Central diabetes insipidus associated with refeeding in anorexia nervosa: A case report.
Anorexia nervosa (AN) has been associated with a multitude of hypothalamic pituitary abnormalities, although it is unknown which aberrations reflect disease causation and which are the consequences of severe malnutrition. Among these endocrinopathies, hypothalamic-posterior pituitary aberrations have been described, including disorders of osmoregulation. We report the case of an adolescent female with a history of severe AN, restricting subtype, treated aggressively with multiple hospitalizations. During hospitalization for severe weakness and lethargy, her course of medical stabilization was complicated by significant polyuria, ultimately diagnosed as central diabetes insipidus (DI). This is the first reported case, to our knowledge, of a severely malnourished adolescent with AN-restricting subtype developing central DI during the refeeding process for medical stabilization, thus adding to the small body of existing literature on disordered osmoregulation in this patient population. This case report raises the question as to whether the frequency of central DI during refeeding is greater than that previously recognized. Additional research should focus on how neuroendocrine dysregulation of water balance might impact the clinical course of AN and its treatment.


Rebuilding the ruins: dental services and manpower in Cambodia.
Between 1975 and 1979 Cambodia suffered a massive destruction of its social structures under the Khmer Rouge. The dental profession was almost annihilated and the dental school in Phnom Penh stripped bare. Dental training has now begun again and the long process of restoration is in progress. The ratio of dentists to the population is still pitifully low and public services are concentrated in Phnom Penh and in provincial towns. Traditional dentists provide the only accessible dental care in many places. A primary oral health care system has yet to be developed.


Sizing the cannabis market: a demand-side and user-specific approach in seven European countries.
Demand-based estimates of total cannabis consumption rarely consider differences among different user types and variation across countries. To describe cannabis consumption patterns and estimate annual consumption for different user types across EU Member States, a web survey in Bulgaria, Czech Republic, Italy, the Netherlands, Portugal, Sweden and United Kingdom (England & Wales) collected data on cannabis use patterns from 3,922 persons who had consumed cannabis at least once in the past year. They were classified into four groups based on their number of use days in the past 12 months: infrequent users or chippers (<11 days), occasional users (11-50 days), regular users (51-250 days) and intensive users (>250 days). User type specific data on typical amounts consumed were matched with data on numbers of users per user type estimated from existing population surveys, taking differences in mode of consumption, age and gender into account. Estimates were supplemented with data from populations of problem users to compensate for under coverage. Results showed remarkably consistent differences among user groups across countries. Both the average number of units consumed per typical use day and the average amount of cannabis consumed per unit increased across user types of increasing frequency of use. In all countries except Portugal, intensive users formed the smallest group of cannabis users but were responsible for the largest part of total annual cannabis consumption. Annual cannabis consumption varied across countries but confidence intervals were wide. Results are compared with previous estimates and discussed in the context of improving estimation methods.


Alginate Hydrogels with Tuneable Properties.
Alginate is a material that has many biomedical applications due to its low toxicity and a variety of favourable physical properties. In particular, the ease in which hydrogels are formed from alginate and the variety of mechanical behaviours that can be imparted on the hydrogels, by understanding alginate chemistry and intuitive design, has made alginate the most widely investigated polysaccharide used for tissue engineering. This chapter provides an overview of alginate, from how the source and natural variations in composition can influence mechanical properties of alginate hydrogels, through to some innovative techniques used to modify and functionalise the hydrogels designed specifically for cell-based therapies. The main focus is on how these strategies of understanding and controlling the chemistry of alginates have resulted in the development of hydrogels that can be tuned to deliver the physical behaviours required for successful application. This will also highlight how research on the physicochemical properties has helped alginate evolve from a structural polysaccharide in brown seaweed into a highly tuneable, multifunctional, smart biomaterial, which is likely to find further biomedical applications in the future.


Outcome of an oral health outreach programme for preschool children in a low socioeconomic multicultural area.
Despite a significant reduction in the prevalence of dental caries, childhood tooth decay is still a public health problem in both developed and developing countries. The aim of this study was to evaluate the caries preventive effect of an oral health programme for preschool children living in a low socioeconomic multicultural area in the city of Malmö, Sweden. Eight hundred and four 2-year-old children were enrolled and recalled every third month between ages 2 and 3 and semi-annually between ages 3 and 5 years. From an outreach facility, parents were instructed on oral health with a focus on toothbrushing and diet, and provided fluoride tablets free of charge. Participants completed a clinical examination and a structured interview at age of 5 years, at which point 651 children (81%) remained in the programme. The results of the intervention group were compared with a non-intervention reference group consisting of 201 5-year-old children from the same district. In the intervention group, 96% attended four or more of their scheduled appointments, and mean caries prevalence was significantly lower than in the reference group (5.4 deft vs. 6.9 deft; P < 0.001). The prevented defs fraction was 27%. Parents' daily assistance with toothbrushing and administering fluoride tablets was significantly better in the intervention group than in the reference group (P < 0.05). This study demonstrated that the early start of oral health programme had a significant beneficial effect on caries prevalence after 3 years.


[Role of dysbacteriosis in the development of surgical infection].
The intestinal microflora was examined in 230 patients operated on for abdominal abnormalities and injuries. There were profound intestinal microbiocenotic impairments as appeared as lower bifidobacteria, intensive growth of opportunistic (coccal) microorganisms. A direct relationship was established between the severity of dysbacteriosis and the incidence of pyoinflammatory complications in the postoperative period. The use of live bacterial preparations in the complex therapy of patients with expected and emergency abdominal diseases or injuries reduced the number of pyoinflammatory complications and improved the therapeutic outcomes of patients with peritonitis.


Comprehensive Assessments of RNA-seq by the SEQC Consortium: FDA-Led Efforts Advance Precision Medicine.
Studies on gene expression in response to therapy have led to the discovery of pharmacogenomics biomarkers and advances in precision medicine. Whole transcriptome sequencing (RNA-seq) is an emerging tool for profiling gene expression and has received wide adoption in the biomedical research community. However, its value in regulatory decision making requires rigorous assessment and consensus between various stakeholders, including the research community, regulatory agencies, and industry. The FDA-led SEquencing Quality Control (SEQC) consortium has made considerable progress in this direction, and is the subject of this review. Specifically, three RNA-seq platforms (Illumina HiSeq, Life Technologies SOLiD, and Roche 454) were extensively evaluated at multiple sites to assess cross-site and cross-platform reproducibility. The results demonstrated that relative gene expression measurements were consistently comparable across labs and platforms, but not so for the measurement of absolute expression levels. As part of the quality evaluation several studies were included to evaluate the utility of RNA-seq in clinical settings and safety assessment. The neuroblastoma study profiled tumor samples from 498 pediatric neuroblastoma patients by both microarray and RNA-seq. RNA-seq offers more utilities than microarray in determining the transcriptomic characteristics of cancer. However, RNA-seq and microarray-based models were comparable in clinical endpoint prediction, even when including additional features unique to RNA-seq beyond gene expression. The toxicogenomics study compared microarray and RNA-seq profiles of the liver samples from rats exposed to 27 different chemicals representing multiple toxicity modes of action. Cross-platform concordance was dependent on chemical treatment and transcript abundance. Though both RNA-seq and microarray are suitable for developing gene expression based predictive models with comparable prediction performance, RNA-seq offers advantages over microarray in profiling genes with low expression. The rat BodyMap study provided a comprehensive rat transcriptomic body map by performing RNA-Seq on 320 samples from 11 organs in either sex of juvenile, adolescent, adult and aged Fischer 344 rats. Lastly, the transferability study demonstrated that signature genes of predictive models are reciprocally transferable between microarray and RNA-seq data for model development using a comprehensive approach with two large clinical data sets. This result suggests continued usefulness of legacy microarray data in the coming RNA-seq era. In conclusion, the SEQC project enhances our understanding of RNA-seq and provides valuable guidelines for RNA-seq based clinical application and safety evaluation to advance precision medicine.


Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective.
Prolongation of ovarian epithelial cancer survival depends on early detection or improved responses to chemotherapy. Gains in either have been modest at best. Understanding the diverse pathogenesis of this disease is critical to early intervention or prevention. This review addresses six important variables, including (i) cell of origin, (ii) site of origin, (iii) initial genotoxic events, (iv) risks imposed by hereditary and other promoting conditions, (v) subsequent factors that promote different patterns of metastatic spread, and (vi) prospects for intervention. This review proposes two distinct pathways to pelvic epithelial cancer. The first initiates in ovarian surface epithelium (OSE), Mullerian inclusions or endometriosis in the ovary. The second arises from the endosalpinx and encompasses a subset of serous carcinomas. The serous carcinogenic sequence in the distal fallopian tube is described and contrasted with lower grade serous tumors based on tumour location, earliest genetic change and ability (or lack of) to undergo terminal (ciliated) differentiation. Ultimately, a clear understanding of tumour origin and the mechanism(s) leading to the earliest phases of the serous and endometrioid carcinogenic sequences may hold the greatest promise for designing prevention strategies and/or developing new therapies.


Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects.
Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects. Thirty-five healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 μg ml(-1), or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models. Propofol had no effect on the stereotypical amygdalar response to emotional arousal, but caused marked suppression of the hippocampal response. Propofol caused memory performance to become uncoupled from amygdalar activation, but it remained correlated with activation in the posterior hippocampus, which decreased in proportion to amnesia. Propofol is relatively ineffective at suppressing amygdalar activation at sedative doses, but abolishes emotional modulation and causes amnesia via mechanisms that commonly involve hyporesponsiveness of the hippocampus. These findings raise the possibility that amygdala-dependent fear systems may remain intact even when a patient has diminished memory of events. This may be of clinical importance in the perioperative development of fear-based psychopathologies, such as post-traumatic stress disorder. NCT00504894.


