Tree species identity and composition shape the epiphytic lichen community of structurally simple boreal forests over vast areas.
Greatly simplified ecosystems are often neglected for biodiversity studies. However, these simplified systems dominate in many regions of the world, and a lack of understanding of what shapes species occurrence in these systems can have consequences for biodiversity and ecosystem services at a massive scale. In Fennoscandia, ~90% of the boreal forest (~21Mha) is structurally simplified with little knowledge of how forest structural elements shape the occurrence and diversity of for example epiphytic lichens in these managed forests. One form of structural simplification is the reduction of the number and frequency of different tree species. As many lichen species have host tree preferences, it is particularly likely that this simplification has a huge effect on the lichen community in managed forests. In a 40-70 years old boreal forest in Sweden, we therefore related the occurrence and richness of all observed epiphytic lichens to the host tree species and beta and gamma lichen diversity at the forest stand level to the stand's tree species composition and stem diameter. Picea abies hosted the highest lichen richness followed by Pinus sylvestris, Quercus robur, Alnus glutinosa, Betula spp., and Populus tremula. However, P. tremula hosted twice as many uncommon species as any of the other tree species. Stand level beta and gamma diversity was twice as high on stands with four compared to one tree species, and was highest when either coniferous or deciduous trees made up 40-50% of the trees. The stem diameter was positively related to lichen richness at the tree and stand level, but negatively to beta diversity. For biodiversity, these findings imply that leaving a few trees of a different species during forest thinning is unlikely as effective as combining life-boat trees for endangered species with an even tree species mixture.


Body dissatisfaction: how is it related to stress and one's perception of individual and cultural ideal body? A comparison of Bosnian and American university students.
Cultural differences in body dissatisfaction, the relationship of stress to body dissatisfaction and individual and cultural body ideals were investigated. Forty-eight United States women and 48 Bosnian women completed the Body Shape Questionnaire (BSQ), the Impact of Event Scale (IES), and a Body Figure Rating Scale. When Body Mass Index was controlled, United States women demonstrated more body dissatisfaction and chose smaller cultural ideal body sizes than Bosnian women, but did not differ on personal ideal body size ratings. Furthermore, stress was only related to body dissatisfaction for Bosnian women. Additional research is needed to further elaborate the body dissatisfaction differences as they relate to cultural values.


The impact of compulsory helmet legislation on cyclist head injuries in New South Wales, Australia: a response.
This article responds to criticisms made in a rejoinder (Accident Analysis and Prevention 2012, 45: 107-109) questioning the validity of a study on the impact of mandatory helmet legislation (MHL) for cyclists in New South Wales, Australia. We systematically address the criticisms through clarification of our methods, extension of the original analysis and discussion of new evidence on the population-level effects of MHL. Extensions of our analysis confirm the original conclusions that MHL had a beneficial effect on head injury rates over and above background trends and changes in cycling participation. The ongoing debate around MHL draws attention away from important ways in which both safety and participation can be improved through investment in well-connected cycling infrastructure, fostering consideration between road users, and adequate legal protection for vulnerable road users. These are the essential elements for providing a cycling environment that encourages participation, with all its health, economic and environmental benefits, while maximising safety.


Biochemical and structural insights into Rab12 interactions with RILP and its family members.
Alongside its biosynthetic functions, the small GTPase Rab12 negatively regulates mast cell (MC) exocytosis by its interaction with RILP to promote retrograde transport of the MC secretory granules. Given the role of Rab effectors in mediating Rab functions, in this study we used biochemical and in silico tools to decipher Rab12 interactions with its RILP family effectors. We show that Rab12 interacts with RILP, RILP-L1 and RILP-L2 independently of each other, whereby lysine-71, in mouse Rab12, is critical for Rab12 interactions with RILP-L1 or RILP-L2, but is dispensable for the binding of RILP. Focusing on RILP, and relying on molecular dynamics simulations, functional mutational analyses and peptide inhibition assays, we propose a model for the Rab12-RILP complex, consisting of a RILP homodimer and a single molecule of active Rab12, that interacts with the RILP homology domain (RHD) of one RILP monomer and a C-terminal threonine in the other monomer via its switch I and switch II regions. Mutational analyses of RILP RHD also demonstrate its involvement in the regulation of MC secretory granule transport. Jointly, our results provide structural and functional insights into the Rab12-RILP complex on the basis of which new tools could be generated for decoding Rab12 functions.


Red Blood Cell Distribution Width Is Associated with All-Cause Mortality in Critically Ill Patients with Cardiogenic Shock.
BACKGROUND There is no previously published epidemiological study exploring the association between red blood cell distribution width (RDW) and mortality in patients with cardiogenic shock (CS). The aim of this study was to examine the association between RDW and the risk of all-cause mortality in these patients. MATERIAL AND METHODS We analyzed clinical data from the MIMIC-III V1.4 database. We collected data on each patient's demographic parameters, vital signs, laboratory parameters, vital signs, comorbidities, and scoring systems on ICU admission. Cox proportional hazards models were used to assess the association between RDW levels and the 30-day, 90-day, and 365-day mortality in patients with CS. RESULTS There were 1131 patients meeting inclusion criteria in our study. In multivariate analysis, following adjustment for age, sex, and ethnicity, higher RDW in tertiles and quintiles were all associated with increased risk of 30-day, 90-day, and 365-day all-cause mortality. Furthermore, after adjusting for more relevant confounders, RDW remained a significant predictor of risk of 30-day, 90-day, and 365-day mortality (tertile 3 versus tertile 1: HR, 95% CI: 1.66, 1.19-2.31; 1.73, 1.28-2.33; 1.80, 1.38-2.34). Similarly significant robust associations were found in RDW levels stratified by quintiles. CONCLUSIONS Higher RDW is associated with increased risk of all-cause mortality in critically ill patients with CS.


Low dose mixture effects of endocrine disrupters: implications for risk assessment and epidemiology.
During the last years, a series of studies on combinations of oestrogenic, thyroid-disrupting and anti-androgenic chemicals at low doses have been published. The available experimental evidence shows that combination effects may result from endocrine disrupters that each produces very small effects, if they are present in sufficiently large numbers. This review examines the implications of these findings for chemicals risk assessment and epidemiology. It is concluded that a lack of knowledge about relevant exposure scenarios presents serious obstacles for better human risk assessment. Epidemiology needs to abandon its focus on single endocrine disrupters and has to embrace the reality of endocrine disrupter mixture effects by developing biomarkers that capture cumulative exposure to endocrine disrupters.


Growth, training response and health in Standardbred yearlings fed a forage-only diet.
The aim of this study was to, from a holistic perspective, describe the effects of a forage-only feeding system and a conventional training program on young Standardbred horses and compare data with similar observations from the literature. Sixteen Standardbred colts fed a forage-only diet for 4 months from breaking (August to December) and with the goal to vigorously trot 5 to 7 km at a speed of 5.6 m/s (3 min/km) were studied. The horses were fed grass haylage (56 to 61% dry matter (DM), 2.80 to 3.02 Mcal DE/kg DM and 130 to 152 g CP/kg DM) ad libitum, 1 kg of a lucerne product and minerals. The amount of training and number of training sessions were documented daily, and feed intake and body development were measured once every month. Heart rate (HR) was measured during and after a standardized exercise test in October and December. In December, a postexercise venous blood sample was collected and analyzed for plasma lactate concentration. Muscle biopsies (m. gluteus medius) were taken and analyzed for glycogen and fiber composition. Health was assessed in October and November by an independent veterinarian using a standardized health scoring protocol. BW and height at withers increased from 402 to 453 kg (root mean square error (RMSE) 6) and from 148.7 to 154.1 cm (RMSE 0.7), respectively, and the body condition score was 4.9 (RMSE 0.2) at the end of the study. Muscle glycogen content was 532 mmol/kg dry weight (s.d. 56). There was a significant decrease in postexercise HR (81 v. 73 bpm, RMSE 8), and the individual amount of training was negatively correlated with HR during and after exercise. Health scores were high and similar at both assessments (8.4 and 8.4 (RMSE 1.0) out of 10; P > 0.05), and the number of lost training days per month due to health problems was <0.9, with the exception of November (5.3 days). It is concluded that yearlings in training fed high-energy forage ad libitum can reach a conventional training goal and grow at least as well as earlier observations on yearlings of other light breeds.


[Can the quality of life be quantified?].
In oncology the question of quality of live leads to a strong but rather academic opposition between practitioners in favor of psychotherapeutic approach and those who prefer psychometric and statistical treatments of such matter. Possibilities of articulations can be found if we don't forget two conditions: first, the very aim of patient's quality of life preoccupation, and secondly, the double meaning, epistemological and ethical of the problem connected with quantification of quality of life. This allows to make a distinction between two strategies in the use questionnaires: do we look for positive definition of Q.O.L. or do we proceed in a negative way, looking for "symptoms". This second way is perfectly compliable with the approach of the patient as a subject in his irreducible singularity. On the opposite positive strategy deals with social imagination. It can produce prescriptive effects and induce the questionnee to certain answers concerning Q.O.L. For instance implicit bad image of illness and overevaluation of definitions modeled by majority consensus. Palliative care implies a concept of medicine which day by day defines goals, and pays attention to "this patient and at this moment" desires and projects. Palliative medicine puts forward a logic of the singular versus a logic of the particular which is determinant in the euthanasia movement. Quantification is necessary and is not, de principio, opposed to the care of a singular subject and patient, if we consider methods used by quantification and results so provided, not as "more objective data" but only "a necessary moment of objectivation". This objectivation in return, implies choices and subjectivities. Statistical quantification is not sheltered from fantasies, nor from political goals, chiefly in the way questionnaire address to the questionnee.


Successful Reduced Intensity Allogeneic Transplant With Full Donor Chimerism and Good Quality of Life in Adolescent Patient With Wiskott-Aldrich Syndrome.
Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema, immune deficiency, and autoimmune phenomena. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Myeloablative conditioning is the most common regimen used for HSCT in patients with WAS to avoid the risk of mixed donor chimerism and autoimmunity post-HSCT. There is limited data on the use of reduced intensity conditioning for HSCT in patients with WAS. Here, we report a case with severe phenotype of WAS transplanted successfully with reduced intensity conditioning, which is an acceptable conditioning regimen and can be considered in patients with WAS with significantly impaired organ functions.


