Efficacy of intradermal hyaluronic acid plus polynucleotides in vulvovaginal atrophy: a pilot study.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of vulvovaginal intradermal injections of polynucleotides (PN) combined with hyaluronic acid (HA) in postmenopausal women affected by vulvovaginal atrophy (VVA). MATERIALS AND METHODS: Postmenopausal women affected by VVA were treated with vulvar and vaginal intradermal injections of one prefilled syringe of 2 ml PN/HA every 2 weeks for four sessions. Patients were evaluated at T0 (baseline), T1 (after session 4) and T2 (1 month after session 4). Evaluation of the treatment was assessed by three international validated questionnaires: Vaginal Health Index (VHI), Vulvar Health Index (VuHI) and Female Sexual Function Index (FSFI). The Wilcoxon matched-paired signed-rank test was used to compare the differences in VHI, VuHI, FSFI and FSFI domains within the groups. Statistical significance was set at p < 0.05. RESULTS: Fifty patients were included in the study (mean age 59.9 ± 7.6 years). Overall, the VHI, VuHI and FSFI reported statistically significant differences between baseline and T1 (p < 0.001) and between baseline and T2 (p < 0.001). All FSFI domains registered a statistically significant increase between baseline and T2 (p < 0.001). No complications or side effects were observed. CONCLUSIONS: Vulvovaginal intradermal injection of PN/HA is a safe, effective treatment, is not expensive and is a reproducible procedure in postmenopausal women with VVA.

Education to legality and doping.

When planning actions to prevent doping in the general population, public health operators may collide against the interests of criminal organizations involved in illicit trafficking of drugs. In addition to technical and professional expertise, or clinical and pharmacological skills, also a deep knowledge of legal and social issues is strongly required to face the problem and assure the effectiveness of the preventive actions. Sports competitions, athletes training or adapted physical activity may all represent conditions and environments at risk for misusing or abusing drugs and dietary supplements. A correct approach to sport and physical activity implies respect of competition rules, attention to own body limits and knowledge of risk factors. Health education campaigns and preventive actions should also consider education to legality in the different settings. The comprehension of the complex net that is available to access doping, locally or globally through online Internet sites, is essential as well as the awareness of the huge economic burden of crime interests behind the illicit trafficking of drugs. A modern whole rounded approach needs to consider doping not only as a violation of sport rules but also of the own body health, representing almost a form of addiction involving individuals and communities, and being supported by crime. Within this frame, doping is considered not just as a sport violation or a risk factor for individual's health, but as a disease of the society, in the society, against the society. A peculiar equilibrium seems to prevail between crime external pressures and resigned internal acceptance, according to the 'mafia hypothesis' model, where hosts accept parasitism to avoid retaliation. Here, main contributes and topics from the Erice 53rd Course are summarized and reviewed, providing links and references for further studies in the field. Health education and education to legality represent two sides of a same question, concerning both the general population and the health authorities. In conclusion, education to legality is a key component for prevention of doping and a priority for public health operators involved in protecting population health.

One-pot selective conversion of lignocellulosic biomass into furfural and co-products using aqueous choline chloride/methyl isobutyl ketone biphasic solvent system.

This study investigated simultaneous lignocellulose fractionation and conversion in a one-pot reaction using an aqueous choline chloride/methyl isobutyl ketone (ChCl/MIBK) biphasic solvent system. Under the optimized condition (170 °C, 60 min, 0.6 wt% H2SO4, 10.7 wt% solid loading), the biphasic solvent solubilized 96% xylan in raw switchgrass, which was simultaneously converted to furfural with a yield of 84.04%. The biphasic solvent was also able to selectively extract lignin, which had a high purity (93.1%), and uncondensed moieties (i.e., Hibbert's ketone), as well as decreased molecular weight and polydispersity index. The resultant pulp was enriched with cellulose (73.3%), which can be completely hydrolyzed into glucose within 48 h via enzymatic hydrolysis. Aqueous ChCl was successfully recycled and reused for atleast three cycles with similar performance in switchgrass fractionation. This study demonstrated that aqueous ChCl/MIBK biphasic system was an effective solvent system for co-production of furfural, high quality technical lignin and digestible cellulose for further upgrading.