Aβ42 Double Mutant Inhibits Aβ42-Induced Plasma and Mitochondrial Membrane Disruption in Artificial Membranes, Isolated Organs, and Intact Cells.
Destabilization of plasma and inner mitochondrial membranes by extra- and intracellular amyloid β peptide (Aβ42) aggregates may lead to dysregulated calcium flux through the plasma membrane, mitochondrial-mediated apoptosis, and neuronal cell death in patients with Alzheimer's disease. In the current study, experiments performed with artificial membranes, isolated mitochondria, and neuronal cells allowed us to understand the mechanism by which a nonaggregating Aβ42 double mutant (designated Aβ42DM) exerts its neuroprotective effects. Specifically, we showed that Aβ42DM protected neuronal cells from Aβ42-induced accumulation of toxic intracellular levels of calcium and from apoptosis. Aβ42DM also inhibited Aβ42-induced mitochondrial membrane potential depolarization in the cells and abolished the Aβ42-mediated decrease in cytochrome c oxidase activity in purified mitochondrial particles. These results can be explained in terms of the amelioration by Aβ42DM of Aβ42-mediated changes in membrane fluidity in DOPC and cardiolipin/DOPC phospholipid vesicles, mimicking plasma and mitochondrial membranes, respectively. These observations are also in agreement with the inhibition by Aβ42DM of phospholipid-induced conformational changes in Aβ42 and with the fact that, unlike Aβ42, the Aβ42-Aβ42DM complex could not permeate into cells but instead remained attached to the cell membrane. Although most of the Aβ42DM molecules were localized on the cell membrane, some penetrated into the cytosol in an Aβ42-independent process, and, unlike Aβ42, did not form intracellular inclusion bodies. Overall, we provide a mechanistic explanation for the inhibitory activity of Aβ42DM against Aβ42-induced membrane permeability and cell toxicity and provide confirmatory evidence for its protective function in neuronal cells.


Competition between Escherichia coli strains expressing either a periplasmic or a membrane-bound nitrate reductase: does Nap confer a selective advantage during nitrate-limited growth?
The physiological role of the periplasmic nitrate reductase, Nap, one of the three nitrate reductases synthesized by Escherichia coli K-12, has been investigated. A series of double mutants that express only one nitrate reductase were grown anaerobically in batch cultures with glycerol as the non-fermentable carbon source and nitrate as the terminal electron acceptor. Only the strain expressing nitrate reductase A grew rapidly under these conditions. Introduction of a narL mutation severely decreased the growth rate of the nitrate reductase A strain, but enhanced the growth of the Nap(+) strain. The ability to use nitrate as a terminal electron acceptor for anaerobic growth is therefore regulated primarily by the NarL protein at the level of transcription. Furthermore, the strain expressing nitrate reductase A had a substantial selective advantage in competition with the strain expressing only Nap during nitrate-sufficient continuous culture. However, the strain expressing Nap was preferentially selected during nitrate-limited continuous growth. The saturation constants for nitrate for the two strains (which numerically are equal to the nitrate concentrations at half of the maximum specific growth rate and therefore reflect the relative affinities for nitrate) were estimated using the integrated Monod equation to be 15 and 50 microM for Nap and nitrate reductase A respectively. This difference is sufficient to explain the selective advantage of the Nap(+) strain during nitrate-limited growth. It is concluded that one physiological role of the periplasmic nitrate reductase of enteric bacteria is to enable bacteria to scavenge nitrate in nitrate-limited environments.


Therapeutic drug monitoring of antiretroviral drugs in HIV-infected patients.
Therapeutic drug monitoring (TDM) may be beneficial when applied to antiretroviral (ARV). Even though TDM can be a valuable strategy in HIV management, its role remains controversial. Areas covered: This review provides a comprehensive update on important issues relating to TDM of ARV drugs in HIV-infected patients. Articles from PubMed with keywords relevant to each topic section were reviewed. Search strategies limited to articles published in English. Expert commentary: There is evidence supporting the use of TDM in HIV treatment. However, some limitations need to be considered. The evidence supporting the use of routine TDM for all patients is limited, as it is not clear that this strategy offers any advantages over TDM for selected indications. Selected groups of patients including patients with physiological changes, patients with drug-drug interactions or toxicity, and the elderly could potentially benefit from TDM, as optimized dosing is challenging in these populations.


New rules for clinical trials of patients with acute bacterial skin and skin-structure infections: do not let the perfect be the enemy of the good.
Over the past decade, the United States has witnessed an epidemic of acute bacterial skin and skin-structure infections (ABSSSIs) caused primarily by community-acquired methicillin-resistant Staphylococcus aureus. To address this medical need as well as the ongoing threat of increasing resistance, new antibiotics are being developed. Clinical trials involving patients with complicated ABSSSI are being implemented to understand the efficacy and safety of these new antibiotic agents. Because antibiotics clearly have an effect on the resolution of the majority of these infections, placebo-controlled trials have been replaced by noninferiority studies. However, to conduct noninferiority trials a noninferiority margin must be determined on the basis of the effect size of the comparator antibiotic. The lack of modern-day placebo-controlled studies of ABSSSI makes determining effect size/noninferiority margin--and as a result, trial design--challenging. The US Food and Drug Administration (FDA) in collaboration with the Foundation for the National Institutes of Health (FNIH) have been working hard to resolve these issues and develop a new guidance to aid investigators in the conduct of these trials. In this article, we first review the 1998 guidance and its shortcomings. Next, we address the ongoing discussion of the new 2010 guidance as we understand it, along with its perceived strengths and weaknesses. Throughout this process, we wish to emphasize that the continued development of antibiotics is essential. Thus, we hope that as the FDA and FNIH move forward they will strike a balance between "The Perfect" statistical solution and "The Good" practical clinical realities.


Shoot Induction in White Eggplant (Solanum melongena L. Cv. Bulat Putih) using 6-Benzylaminopurine and Kinetin.
Solanum melongena L. commonly known as the eggplant or brinjal comes from the family of Solanaceae, sharing the same ancestor with the tomato and potato. It is an economically important crop worldwide, being well studied for its medicinal properties, nutritional values and its role as an alternative model plant. The eggplant fruit has been previously used for treatments of various diseases such as bronchitis, asthma, arthritis and diabetes as well as its nutritive properties that are beneficial to the human diet. Plant transformation studies on the eggplant have been widely done for the production of transgenic eggplants harbouring genes that are beneficial for optimal plant growth and fruit production. Shoot induction is an essential step required for the successful regeneration of transformed plant tissues and therefore is an essential pre-requisite in Agrobacterium-mediated transformation. The local eggplant cv. Bulat Putih is a local cultivar of eggplant in Malaysia with white and round fruits making it a potential model plant colour pigment accumulation studies in fruit crops. The current work aims to investigate the shoot induction potential of 6-benzylaminopurine (BAP) and Kinetin from cotyledon explants of eggplant cv. Bulat Putih. Results indicated that both BAP and Kinetin were able to induce the regeneration of callus from cotyledon explants. On the other hand, Kinetin at the concentration of 2.0 mg/L successfully induced shoots at the value of 1.50 ± 0.22 shoots per explant, whereas BAP alone did not trigger any formation of shoots. This study indicated that kinetin alone is sufficient to induce shoots in eggplant cv. Bulat Putih without the presence of BAP.


Increased amplification of plasmids pBR322 and pBR327 by low concentrations of chloramphenicol.
The replication and amplification of plasmids pBR322 and pBR327 is maximal during partial inhibition of protein synthesis by low concentrations (10-20 micrograms/ml) of chloramphenicol in rich medium (LB). In this manner, 5- to 10-fold greater yields of plasmid DNA at 2- to 5-fold greater initial purity (less protein and chromosomal DNA content) can be obtained than by using the standard high concentrations of chloramphenicol. These results have been obtained with an improved method of plasmid quantitation in unfractionated bacterial lysates.


Radioactive waste minimization at a large academic medical facility.
The University of Texas Medical Branch (UTMB) at Galveston is a large academic medical center with about 12,700 employees, 350 radioisotope research labs and 200 permitted radioactive materials users. Consequently, UTMB generates a fairly large amount of radioactive waste. The majority of this waste contains short-lived radionuclides, such as 32P, 33P, and 35S, which are held for decay and then disposed at a sanitary landfill. However, some waste, including long-lived waste and stock vials, is compacted into drums and stored in a warehouse facility, on-site, until disposal at a low-level radioactive waste (LLRW) facility. Space in the warehouse is limited but disposal is currently cost prohibitive. A reevaluation of our program was conducted to see if volumes of LLRW requiring disposal at a commercial LLRW facility could be reduced. A reevaluation of the waste streams resulted in the shifting of most of the material that was being drummed for shipment to a LLRW facility to disposal by landfill or incineration. Materials that were previously assumed to be radioactive are now being evaluated prior to disposal to determine if they may be disposed of as non-radioactive waste. Following the initial evaluation, the amount of compacted dry solids assumed to contain long-lived radionuclides was reduced. The space that was saved due to the decrease in drumming for disposal is now used to hold the increased volume of decay-in-storage material. The monetary savings will amount to about $45,000 per year. This program is currently being expanded to reduce other waste streams at the university.


Sorption and diffusion of carbon dioxide and nitrogen in poly(methyl methacrylate).
Molecular dynamics simulations are performed to determine the solubility and diffusion coefficient of carbon dioxide and nitrogen in poly(methyl methacrylate) (PMMA). The solubilities of CO2 in the polymer are calculated employing our grand canonical ensemble simulation method, fixing the target excess chemical potential of CO2 in the polymer and varying the number of CO2 molecules in the polymer matrix till establishing equilibrium. It is shown that the calculated sorption isotherms of CO2 in PMMA, employing this method well agrees with experiment. Our results on the diffusion coefficients of CO2 and N2 in PMMA are shown to obey a common hopping mechanism. It is shown that the higher solubility of CO2 than that of N2 is a consequence of more attractive interactions between the carbonyl group of polymer and the sorbent. While the residence time of CO2 beside the carbonyl group of polymer is about three times higher than that of N2, the diffusion coefficient of CO2 in PMMA is higher than that of N2. The higher diffusion coefficient of CO2, compared to N2, in PMMA is shown to be due to the higher (≈3 times) swelling of polymer upon CO2 uptake.