Progress of solid-phase microextraction coatings and coating techniques.
Solid-phase microextraction (SPME) has been popular as an environmentally friendly sample pretreatment technique to extract a very wide range of analytes. This is partly owing to the development of SPME coatings. One of the key factors affecting the extraction performances, such as the sensitivity, selectivity, and reproducibility, is the properties of the coatings on SPME fibers. This paper classifies the materials used as SPME coatings and introduces some common preparation techniques of SPME coating in detail, such as sol-gel technique, electrochemical polymerization technique, particle direct pasting technique, restricted access matrix SPME technique, and molecularly imprinted SPME technique.


Scarless and sequential gene modification in Pseudomonas using PCR product flanked by short homology regions.
The lambda Red recombination system has been used to inactivate chromosomal genes in various bacteria and fungi. The procedure consists of electroporating a polymerase chain reaction (PCR) fragment containing antibiotic cassette flanked by homology regions to the target locus into a strain that can express the lambda Red proteins (Gam, Bet, Exo). Here a scarless gene modification strategy based on the Red recombination system has been developed to modify Pseudomonas genome DNA via sequential deletion of multiple targets. This process was mediated by plasmid pRKaraRed encoding the Red proteins regulated by PBAD promoter, which was functional in P. aeruginosa as well as in other bacteria. First the target gene was substituted for the sacB-bla cassette flanked by short homology regions (50 bp), and then this marker gene cassette could be replaced by the PCR fragment flanking itself, generating target-deleted genome without any remnants and no change happened to the surrounding region. Twenty genes involved in the synthesis and regulation pathways of the phenazine derivate, pyocyanin, were modified, including one single-point mutation and deletion of two large operons. The recombination efficiencies ranged from 88% to 98%. Multiple-gene modification was also achieved, generating a triple-gene deletion strain PCA (PAO1, DeltaphzHDeltaphzMDeltaphzS), which could produce another phenazine derivate, phenazine-1-carboxylic acid (PCA), efficiently and exclusively. This lambda Red-based technique can be used to generate scarless and sequential gene modification mutants of P. aeruginosa efficiently, using one-step PCR product flanked by short homology regions. Single-point mutation, scarless deletion of genes can be achieved easily in less than three days. This method may give a new way to construct genetically modified P. aeruginosa strains more efficiently and advance the regulatory network study of this organism.


Methodological approach towards a Gap Assessment of the Serbian microbiology system in the function of surveillance in line with EU standards and acquis.
Italian and Serbian Health authorities performed an in-depth Gap Assessment of the Serbian microbiology system in the function of communicable disease surveillance using a methodology adapted to context and information needs. There were two study phases: a capacity based survey and an equipment mapping survey. Invited participants included national health authorities, heads of national reference laboratories and of public/private diagnostic laboratories in Serbia. Findings were analysed preliminarily and identified gaps were discussed, prioritized and validated through two ad hoc workshops involving all concerned institutions. The Gap Assessment was performed between September and December 2017. The overall response rate was 69% for phase one and 74% for phase two. Identified gaps were assessed as highly relevant during the project workshops. Gaps and priorities were highlighted, validated, and studied with a suitable level of detail to develop a concrete action-plan. The same methodological approach could be used to monitor progress in Serbia as well as in other EU candidate countries.


Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma.
Proliferation of fibrotic tissue (desmoplasia) is one of the hallmarks of several epithelial tumors including pancreatic adenocarcinoma. This tissue reaction may be deleterious or advantageous to the host or tumor. In a systematic analysis, we identified two growth factors expressed by human pancreatic carcinoma cells that are positively correlated with the ability to induce fibroblast proliferation both in vitro and in vivo, i.e., transforming growth factor (TGF)-beta1 and fibroblast growth factor-2. Here we demonstrate that the overexpression of TGF-beta1 induced up-regulation of matrix proteins and growth factors in the TGFbeta1-transfected pancreatic tumor cells. Furthermore, transfection of PANC-1 cells induces the same change in fibroblasts in either cocultivation experiments or when they are grown in conditioned medium from TGF-beta1-transfected PANC-1 cells. TGF-beta1-transfected pancreatic tumor cells induced a rich stroma after orthotopical transplantation in the nude mouse pancreas. The transfer of a single growth factor, TGF-beta1, conveys the ability to induce a fibroblast response similar to that seen in desmoplasia in human pancreatic adenocarcinoma. This effect cannot only be attributed to direct effects of TGF-beta1 but also results from the up-regulation of several other factors including collagen type I, connective tissue growth factor, and platelet-derived growth factor.


Rates for repair of pBR 322 DNA radicals by thiols as measured by the gas explosion technique: evidence that counter-ion condensation and co-ion depletion are significant at physiological ionic strength.
Rates of repair of pBR 322 plasmid DNA radicals by thiols of varying net charge (Z) at pH 7 and physiological ionic strength were measured using the oxygen explosion technique. The extent of conversion of supercoiled to relaxed circular plasmid was measured by HPLC as a function of the time of oxygen exposure before or after irradiation, the time-courses being fitted by a pseudo-first-order kinetic expression with k1 = k2[RSH]. Values of k2 (M-1 S-1) were: 2.1 x 10(5) (GSH, Z = -1), 1.4 x 10(6) (2-mercaptoethanol, Z = 0), 1.2 x 10(7) (cysteamine, Z = +1), 6.6 x 10(7) (WR-1065 or N-(2-mercaptoethyl)-1,3-diaminopropane, Z = +2). The approximately 6-fold increase in rate with each unit increase in Z is attributed to concentration of cationic thiols near DNA as a consequence of counter-ion condensation and reduced levels of anionic thiols near DNA owing to co-ion depletion. The results are quantitatively consistent with chemical repair as a significant mechanism for radioprotection of cells by neutral and cationic thiols under aerobic conditions, but indicate that repair by GSH will compete effectively with oxygen only at low oxygen tension.


CD-loop Extension in Zika Virus Envelope Protein Key for Stability and Pathogenesis.
With severe disease manifestations including microcephaly, congenital malformation, and Guillain-Barré syndrome, Zika virus (ZIKV) remains a persistent global public health threat. Despite antigenic similarities with dengue viruses, structural studies have suggested the extended CD-loop and hydrogen-bonding interaction network within the ZIKV envelope protein contribute to stability differences between the viral families. This enhanced stability may lead to the augmented infection, disease manifestation, and persistence in body fluids seen following ZIKV infection. To examine the role of these motifs in infection, we generated a series of ZIKV recombinant viruses that disrupted the hydrogen-bonding network (350A, 351A, and 350A/351A) or the CD-loop extension (Δ346). Our results demonstrate a key role for the ZIKV extended CD-loop in cell-type-dependent replication, virion stability, and in vivo pathogenesis. Importantly, the Δ346 mutant maintains similar antigenicity to wild-type virus, opening the possibility for its use as a live-attenuated vaccine platform for ZIKV and other clinically relevant flaviviruses.


[Treatment of moderate and severe pain. Ketorolac--a new analgesic].
Overall, the studies available to date show that ketorolac is a powerful analgesic with no action on the central nervous system and a long-lasting effect of rapid onset. The analgesic effectiveness of ketorolac in the treatment of moderate to severe pain, is comparable with that of 10-12 mg of morphine, 100 mg of pethidine, or 30 mg of pentazocine. However, ketorolac, an inhibitor of prostaglandin synthesis, is not subject to the strict regulations of the narcotic drugs law. On account of its favorable adverse reactions profile, ketorolac is particularly well suited for the treatment of postoperative pain. Further major indications are pain associated with trauma to bones and muscles, as also cancer-related pain, in which area, a "saving effect" on simultaneously employed opiates and opioids can be achieved.


Comparative toxicity of nano-ZnO and bulk ZnO suspensions to zebrafish and the effects of sedimentation, ˙OH production and particle dissolution in distilled water.
With the common application of nanoscale zinc oxide (nZnO) and significant potential for its release directly into aquatic environments, it is urgent to carry out research on ecotoxicological impact of nZnO. The characterization of nZnO, the amount of ˙OH in suspensions in the presence of light and the acute toxicity of nZnO and its bulk counterpart suspensions, as well as the acute toxicity of Zn(2+) solution to zebrafish (Danio rerio) at 96 h were studied. It was found that nZnO aggregated into irregular shapes in suspensions, and showed a relationship between its size distribution and concentration. In the presence of light, nZnO suspensions could generate ˙OH, the concentration of which increased with time. Although it was generally thought that ˙OH played a role in the biotoxicity to zebrafish, similar toxicity was observed for the nZnO and bulk ZnO suspensions (96 h LC(50) 3.969 mg L(-1), 2.525 mg L(-1), respectively). Furthermore, the sedimentation of nZnO and bulk ZnO in suspensions, and the accumulation of Zn in zebrafish were studied. The results showed that dissolved Zn(2+), from nZnO and bulk ZnO in suspensions, were toxic to zebrafish, while the aggregation and sedimentation of nZnO suspensions reduced the toxicity of nZnO. However, Zn(2+) may not be the main source of acute toxicity of nZnO and bulk ZnO to zebrafish. The experimental results highlight the importance of a systematic assessment of toxicity mechanisms of metal oxide nanoparticles (NPs) to determine definitively whether their toxicity is caused by nano-effects.