Spatiotemporal drought variability on the Mongolian Plateau from 1980-2014 based on the SPEI-PM, intensity analysis and Hurst exponent.

Knowledge about variations of drought can provide a scientific basis for water resource planning and drought mitigation. In this study, the variations and patterns of drought identified by the Standardized Precipitation Evapotranspiration Index (SPEI) were investigated on the Mongolian Plateau for the period 1980-2014, based on intensity analysis, linear regression, the Mann-Kendall test, wavelet analysis, and Hurst exponent. The results show that: 1) the annual SPEI decreased at a rate of -0.0133/yr over the past 35years, and a major abrupt change occurred in 1999; 2) drought on the Mongolian Plateau intensified from 1980 to 2014, and the drought in Mongolia has been more serious than in Inner Mongolia since the beginning of the 21st century; 3) the rate of drought/wet changes in 1980s-1990s and 1990s-2000s were faster than in 2000s-2010s. In 1980s-1990s, the different drought levels were transformed into various wet levels. In 1990s-2000s, the wet levels were transformed into drought, and in 2000s-2010s, the losses of drought levels were larger than the gains in wet levels; 4) the Hurst exponent is a reliable way to predict drought tendency, with a predictive accuracy as high as 91.7%; 5) the mean H value of the SPEI time series during 1980-2014 was 0.533, indicating that the future drought trend is generally consistent with the current state. In the future, the proportion of area with increasingly severe drought (72.2%) will be larger than that with increasingly wetter conditions (27.8%) on the Mongolian Plateau.

Compound osteosynthesis in the thoracic spine for treatment of vertebral metastases: technical report

Metastases to vertebrae often cause bone destruction leading to instability and neural compression. Anterior surgical approaches allow tumor resection and direct neural decompression. For patients with a short life expectancy, vertebral body replacement with methyl-methacrylate polymerized in situ can be used for load sharing in the axial plane. Screws hung from the rod into the corpectomy site are incorporated into the acrylic cement. The technique described in this article allows for immediate spinal stabilization and provides a protective environment for the neural elements. All the patients tolerated the procedure well and were able to ambulation without an orthoses.

Stability of Mercury Dilute Aqueous Solutions: An Open Issue

In the framework of the activities of the European Commission Reference Laboratory (CRL) for residues at the Istituto Superiore di Sanita a number of analytical quality control trials on determination of trace analytes are being carried out. As regards trace elements it soon became apparent that the stability of Hg dilute aqueous solutions is rather unsatisfactory. An investigation was thus undertaken to ascertain the conditions under which the concentration of this metal does not appreciably change. Mercury solutions were prepared in high purity deionized water in the concentration range 1-10 ng g-1 and the effect of various amounts of HNO3 and K2Cr2O7 (alone or in combination) was elucidated by measuring the variations with time in the actual concentration of Hg. Determinations were performed by both inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. Results show that solutions added with 5% (w/w) HNO3 and 0.01% (w/w) K2Cr2O7 do not undergo any significant alteration in the nominal content of the analyte for at least 1 month. Similar conclusions are reached in the case of solutions enriched in CaCO3, NaCl, NaNO3, KH2PO4, KNO3, and Mg(NO3)2.6H2O to mimic acid digests of meat samples. The improvement ensuing from the adoption of this approach on the performance of the Hg analytical quality control trials is discussed in detail.

Syntheses and biological activities of 13-substituted avermectin aglycons.