Collagen 1Alpha1 and transforming growth factor-beta polymorphisms in women with cervical insufficiency.
To estimate whether polymorphisms in the collagen 1Alpha1 gene (COL1Alpha1) and the transforming growth factor-beta gene (TGF-beta;1) are more common in women with cervical insufficiency than in those without the condition. Medical, obstetric, and family histories and blood were obtained from women with (n=121) and those without (n=165) cervical insufficiency. DNA was extracted and purified by using commercial DNA isolation kits. Samples were analyzed for variants in two genes, the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphism, by using an allele-specific polymerase chain reaction assay. Thirty-four of 125 (27.2%) women with cervical insufficiency had at least one first-degree female relative affected. The frequency of the homozygous TT genotype in the COL1A1 gene was increased in women with a history of cervical insufficiency compared with controls (10.8% compared with 3.1%, P=.04). The TGF-beta polymorphisms (ArgPro and ProPro) also were increased in cases (38.3% compared with 14.6%, P<.001). Over one fourth of women with cervical insufficiency have a family history of cervical insufficiency, and the COL1A1 intron 1SP1 and TGF-beta Arg-25-Pro polymorphisms are associated with the condition. These observations suggest that, in part, cervical insufficiency is mediated by genetic factors. II.


Honey bee colony performance affected by crop diversity and farmland structure: a modeling framework.
Forage availability has been suggested as one driver of the observed decline in honey bees. However, little is known about the effects of its spatiotemporal variation on colony success. We present a modeling framework for assessing honey bee colony viability in cropping systems. Based on two real farmland structures, we developed a landscape generator to design cropping systems varying in crop species identity, diversity, and relative abundance. The landscape scenarios generated were evaluated using the existing honey bee colony model BEEHAVE, which links foraging to in-hive dynamics. We thereby explored how different cropping systems determine spatiotemporal forage availability and, in turn, honey bee colony viability (e.g., time to extinction, TTE) and resilience (indicated by, e.g., brood mortality). To assess overall colony viability, we developed metrics, PH and PP, which quantified how much nectar and pollen provided by a cropping system per year was converted into a colony's adult worker population. Both crop species identity and diversity determined the temporal continuity in nectar and pollen supply and thus colony viability. Overall farmland structure and relative crop abundance were less important, but details mattered. For monocultures and for four-crop species systems composed of cereals, oilseed rape, maize, and sunflower, PH and PP were below the viability threshold. Such cropping systems showed frequent, badly timed, and prolonged forage gaps leading to detrimental cascading effects on life stages and in-hive work force, which critically reduced colony resilience. Four-crop systems composed of rye-grass-dandelion pasture, trefoil-grass pasture, sunflower, and phacelia ensured continuous nectar and pollen supply resulting in TTE > 5 yr, and PH (269.5 kg) and PP (108 kg) being above viability thresholds for 5 yr. Overall, trefoil-grass pasture, oilseed rape, buckwheat, and phacelia improved the temporal continuity in forage supply and colony's viability. Our results are hypothetical as they are obtained from simplified landscape settings, but they nevertheless match empirical observations, in particular the viability threshold. Our framework can be used to assess the effects of cropping systems on honey bee viability and to develop land-use strategies that help maintain pollination services by avoiding prolonged and badly timed forage gaps.


Cellulose Nanocrystal-Based Emulsion of Thyme Essential Oil: Preparation and Characterisation as Sustainable Crop Protection Tool.
Essential oil-based pesticides, which contain antimicrobial and antioxidant molecules, have potential for use in sustainable agriculture. However, these compounds have limitations such as volatility, poor water solubility, and phytotoxicity. Nanoencapsulation, through processes like micro- and nanoemulsions, can enhance the stability and bioactivity of essential oils. In this study, thyme essential oil from supercritical carbon dioxide extraction was selected as a sustainable antimicrobial tool and nanoencapsulated in an oil-in-water emulsion system. The investigated protocol provided high-speed homogenisation in the presence of cellulose nanocrystals as stabilisers and calcium chloride as an ionic crosslinking agent. Thyme essential oil was characterised via GC-MS and UV-vis analysis, indicating rich content in phenols. The cellulose nanocrystal/essential oil ratio and calcium chloride concentration were varied to tune the nanoemulsions' physical-chemical stability, which was investigated via UV-vis, direct observation, dynamic light scattering, and Turbiscan analysis. Transmission electron microscopy confirmed the nanosized droplet formation. The nanoemulsion resulting from the addition of crosslinked nanocrystals was very stable over time at room temperature. It was evaluated for the first time on Pseudomonas savastanoi pv. savastanoi, the causal agent of olive knot disease. In vitro tests showed a synergistic effect of the formulation components, and in vivo tests on olive seedlings demonstrated reduced bacterial colonies without any phytotoxic effect. These findings suggest that crosslinked cellulose nanocrystal emulsions can enhance the stability and bioactivity of thyme essential oil, providing a new tool for crop protection.


Spin-label study of the mobility of enzyme-bound lipoic acid in the pyruvate dehydrogenase multienzyme complex of Escherichia coli.
The lipoic acid residues covalently bound to the transacetylase component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli were selectively modified by reaction with 4-maleimido-2,2,6,6-tetramethylpiperidino-oxyl. The electron-spin-resonance spectrum of the spin-labelled enzyme indicates that the bound nitroxide groups have high mobilities relative to the protein molecule. This physicochemical evidence is consistent with the view that the dithiolane ring of a lipoyl residue is capable of rapid migration between the active sites of the component enzymes in the catalytic mechanism.


Recent progress of liposomes in nanomedicine.
Liposomes, spherical vesicles consisting of one or more lipid bilayer membrane(s) encapsulating an aqueous medium, are among the prominent players in the field of nanomedicine. Herein, we highlight the newest, atypical applications of liposomes towards their use in biomedicine. In particular, we put special emphasis on innovative chemical modification of liposomes, the interactions of liposomes with cells under the influence of shear stress, and the utilisation of liposomes as drug deposits in polymeric films and as components in synthetic cell mimics.


Zinc-Mediated Radiosynthesis of Unprotected Fluorine-18 Labelled α-Tertiary Amides.
This report describes the development of a Zn(OTf)2 -mediated method for converting α-tertiary haloamides to the corresponding fluorine-18 labelled α-tertiary fluoroamides with no-carrier-added [18 F]tetramethylammonium fluoride. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C-H radiofluorination process using N-sulphonyloxyamide substrates.


A Flexible PDMS-Based Optical Biosensor for Stretch Monitoring in Cardiac Tissue Samples.
Cardiotoxicity, characterized by adverse impacts on normal heart function due to drug exposure, is a significant concern due to the potentially serious side effects associated with various pharmaceuticals. It is essential to detect the cardiotoxicity of a drug as early as possible in the testing phase of a medical composite. Therefore, there is a pressing need for more reliable in vitro models that accurately mimic the in vivo conditions of cardiac biopsies. In a functional beating heart, cardiac muscle cells are under the effect of static and cyclic stretches. It has been demonstrated that cultured cardiac biopsies can benefit from external mechanical loads that resemble the in vivo condition, increasing the probability of cardiotoxicity detection in the early testing stages. In this work, a biosensor is designed and fabricated to allow for stretch monitoring in biopsies and tissue cultures using an innovative sensing mechanism. The detection setup is based on a biocompatible, thin, flexible membrane-where the samples are attached-which is used as an optical waveguide to detect pressure-caused shape changes and stretches. Various prototypes have been fabricated with a cost-effective process, and different measurements have been carried out to experimentally validate the proposed measurement technique. From these evaluations, stretches of up to 1.5% have been measured, but the performed simulations point towards the possibility of expanding the considered technique up to 10-30% stretches.


Novel behavioural characteristics of female APPSwe/PS1ΔE9 double transgenic mice.
Murine models are commonly used to evaluate progression of Alzheimer's disease. APPSwe/PS1ΔE9 (APPxPS1) mice have previously been reported to demonstrate impaired learning and memory in the Morris water maze test. However, this paradigm introduces a variety of behaviours that may confound performance of the mice, thus an alternative was sought. A battery of behavioural tests (light-dark test, elevated plus maze, novel object recognition task, social recognition test, cheeseboard task and prepulse inhibition) was used to investigate various behavioural and cognitive domains with relevance to Alzheimer's disease. We found 9-month old female APPxPS1 mice exhibited impaired spatial memory in the reversal cheeseboard task. In addition, task-dependent hyperlocomotion and anxiolytic-like behaviours were observed in the light-dark test. Female APPxPS1 demonstrated intact object recognition memory and sensorimotor gating was not significantly decreased compared to control mice except for one particular interstimulus interval. The social recognition test failed to detect preference for social novelty in control females. In conclusion, this is the first study to describe a memory deficit in female APPxPS1 mice in the hidden cheeseboard task. Transgenic females also exhibited task-dependent reduction in anxiety behaviours and hyperlocomotion. These novel findings enhance our understanding of the behavioural phenotype of APPxPS1 females and present the cheeseboard as a valid alternative to other established spatial memory tests. Furthermore, the task-dependency of some of our findings suggests that behavioural profiling of APPxPS1 transgenic mice should be assessed using a variety of behavioural paradigms.


Radon as a natural tracer of gas transport through trees.
Trees are sources, sinks, and conduits for gas exchange between the atmosphere and soil, and effectively link these terrestrial realms in a soil-plant-atmosphere continuum. We demonstrated that naturally produced radon-222 (222 Rn) gas has the potential to disentangle the biotic and physical processes that regulate gas transfer between soils or plants and the atmosphere in field settings where exogenous tracer applications are challenging. Patterns in stem radon emissions across tree species, seasons, and diurnal periods suggest that plant transport of soil gases is controlled by plant hydraulics, whether by diffusion or mass flow via transpiration. We establish for the first time that trees emit soil gases during the night when transpiration rates are negligible, suggesting that axial diffusion is an important and understudied mechanism of plant and soil gas transmission.