Development of an immunotherapeutic adenovirus targeting hormone-independent prostate cancer.
To develop a targeting therapy for hormone-independent prostate cancer, we constructed and characterized conditionally replicating oncolytic adenovirus (Ad) equipped with mRFP (monomeric red fluorescence protein)/ttk (modified herpes simplex virus thymidine kinase). This construct was then further modified to express both mRFP/ttk and a soluble form of cytokine FLT3L (fms-related tyrosine kinase 3 ligand) simultaneously. To construct the recombinant oncolytic adenovirus, E1a and E4 genes, which are necessary for adenovirus replication, were controlled by the prostate-specific enhancer sequence (PSES) targeting prostate cancer cells expressing prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). Simultaneously, it expressed the mRFP/ttk fusion protein in order to be able to elicit the cytotoxic effect. The Ad5/35PSES.mRFP/ttk chimeric recombinant adenovirus was generated successfully. When replication of Ad5/35PSES.mRFP/ttk was evaluated in prostate cancer cell lines under fluorescence microscopy, red fluorescence intensity increased more in LNCaP cells, suggesting that the mRFP/ttk fusion protein was folded functionally. In addition, the replication assay including wild-type adenovirus as a positive control showed that PSES-positive cells (LNCaP and CWR22rv) permitted virus replication but not PSES-negative cells (DU145 and PC3). Next, we evaluated the killing activity of this recombinant adenovirus. The Ad5/35PSES. mRFP/ttk killed LNCaP and CWR22rv more effectively. Unlike PSES-positive cells, DU145 and PC3 were resistant to killing by this recombinant adenovirus. Finally, in order to potentiate therapeutic efficacy, we developed a recombinant adenovirus expressing multiexogenous genes, mRFP/ttk and sFLT3L. In the present study, a replication-competent adenovirus was successfully designed to replicate conditionally in PSA-positive and PSMA-positive prostate cancer cells. This recombinant adenovirus is equipped with the fusion protein of suicidal and red-fluorescence fusion protein together with sFLT3L. This construct would be expected to have potent antitumor effects and deserves more extensive investigation.


Methyl oleate for plant protection products formulations: enzymatic synthesis, reaction kinetics and application testing.
This study presents a solvent-free enzymatic approach for the synthesis of fatty acid methyl esters (FAMEs), such as methyl oleate, for their application as adjuvant in plant protection products (PPP) formulations. The direct esterification between free fatty acid and methanol was optimized to achieve 98% acid conversion. The kinetics of this conversion was accurately described by a simple second order mechanism and non-linear regression was applied to calculate the rate constants of the forward and backward reactions based on full progress curves data. The rate constant of the forward reaction (synthesis) was one order of magnitude higher than the backward reaction (hydrolysis) and favored formation of the target methyl ester product, rendering the removal of water unnecessary. Enzymatically synthesized methyl oleate was benchmarked against the chemically synthesized compound, showing matching results in terms of stability, spreadability and emulsifying capacity in plant care formulations. The enzymatic synthesis of FAMEs under solvent free conditions allows to achieve a safer and more sustainable character for carrier solvents in PPP formulations.


Structure of an SspH1-PKN1 complex reveals the basis for host substrate recognition and mechanism of activation for a bacterial E3 ubiquitin ligase.
IpaH proteins are bacterium-specific E3 enzymes that function as type three secretion system (T3SS) effectors in Salmonella, Shigella, and other Gram-negative bacteria. IpaH enzymes recruit host substrates for ubiquitination via a leucine-rich repeat (LRR) domain, which can inhibit the catalytic domain in the absence of substrate. The basis for substrate recognition and the alleviation of autoinhibition upon substrate binding is unknown. Here, we report the X-ray structure of Salmonella SspH1 in complex with human PKN1. The LRR domain of SspH1 interacts specifically with the HR1b coiled-coil subdomain of PKN1 in a manner that sterically displaces the catalytic domain from the LRR domain, thereby activating catalytic function. SspH1 catalyzes the ubiquitination and proteasome-dependent degradation of PKN1 in cells, which attenuates androgen receptor responsiveness but not NF-κB activity. These regulatory features are conserved in other IpaH-substrate interactions. Our results explain the mechanism whereby substrate recognition and enzyme autoregulation are coupled in this class of bacterial ubiquitin ligases.


[Capabilities of magnetic resonance imaging to diagnose infiltrating pelvic endometriosis].
Deep infiltrating endometriosis is a disease in reproductive-aged women, resulting in varying chronic pelvic pains and infertility, which requires surgical treatment. Objective--to determine the capabilities of magnetic resonance imaging (MRI) to diagnose pelvic endometriosis and to elaborate an optimal scanning protocol if this disease is suspected. Small pelvic MRI has a high accuracy in the diagnosis of endometriosis and can visualize most endometrioid implants, including those that are located under adhesions and in the subperitoneal regions. Just the same, a radiodiagnostician should not forget that MRI is of low informative value in identifying bowel endometriosis. Hence, when diagnosing deep infiltrating endometriosis, MRI should be complemented with transvaginal ultrasonography to detect endometrioid implants on the bowel walls as the informative value in this aspect is above.


Breast Cancer Detection in Qatar: Evaluation of Mammography Image Quality Using A Standardized Assessment Tool.
Compared with other countries in the Middle East, Qatar has one of the highest breast cancer incidence and mortality rates. Poor quality mammography images may be associated with advanced stage breast cancer, however there is limited information about the quality of breast imaging in Qatar. Our purpose was to evaluate the clinical image quality of mammography examinations performed at a tertiary care center in Doha, Qatar using a standardized assessment tool. Bilateral mammograms from consecutive patients from a tertiary care cancer center in Doha, Qatar were obtained. Proportions of examinations deemed adequate for interpretation were estimated. Standardized clinical image quality assessment form was utilized to evaluate image quality components. For each image, image quality components were given grades on a 1-5 scale (5-excellent, 4-good, 3-average, 2-fair, 1-poor). Mean scores with 95% confidence intervals were estimated for each component. Consecutive sample of 132 patients was obtained representing 528 mammographic images. Overall, 99.2% of patients underwent examinations rated as acceptable for interpretation. Mean scores for each image quality component ranged from 4.045 to 5.000 (lowest score for inframammary fold). Image quality component scores were 93.0% excellent, 5.2% good, 1.1% average, 0.6% fair, and 0.1% poor. Overall image quality at a tertiary care center in Doha, Qatar was acceptable for interpretation with minimal areas identified for improvement.


Host specificity of a parasitic fluke: is Posthodiplostomum minimum a centrarchid-infecting generalist or specialist?
Parasite host specificity has important implications for species diversity estimates, food web dynamics, and host shifts. "White grub" is the metacercaria stage of a fluke ( Posthodiplostomum minimum ) that occurs in many fish species, but no attempt has been made to quantify variation in host use by this worm. Here we used 2 approaches to evaluate host specificity within the strain that infects centrarchids ( P. minimum centrarchi). First, we measured parasite loads in 2 centrarchid hosts, bluegill ( Lepomis macrochirus ) and white crappie ( Pomoxis annularis ), from Spring Lake in McDonough County, Illinois. We found that infection levels differed significantly between these hosts. Prevalence in bluegill was 100% and the median intensity was 940 metacercariae, but only 57% of white crappie were infected (median intensity = 4). Site specificity of white grub also differed significantly between the 2 hosts. In bluegills, kidneys were most heavily infected, whereas in white crappies, livers harbored the most worms. We also performed a literature survey of P. minimum prevalence estimates from 14 centrarchid species from other localities. We calculated the mean white grub prevalence for each host species and used this to calculate STD*, a quantitative index of host specificity. STD* was 1.33, significantly closer to the value for a specialist (STD* = 1.00) than a generalist (STD* = 2.00). This reflects the fact that P. minimum prevalence is higher in Lepomis species than it is in centrarchids outside this genus. These data show that P. minimum centrarchi specializes on Lepomis species, but the causes of this specialization are unknown. This worm may be a single species that differs in host use due to ecological or physiological host differences, or it may be a complex of species that vary in host use for similar reasons. Genetic data are required to evaluate these possibilities.


The PIT1 gene polymorphisms were associated with chicken growth traits.
With crucial roles on the differentiation of anterior pituitary and the regulation of the prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone-beta (TSH-beta) genes, the chicken PIT1 gene is regarded as a key candidate gene for production traits. In this study, five reported polymorphisms (MR1-MR5) of the PIT1 gene were genotyped in a full sib F2 resource population to evaluate their effects on growth, carcass and fatty traits in chickens. Marker-trait association analyses showed that, MR1 was significantly associated with shank diameters (SD) at 84 days (P < 0.05), hatch weight (HW) and shank length (SL) at 84 days (P < 0.01), MR2 was significantly associated with BW at 28, 42 days and average daily gain (ADG) at 0-4 weeks (P < 0.05), and MR3 was significantly associated with ADG at 4-8 weeks (P < 0.05). MR4 was associated with SL at 63, 77, 84 days and BW at 84 days (P < 0.05), as well as SD at 77 days (P < 0.01). Significant association was also found of MR5 with BW at 21, 35 days and SD at 63 days (P < 0.05), BW at 28 days and ADG at 0-4 weeks (P < 0.01). Both T allele of MR4 and C allele of MR5 were advantageous for chicken growth. The PIT1 haplotypes were significantly associated with HW (P = 0.0252), BW at 28 days (P = 0.0390) and SD at 56 days (P = 0.0400). No significant association of single SNP and haplotypes with chicken carcass and fatty traits was found (P > 0.05). Our study found that polymorphisms of PIT1 gene and their haplotypes were associated with chicken growth traits and not with carcass and fatty traits.


[Cosmology, environment, and health: Baniwa food myths and rites].
The Baniwa people, a member of the Aruak group which lives in the northwestern Amazon, has a rich mythic tradition that influences how the political, ethical, and practical dimensions of their social life are expressed and that guides the ancestral knowledge that guarantees the group's survival under adverse environmental conditions. The article analyzes myths and rites built around fish as a food source; these have an intimate relationship with cosmological explanations of the origin of the gods, water bodies, and the micro-ecosystems that foster the reproduction of aquatic fauna. Baniwa mythology draws an association between the reproductive processes of fish and a set of social relations involving human and nonhuman societies. Predation and edibility--notions underlying food rites--are viewed as part of a set of practices meant to produce and maintain kinship alliances, ease the food/prey peril, and maintain the cosmic balance that sustains life.


Altered lung physiology in two cohorts after COVID-19 infection as assessed by computed cardiopulmonography.
The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O2. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po2 gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease.NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.


