Role of Statistical Random-Effects Linear Models in Personalized Medicine.
Some empirical studies and recent developments in pharmacokinetic theory suggest that statistical random-effects linear models are valuable tools that allow describing simultaneously patient populations as a whole and patients as individuals. This remarkable characteristic indicates that these models may be useful in the development of personalized medicine, which aims at finding treatment regimes that are appropriate for particular patients, not just appropriate for the average patient. In fact, published developments show that random-effects linear models may provide a solid theoretical framework for drug dosage individualization in chronic diseases. In particular, individualized dosages computed with these models by means of an empirical Bayesian approach may produce better results than dosages computed with some methods routinely used in therapeutic drug monitoring. This is further supported by published empirical and theoretical findings that show that random effects linear models may provide accurate representations of phase III and IV steady-state pharmacokinetic data, and may be useful for dosage computations. These models have applications in the design of clinical algorithms for drug dosage individualization in chronic diseases; in the computation of dose correction factors; computation of the minimum number of blood samples from a patient that are necessary for calculating an optimal individualized drug dosage in therapeutic drug monitoring; measure of the clinical importance of clinical, demographic, environmental or genetic covariates; study of drug-drug interactions in clinical settings; the implementation of computational tools for web-site-based evidence farming; design of pharmacogenomic studies; and in the development of a pharmacological theory of dosage individualization.


Blood Interactions, Pharmacokinetics, and Depth-Dependent Ablation of Rat Mammary Tumors with Photoactivatable, Liposomal Doxorubicin.
Photosensitizers can be integrated with drug delivery vehicles to develop chemophototherapy agents with antitumor synergy between chemo- and photocomponents. Long-circulating doxorubicin (Dox) in porphyrin-phospholipid (PoP) liposomes (LC-Dox-PoP) incorporates a phospholipid-like photosensitizer (2 mole %) in the bilayer of Dox-loaded stealth liposomes. Hematological effects of endotoxin-minimized LC-Dox-PoP were characterized via standardized assays. In vitro interaction with erythrocytes, platelets, and plasma coagulation cascade were generally unremarkable, whereas complement activation was found to be similar to that of commercial Doxil. Blood partitioning suggested that both the Dox and PoP components of LC-Dox-PoP were stably entrapped or incorporated in liposomes. This was further confirmed with pharmacokinetic studies in Fischer rats, which showed the PoP and Dox components of the liposomes both had nearly identical, long circulation half-lives (25-26 hours). In a large orthotopic mammary tumor model in Fischer rats, following intravenous dosing (2 mg/kg Dox), the depth of enhanced Dox delivery in response to 665 nm laser irradiation was over 1 cm. LC-Dox-PoP with laser treatment cured or potently suppressed tumor growth, with greater efficacy observed in tumors 0.8 to 1.2 cm, compared with larger ones. The skin at the treatment site healed within approximately 30 days. Taken together, these data provide insight into nanocharacterization and photo-ablation parameters for a chemophototherapy agent.


A Proposed System for Multi-UAVs in Remote Sensing Operations.
This paper proposes the design of the communications, control systems, and navigation algorithms of a multi-UAV system focused on remote sensing operations. A new controller based on a compensator and a nominal controller is designed to dynamically regulate the UAVs' attitude. The navigation system addresses the multi-region coverage trajectory planning task using a new approach to solve the TSP-CPP problem. The navigation algorithms were tested theoretically, and the combination of the proposed navigation techniques and control strategy was simulated through the Matlab SimScape platform to optimize the controller's parameters over several iterations. The results reveal the robustness of the controller and optimal performance of the route planner.


RNase III and RNase E Influence Posttranscriptional Regulatory Networks Involved in Virulence Factor Production, Metabolism, and Regulatory RNA Processing in Bordetella pertussis.
Bordetella pertussis has been shown to encode regulatory RNAs, yet the posttranscriptional regulatory circuits on which they act remain to be fully elucidated. We generated mutants lacking the endonucleases RNase III and RNase E and assessed their individual impact on the B. pertussis transcriptome. Transcriptome sequencing (RNA-Seq) analysis showed differential expression of ∼25% of the B. pertussis transcriptome in each mutant, with only 28% overlap between data sets. Both endonucleases exhibited substantial impact on genes involved in amino acid uptake (e.g., ABC transporters) and in virulence (e.g., the type III secretion system and the autotransporters vag8, tcfA, and brkA). Interestingly, mutations in RNase III and RNase E drove the stability of many transcripts, including those involved in virulence, in opposite directions, a result that was validated by qPCR and immunoblotting for tcfA and brkA. Of note, whereas similar mutations to RNase E in Escherichia coli have subtle effects on transcript stability, a striking >20-fold reduction in four gene transcripts, including tcfA and vag8, was observed in B. pertussis. We further compared our data set to the regulon controlled by the RNA chaperone Hfq to identify B. pertussis loci influenced by regulatory RNAs. This analysis identified ∼120 genes and 19 operons potentially regulated at the posttranscriptional level. Thus, our findings revealed how changes in RNase III- and RNase E-mediated RNA turnover influence pathways associated with virulence and cellular homeostasis. Moreover, we highlighted loci potentially influenced by regulatory RNAs, providing insights into the posttranscriptional regulatory networks involved in fine-tuning B. pertussis gene expression. IMPORTANCE Noncoding, regulatory RNAs in bacterial pathogens are critical components required for rapid changes in gene expression profiles. However, little is known about the role of regulatory RNAs in the growth and pathogenesis of Bordetella pertussis. To address this, mutants separately lacking ribonucleases central to regulatory RNA processing, RNase III and RNase E, were analyzed by RNA-Seq. Here, we detail the first transcriptomic analysis of the impact of altered RNA degradation in B. pertussis. Each mutant showed approximately 1,000 differentially expressed genes, with significant changes in the expression of pathways associated with metabolism, bacterial secretion, and virulence factor production. Our analysis suggests an important role for these ribonucleases during host colonization and provides insights into the breadth of posttranscriptional regulation in B. pertussis, further informing our understanding of B. pertussis pathogenesis.