Reactogenicity of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) against COVID-19 in workers of a tertiary hospital.
To analyze the local and systemic reactions that appeared after the first and second dose of the BNT162b2 vaccine against COVID‑19 (Pfizer- BioNTech) in a sample of workers from a tertiary hospital, and to identify the factors related to greater vaccine reactogenicity. A self-administered questionnaire was used to interview 291 workers from a tertiary hospital who received the BNT162b2 vaccine against COVID-19 between January and March 2021. The questionnaire included questions about the sociodemographic variables of the participants, previous COVID-19 infection, and local and systemic reactions after the first and second dose of the vaccine. The most common adverse reaction was soreness at the injection site, which was reported more frequently after the first dose of the vaccine. The systemic reactions evaluated were reported more frequently after the second dose of the vaccine. Women, younger adults, and subjects with a prior COVID-19 infection reported increased reactogenicity. Furthermore, high reactogenicity after the first dose was found to be related to a higher number of adverse reactions after the second dose of the vaccine. The distribution of reactogenicity in the present study is consistent with the data reported in previous studies on the BNT162b2 vaccine, especially in terms of its association with the participants' characteristics. These findings could facilitate the identification of people at a higher risk of developing high reactogenicity to the vaccine, thereby making it possible to anticipate the appearance of adverse reactions and plan for their treatment.


Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031.
We previously reported preliminary findings that post induction imatinib mesylate (340 mg/m(2)/day), in combination with intensive chemotherapy, resulted in outcomes similar to blood and marrow transplant (BMT) for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1-21 years) with and without allogeneic BMT (N=91). We explore the impacts of additional chromosomal abnormalities and minimal residual disease (MRD) by flow cytometry on outcomes. The 5-year disease-free survival was similar for Cohort 5 patients, treated with chemotherapy plus imatinib (70%±12%, n=28), sibling donor BMT patients (65%±11%, n=21) and unrelated donor BMT patients (59±15%; P=0.60, n=13). Patients with additional cytogenetic abnormalities had worse outcomes (P=0.05). End induction (pre-imatinib) MRD was not prognostic for Cohort 5 or allogeneic BMT patients, although limited by small numbers. The re-induction rate following relapse was similar to other higher-risk ALL groups. Longer-term follow-up confirms our initial observation of substantially good outcomes for children and adolescents with Ph+ ALL treated with imatinib plus intensive chemotherapy with no advantage for allogeneic BMT.


A Critical Review on Vasoactive Nutrients for the Management of Endothelial Dysfunction and Arterial Stiffness in Individuals under Cardiovascular Risk.
Pathophysiological conditions such as endothelial dysfunction and arterial stiffness, characterized by low nitric oxide bioavailability, deficient endothelium-dependent vasodilation and heart effort, predispose individuals to atherosclerotic lesions and cardiac events. Nitrate (NO3-), L-arginine, L-citrulline and potassium (K+) can mitigate arterial dysfunction and stiffness by intensifying NO bioavailability. Dietary compounds such as L-arginine, L-citrulline, NO3- and K+ exert vasoactive effects as demonstrated in clinical interventions by noninvasive flow-mediated vasodilation (FMD) and pulse-wave velocity (PWV) prognostic techniques. Daily L-arginine intakes ranging from 4.5 to 21 g lead to increased FMD and reduced PWV responses. Isolated L-citrulline intake of at least 5.6 g has a better effect compared to watermelon extract, which is only effective on endothelial function when supplemented for longer than 6 weeks and contains at least 6 g of L-citrulline. NO3- supplementation employing beetroot at doses greater than 370 mg promotes hemodynamic effects through the NO3--NO2-/NO pathway, a well-documented effect. A potassium intake of 1.5 g/day can restore endothelial function and arterial mobility, where decreased vascular tone takes place via ATPase pump/hyperpolarization and natriuresis, leading to muscle relaxation and NO release. These dietary interventions, alone or synergically, can ameliorate endothelial dysfunction and should be considered as adjuvant therapies in cardiovascular diseases.


Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops.
Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional gene silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. Additionally, a subset of PRC1/PRC2 targets engage in long-range interactions whose functions in gene silencing are poorly understood. Using a CRISPR screen in mouse embryonic stem cells, we found that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of a subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not linked to loss of Polycomb chromatin domains. Instead, PDS5A removal causes aberrant cohesin activity leading to ectopic insulation sites, which disrupt the formation of ultra-long Polycomb loops. We show that these loops are important for robust silencing at a subset of PRC1/PRC2 target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.


Gestational cocaine exposure increases opiate receptor binding in weanling offspring.
The use of cocaine during pregnancy produces a variety of adverse effects in offspring. Gestational cocaine exposure is known to affect developing dopamine systems, but other neurochemical systems may also be at risk. Regional density of opiate receptors labeled with [3H]naloxone was examined in the brains of 21-day-old male rats exposed to cocaine (0, 10, 20, or 40 mg/kg/day s.c.) between gestation days 8 and 20. Gestational cocaine exposure significantly increased labeling in a dose-dependent fashion in dopaminergic terminal (e.g. the nucleus accumbens, medial prefrontal cortex, olfactory tubercle, and caudatoputamen), limbic (e.g. basolateral amygdaloid nucleus, lateral habenula, hippocampus, dentate gyrus, entorhinal and cingulate cortices) and neocortical (e.g. somatosensory and motor cortices) regions, but had little effect in diencephalic or brainstem regions. The results suggest a functional linkage whereby drug-induced alteration of dopamine systems can regulate developing opioid systems in the brain. Moreover, gestational cocaine exposure produced long-lasting changes of opiate receptor labeling in certain brain regions. The implications of these results are uncertain. However, such effects on endogenous opioid systems could contribute to a developmental delay, cognitive or motor dysfunction.


Clinical, histologic, and ultrastructural changes after use of human growth factor and cytokine skin cream for the treatment of skin rejuvenation.
The present study reports the clinical, histologic, and ultrastructural changes observed after the 6-month application of a novel skin cream containing a mixture of human growth factors and cytokines. Participants were asked to apply the human growth factor and cytokine skin cream twice daily to their entire face over a period of 6 months. A 3-mm punch biopsy was taken from the preauricular skin area before and after the treatment period. Further evaluations included photographic and clinical assessment of facial skin for wrinkles. After the treatment period, improved clinical appearance of periorbital and perioral wrinkles by 33% and 25% on average, respectively, was demonstrated. Histologic evaluation indicated moderate changes in the epidermal thickness as well as an increased fibroblast density in the superficial dermis at the end of the 6-month treatment period. Ultrastructural changes consistent with new collagen formation were shown by electron microscopy. This study, together with earlier studies, corroborates that topical application of growth factors and cytokines are beneficial in reducing signs of facial skin aging.


Re-evaluation of learned information in Drosophila.
Animals constantly assess the reliability of learned information to optimize their behaviour. On retrieval, consolidated long-term memory can be neutralized by extinction if the learned prediction was inaccurate. Alternatively, retrieved memory can be maintained, following a period of reconsolidation during which it is labile. Although extinction and reconsolidation provide opportunities to alleviate problematic human memories, we lack a detailed mechanistic understanding of memory updating. Here we identify neural operations underpinning the re-evaluation of memory in Drosophila. Reactivation of reward-reinforced olfactory memory can lead to either extinction or reconsolidation, depending on prediction accuracy. Each process recruits activity in specific parts of the mushroom body output network and distinct subsets of reinforcing dopaminergic neurons. Memory extinction requires output neurons with dendrites in the α and α' lobes of the mushroom body, which drive negatively reinforcing dopaminergic neurons that innervate neighbouring zones. The aversive valence of these new extinction memories neutralizes previously learned odour preference. Memory reconsolidation requires the γ2α'1 mushroom body output neurons. This pathway recruits negatively reinforcing dopaminergic neurons innervating the same compartment and re-engages positively reinforcing dopaminergic neurons to reconsolidate the original reward memory. These data establish that recurrent and hierarchical connectivity between mushroom body output neurons and dopaminergic neurons enables memory re-evaluation driven by reward-prediction error.


Involvement of Protein Kinase C and RhoA in Protease-Activated Receptor 1-Mediated F-Actin Reorganization and Cell Growth in Rat Cardiomyocytes.
Protease-activated receptor 1 (PAR1) that can be activated by serine proteinases such as thrombin has been demonstrated to contribute to the development of cardiac remodeling and hypertrophy after myocardial injury. Here, we investigated the mechanisms by which PAR1 leads to hypertrophic cardiomyocyte growth using cultured rat neonatal ventricular myocytes. PAR1 stimulation with thrombin (1 U/ml) or a synthetic agonist peptide (TFLLR-NH2, 50 μM) for 48 h induced an increase in cell size and myofibril formation associated with BNP (brain natriuretic peptide) production. This actin reorganization assessed by fluorescein isothiocyanate (FITC)-conjugated phalloidin staining appeared at 1 h after PAR1 stimulation, and this response was reduced by a protein kinase C (PKC) inhibitor, chelerythrine, inhibitors of Rho (simvastatin) and Rho-associated kinase (ROCK) (Y-27632), but not by pertussis toxin (PTX). By Western blot analysis, translocation of PKCα or PKCε from the cytosol to membrane fractions was observed in cells stimulated with thrombin or TFLLR-NH2 for 2 - 5 min. In addition, PAR1 stimulation for 3 - 5 min increased the level of active RhoA. Furthermore, inhibitors of PKC and ROCK and Rho abrogated PAR1-mediated increase in cell size. Depletion of PKCα or PKCε by specific small interfering RNA also suppressed both actin reorganization and cell growth. These results suggest that PAR1 stimulation of cardiomyocytes induces cell hypertrophy with actin cytoskeletal reorganization through activation of PKCα and PKCε isoforms and RhoA via PTX-insensitive G proteins.


Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility.
The incidence of neuroendocrine neoplasms (NEN) is increasing, but established biomarkers have poor diagnostic and prognostic accuracy. Here, we aim to define the systemic metabolic consequences of NEN and to establish the diagnostic utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) for NEN in a prospective cohort of patients through a single-centre, prospective controlled observational study. Urine samples of 34 treatment-naïve NEN patients (median age: 59.3 years, range: 36-85): 18 had pancreatic (Pan) NEN, of which seven were functioning; 16 had small bowel (SB) NEN; 20 age- and sex-matched healthy control individuals were analysed using a 600 MHz Bruker 1H-NMR spectrometer. Orthogonal partial-least-squares-discriminant analysis models were able to discriminate both PanNEN and SBNEN patients from healthy control (Healthy vs. PanNEN: AUC = 0.90, Healthy vs. SBNEN: AUC = 0.90). Secondary metabolites of tryptophan, such as trigonelline and a niacin-related metabolite were also identified to be universally decreased in NEN patients, while upstream metabolites, such as kynurenine, were elevated in SBNEN. Hippurate, a gut-derived metabolite, was reduced in all patients, whereas other gut microbial co-metabolites, trimethylamine-N-oxide, 4-hydroxyphenylacetate and phenylacetylglutamine, were elevated in those with SBNEN. These findings suggest the existence of a new systems-based neuroendocrine circuit, regulated in part by cancer metabolism, neuroendocrine signalling molecules and gut microbial co-metabolism. Metabonomic profiling of NEN has diagnostic potential and could be used for discovering biomarkers for these tumours. These preliminary data require confirmation in a larger cohort.


Thermal AND Gate Using a Monolayer Graphene Nanoribbon.
The first ever implementation of a thermal AND gate, which performs logic calculations with phonons, is presented using two identical thermal diodes composed of asymmetric graphene nanoribbons (GNRs). Employing molecular dynamics simulations, the characteristics of this AND gate are investigated and compared with those for an electrical AND gate. The thermal gate mechanism originates through thermal rectification due to asymmetric phonon boundary scattering in the two diodes, which is only effective at the nanoscale and at the temperatures much below the room temperature. Due to the high phonon velocity in graphene, the gate has a fast switching time of ≈100 ps.


Ultrasound assessment of cranial spread during caudal blockade in children: Effect of different volumes of local anesthetic.
Ultrasound-guided caudal block injection is a simple, safe, and effective method of anesthesia/analgesia in pediatric patients. The volume of caudal drug required has always been a matter of debate. This present prospective, randomized, double-blinded study aimed to measure extent of the cranial spread of caudally administered levobupivacaine in Indian children by means of real-time ultrasonography. Ninety American Society of Anesthesiologists I/II children scheduled for urogenital surgeries were enrolled in this trial. Anesthesia and caudal analgesia were administered in a standardized manner in the patients. The patients received 0.5 ml/kg or 1 ml/kg or 1.25 ml/kg of 0.125% levobupivacaine according to the group allocated. Cranial spread of local anesthetic was noted using ultrasound. There was no difference in the spread when related to age, sex, weight, or body mass index. A significant difference of ultrasound-assessed cranial spread of the local anesthetic was found between Group 1 (0.5 ml/kg) with both Group 2 (1 ml/kg) (P = 0.001) and with Group 3 (1.125 ml/kg) (P < 0.001) but there is no significant difference between Group 2 and Group 3 (P = 0.451) revealing that spinal level spread is only different between 0.5 ml/kg and 1 ml/kg of local anesthetic. In conclusion, the ultrasound assessment of local anesthetic spread after a caudal block showed that cranial spread of the block is dependent on the volume injected into the caudal space. Since there was no difference between 1 ml/kg and 1.25 ml/kg, to achieve a dermatomal blockade up to thoracic level, we might have to increase the dose beyond 1.25 ml/kg, keeping the toxic dose in mind.


The safety of nurse-administered procedural sedation compared to anesthesia care in a historical cohort of advanced endoscopy patients.
In April 2010, in response to a change in Centers for Medicare and Medicaid Services regulation placing deep sedation under hospital anesthesia services, our institution began providing anesthesia care for all advanced endoscopic procedures. Because it remains unknown whether anesthesia care reduces sedation-related complications or improves quality of care versus nurse-administered sedation for endoscopic retrograde cholangiopancreatography and endoscopic ultrasound patients, we retrospectively compared complications in a 5-year historical cohort before and after the policy change. We reviewed a historical cohort of 9598 consecutive endoscopic retrograde cholangiopancreatography and endoscopic ultrasound examinations for adult patients at a single institution during a 5-year period (October 2007-October 2012). We compared procedures performed before and after the policy change for the incidence of sedation, endoscopic, and total complications, and for major morbidity and mortality. The incidence of reported sedation-related complications was 0.38% (17 of 4514) before the policy change and 0.08% (4 of 5084) after the policy change, which was statistically significant (P = 0.002, diff = 0.3, 95% confidence interval, 0.11%-0.53%). Endoscopic complications were not significantly different before versus after: 0.66% vs 0.87% (P = 0.293, diff = 0.2, 95% confidence interval, -0.16% to 0.56%). Total complications (1.11% vs 1.00%, P = 0.618) and major morbidity and mortality (0.27% vs 0.33%, P = 0.581) did not differ between the 2 time periods. Anesthesia care for advanced endoscopy in a high-risk population significantly reduced sedation complications compared with nurse-administered sedation. Endoscopic complications were unchanged. The sedation risk reduction did not reduce major morbidity, mortality, or total complications.


Analysis of mechanical oscillations by speckling.
The application of the speckle phenomenon to the analysis of in-plane translations and oscillations is first reviewed briefly. Then a practical method of investigating out-of-plane rotations (tilts) even in the presence of in-plane movements is studied. This goal can be achieved by recording the speckle patterns in the Fourier transform plane before and after the tilt or as a time-average exposure for an oscillating object. Young's fringes related to the tilts are observed in the Fraunhofer diffraction pattern when the developed photographic plate is illuminated with coherent light. This leads to a very simple engineering tool for the analysis of movements. Theoretical and experimental results will be shown.


Prostate cancer old problems and new approaches : Part I. epidemiology, incidence and genetic alterations.
Rates of prostate cancer (PCa) have increased so dramatically over the last decade that the age adjusted incidence rate for PCa is now greater than that any other cancer among men in the United States. This review, published as a three part series, provides a state-of-art assessment of the PCa problem in its divergent aspects.Part 1 covers epidemiology, incidence and progression. Several epidemiological studies have demostrated that first degree male relatives of men with PCa are at increased risk of developing the disease. Familial and genetic factors as well as medical, anthropometric, dietary, hormonal and occupational factors involved in PCa are discussed. Postmortem examination of the prostate in men without evidence of PCa documented a high frequency of adenocarcinoma. Latent disease occurred as early as the second decade of life. Although there is no significant difference in incidence between Caucasian and African-American males, high grade prostatic intraepithelial neoplasia (HGPIN) is higher in the latter group. While dietary fat, androgens and certain environmental factors may be determinants for PCa, the exact mechanism of tumorigenesis is still relatively unknown. The current thinking of the role of genomic instability, chromosomal alterations, tumor suppressor genes and the androgen receptor are explored.


Highly accurate optical material parameter determination with THz time-domain spectroscopy.
We improve the existing data extraction algorithms for THz time-domain spectroscopy (THz TDS) in two aspects. On the one hand, we merge the up-to-date knowledge of THz TDS signal processing into a single powerful optical material parameter extraction algorithm. On the other hand, we introduce a novel iterative algorithm that further enhances the accuracy of the parameter extraction. In contrast to most of the published experiments, we are able to reliably investigate samples with thicknesses as small as 100microm, samples with low indexes of refraction, i.e. close to 1, as well as samples with sharp peaks in the material parameter curves.


Mathematical beta cell model for insulin secretion following IVGTT and OGTT.
Evaluation of beta cell function is conducted by a variety of glucose tolerance tests and evaluated by a number of different models with less than perfect consistency among results obtained from different tests. We formulated a new approximation of the distributed threshold model for insulin secretion in order to approach a model for quantifying beta cell function, not only for one, but for several different experiments. Data was obtained from 40 subjects that had both an oral glucose tolerance test (OGTT) and an intravenous tolerance test (IVGTT) performed. Parameter estimates from the two experimental protocols demonstrate similarity, reproducibility, and indications of prognostic relevance. Useful first phase indexes comprise the steady state amount of ready releasable insulin A0 and the rate of redistribution krd, where both yield a considerable correlation (both r=0.67) between IVGTT and OGTT estimates. For the IVGTT, A0 correlates well (r=0.96) with the 10 min area under the curve of insulin above baseline, whereas krd represents a new and possibly more fundamental first phase index. For the useful second phase index gamma, a correlation of 0.75 was found between IVGTT and OGTT estimates.


Special considerations concerning the use of antiretroviral drugs in children.
Antiretroviral therapy is extremely effective in both children and adults infected with HIV. Treatment indications have rapidly expanded; ideally, with rare exceptions, all infected children should now be treated. Areas covered: The use of antiretroviral drugs in children is based largely on extrapolations from experience with adult patients. Pharmacokinetic studies are required in addition to formal studies, which are difficult to conduct in pediatric situations, extending from birth to adolescence. However, despite often inadequate galenic formulation, treatment of children is easier than generally thought. No major or irreversible toxicity has been observed with the latest generation of molecules. Several observations suggest that very early treatment, beginning shortly after birth, provides better long-term immunological control of infection. Expert commentary: All HIV-infected children should be treated with antiretroviral drugs. Manufacturers should propose appropriate dosage forms, including combined forms in particular, and should support pharmacological and tolerance studies in pediatric patients of various ages. Very early treatment maximizes the chances of long-term immunological control.