Trunk, abdomen, and pressure sore reconstruction.
After reading this article, the participant should be able to: 1. Describe the principles of wound closure, torso reconstruction, and pressure sore reconstruction. 2. Outline standard options to treat defects of the chest, abdomen, and back and pressure ulcers in all anatomical areas. 3. Manage and prevent pressure ulcers. Chest wall reconstruction is indicated following tumor resection, radiation wound breakdown, or intrathoracic sepsis. Principles of wound closure and chest wall stabilization, where indicated, are discussed. Principles of abdominal wall reconstruction continue to evolve with the introduction of newer bioprosthetics and the application of functional concepts for wound closure. The authors illustrate these principles using commonly encountered clinical scenarios and guidelines to achieve predictable results. Pressure ulcers continue to be devastating complications to patients' health and a functional hazard when they occur in the bedridden, in patients with spinal cord injuries, and in patients with neuromuscular disease. Management of pressure ulcers is also very expensive. The authors describe standard options to treat defects of the chest, abdomen, and back and pressure ulcers in all anatomical areas. A comprehensive understanding of principles and techniques will allow practitioners to approach difficult issues of torso reconstruction and pressure sores with a rational confidence and an expectation of generally satisfactory outcomes. With pressure ulcers, prevention remains the primary goal. Patient education and compliance coupled with a multidisciplinary team approach can reduce their occurrence significantly. Surgical management includes appropriate patient selection, adequate débridement, soft-tissue coverage, and use of flaps that will not limit future reconstructions if needed. Postoperatively, a strict protocol should be adapted to ensure the success of the flap procedure. Several myocutaneous flaps commonly used for the surgical management of pressure are discussed. Commonly used flaps in chest and abdominal wall reconstruction are discussed and these should be useful for the practicing plastic surgeon.


Outcomes of adult living donor liver transplantation: comparison of the Adult-to-adult Living Donor Liver Transplantation Cohort Study and the national experience.
The study objectives were to determine whether the findings of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) reflect the U.S. national experience and to define risk factors for patient mortality and graft loss in living donor liver transplantation (LDLT). A2ALL previously identified risk factors for mortality after LDLT, which included early center experience, older recipient age, and longer cold ischemia time. LDLT procedures at 9 A2ALL centers (n = 702) and 67 non-A2ALL centers (n = 1664) from January 1998 through December 2007 in the Scientific Registry of Transplant Recipients database were analyzed. Potential predictors of time from transplantation to death or graft failure were tested using Cox regression. No significant difference in overall mortality between A2ALL and non-A2ALL centers was found. Higher hazard ratios (HRs) were associated with donor age (HR = 1.13 per 10 years, P = 0.0002), recipient age (HR = 1.20 per 10 years, P = 0.0003), serum creatinine levels (HR = 1.52 per loge unit increase, P < 0.0001), hepatocellular carcinoma (HR = 2.12, P<0.0001) or hepatitis C virus (HR = 1.18, P = 0.026), intensive care unit stay (HR = 2.52, P< 0.0001) or hospitalization (HR = 1.62, P < 0.0001) versus home, earlier center experience (LDLT case number 15: HR = 1.61, P < 0.0001, and a cold ischemia time >4.5 hours (HR = 1.79, P = 0.0006). Except for center experience, risk factor effects between A2ALL and non-A2ALL centers were not significantly different. Variables associated with graft loss were identified and showed similar trends. In conclusion, mortality and graft loss risk factors were similar in A2ALL and non-A2ALL centers. These analyses demonstrate that findings from the A2ALL consortium are relevant to other centers in the U.S. performing LDLT, and conclusions and recommendations from A2ALL may help to guide clinical decision making.


Delayed hepato-spleno-renal bypass for renal salvage following malposition of an infrarenal aortic stent-graft.
To report a salvage maneuver for accidental coverage of both renal arteries during endovascular aneurysm repair (EVAR) of an infrarenal aortic aneurysm (AAA) and survey our surgical colleagues in the UK for their use of this bypass procedure. A 74-year-old woman who had an EVAR complicated by renal failure secondary to malposition of the stent-graft underwent successful delayed renal revascularization with hepatorenal and splenorenal bypasses. This case prompted a literature review and preparation of an online 6-part questionnaire regarding the incidence and management of renal impairment following EVAR. The survey invitation was sent to all listed members of the Vascular Society of Great Britain and Ireland. Responses from 68 (10.5%) of the 650 vascular surgeons invited to participate in the survey were analyzed. The combined experience of those who completed the survey was >1500 EVAR procedures per annum. Forty percent (27/68) of the respondents had experienced a case of bilateral renal artery occlusion during EVAR. Two thirds (67%, 18/27) of these surgeons stated a preference for revascularizing the kidneys endovascularly, 7 surgeons would convert to open repair, 1 surgeon favored iliorenal bypass, and another suggested splenorenal bypass. Following intervention, 15 (56%) of 27 surgeons achieved revascularization that resulted in a return to baseline serum creatinine, 7 (26%) achieved partial recovery of the patient's serum creatinine, 3 (11%) had a patient on permanent dialysis, and 2 (7%) had patients who died (after open repair and endovascular procedure, respectively). Bilateral renal artery occlusion caused by malposition of a stent-graft is probably underreported. If revascularization of the kidneys by endovascular techniques fails, there is no consensus as to the optimal approach. Delayed revascularization should be considered if the kidneys show concentration of imaging contrast. Hepato-spleno-renal bypass, which has not heretofore been indicated for renal salvage post EVAR, can provide a good functional result in this situation.


Blood gas and hemodynamic effects of sedatives and analgesics when used as a supplement to local anesthesia in plastic surgery.
In 20 patients undergoing a rhinoplasty or rhytidectomy under local anesthesia combined with intravenous sedatives and hypnotics, fairly satisfactory operating conditions were obtained. This technique was associated with respiratory depression and hypoxia, however, with statistically significant elevations in the arterial carbon dioxide tensions, and depressions in the arterial oxygen tensions. We now advocate the routine use of supplement oxygen and periodic deep breathing during the operation, and in the immediate postoperative period. We will continue to advise the use of general anesthesia in patients with cardiopulmonary disease. The mental detachment and inability to articulate discomfort during the procedure are major disadvantages to the use of fentanyl and droperidol in these patients.


Prediction of heterogeneous differential genes by detecting outliers to a Gaussian tight cluster.
Heterogeneously and differentially expressed genes (hDEG) are a common phenomenon due to bio-logical diversity. A hDEG is often observed in gene expression experiments (with two experimental conditions) where it is highly expressed in a few experimental samples, or in drug trial experiments for cancer studies with drug resistance heterogeneity among the disease group. These highly expressed samples are called outliers. Accurate detection of outliers among hDEGs is then desirable for dis- ease diagnosis and effective drug design. The standard approach for detecting hDEGs is to choose the appropriate subset of outliers to represent the experimental group. However, existing methods typically overlook hDEGs with very few outliers. We present in this paper a simple algorithm for detecting hDEGs by sequentially testing for potential outliers with respect to a tight cluster of non- outliers, among an ordered subset of the experimental samples. This avoids making any restrictive assumptions about how the outliers are distributed. We use simulated and real data to illustrate that the proposed algorithm achieves a good separation between the tight cluster of low expressions and the outliers for hDEGs. The proposed algorithm assesses each potential outlier in relation to the cluster of potential outliers without making explicit assumptions about the outlier distribution. Simulated examples and and breast cancer data sets are used to illustrate the suitability of the proposed algorithm for identifying hDEGs with small numbers of outliers.


Treatment of venous thrombosis associated with Behcet's disease: immunosuppressive therapy alone versus immunosuppressive therapy plus anticoagulation.
The aim of this study was to compare the efficacy of immunosuppressive therapy alone with that of combination therapy involving immunosuppressants and anticoagulation for the treatment of venous thrombosis in Behcet's disease (BD). A retrospective analysis was made of 37 patients with venous thrombosis in BD. BD patients with venous thrombosis were divided into three groups: one group (N = 16) received immunosuppressive therapy alone, another group (N = 17) received immunosuppressant and anticoagulation combination therapy, and the third group (N = 4) received anticoagulation therapy only. Clinical and laboratory parameters and the recurrence of venous thrombosis were assessed. Venous thrombosis in BD appeared to have a more diffuse pattern than idiopathic type and a predilection for lower limbs. The most commonly involved sites were the superficial and common femoral veins. Recurrence of venous thrombosis occurred in two cases in the immunosuppressant group (12.5%), one case in the combination therapy group (5.9%), and three cases in the anticoagulant group (75%). No significant difference was found between recurrence in the immunosuppressant and combination therapy groups. Acute phase reactants were elevated in all six patients at the time of venous thrombosis recurrence. Our study suggests that immunosuppressive therapy is essential and that anticoagulation therapy might not be required for the treatment of deep venous thrombosis associated with BD.


Long-term results in non randomized patients with acute myelogenous leukemia: a single institution experience.
Sixty-three non randomized adults with acute myelogenous leukemia were treated with an idarubicin-based protocol. The patients achieving complete remission received autologous bone marrow transplantation or (if > 50 years or refusing autologous bone marrow transplantation) high-dose Ara-C, as late intensification. Fifty-two patients (82.5%) achieved complete remission, 45 after one induction course and 16 of them underwent autologous bone marrow transplantation a median of 11 months later. As of December 1997 (median follow-up 112 months, range 50-135 months), 16 patients were still in complete remission (10 after autologous bone marrow transplantation, 6 after high-dose Ara-C) and 29 had relapsed (median time to relapse 14 months, range 2-75 months). Four patients died in complete remission. The median disease-free survival was 25 months; the 50-months and 10-year disease-free survival were 41% and 35% respectively. No significant differences were observed between the autologous bone marrow transplantation and high-dose Ara-C treated patients whose complete remission had lasted more than 11 months. The median disease-free survival in the autografted patients had not been reached after 120 months (the 50-month and 10-year disease-free survival chances were both 67%). Age was the only predictive variable for leukemic relapse. These long-term results confirm the antileukemic efficacy of an idarubicin-containing protocol, which led to high complete remission rates and favorably influenced disease-free survival. Furthermore, the efficacy of late intensification treatment with either autologous bone marrow transplantation or high-dose Ara-C is underscored. The disease-free survival chances after autologous bone marrow transplantation are comparable with those published for allogeneic bone marrow transplantation; however, disease-free survival of the patients receiving a high-dose Ara-C intensification regimen is not significantly worse than that seen after autologous bone marrow transplantation.