The reactions of sulfonate esters of the allylic/homoallylic 13-alcohol of 5-O-(tert-butyldimethylsilyl)-22,23-dihydroavermectin B1a aglycon (1a) were investigated. Nucleophilic substitution gave 13 beta-chloro and 13 beta-iodo derivatives, while solvolytic reaction conditions yielded 13 alpha-methoxy, 13 alpha-fluoro, and 13 alpha-chloro products. A mixture of 13 alpha- and 13 beta-fluorides was obtained upon reaction with DAST. The 13 beta-iodide gave, upon elimination with lutidine, the 8(9),10(11),12(13),14(15)-tetraene. The 13 beta-alcohol and the rearranged 15-ol 13(14)-ene and 15-amino 13(14)-ene derivatives were obtained by substitution via the allylic carbonium ion. MEM ethers 11 and 12 of the two epimeric 13-ols were prepared by alkylation with MEM chloride. In contrast, methylation of 1a with MeI and Ag2O in CH2Cl2 occurred exclusively at the tertiary 7-hydroxy group and not at the secondary 13 alpha-ol. Oxidation of the allylic alcohol 1a proceeded under Swern conditions but not with MnO2 to the 13-oxo aglycon, which was reduced by NaBH4 exclusively to the natural 13 alpha-ol, while reductive amination with NaCNBH3-NH4OAc gave the 13 alpha-amine. The methoxime derivative was obtained in the form of the two geometric isomers. Anthelmintic activities against the sheep nematode Trichostrongylus colubriformis, miticidal activities against the two-spotted spider mite (Tetranychus urticae), and insecticidal activities against the southern armyworm (Spodoptera eridania) as well as the binding constants to a free living nematode (Caenorhabditis elegans) derived receptor assay were obtained and compared to avermectin B1a, 22,23-dihydroavermectin B1a, and the 13-deoxy-22,23-dihydroavermectin B1 aglycon related to the milbemycins. None of the newly prepared derivatives exceeded the potency of the three reference compounds. Lipophilic 13-substituents such as halogen, alkoxy, and methoxime retained high biological activities in all assays, while the more polar substituents hydroxy and amino had weaker activities. Rearranged 15-substituted 13(14)-ene derivatives were completely inactive. The 13-oxo and the 12,13-dehydro analogues were only weakly active in vivo despite having good binding affinity to the receptor, possibly due to instability or poor absorption.

Ivermectin, a new broad-spectrum antiparasitic agent.

22,23-Dihydroavermectin B1, ivermectin, derived from avermectin B1 by selective hydrogenation using Wilkinson's homogenous catalyst [Ph3P)3RhCl], was shown to be a highly effective drug for the treatment of a wide variety of metazoan parasitic diseases in animals.

Methyl 6-(phenylsulfinyl)imidazo[1,2-a]pyridine-2-carbamate, a potent, new anthelmintic.

A series of methyl imidazo-[11,2-a]pyridine-2-carbamates was synthesized for anthelmintic testing. The preparation of this class of compounds was simplified by utilization of a novel one-step condensation of the appropriately substituted 2-aminopyridine and methyl chloroacetylcarbamate. The most potent compound, methyl 6-(phenylsulfinyl)-imidazo[1,2-a]pyridine-2-carbamate, was orally effective against a broad range of helminths in sheep and cattle, at a dosage of 2.5 mg/kg. Limited trials in swine and dogs demonstrated anthelmintic activity at higher dosages. Limited observations in sheep and cattle indicated that, in both species, a single oral dose of 200 mg/kg was well tolerated.

Anthelmintic dihydroquinoxalino[2,3-b]quinoxalines.

A series of dihydroquinoxalino[2,3-b]quinoxalines was synthesized and tested for anthelmintic activity in a model assay. The most promising compound, 5,12-diacetyl-5,12-dihydroquinoxalino[2,3-b]quinoxaline, was orally effective in sheep at a dose of 200 mg/kg against a broad range of helminths.

4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide, a new, potent fasciolicide.

The synthesis and fasciolicidal activity of 4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide are reported. A single dose of 15 mg/kg was effective in removing over 90% of immature Fasciola hepatica from sheep (6 weeks after infection) and calves (8 weeks after infection). A 2.5 mg/kg dose removed over 90% of mature (16 weeks old) liver fluke from sheep. Single oral doses up to 400 mg/kg were tolerated by sheep without gross toxic symptoms.