Utility of accelerated T2-weighted turbo spin-echo imaging with deep learning reconstruction in female pelvic MRI: a multi-reader study.
To determine the clinical feasibility of T2-weighted turbo spin-echo (T2-TSE) imaging with deep learning reconstruction (DLR) in female pelvic MRI compared with conventional T2 TSE in terms of image quality and scan time. Between May 2021 and September 2021, 52 women (mean age, 44 years ± 12) who underwent 3-T pelvic MRI with additional T2-TSE using a DLR algorithm were included in this single-center prospective study with patient's informed consents. Conventional, DLR, and DLR T2-TSE images with reduced scan times were independently assessed and compared by four radiologists. The overall image quality, differentiation of anatomic details, lesion conspicuity, and artifacts were evaluated using a 5-point scale. Inter-observer agreement of the qualitative scores was compared and reader protocol preferences were then evaluated. In the qualitative analysis of all readers, fast DLR T2-TSE showed significantly better overall image quality, differentiation of anatomic regions, lesion conspicuity, and lesser artifacts than conventional T2-TSE and DLR T2-TSE, despite approximately 50% reduction in scan time (all p < 0.05). The inter-reader agreement for the qualitative analysis was moderate to good. All readers preferred DLR over conventional T2-TSE regardless of scan time and preferred fast DLR T2-TSE (57.7-78.8%), except for one who preferred DLR over fast DLR T2-TSE (53.8% vs. 46.1%). In female pelvic MRI, image quality and accelerated image acquisition for T2-TSE can be significantly improved by using DLR compared to conventional T2-TSE. Fast DLR T2-TSE was non-inferior to DLR T2-TSE in terms of reader preference and image quality. DLR of T2-TSE in female pelvic MRI enables fast imaging along with maintaining optimal image quality compared with parallel imaging-based conventional T2-TSE. • Conventional T2 turbo spin-echo based on parallel imaging has limitations for accelerated image acquisition while maintaining good image quality. • Deep learning image reconstruction showed better image quality in both images obtained using the same or accelerated image acquisition parameters compared with conventional T2 turbo spin-echo in female pelvic MRI. • Deep learning image reconstruction enables accelerated image acquisition while maintaining good image quality in the T2-TSE of female pelvic MRI.


Suppression of tumor angiogenesis by targeting the protein neddylation pathway.
Inhibition of protein neddylation, particularly cullin neddylation, has emerged as a promising anticancer strategy, as evidenced by the antitumor activity in preclinical studies of the Nedd8-activating enzyme (NAE) inhibitor MLN4924. This small molecule can block the protein neddylation pathway and is now in clinical trials. We and others have previously shown that the antitumor activity of MLN4924 is mediated by its ability to induce apoptosis, autophagy and senescence in a cell context-dependent manner. However, whether MLN4924 has any effect on tumor angiogenesis remains unexplored. Here we report that MLN4924 inhibits angiogenesis in various in vitro and in vivo models, leading to the suppression of tumor growth and metastasis in highly malignant pancreatic cancer, indicating that blockage of angiogenesis is yet another mechanism contributing to its antitumor activity. At the molecular level, MLN4924 inhibits Cullin-RING E3 ligases (CRLs) by cullin deneddylation, causing accumulation of RhoA at an early stage to impair angiogenic activity of vascular endothelial cells and subsequently DNA damage response, cell cycle arrest and apoptosis due to accumulation of other tumor-suppressive substrates of CRLs. Furthermore, we showed that inactivation of CRLs, via small interfering RNA (siRNA) silencing of its essential subunit ROC1/RBX1, recapitulates the antiangiogenic effect of MLN4924. Taken together, our study demonstrates a previously unrecognized role of neddylation in the regulation of tumor angiogenesis using both pharmaceutical and genetic approaches, and provides proof of concept evidence for future development of neddylation inhibitors (such as MLN4924) as a novel class of antiangiogenic agents.


Tubular vs Profile Plate in Peroneal or Bimalleolar Fractures: is There a Real Difference in Skin Complication? A Retrospective Study in Three Level I Trauma Center.
Not enough literature is available to evalute the wound complication rate of plates type in distal fibular fractures. The aim of our study was to compare wound complications of using a third tubular plate compared to LCP distal fibula plate. This study is a retrospective single-centre study in which was performed plating of fibula in closed ankle fractures. 93 patients were included in our study and assigned in two groups, based on using of different implant : in group A 48 patients were treated with one-third tubular and in group B 45 patients were treated with LCP distal fibula plate. There were no significant differences in the baseline characterisctics. Patients received the same surgical procedure and the same post-operative care, then they were radiologically evalueted at 1-3-12 months and clinical examination was made at 12 months using AOFAS clinical rating system. Categorical data, grouped into distinct categories, were evalueted using Chi-square test. We considered a p value < 0.05 as statistically significant. The wound complications rate of the overall study group was 7.6%. There were no statistical differences in the rate of wound complications between the two groups. There were no differences between both group in percentage of hardware removal at follow-up (overall 5.4%); plate removal was performed earlier in the locking plate because of wound complications. Our study has shown no difference in radiographic bone union rate, no significant differences in terms of clinical outcomes, in time of bone reduction and wound complication rate between the LCP distal fibula plate and conventional one-third tubular plate. Controversy still exists about the best method for the fracture reduction.


Oxidative stress, protein glycation and nutrition--interactions relevant to health and disease throughout the lifecycle.
Protein glycation has been studied for over a century now and plays an important role in disease pathogenesis throughout the lifecycle. Strongly related to diabetic complications, glycation of Hb has become the gold standard method for diabetes diagnosis and monitoring. It is however attracting attention in normoglycaemia as well lately. Longitudinal studies increasingly suggest a positive relationship between glycation and the risk of chronic diseases in normoglycaemic individuals, but the mechanisms behind this association remain unclear. The interaction between glycation and oxidative stress may be particularly relevant in the normoglycaemic context, as suggested by recent epidemiological and in vitro evidence. In that context nutritional and lifestyle factors with an influence on redox status, such as smoking, fruit and vegetable and antioxidants consumption, may have the capacity to promote or inhibit glycation. However, experimental data from controlled trials are lacking the quality and rigour needed to reach firm conclusions. In the present review, we discuss the importance of glycation for health through the lifecycle and focus on the importance of oxidative stress as a driver for glycation. The importance of nutrition to modulate glycation is discussed, based on the evidence available and recommendations towards higher quality future research are made.


Analysis of mitochondrial respiratory function in tissue biopsies and blood cells.
The review provides an overview on latest methodological strategies to assess mitochondrial respiratory function in tissue biopsies or blood cells. In addition, it summarizes the recent literature related to this topic. Today, the study of mitochondrial function in key metabolic active tissues has been become more relevant, with increasing focus in clinical applications. In addition, assessment of mitochondrial function in blood cells by respirometry might be a sensitive biomarker of disease progression. High-Resolution Respirometry provides a modern tool to study mitochondrial respiratory physiology which allows direct measurement of cellular metabolic function during health and disease. Moreover, standard operating procedures are required regarding instrumental settings, sample collection and preparation, protocol design and respirometric data analysis of mitochondrial respiratory function in tissue biopsies (such as skeletal muscle, liver and adipose tissue), as well as isolated blood cells. Mitochondrial function is a key factor in many metabolic diseases. Although various analytical approaches are available, certain well-established protocols for isolated mitochondria are limited for the analysis of mitochondrial function in tissue biopsies or blood cells. Thus, cautious considerations in selecting appropriate protocols and analytical endpoints are crucial for the interpretation of the gained data and to draw robust conclusions.


Use of an electronic problem list by primary care providers and specialists.
Accurate patient problem lists are valuable tools for improving the quality of care, enabling clinical decision support, and facilitating research and quality measurement. However, problem lists are frequently inaccurate and out-of-date and use varies widely across providers. Our goal was to assess provider use of an electronic problem list and identify differences in usage between medical specialties. Chart review of a random sample of 100,000 patients who had received care in the past two years at a Boston-based academic medical center. Counts were collected of all notes and problems added for each patient from 1/1/2002 to 4/30/2010. For each entry, the recording provider and the clinic in which the entry was recorded was collected. We used the Healthcare Provider Taxonomy Code Set to categorize each clinic by specialty. We analyzed the problem list use across specialties, controlling for note volume as a proxy for visits. A total of 2,264,051 notes and 158,105 problems were recorded in the electronic medical record for this population during the study period. Primary care providers added 82.3% of all problems, despite writing only 40.4% of all notes. Of all patients, 49.1% had an assigned primary care provider (PCP) affiliated with the hospital; patients with a PCP had an average of 4.7 documented problems compared to 1.5 problems for patients without a PCP. Primary care providers were responsible for the majority of problem documentation; surgical and medical specialists and subspecialists recorded a disproportionately small number of problems on the problem list.


[Effect of hypothalamic extracts and synthetic LH-RH on proteic synthesis by rat hypothalamus in vitro (author's transl)].
The incorporation of 14C-Leucine in pituitary proteins in rats, in vitro, has been studied. In absence of stimulation, the pituitaries of adult female rats have shown approximately twice the capacity of protein biosynthesis in vitro than the pituitaries of prepuberal female rats (21 days old). For the stimulation in vitro of the pituitaries, synthetic LH-RH or hypothalamic extracts from adult or prepuberal female rats were used. The pituitaries of adult female rats did not respond to any of the stimulation tests employed. The pituitaries of prepuberal female rats increased their biosynthetic activity significantly, when synthetic LH-RH or adult female rat hypothalamic extract was added to the culture medium. The addition of prepuberal female rat hypothalamic extract did not alter the basic response. The female prepuberal rats injected during 5 consecutive days with FSH and LH, have shown a greater sensibility to LH-RH in vitro than the ones injected with estradiol and progesterone, or with synthetic LH-RH.