Type 2 Diabetes Remission and Lifestyle Medicine: A Position Statement From the American College of Lifestyle Medicine.
Objectives. The present review represents the position of the American College of Lifestyle Medicine on type 2 diabetes (T2D) and remission treatment. Background. Research now reveals that sufficiently intensive lifestyle interventions can produce remission of T2D with similar success to bariatric surgery, but with substantially fewer untoward side effects. Methods. A literature review was conducted to examine lifestyle modifications targeting T2D remission, with most studies using a combination of blood glucose markers and treatment history. Results. There were notable differences in the dosing intensity of lifestyle interventions between therapeutic interventions and subtherapeutic interventions. Studies with therapeutic dosing typically used very low energy diets (600-1100 kcal/day) with a weighted mean remission rate of 49.4%, while studies with subtherapeutic dosing typically used more moderate caloric restrictions (reducing energy intake by 500-600 kcal/day) and the weighted mean remission rate was 6.9%. Conclusions. Remission should be the clinical goal in T2D treatment, using properly dosed intensive lifestyle interventions as a primary component of medical care for T2D patients.


Influence of nanomechanical stress induced by ZnO nanoparticles of different shapes on the viability of cells.
There is growing interest in nanostructures interacting with living organisms. However, there are still no general rules for the design of biocompatible nanodevices. Here, we present a step towards understanding the interactions between nanostructures and living cells. We study the influence of nanomechanical stress induced by zinc oxide (ZnO) nanostructures of different shapes on the viability of both prokaryotic (Gram-negative bacteria: Escherichia coli and Enterobacter aerogenes, and Gram-positive bacteria: Staphylococcus epidermidis and Corynebacterium glutamicum) and eukaryotic cells (yeast Saccharomyces cerevisiae and liver cancer cell line HepG2). Nanoparticles (NPs) and nanorods (NRs) of matching crystallographic structure (P63mc) and active surface area (in the order of 5 × 10(-2)μm(2)) are almost non-toxic for cells under static conditions. However, under conditions that enable collisions between ZnO nanostructures and cells, NRs appear to be more damaging compared to NPs. This is due to the increased probability of mechanical damage caused by nanorods upon puncturing of the cell wall and membranes. Gram-positive bacteria, which have thicker cell walls, are more resistant to nanomechanical stress induced by NRs compared to Gram-negative strains and eukaryotic cells. The presented results may be exploited to improve the properties of nanotechnology based products such as implants, drug delivery systems, antibacterial emulsions and cosmetics.


A mouse model of allogeneic corneal endothelial cell transplantation.
Corneal endothelial cell (CEC) transplantation should become clinically applicable in the near future. However, the immunologic changes after allo-CEC transplantation are poorly understood at present. We tried to establish a mouse model of allogeneic CEC transplantation for immunologic studies. Benzalkonium chloride was injected into the anterior chamber of the eyes of recipient BALB/c mice to create bullous keratopathy. Full-thickness corneal transplantation was performed by using 4 types of corneas: BALB/c corneas (isograft group), BALB/c corneas denuded of CEC (no endothelium group), C3H/He mouse corneas (allograft group), and corneas reconstituted by seeding immortalized C3H/He mouse CECs onto BALB/c corneas denuded of endothelium (CEC allograft group). Eyes were observed with an operating microscope for 4 weeks after transplantation and were subjected to histologic examination and fluorescein microscopy. All corneal grafts were transparent in the isograft group (n = 12), whereas none of the grafts were clear by 4 weeks after transplantation in the no endothelium group (n = 13). Corneal grafts were transparent at 4 weeks in 75% of the CEC allograft group (n = 12). The histologic rejection rate was 0% in the CEC allograft group, which was significantly lower than in the allograft group (67%; n = 18; P < 0.01). We established a mouse allo-CEC transplantation model by using cultured cells. This model should be useful for studying the immunologic processes after CEC transplantation.


PROTOCOL FOR LIVER TRANSPLANTATION IN HILAR CHOLANGIOCARCINOMA.
Hilar cholangiocarcinoma represents more than half of all cholangiocarcinoma cases, having poor prognosis and presenting a median overall survival after diagnosis of 12-24 months. In patients who have unresectable tumors with a better prognosis, the proposal to perform liver transplantation emerged for expanding the possibility of free margins by performing total hepatectomy. To provide a Brazilian protocol for liver transplantation in patients with hilar cholangiocarcinoma. The protocol was carried out by two Brazilian institutions which perform a large volume of resections and liver transplantations, based on the study carried out at the Mayo Clinic. The elaboration of the protocol was conducted in four stages. A protocol proposal for this disease is presented, which needs to be validated for clinical use. The development of a liver transplantation protocol for cholangiocarcinoma aims not only to standardize the treatment, but also enable a better assessment of the surgical results in the future.


Evaluation of hydrogenated resin acids as molecular markers for tire-wear debris in urban environments.
To propose new molecular markers for tire-wear emissions, four dihydroresin acids, that is, 8-isopimaren-18-oic acid (I), 8-pimaren-18-oic acid (II), 13β(H)-abieten-18-oic acid (III), and 13α(H)-abiet-8-en-18-oic acid (IV), were identified and investigated for source specificities, distributions, and environmental stabilities. The absence of I-IV in natural sources and the linear correlations between dihydroresin acids with different skeletons in tires and in environmental samples demonstrated that I-IV are specific markers for synthetic rubbers. The ratio of III + IV to the sum of III + IV plus abietic acid showed the resin acids distribution between different environmental compartments receiving contributions from traffic and natural sources. The physicochemical properties and results of photolysis experiments suggested that I-IV can set lower limits for tire-wear contributions to environmental loads of particulate matter (PM) and polycyclic aromatic hydrocarbons with molecular weight ≥202. By comparing III + IV concentrations or (III+IV)/pyrene or (III+IV)/benzo[a]pyrene ratios in tires and those in environmental matrices, the contributions of tire-wear emissions to PM, pyrene, and benzo[a]pyrene were estimated to be 0.68 ± 0.54%, 6.9 ± 4.8%, and 0.37 ± 0.18% in roadside PM and 0.83 ± 0.21%, 0.88 ± 0.52%, and 0.08 ± 0.06% in rooftop PM.


[Nervous regulation of bone metabolism].
This review is focused on the issues pertaining to the control of bone metabolism by adrenergic and serotoninergic regions of the vegetative nervous system. It is shown that mediators, enzymes, and receptors of these regions regulate bone remodeling processes. Data on the effects of regulatory peptides and nitric oxide on bone cells are presented.


[Correction of free-radical processes in patients with chronic brain ischemia with intravenous laser irradiation of blood].
We examined lipid peroxidation (LPO) in 130 patients with chronic brain ischemia (CBI). Primary and secondary LPO products, oxidative and antioxidative enzymes were studied in the course of therapy with antioxidant drug cytoflavin and intravenous laser radiation of blood (ILRB). The latter proved to have a normalizing action on LPO and antioxidant defense. With progression of CBI, effects of ILRB on enzymatic activity weakens due to depletion of endogenic antioxidants. This necessitates administration of exogenic antioxidants (cytoflavin) for complex correction of free radical processes. This conclusion allows recommending combined schemes of therapy for patients with CBI stage II and III.


Regulation of the sulfate starvation response in Pseudomonas aeruginosa: role of cysteine biosynthetic intermediates.
Pseudomonas aeruginosa PAO1 grew in defined synthetic medium with any of a broad variety of single sulfur sources, including sulfate, cysteine, thiocyanate, alkanesulfonates, organosulfate esters and methionine, but not with aromatic sulfonates, thiophenols or organothiocyanates or isothiocyanates. During growth with any of these compounds except sulfate, cysteine or thiocyanate, a set of 10 sulfate starvation-induced (SSI) proteins was strongly up-regulated, as observed by two-dimensional protein electrophoresis of total cell extracts. A comparable level of up-regulation was found for the hydrolytic enzyme arylsulfatase, which has previously been used as a marker enzyme for the sulfate starvation response. One of the SSI proteins was identified by N-terminal sequencing as a high-affinity periplasmic sulfate-binding protein, and another was related to thiol-specific antioxidants, but the N-terminal sequences of the other SSI proteins revealed no similarity to N-termini of proteins of known function, and they probably represent uncharacterized enzymes involved in sulfur scavenging when preferred sulfur sources are absent. To study the role that cysteine biosynthetic intermediates play in the synthesis of these proteins in vivo, we isolated mini-Tn5 transposon mutants of P. aeruginosa with insertions in the cysN and cysI genes, which encode subunits of ATP-sulfurylase and sulfite reductase, respectively. These two genes were cloned and sequenced. cysI showed high similarity to the cognate gene in Escherichia coli, whereas cysN encoded a 69.3 kDa protein with two domains corresponding to the E. coli CysN and CysC proteins. Sulfate no longer repressed synthesis of the SSI proteins in cysN mutants, but repression was restored by sulfite; in the cysI mutant, sulfate, sulfite and sulfide all led to repression of SSI protein synthesis. This suggests that there are at least two independent corepressors of the sulfate starvation response in this species.


Rheology and microstructure of carrot and tomato emulsions as a result of high-pressure homogenization conditions.
High-pressure homogenization, as a way to further mechanically disrupt plant cells and cell walls compared to conventional blending, has been applied to thermally treated and comminuted carrot and tomato material in the presence of 5% olive oil. Mixes of both vegetables in a 1:1 ratio were also included. Both the effect of homogenization pressure and the effect of multiple process cycles were studied. The different microstructures generated were linked to different rheological properties analyzed by oscillatory and steady state measurements. The results showed that while carrot tissue requires a high shear input to be disrupted into cells and cell fragments, tomato cells were broken across the cell walls already at moderate shear input, and the nature of the tomato particles changed to amorphous aggregates, probably composed of cell contents and cell wall polymers. All the plant stabilized emulsions generated were stable against creaming under centrifugation. While for tomato a low-pressure multiple cycle and a high-pressure single-cycle process led to comparable microstructures and rheological properties, carrot showed different rheological properties after these treatments linked to differences in particle morphology. Mixes of carrot and tomato showed similar rheological properties after homogenizing in a single or in a split-stream process. Practical Application: Following consumers' demand, the food industry has shown a growing interest in manufacturing products free of gums and stabilizers, which are often perceived as artificial. By tailored processing, fresh plant material could be used to structure food products in a more natural way while increasing their nutritional quality.


A large yolk sac may be important in the early diagnosis of gestational trophoblastic disease: a case report.
A large yolk sac in a deformed shape gestational sac was detected by ultrasonography in an 8 week pregnant woman. The disappearance of the yolk sac and the gestational sac, enlargement of the uterine cavity and a heterogeneous appearance similar to early gestational trophoblastic disease were recognized when ultrasonographic examination was performed 2 weeks later. After uterine evacuation, partial hydatidiform mole was diagnosed by histopathological evaluation of the curettage material. In our study, the role of the large yolk sac in predicting trophoblastic disease is discussed.


