mortality rate. The pathogenesis of this serious disease seems to be multifactorial, where several cytokines, particularly interleukin-1 and tumor necrosis factor-alpha, are strongly involved in the induction and perpetuation of the chronic inflammatory process of the joints in RA and in the systemic manifestations of the disease. Other factors, such as reactive oxygen species and metalloproteinases, may also participate in the destruction of the rheumatoid joint. Current treatments of RA are inadequate in that they only partially control established RA, and despite optimal use of current antirheumatic agents, the outcome of many patients with RA consists of pain, severe functional decline, and premature death. The gloomy recent data regarding the prognosis of RA with the use of the current treatments stress the need for new therapeutic regimens with the ability to effectively control the inflammatory process in the rheumatoid joint and to induce long-term remission or even cure. Controlling the production and the activity of the factors involved in the pathogenesis of the disease represents the major therapeutic goal. Since several factors are involved in the pathogenesis of RA, neutralizing one or some of these factors may be of only limited benefit. In this regard, interleukin-4 may be a very promising agent for an effective treatment of RA, because this cytokine is not limited by its inhibitory effects to a single factor, but rather it inhibits most of the main factors involved in the pathogenesis of the disease. Although recent data strongly support this approach with interleukin-4, controlled long-term clinical trails should be undertaken in order to prove the validity and the effectiveness of this promising approach.