Intraluminal assessment of inflammatory factors in patients with intracranial aneurysms.
The formation, growth, and rupture of intracranial aneurysms (IA) are due to several pathophysiological mechanisms, including focal hemodynamic injury and inflammation of the arterial wall. We investigated the differences between venous, parent artery, and intra-aneurysmal blood by measuring inflammatory factors and antibodies in patients with ruptured (rIA) or unruptured intracranial aneurysms (uIA). A prospective study was performed in patients who presented with IA and required endovascular treatment. Blood was drawn from the lumen of the aneurysm sac, the parent artery, and the peripheral veins, to determine the serum concentrations of complement factors C3, C4, IgG, IgM, IgA antibodies, and C-reactive protein (CRP). Thirty-six patients (15 with uIA and 21 with rIA) were enrolled in the study. In both groups, C3, C4, IgM, IgG, and IgA showed a gradual decrease from venous to intra-aneurysmal samples, but only IgG in the parent artery and intra-aneurysmal samples reached a significant decrease in uIA compared with venous samples. Accordingly, C3 and IgG concentrations in the intra-aneurysmal samples showed a significant decrease in rIA compared with venous samples. A significant increase in CRP concentrations was observed in parent artery and intra-aneurysmal samples from patients with rIA compared with patients with uIA; a significant increase in C3 concentrations was observed in parent artery samples from patients with rIA compared with patients with uIA, and a significant decrease in IgM concentrations was observed in venous, parent artery, and intra-aneurysmal samples from patients with rIA compared with patients with uIA. A decrease in C3 and IgG in the aneurysm sac indicates activation of the complement system in the arterial wall. CRP in the aneurysm sac and lumen of the parent artery was significantly increased in ruptured compared with unruptured aneurysms, whereas venous, parent artery, and intra-aneurysmal IgM were decreased in ruptured compared with unruptured aneurysms. These results argue for the role of an ongoing inflammatory process in aneurysms leading to their growth and rupture.


Ozone pollution, oxidative stress, synaptic plasticity, and neurodegeneration.
Overpopulation and industrial growth result in an increase in air pollution, mainly due to suspended particulate matter and the formation of ozone. Repeated exposure to low doses of ozone, such as on a day with high air pollution levels, results in a state of chronic oxidative stress, causing the loss of dendritic spines, alterations in cerebral plasticity and in learning and memory mechanisms, and neuronal death and a loss of brain repair capacity. This has a direct impact on human health, increasing the incidence of chronic and degenerative diseases. We performed a search of the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2000 and 2018 and addressing the main consequences of ozone exposure on synaptic plasticity, information processing in cognitive processes, and the alterations that may lead to the development of neurodegenerative diseases. This review describes one of the pathophysiological mechanisms of the effect of repeated exposure to low doses of ozone, which causes loss of synaptic plasticity by producing a state of chronic oxidative stress. This brain function is key to both information processing and the generation of structural changes in neuronal populations. We also address the effect of chronic ozone exposure on brain tissue and the close relationship between ozone pollution and the appearance and progression of neurodegenerative diseases.


Assessment of allergenic activity of a heat-coagulated ovalbumin after in vivo digestion.
We often eat heat-coagulated (H-C) food proteins, but there have been few studies on the allergenic activity of H-C proteins after digestion and absorption in vivo. To show that H-C protein is not an allergen after digestion, mice were used to investigate the digestion and absorption of the protein through the intestinal epithelium into portal blood employing immunoblotting and competitive inhibition ELISA. Ovalbumin (OVA) was used as the model protein, and H-C OVA was prepared by heating a 5% OVA solution for 15 min in boiling water. Antigenic OVA was not detected in the soluble fraction of gastrointestinal contents or the portal blood of mice administered H-C OVA. Also, voluntary physical activities, as an assessment of anaphylaxis, were monitored for 15 h using OVA sensitized mice. Compared to the voluntary physical activities of sensitized mice without any load, no decrease in activity was observed in the group administered H-C OVA, but a significant decrease in activity was found in the mice administered unheated OVA. These results strongly indicate that H-C OVA does not retain allergenic properties.


Resilience and syndemic risk factors among African-American female sex workers.
Research on street-based female sex workers documents a multitude of problems faced by these women, such as substance use, HIV risk, mental health problems, victimization, and homelessness. The presence of problems such as these is understood as a syndemic, or co-occurrence of two or more risk factors that act synergistically to create an excess burden of disease. However, the syndemic framework has not previously incorporated the examination of resilience to understand what protective factors enable female sex workers to cope with syndemic risk. Using 562 baseline interviews from street-based African-American female sex workers enrolled in a randomized intervention trial, this study is the first to investigate expressions of resilience among this vulnerable population. Specifically, these analyses examine high levels of resilience, as measured by personal mastery, in order to understand the contributions of syndemic risk factors and protective factors on the expression of resilience. In bivariate logistic regression models, women with high resilience reported significantly higher odds of high school education, greater access to transportation, and more social support, in addition to lower odds of foster care history, homelessness, substance dependence, severe mental distress, victimization, and HIV risk. In the multivariate model, higher odds of high school education and increased social support, in addition to lower odds of mental distress and HIV risk remained associated with high resilience. The findings suggest specific targets for intervention to assist female sex workers in coping with syndemic risk factors and achieving better health outcomes. These include the prioritizing of education and training opportunities and the enhancement of social support.


Further thoughts on the aluminum-Alzheimer's disease link.
STUDY OBJECTIVE AND METHOD: The results of studies on aluminum (Al) and Alzheimer's disease (AD) from groups in Newcastle, UK and Ontario, Canada were compared in order to explain why the former were unable to detect a link while the latter could, and to suggest alternative ways of examining the data. The Al concentrations in the Newcastle study were relatively small compared with the Ontario ones. When Al concentrations > 250 micrograms/l were used, the RRs were greater for AD than for other forms of dementia, and the RRs were lower for those under 75 years and greater at ages 85 years and over than at ages above 75 years. The relationship between dementia and Al concentrations was U or J shaped--there was a minimum at an Al concentration of 100 micrograms/l. Other constituents or properties such as silicic acid, fluoride, turbidity, iron, and pH all have an effect on the relationship. Analyses of the type reported from Newcastle can yield further information if they are extended to include multivariate analyses that take account of other water constituents which can affect the relationship between Al water concentrations and AD are carried out. The relationship between Al and dementia may be U or J shaped rather than linear. With regard to AD, the group aged less than 65 years is not the best one in which to explore a relationship. Lastly, it may be that a link with AD is most meaningful at relatively high Al water concentrations.


Stress induced neuroendocrine-immune plasticity: A role for the spleen in peripheral inflammatory disease and inflammaging?
Research over the past decade has revealed close interaction between the nervous and immune systems in regulation of peripheral inflammation linking psychosocial stress with chronic somatic disease and aging. Moreover emerging data suggests that chronic inflammations lead to a pro-inflammatory status underlying premature aging called inflammaging. In this context, the spleen can be seen as a switch board monitoring peripherally derived neuroendocrine-immune mediators in the blood and keeping up a close communication with the central stress response via its mainly sympathetic innervation. The effect aims at balanced and well-timed stress axis activation and immune adaptation in acute peripheral inflammatory events. Constant adjustment to the needs generated by environmental and endogenous challenges is provided by neuroendocrine-immune plasticity. However, maladaptive plasticity induced e.g., by chronic stress-axis activation and excessive non-neuronal derived neuroendocrine mediators may be at the heart of the observed stress sensitivity promote inflammaging under chronic inflammatory conditions. We here review the role of neurotransmitters, neuropeptides and neurotrophins as stress mediators modulating the immune response in the spleen and their potential role in inflammaging.


Brain networks associated with anticipatory postural adjustments in Parkinson's disease patients with freezing of gait.
Specific impairments of anticipatory postural adjustment (APA) during step initiation have been reported in patients with Parkinson's disease (PD) and freezing of gait (FoG). Although APA disruption has been associated with FoG, there is scarce knowledge about its neural correlates. We sought to better understand the neural networks involved with APA in patients with FoG by assessing the level of hemodynamic response of specific brain regions and the functional connectivity during the leg lifting task. In the current investigation, APAs of patients with PD, with and without (nFoG) freezing were assessed during a leg lifting task in an event-related, functional magnetic resonance imaging (er-fMRI) protocol. Results identified a high hemodynamic response in the right anterior insula (AI) and supplementary motor area (SMA) in the FoG group when an APA was required. The nFoG had stronger connectivity between the right and left insulae than the FoG group. The strength of this connectivity was negatively correlated with the severity of FoG. Both groups showed different brain network organizations comprising the SMA and the bilateral AI. The SMA was found to be a hub in patients with FoG when an APA was required for the task. Our findings suggest that both groups used compensatory mechanism comprising the insulae during APA. Neither group used the entire network comprised of the insulae and SMA to accomplish the task. The FoG group relied more on SMA as a hub than as part of a broader network to exchange information during the APA.


Inhibitory agents and chemical and mechanisms in the dihalomethane-mediated nitrosation of amines with solid nitrite.
Methylene chloride and certain other dihaloalkanes react efficiently with dissolved secondary amines and, in presence of insoluble sodium nitrite, yield N-nitroso compounds. Mechanistic studies indicate that the intermediates in the nitrosation mixture include the formaldiminium ion, the amine hydrochloride and the diaminomethane (aminal). They also indicate that the formaldiminium ion is by far the most reactive toward sodium nitrite, which probably reacts with the former by nucleophilic attack. Ascorbic acid, ascorbyl palmitate, dehydroascorbic acid, potassium iodide and potassium carbonate inhibited the reaction, whereas alpha-tocopherol, Trolox and sodium ascorbate were found to be ineffective. Ascorbic acid reacted with the secondary amine in a complex fashion. The mode of inhibition probably does not involve reduction of the solid nitrite.


IL-23 Contributes to Campylobacter jejuni-Induced Intestinal Pathology via Promoting IL-17 and IFNγ Responses by Innate Lymphoid Cells.
Human pathogen Campylobacter jejuni is a significant risk factor for the development of long-term intestinal dysfunction although the cellular and molecular mechanisms remain scantily defined. IL-23 is an emerging therapeutic target for the treatment of inflammatory intestinal diseases, however its role in C. jejuni-driven intestinal pathology is not fully understood. IL-10 deficient mice represent a robust model to study the pathogenesis of C. jejuni infection because C. jejuni infection of mice lacking IL-10 results in symptoms and pathology that resemble human campylobacteriosis. To determine the role of IL-23 in C. jejuni-driven intestinal inflammation, we studied the disease pathogenesis in IL-23-/- mice with inhibited IL-10Rα signaling. These mice exhibited reduced intestinal pathology independent from bacterial clearance. Further, levels of IFNγ, IL-17, IL-22, TNF, and IL-6 were reduced and associated with reduced accumulation of neutrophils, monocytes and macrophages in the colon. Flow cytometry analysis revealed reduced production of IL-17 and IFNγ by group 1 and 3 innate lymphoid cells. Thus, our data suggest that IL-23 contributes to intestinal inflammation in C. jejuni infected mice by promoting IL-17 and IFNγ production by innate lymphoid cells.