Changes in regular condom use among immigrant transsexuals attending a counselling and testing reference site in central Rome: a 12 year study.
To analyse data from male to female transsexuals attending between 1992 and 2003 an outpatient clinic considered the main HIV counselling and testing site in Rome for foreign people. Data collected between 1992 and 2003, from a routine anti-HIV testing and counselling activity, were analysed. A brief standard interview was performed at each test. A cross sectional analysis to assess the association of regular condom use with demographic and behavioural variables using multiple logistic regression was performed. A follow up analysis to define the effect of single factors on the occurrence of new anti-HIV seroconversions was also performed. The incidence of anti-HIV seroconversion was calculated in person years of observation. Overall, 473 transsexuals sex workers were tested. Most of them (99%) were from South America (mainly Columbia and Brazil). Anti-HIV prevalence was 32%, but a progressive decrease over time was observed (from 57% in 1993 to 12% in 2003). The proportion of patients reporting regular condom use at enrolment was 75%. A progressive increase in regular condom use was reported over time (from 43% in 1992-3 to 79% in 2002-3). 15 new HIV infections were observed during follow up (incidence 2.1 per 100 person years). Though the proportion of patients reporting regular condom use increased over time, 10 out of the 15 new infections occurred in patients reporting unprotected sex during follow up (rate 8.4 per 100 person years). Our data suggest that counselling may lead to an increase in safe sex practices among immigrant transsexuals. However, the incidence of new HIV infections is still high and mainly related to non-regular condom use, which still remains the primary objective of prevention.


An entorhinal-like region in food-caching birds.
The mammalian entorhinal cortex routes inputs from diverse sources into the hippocampus. This information is mixed and expressed in the activity of many specialized entorhinal cell types, which are considered indispensable for hippocampal function. However, functionally similar hippocampi exist even in non-mammals that lack an obvious entorhinal cortex or, generally, any layered cortex. To address this dilemma, we mapped extrinsic hippocampal connections in chickadees, whose hippocampi are used for remembering numerous food caches. We found a well-delineated structure in these birds that is topologically similar to the entorhinal cortex and interfaces between the hippocampus and other pallial regions. Recordings of this structure revealed entorhinal-like activity, including border and multi-field grid-like cells. These cells were localized to the subregion predicted by anatomical mapping to match the dorsomedial entorhinal cortex. Our findings uncover an anatomical and physiological equivalence of vastly different brains, suggesting a fundamental nature of entorhinal-like computations for hippocampal function.


8-Methyltryptanthrin-induced differentiation of P19CL6 embryonal carcinoma cells into spontaneously beating cardiomyocyte-like cells.
Enhancement of cardiac differentiation is critical to stem cell transplantation therapy for severe ischemic heart disease. The aim of this study was to investigate whether several derivatives of tryptanthrin (1), extracted from the medicinal plant Polygonum tinctorium, induce the differentiation of P19CL6 mouse embryonal carcinoma cells into beating cardiomyocyte-like cells. P19CL6 cells were cultured in α-MEM supplemented with 10% FBS including a test compound or vehicle. Drug-induced differentiation was assessed by measuring the number of beating and nonbeating aggregates and the area of beating aggregates, and the expression of genes involved in cardiac differentiation was evaluated by real-time PCR. A 1 μM concentration of 8-methyltryptanthrin (2) induced the differentiation of P19CL6 cells into cardiomyocyte-like cells to a significantly greater degree than 1% dimethyl sulfoxide (DMSO), a conventional differentiation inducer of P19CL6 cells. Furthermore, 2 strongly increased both the number and the area of spontaneously beating aggregates in comparison with DMSO. Two distinct genes of the calcium channel family, Cav1.2 and Cav3.1, underlying cardiac automaticity were significantly expressed in the presence of 2. Gap junction genes GJA1 and GJA5 contributing to the synchronized contraction of the myocardium were also induced significantly by 2. These results suggest that 2 successfully differentiated P19CL6 cells into spontaneously beating cardiomyocyte-like cells by activating the gene expression of pacemaker channels and gap junctions.


Development of plant-based mucosal vaccines against widespread infectious diseases.
Mucosal vaccination is a perspective for the control of infectious diseases, since it is capable of inducing humoral and cell-mediated responses. In addition, the delivery of vaccines to mucosal surfaces makes immunization practice safe and acceptable, and eliminates needle-associated risks. Transgenic plants can be used as bioreactors for the production of mucosally delivered protective antigens. This technology shows great promise to simplify and decrease the cost of vaccine delivery. Herein, we review the development of mucosally administered vaccines expressed in transgenic plants. In particular, we evaluate the advantages and disadvantages of using plants for the production of mucosal vaccines against widespread infectious diseases such as HIV, hepatitis B and TB.


Gene expression profile of estrogen receptor alpha and beta in the ovaries of Zi geese (Anser cygnoides).
The profile of ERalpha and ERbeta gene expression in the ovaries of Zi geese at 1 day and 1,2, 3, 4, 5 and 8 months of age (n=8, respectively) was examined by quantitative real-time PCR (qRT-PCR). The results showed that the expression of ERalpha and ERbeta mRNA was greater at 1 to 5 and 8 months compared with that observed at 1 day. In particular, the level of expression of ERalpha and ERbeta at 8 months was greater, 2.47 +/- 0.23 fold and 29.07 +/- 1.25 fold, respectively, compared with that at 1 day (P<0.05). The expression of ERalpha mRNA was not significantly different at 1, 2, 3 and 4 months (P>0.05). The level of expression of ERalpha mRNA at 5 months was 1.86 +/- 0.17 fold higher than at 1 day (P<0.05). The level of expression of ERbeta mRNA at 2, 3, 4, 5 and 8 months (1.96 +/- 0.13, 2.58 +/- 0.08, 2.08 +/- 0.05, 3.25 +/- 0.11 and 29.07 +/- 1.25 fold, respectively, P<0.05) was significantly higher than at 1 day. In summary, the expression of ERalpha and ERbeta mRNA in the ovaries of geese was increased between newborn and the laying stage. These results suggest that ERalpha and ERbeta mediate the process of ovarian development and egg laying in geese. In addition, ERbeta may play a more important role in regulating the response of the ovary to estrogen during the developmental and egg-laying stages.


The cross-lagged association between depressive symptoms and health-related quality of life in patients receiving maintenance hemodialysis: a three-wave longitudinal study.
To examine the cross-lagged relationship between depressive symptoms and health-related quality of life (HRQoL) in patients receiving maintenance hemodialysis. A longitudinal, observational study was conducted in two public hospitals in Shanghai, China. The sample consisted of 204 patients at baseline (T1). Of these, 144 completed the 12-month follow-up survey (T2), and 135 completed the 24-month follow-up survey (T3). Depressive symptoms were assessed using the depression subscale of the Hospital Anxiety and Depression Scale, and HRQoL was assessed using the Kidney Disease Quality of Life 36 short form. Cross-lagged path analysis was used to examine the temporal relationship between depressive symptoms and domains of health-related quality of life. Lower levels of three out of five domains of HRQoL (physical functioning, burden of kidney disease, and symptoms of kidney disease) at T1 were associated with increases in depressive symptoms at T2. Moreover, higher depressive symptoms at T2 were associated with decreases in four domains of HRQoL (mental functioning, burden of kidney disease, symptoms of kidney disease, and effects of kidney disease) at T3. Patients who had poor HRQoL were more likely to report more subsequent depressive symptoms, which in turn predict lower HRQoL over time. It indicates a need to break this cycle in patients receiving maintenance hemodialysis.


Recurrence and malignant risk of ameloblastoma: A demographic study of 1626 cases from east China.
Ameloblastoma is characterized by aggressive nature, high recurrence rate, occasional malignant transformation, but recurrence and malignant incidence of ameloblastoma are not yet addressed by a large-scale case series study. This study provided a detailed description of the relationship between demographic characteristics and recurrence and malignant cases with different clinical types of ameloblastoma (n = 1626). The overall incidence of recurrence and malignancy was 17.2 % and 3.4 %, respectively. Notably, we observed that there were multiple recurrent episodes (mean time, 24.3-28.7 months) among ameloblastoma patients. Multivariate analysis revealed that age of > 45 years (odds ratios (OR), 2.10; 95 % confidence interval (CI), 1.17-3.76), male (OR, 3.24; 95 %CI, 1.49-6.99), maxilla (OR, 5.58; 95 %CI, 3.11-10.0), and pre-existing recurrence (OR, 3.79; 95 %CI, 2.05-7.01) as independent factors were associated significantly with increased risk of malignancy. Identification of the clinical factors responsible for increased risk of malignancy provides better insight in management planning for ameloblastoma.


Site-directed mutagenesis of the region around Cys-241 of complement component C2. Evidence for a C4b binding site.
We probed the functional significance of the region around Cys-241 in human C2 by testing the hemolytic activity of a series of mutant rC2. Mutant C2 cDNA were constructed by oligonucleotide-directed site-specific mutagenesis and expressed transiently in COS cells. Wild-type rC2 had threefold higher specific hemolytic activity than native serum C2. Substitution of Gly, Ala, or Ser for Cys-241 resulted in a slightly, but significantly, increased activity. In addition, I2 had no effect on the activity of these mutant C2. Substitution of Lys for Gln-243 increased the hemolytic activity by more than two-fold. Increased activity in all cases was due to slower decay rates of the C3 convertase. Finally, substitution of Leu or Ala for Asp-240 or Ser-244, respectively, resulted in more than 100-fold decrease of hemolytic activity. The results suggest that residues 240 to 244 of human C2 represent an important structural determinant of the C4b binding site of C2a. They also confirm that Cys-241 is the residue responsible for the increased activity of C2 reacted with I2.


S6K1 promotes invasiveness of breast cancer cells in a model of metastasis of triple-negative breast cancer.
Breast cancer is the second-leading cause of oncology-related death in US women. Of all invasive breast cancers, patients with tumors lacking expression of the estrogen and progesterone hormone receptors and overexpression of human epidermal growth factor receptor 2 have the poorest clinical prognosis. These referred to as triple-negative breast cancer (TNBC) represent an aggressive form of disease that is marked by early-onset metastasis, high tumor recurrence rate, and low overall survival during the first three years post-diagnosis. In this report, we discuss a novel model of early-onset TNBC metastasis to bone and lungs, derived from MDA-MB-231 cells. Breast cancer cells injected intravenously produced rapid, osteolytic metastases in long bones and spines of athymic nude mice, with concurrent metastasis to lungs, liver, and soft tissues. From the bone metastases, we developed a highly metastatic luciferase-tagged cell line variant named MDA-231-LUC Met. In this report, we demonstrate that the Akt/mTOR/S6K1 axis is hyperactivated in these cells, leading to a dramatic increase in phosphorylation of S6 ribosomal protein at Ser235/236. Lastly, we provide evidence that inhibition of the furthest downstream kinase in the mTOR pathway, S6K1, with a highly specific inhibitor PF-4708671 inhibits cell migration, and thus may provide a potent anti-metastatic adjuvant therapy approach.


E-health Support in People with Parkinson's Disease with Smart Glasses: A Survey of User Requirements and Expectations in the Netherlands.
Recent advances in smart glasses, wearable computers in the form of glasses, bring new therapeutic and monitoring possibilities for people with Parkinson's disease (PD). For example, it can provide visual and auditory cues during activities of daily living that have long been used to improve gait disturbances. Furthermore, smart glasses can personalize therapies based on the state of the user and/or the user environment in real-time using object recognition and motion tracking. To provide guidelines for developers in creating new PD applications for smart glasses, a self-reported questionnaire was designed to survey the requirements, constraints, and attitudes of people with PD with respect to this new technology. The survey was advertised online over an 11 month period on the website of the Parkinson Vereninging. The results were derived from 62 participants (54.8% men and 45.2% women, average age of 65.7 ± 9.1), representing a response rate of 79.5% . The participants were overall very enthusiastic about smart glasses as an assistive technology to facilitate daily living activities, especially its potential to self-manage motor problems and provide navigational guidance, thereby restoring their confidence and independence. The reported level of usage of mobile technologies like tablets and smartphones suggests that smart glasses could be adopted relatively easily, especially by younger people with PD. However, the respondents were concerned about the cost, appearance, efficacy, and potential side effects of smart glasses. To accommodate a wide range of symptoms, personal preferences, and comfort level with technology, smart glasses should be designed to allow simple operation and personalization.


Cardiac sympathetic hyperinnervation after myocardial infarction: a systematic review and qualitative analysis.
Cardiac sympathetic hyperinnervation after myocardial infarction (MI) is associated with arrhythmogenesis and sudden cardiac death. The characteristics of cardiac sympathetic hyperinnervation remain underexposed. To provide a systematic review on cardiac sympathetic hyperinnervation after MI, taking into account: (1) definition, experimental model and quantification method and (2) location, amount and timing, in order to obtain an overview of current knowledge and to expose gaps in literature. References on cardiac sympathetic hyperinnervation were screened for inclusion. The included studies received a full-text review and quality appraisal. Relevant data on hyperinnervation were collected and qualitatively analysed. Our literature search identified 60 eligible studies performed between 2000 and 2022. Cardiac hyperinnervation is generally defined as an increased sympathetic nerve density or increased number of nerves compared to another control group (100%). Studies were performed in a multitude of experimental models, but most commonly in male rats with permanent left anterior descending (LAD) artery ligation (male: 63%, rat: 68%, permanent ligation: 93%, LAD: 97%). Hyperinnervation seems to occur mainly in the borderzone. Quantification after MI was performed in regions of interest in µm2/mm2 (41%) or in percentage of nerve fibres (46%) and the reported amount showed a great variation ranging from 439 to 126,718 µm2/mm2. Hyperinnervation seems to start from three days onwards to >3 months without an evident peak, although studies on structural evaluation over time and in the chronic phase were scarce. Cardiac sympathetic hyperinnervation after MI occurs mainly in the borderzone from three days onwards and remains present at later timepoints, for at least 3 months. It is most commonly studied in male rats with permanent LAD ligation. The amount of hyperinnervation differs greatly between studies, possibly due to differential quantification methods. Further studies are required that evaluate cardiac sympathetic hyperinnervation over time and in the chronic phase, in transmural sections, in the female sex, and in MI with reperfusion.


The response of the neuronal adaptive system to background illumination and readaptation to dark in the immature retina.
Developmental characteristics of the neuronal adaptive system of the retina, focusing on background light (BGL) adaptation and readaptation functions, were studied by measuring the oscillatory response (SOP) of the electroretinogram (ERG). Digitally filtered and conventional ERGs were simultaneously recorded. Rats aged 15 and 17 days were studied during exposure to BGLs of two mesopic intensities and during readaptation to dark. Results were compared to adult rats. In 'low mesopic' BGL SOP instantly dropped significantly to about half of its dark-adapted (DA) value contrary to mature rats, in which the SOP significantly increased. In 'high mesopic' BGL SOP decreased to about 20% and 30% of DA values in immature and adult rats, respectively. The process of recovery of SOP in darkness lacked the transient enhancement immediately as BGL was turned off, characteristic of adult rats. There were no major age differences in adaptive behaviour of a-wave. In young rats, recovery of b-wave was relatively slower. Properties of BGL adaptation and readaptation functions of the neuronal adaptive system in baby retina differed compared to the adult one by being less forceful and more restrained. Handling of mesopic illumination and recovery in the dark was immature. Development of these functions of the neuronal adaptive system progresses postnatally and lags behind that of the photoreceptor response and seems to be delayed also compared to that of the bipolar response.


A DNA-activated protein kinase from HeLa cell nuclei.
A DNA-activated protein kinase (DNA-PK) was purified from nuclei of HeLa cells. Activity was associated with a single high-molecular-mass (approximately-300,000 Da) polypeptide when analyzed by gel filtration, denaturing polyacrylamide gel electrophoresis, and Western immunoblotting using a monoclonal antibody that also inhibits enzyme activity. Nuclear localization was indicated by subcellular fractionation and confirmed by immunofluorescence on whole cells. Double-stranded DNA stimulated phosphorylation of the 300-kDa polypeptide in purified preparations as well as phosphorylation of the exogenous substrates alpha-casein, simian virus 40 large T antigen, and the human heat shock protein hsp90. Autophosphorylation led to inactivation of the enzyme. The phosphorylation of casein was stimulated over 30-fold by DNA and was specific for serine and threonine residues. Bovine serum albumin and histone H1 were poor substrates for DNA-PK, and no phosphorylation of immunoglobulin G or histones other than H1 was observed. Supercoiled or heat-denatured DNA and synthetic double-stranded RNA or RNA-DNA copolymers did not stimulate casein phosphorylation by DNA-PK. Interaction of the enzyme with DNA in the absence of exogenous substrates was demonstrated by thermal inactivation and gel mobility shifts. These characteristics identify DNA-PK as distinct from other protein kinases described in the literature and suggest that activation by DNA is an important feature of the enzyme's in vivo function.


Changes in Behaviour Symptoms of Patients with Attention Deficit/Hyperactivity Disorder during Treatment: Observation from Different Informants.
The aim of this study was to determine changes in behaviour among patients with attention deficit/hyperactivity disorder (ADHD) by different informants during treatment in the clinical setting. Seventy-nine patients with ADHD were recruited. They completed 12-months of treatment with oral short-acting methylphenidate, two-to-three times per day, at a dose of 0.3-1.0 mg/kg. Among the 79 patients (mean age, 9.1±1.9 years), 39 were classified as the ADHD-C/H type (hyperactive-impulsive type and combined type) and 40 as the ADHD-I type (inattentive type). At baseline, and after 12 months, their behaviour was assessed using the Child Behaviour Checklist (CBCL), Teacher's Report Form (TRF), ADHD Rating Scale (ADHD-RS), and Clinical Global Impression-Severity (CGI-S). Patients classified as the ADHD-C/H type had higher scores on three CBCL subscales, on the ADHD-RS and CGI-S compared to the ADHD-I type patients. After 12-months of treatment, for all patients, there were significant improvements in the four subscales of the TRF as well as the ADHD-RS and CGI-S scores, but not on the CBCL. In addition, the patients with the ADHD-C/H type had greater improvements on the four subscales of the TRF after treatment. However, there were no differences noted on the CBCL, ADHD-RS and CGI-S. The results of this study showed that during treatment, in the clinical setting, there are different assessments of behaviour symptoms, associated with ADHD, reported by different informants. Assessments of behaviour profiles from multiple informants are crucial for establishing a fuller picture of patients with ADHD.


Predicting future asthma morbidity in preschool inner-city children.
Children living in the inner city are particularly vulnerable to asthma. While we know much about factors that affect near-term outcomes in inner-city children, there is little evidence to guide clinicians on what to expect in the coming years, especially in preschool children. The purpose of our study was to determine which clinical and environmental factors are predictive of poor long-term asthma control in preschool inner-city children. Baseline characteristics determined to be potential predictors of asthma severity were examined: demographics, asthma symptoms, medication use, healthcare utilization, early life medical history, family history, allergen exposure and allergic disease, and pollutant exposure. Bivariate and multivariate analyses were performed using logistic regression to examine the association of predictors of asthma severity with healthcare utilization at 2 years. Of the 150 children at baseline, the follow-up rate was 83% at 2 years; therefore, 124 children were included in final analyses. At baseline, the mean age was 4.4 years and participants were predominantly African-American (90%). Most of the children were atopic and 32.5% reported using inhaled corticosteroids. Nighttime awakening from asthma and a history of pneumonia were predictive of future poor control. Preschool children with nighttime awakening from asthma and a history of pneumonia may deserve closer monitoring to prevent future asthma morbidity.


[The role of vasopressin and oxytocin in the regulation of glycemia levels and carbohydrate metabolism in the liver].
Vasopressin and oxytocin administered subcutaneously and intravenously in a dose of 0.5 IU/kg were studied in experiments on albino male rats for their effect on the glycogen content and gluconeogenesis enzymes activity in the liver as well as on the glycemia level. Neurohormones injected subcutaneously have no effect on the values of the measured indices. Vasopressin already the first 15-60 min after its intravenous injection in the mentioned dose leads to an essential decrease of the glucose content in blood, glycogen amount, glucose-6-phosphatase and fructose-1.6-diphosphatase (EC 220.127.116.11 and 184.108.40.206) activity in the liver of test animals. The intravenous injection of oxytocin in the same dose induces changes in the carbohydrate metabolism indices similar in their direction and magnitude to the effects of intravenous injection of vasopressin.