Biology and Epidemiology of Venturia Species Affecting Fruit Crops: A Review.
The fungal genus Venturia Sacc. (anamorph Fusicladium Bonord.) includes plant pathogens that cause substantial economic damage to fruit crops worldwide. Although Venturia inaequalis is considered a model species in plant pathology, other Venturia spp. also cause scab on other fruit trees. Relative to the substantial research that has been conducted on V. inaequalis and apple scab, little research has been conducted on Venturia spp. affecting other fruit trees. In this review, the main characteristics of plant-pathogenic species of Venturia are discussed with special attention to V. inaequalis affecting apple, V. pyrina affecting European pear, V. nashicola affecting Asian pear, V. carpophila affecting peach and almond, Fusicladium oleagineum affecting olive, F. effusum affecting pecan, and F. eriobotryae affecting loquat. This review has two main objectives: (i) to identify the main gaps in our knowledge regarding the biology and epidemiology of Venturia spp. affecting fruit trees; and (ii) to identify similarities and differences among these Venturia spp. in order to improve disease management. A thorough review has been conducted of studies regarding the phylogenetic relationships, host ranges, biologies, and epidemiologies of Venturia spp. A multiple correspondence analysis (CA) has also been performed on the main epidemiological components of these Venturia spp. CA separated the Venturia spp. into two main groups, according to their epidemiological behavior: the first group included V. inaequalis, V. pyrina, V. nashicola, and V. carpophila, the second F. oleagineum and F. eriobotryae, with F. effusum having an intermediate position. This review shows that Venturia spp. affecting fruit trees are highly host-specific, and that important gaps in understanding the life cycle exist for some species, including V. pyrina; gaps include pseudothecia formation, ascospore and conidia germination, and mycelial growth. Considering the epidemiological information reviewed, this paper shows that the use of Mills tables to predict infection periods should be avoided for Venturia spp. other than V. inaequalis.


Effect of coronaphobia on smoking habits.
Coronavirus disease 2019 (COVID-19) epidemic had exhibited negative effects on patients with a nicotine use disorder because of social stress situations. The objective of this study is to investigate the changes that occurred in the smoking habits of the patients who applied to our smoking cessation clinic because of the COVID-19 outbreak's effect (coronaphobia) on their mental health. In this study, we included the patients who applied to our smoking cessation clinic between January 1 and June 30, 2020. We conducted telephonic and face-to-face interviews with the patients during the outbreak, and inquired about the changes in their smoking habits. In total, 114 volunteers (mean age: 41.2 years [min-max: 18-82 years], M/F: 70/44 [61.4/38.6%]) who registered in the smoking cessation clinic of Chest Diseases Clinic were included in the study. The number of people with and without coronaphobia was 64 (56.1%) and 50 (43.9%), respectively. The analyses of the changes in smoking behaviors because of coronaphobia demonstrated that people with coronaphobia exhibited a significantly higher decrease or cessation of smoking as compared to no change in smoking behavior or increase in the number of cigarettes (p: .006). Success in smoking cessation can be increased with the accurate analyses of the anxiety effects caused by coronaphobia after COVID-19 outbreak on the desire of smoking cessation. This resolution depends on the solution-oriented strategies that will increase the awareness of physicians and patients, a close follow-up of patients with tools such as telemedicine, and a quick determination of their needs.


[The diagnostic of chronic infection Helicobacter pylori in children].
The epidemiological studies testify an extremely high prevalence of chronic infection of children with Helicobacter pylori in Russia. The affection consists from 50% to 80% depending on region and age of examined children. The currently in force recommendations "Maastricht IV" concerning diagnostic and treatment of Helicobacter pylori infection adult patients are applied not in its fullness to children adolescent population. At the same time recently published joint conciliatory document of the European and North American associations of pediatric gastroenterologists is oriented to populations with low prevalence of Helicobacter pylori infection and particular profile of drug resistance. Hence, an urgent need exists to develop modern local algorithm concerning diagnostic, treatment and control of eradication of Helicobacter pylori infection among children and adolescents in Russia. The review presents analysis of admissibility of application in Russia's conditions of the international conciliatory documents concerning diagnostic of Helicobacter pylori infection in children. The data from conciliatory document of the European (ESPGHAN) and North American (NASPGHAN) associations of pediatric gastroenterologists, particular orginal research studies and one's own clinical experience were used. The advantages and shortcomings of actual methods of laboratory diagnostic of Helicobacter pylori infection are discussed. The approaches to application of particular diagnostic methods are considered. The enhanced indications to detection of infection and implementation of eradication therapy are proposed.


A chromosome assay method for the detection of heterokaryon incompatibility (het) genes operating between members of different heterokaryon compatibility (h-c) groups in Aspergillus nidulans.
Protoplast fusion has made possible the isolation of a diploid strain from haploid parents belonging to heterokaryon compatibility (h-c) groups Q and Gl of Aspergillus nidulans. This diploid was not fully heterokaryon compatibility tests conducted between selected pairs of parasexually derived progeny strains facilitated a chromosome assay method for the detection of heterokaryon incompatibility (het) genes. Despite the lack of segregation for the linkage group VI marker, it proved possible to locate het genes on linkage groups III, V, VI and VII. Backcross data detected five het gene differences operating between the h-cQ and h-cGl parental strains. Two het loci were located on linkage group III.


Incidence and significance of argentaffin and paneth cells in some tumours of the large intestine.
The incidence of argentaffin and Paneth cells in epithelial tumours of the large intestine was investigated. Argentaffin cells were found in adenomatous polyps, villus adenomas, polyposis coli, Peutz-Jehgers' polyps, juvenile polyposis, and adenocarcinomas. Paneth cells were not found in metaplastic or juvenile polyps. The crypt unit was destroyed in neoplasia and argentaffin and Paneth cells occurred either as a result of sequestration or were taking part in the neoplastic process. The crypt unit was retained in the disorders of epithelial growth. The identification of argentaffin and Paneth cells enabled the crypt to be defined and thus provided a useful, practical aid in the differentiation between neoplasms and disorders of epithelial growth.


[Perception of work conditions in a traditional farming community in Boa Esperança, Nova Friburgo, Rio de Janeiro State, Brazil].
The impact of pesticide use on human and environmental health has received attention from the international scientific community for some time, especially in developing countries where such chemical agents are used extensively and indiscriminately. The present study adopts a methodological approach to risk perception analysis based on rapid surveys, including: participatory observation; semi-structured interviews with key informants; and evaluation of local work processes. Field data analysis revealed several issues related to the risk perception profile of the study population, including the development of defensive strategies toward work hazards, subjective responses to potentially hazardous situations, and the role of individual risk perception as a determinant of human exposure to pesticides.


Redox Stimuli Delivery Vehicle Based on Transferrin-Capped MSNPs for Targeted Drug Delivery in Cancer Therapy.
Cancer has become one of the major diseases of human health around the world. Conventional antitumor drugs cannot specifically target cancers and result in serious side effects. To achieve better therapy, innovative functional drug delivery platforms that will aid specific targeting for cancer cells need to be developed. In this study, transferrin (Tf), which can target cancer cells, is covalently anchored onto the surface of MSNPs via disulfide linkage, which is used for glutathione-triggered intracellular drug release in tumor cells. The successful functionalization of redox-responsive MSNPs is confirmed by using BET/BJH, TEM, TGA, NMR, and FT-IR (BET, Brunauer-Emmett-Teller; BJH, Barrett-Joyner-Halenda). In addition, polyethylene glycol (PEG) is further grafted onto the surface of MSNPs to improve the biocompatibility and stability under physiological conditions for longer blood circulation. Our in vitro studies demonstrate that DOX-loaded MSNP-SS-Tf@PEG can selectively be internalized into cancer cells via Tf/Tf receptor interactions, and then, DOX is released in HT-29 and MCF-7 cells triggered by high GSH concentration in tumor cells. Remarkably, in vivo studies demonstrate that DOX-loaded MSNP-SS-Tf@PEG can significantly inhibit tumor growth with minimized side effects through cell apoptosis determined by TUNEL assay, whereas MSNP-SS-Tf@PEG revealed no significant inhibition. In conclusion, DOX-MSNP-SS-Tf@PEG with active targeting moieties and a redox-responsive strategy has been demonstrated as a great effective drug carrier for tumor therapy in vitro and in vivo.


Absence of BRAF mutations in UV-protected mucosal melanomas.
Mutations in BRAF have recently been identified in a significant percentage of primary and metastatic cutaneous malignant melanomas. As ultraviolet (UV) exposure may play a role in the development of cutaneous melanoma lesions with BRAF mutations, BRAF mutation frequency in melanomas arising in sites protected from sun exposure may be lower than those from sun-exposed areas. Thus, we determined the BRAF mutation frequency in a panel of 13 mucosal melanomas and compared those data with data from all currently published series of cutaneous melanomas. BRAF exon 15 DNA from 13 archival primary mucosal melanomas (eight vulvar, four anorectal, and one laryngeal) was sequenced using intron-based primers. As archival DNA occasionally produces poor-quality template, results were confirmed with a TspRI restriction fragment length polymorphism (RFLP) that distinguishes wild-type BRAF from the common mutant form V599E. A binomial test was used to compare the mutation frequency in the mucosal melanomas with the published mutation frequency in cutaneous melanomas. None of the 13 mucosal melanomas in this series had an exon 15 BRAF mutation, as compared to 54/165 (33%) primary cutaneous melanomas with BRAF mutations in a compilation of all current published studies (p = 0.006). These data suggest that UV exposure, plays a role in the genesis of BRAF mutations in cutaneous melanoma, despite the absence of the characteristic C>T or CC>TT mutation signature associated with UV exposure, and suggests mechanisms other than pyrimidine dimer formation are important in UV-induced mutagenesis.