Emperor penguin body surfaces cool below air temperature.
Emperor penguins Aptenodytes forsteri are able to survive the harsh Antarctic climate because of specialized anatomical, physiological and behavioural adaptations for minimizing heat loss. Heat transfer theory predicts that metabolic heat loss in this species will mostly depend on radiative and convective cooling. To examine this, thermal imaging of emperor penguins was undertaken at the breeding colony of Pointe Géologie in Terre Adélie (66°40' S 140° 01' E), Antarctica in June 2008. During clear sky conditions, most outer surfaces of the body were colder than surrounding sub-zero air owing to radiative cooling. In these conditions, the feather surface will paradoxically gain heat by convection from surrounding air. However, owing to the low thermal conductivity of plumage any heat transfer to the skin surface will be negligible. Future thermal imaging studies are likely to yield further insights into the adaptations of this species to the Antarctic climate.


Aminoglycosides: therapeutics, ototoxicity and hypersensitivity of mitochondrial genetic origin.
Aminoglycosides such as streptomycin or gentamycin are employed to treat stubborn infections. In México, tuberculosis patients are successfully treated with 1 g/day for over 6 months. Ototoxicity is often seen as a consequence of prolonged treatment with aminoglycosides. In young people STP damages the vestibule of the ear; in elder patients it diminishes hearing and balance. These effects are due to streptidine, a metabolite of STP produced in elder patients and detected in blood by liquid chromatography. On occasion, sudden deafness is established after only a short treatment period as the result of the presence of a single nucleotide mutation in the mitochondrial 12S rRNA gene. In patients with this polymorphism, aminoglycosides produce a stereotypic conformation similar to the bacterial 16S rRNA thus inhibiting the synthesis of proteins. Many aminoglycoside-sensitive mutations have been described in several ethnic groups, causing sudden deafness. We started similar studies in Mexican individuals, treated or not with an aminoglycoside, to determine whether similar alterations could be detected. To date in over 60 individuals analyzed we found only one case of polymorphism in a streptomycin treated patient. We developed a simple method to identify such mitochondrial gene in a larger population to make recommendations to use an alternative treatment which do not cause ototoxicity in the mutation bearing patient.


Photosynthesis, leaf hydraulic conductance and embolism dynamics in the resurrection plant Barbacenia purpurea.
The main parameters determining photosynthesis are stomatal and mesophyll conductance and electron transport rate, and for hydraulic dynamics they are leaf hydraulic conductance and the spread of embolism. These parameters have scarcely been studied in desiccation-tolerant (resurrection) plants exposed to drought. Here, we characterized photosynthesis and hydraulics during desiccation and rehydration in a poikilochlorophyllous resurrection plant, Barbacenia purpurea (Velloziaceae). Gas exchange, chlorophyll fluorescence, and leaf water status were monitored along the whole dehydration-rehydration cycle. Simultaneously, embolism formation and hydraulic functioning recovery were measured at leaf level using micro-computed tomography imaging. Photosynthesis and leaf hydraulic conductance ceased at relatively high water potential (-1.28 and -1.54 MPa, respectively), whereas the onset of leaf embolism occurred after stomatal closure and photosynthesis cessation (<-1.61 MPa). This sequence of physiological processes during water stress may be associated with the need to delay dehydration, to prepare the molecular changes required in the desiccated state. Complete rehydration occurred rapidly in the mesophyll, whereas partial xylem refilling, and subsequent recovery of photosynthesis, occurred at later stages after rewatering. These results highlight the importance of stomata as safety valves to protect the vascular system from embolism, even in a plant able to fully recover after complete embolism.


Electronmicroscopic studies of leiomyomatosis peritonealis diseminata.
Leiomyomatosis peritonealis disseminata (LPD) is a rare clinical entity which is currently the object of serious study. Electron microscopic studies to further elucidate the ultrastructural features of the pathology are discribed here.


Usual Interstitial Pneumonia in Contemporary Surgical Pathology Practice: Impact of International Consensus Guidelines for Idiopathic Pulmonary Fibrosis on Pathologists.
Idiopathic pulmonary fibrosis is a clinical syndrome characterized by the presence of usual interstitial pneumonia (UIP) radiologically and pathologically. Per consensus criteria adopted in 2011, diagnosis of idiopathic pulmonary fibrosis no longer requires a biopsy in an appropriate context if UIP is seen on imaging. As a result, lung biopsies are now typically reserved for patients having indeterminate clinical or imaging findings or suspicion for alternative diagnoses, but the impact of updated guidelines on pathology practice remains unclear. To determine the frequency of histologic UIP before and after 2011. Surgical lung biopsies from adults were studied within two 4-year periods: July 1, 2006 through June 30, 2010 and January 1, 2012 through December 31, 2015. Pathology slides were reviewed in a fashion blinded to clinical information and were classified using current guidelines. Biopsies from 177 and 86 patients (mean [SD] age, 62 [12] and 59 [14] years; 50.3% [89 of 177] and 48.8% [42 of 86] men) before and after 2011, respectively, were reviewed. Probable UIP or UIP was less-frequently encountered after 2011 in all patients with fibrosis (9 of 54 [16.7%] versus 41 of 119 [34.5%] before 2011, P = .02) and also in patients 50 years old and older (8 of 46 [17.4%] versus 39 of 109 [35.8%] before 2011, P = .02), with a concomitant rise in cases indeterminate for UIP or showing alternative diagnoses. Histology for UIP is less frequently encountered in our contemporary practice compared with the historic era. The pretest probability of a non-UIP diagnosis is now high, even in elderly patients, underscoring the need for pathologists to be familiar with the histologic features of alternative diagnoses.


Affinity chromatography purification of Pseudomonas aeruginosa exotoxin A on specifically linked NAD agarose.
The specific binding of P. aeruginosa exotoxin A to NAD was exploited for the rapid purification of the toxin. Affinity chromatography on a column of agarose-N6-(aminohexyl)carbamoylmethyl-NAD resulted in an enzymatically, biologically, and immunologically active purified toxin preparation. Other NAD-agarose resins were not efficient substrates for toxin purification.


Frequency, clinicopathological features and phylogenetic analysis of feline morbillivirus in cats in Istanbul, Turkey.
Objectives The aim of the study was to investigate feline morbillivirus (FmoPV) frequency, phylogeny and associated pathology in cats in Istanbul, Turkey. Methods Samples from sick (n = 96) and dead ( n = 15) cats were analysed using reverse transcription PCR. Blood and urine analyses and histopathology were also performed. Results FmoPV RNA was detected in six cats (5.4%), including three sick (in the urine) and three dead cats (tissues). A significantly greater proportion of FmoPV RNA-positive cats had street access compared with non-infected cats. Blood samples from the morbillivirus-positive cats were negative for morbillivirus RNA. Tubular parenchymal cells, lymphoid and plasma cells in kidney and hepatocytes, lymphoid and plasma cells in liver from dead cats were also positive by immunohistochemistry for the viral N protein. Two FmoPV-positive cats were also positive for feline coronavirus RNA and one cat for feline immunodeficiency virus RNA and feline leukaemia virus proviral DNA. Phylogenetic analysis of the six FmoPV-positive cats showed that the strains were grouped into cluster D and had high similarity (98.5-100%) with strains from Japan and Germany. In the three FmoPV RNA-positive sick cats, respiratory, urinary and digestive system signs were observed as well as weight loss, fever and depression in some cats. Similar clinical signs were also seen in the morbillivirus RNA-negative sick cats. FmoPV RNA-positive cats had lower median red blood cell count, haemoglobin, albumin, albumin/globulin and urobilinogen and higher alanine transaminase, alkaline phosphatase and bilirubin compared with non-infected cats. Significant histopathology of FmoPV RNA-positive dead cats included tubulointerstitial nephritis characterised by severe granular and vacuolar degeneration of the epithelial cells of the cortical and medullary tubules as well as mononuclear cell infiltrates. Widespread lymphoid cell infiltrates were detected in the renal cortex and medullary regions of the kidneys. Cellular infiltration, cholangiohepatitis and focal necrosis in the liver were also found. Although virus-infected cells were found in the kidney and liver of FmoRV RNA-positive cats, tubulointerstitial nephritis, cholangiohepatitis and focal necrosis seen in FmoRV RNA-positive cats were similar to those observed in FmoRV RNA-negative cats. Conclusions and relevance This is the first study to show the presence of FmoPV infection in cats in Turkey. Sick cats, particularly those with kidney disease, should be tested for this virus. The genotypes found in this study were similar to previously reported strains, indicating that circulating morbilliviruses in Turkey are conserved.


Multimodal Therapy Involving High-Intensity Interval Training Improves the Physical Fitness, Motor Skills, Social Behavior, and Quality of Life of Boys With ADHD: A Randomized Controlled Study.
To compare the effects of multimodal therapy including supervised high-intensity interval training (HIIT) with those of standard multimodal therapy (TRAD) concerning key variables of physical fitness (peak power and oxygen uptake), motor skills, social behavior, and quality of life in boys with ADHD. A single-center, two-arm randomized, controlled design was used, with 28 boys (8-13 years of age, IQ = 83-136) being randomly assigned to multimodal HIIT (three sessions/week, 4 × 4-min intervals at 95% of peak heart rate) or TRAD. The Movement Assessment Battery for Children II evaluated motor skills and the German version of the hyperkinetic disorder questionnaire for external evaluation by the guardians (FBB-HKS) or German version of the hyperkinetic disorder questionnaire for self-assessment by the children (SBB-HKS) and the KINDL-R questionnaires mental health and health-related quality of life. Both interventions enhanced peak power, and HIIT also reduced submaximal oxygen uptake. HIIT was more effective than TRAD in improving the total score for motor skills (including manual dexterity and ball skills; p < .05), self-esteem, friends, and competence ( p < .05) and, moreover, improved subjective ratings of attention. Three weeks of multimodal therapy including HIIT improved physical fitness, motor skills, certain aspects of quality of life, competence, and attention in boys with ADHD.