A Christmas themed physical activity intervention to increase participation in physical activity during Advent: pilot randomised controlled trial.
To examine the recruitment, retention, and preliminary effects of a Christmas themed physical activity intervention designed to increase participation in physical activity and decrease sedentary behaviour in inactive adults. Pilot randomised controlled trial. Recruitment from social medial platforms, workplaces, and community groups in the UK. 107 inactive adults (who did not meet the UK guidelines for physical activity) aged 18-75 years. The intervention consisted of an email sent to participants each day of Advent (1-24 December 2021), which contained a Christmas themed physical activity idea to be completed that day. Each physical activity idea was presented in three intensity formats, including Easy Elf (light intensity), Moderate Mrs Claus (moderate intensity), and Strenuous Santa (vigorous intensity). The comparator group received a leaflet about healthy living on the 1 December. Participants were randomly assigned (2:1) to either the intervention or control and were masked to group allocation before randomisation. Primary outcomes were recruitment rate, retention, and weekly minutes of participation in self-reported moderate-to-vigorous intensity physical activity by use of the exercise vital signs questionnaire. Primary analysis compared change in minutes of moderate-to-vigorous intensity physical activity from baseline to weeks one, two, and three during the Active Advent intervention. Secondary outcomes were participation in muscle strengthening based physical activity (days per week), accelerometer measured moderate-to-vigorous intensity physical activity, light intensity physical activity, total physical activity, and sedentary time (minutes per day), and enjoyment of and adherence to the intervention. 323 individuals expressed interest in participating in the trial and 107 were randomly assigned to the intervention (n=71) or the comparator (n=36) group. The recruitment target (n=105) was reached within 19 days of starting recruitment. 23 (21%) of 107 participants were lost to follow-up. On average, the groups reported participation in similar minutes of moderate-to-vigorous intensity physical activity in weeks one and two. At week three, the adjusted mean difference between groups was 20.6 minutes of participation in moderate-to-vigorous intensity physical activity per week (95% confidence interval -29.7 to 70.9) in favour of the intervention group. Accelerometer data showed that the intervention group spent fewer minutes sedentary per day than comparators (mean difference -58.6 (-113.5 to -3.8)). Overall, 42 (70%) of 60 participants in the intervention group reported that they liked the intervention and 41 (69%) of 59 reported that they completed the Active Advent intervention ideas each day. The public were interested to participate in a Christmas themed physical activity intervention during Advent, which might increase physical activity and reduce time sedentary. Enjoyment of, and adherence to the intervention shows the potential benefit that Christmas themed physical activity campaigns/initiatives might have for improving public health. ISRCTN12415556.


Isoniazid liver injury: clinical spectrum, pathology, and probable pathogenesis.
The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years. A possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug has been found. Examination of isoniazid metabolites showed that patients with rapid acetylator phenotype hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. It seems likely that formation of chemically reactive metabolites is also the biochemical event initiating isoniazid liver injury in man. Recognition of the seriousness of isoniazid hepatic injury, not readily accepted at first, has led to revisions in the uses of isoniazid prophylaxis.


Ethnicity-specific gene-gene interaction between IL-13 and IL-4Ralpha among African Americans with asthma.
Genes in the interleukin (IL)-4/IL-13/IL-4Ralpha pathway have been shown to be associated with asthma and related phenotypes in some populations, but not in others. Furthermore, interaction between these genes has been shown to affect asthma in white and Chinese populations. To determine whether there are IL-4/IL-13 and IL-4Ralpha gene-gene interactions that are associated with asthma in African Americans. Eighteen single-nucleotide polymorphisms (SNPs) in IL-4, IL-13, and IL-4Ralpha genes were genotyped in 264 African Americans with asthma and 176 healthy control subjects. We tested the SNPs for genetic associations and gene-gene interactions with asthma, baseline lung function, bronchodilator drug response, and total serum IgE levels. We identified 94 SNPs in IL-4, IL-13, and IL-4Ralpha genes by directly sequencing these genes in 24 African-American subjects with asthma. Seventeen SNPs were analyzed for association with asthma and related phenotypes. We found no evidence of association in the IL-4 gene. One SNP in the IL-13 gene (A-646G, rs2069743) and two SNPs in the IL-4Ralpha gene (A+4679G, rs1805010, and C+22656T, rs1805015) showed association with lung function (both baseline and post-bronchodilator). Although the association between individual SNPs and asthma-related phenotypes differed from previous studies performed in white and Chinese populations, significant gene-gene interaction was found between the IL-13 (A-646G) and IL-4Ralpha (A+4679G) SNPs for baseline lung function among African-American subjects with asthma. Gene-gene interaction between the IL-13 and IL-4Ralpha genes may play an important role in asthma among African Americans.


Macrophage deactivation by interleukin 10.
Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes. m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi. IL-10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently.


I want to talk to a real person: theorising avoidance in the acceptance and use of automated technologies.
Automated communication systems are increasingly common in mobile and ehealth contexts. Yet, there is reason to believe that some high risk segments of the population might be prone to avoid automated systems even though they are often designed to reach these groups. To facilitate research in this area, avoidance of automated communication (AAC) is theorized - and a measurement instrument validated - across two studies. In study 1, an AAC scale was found to be unidimensional and internally reliable as well as negatively correlated with comfort, perceptions, and intentions to use technology. Moreover, individuals with social phobia had lower AAC scores which was consistent with the idea that they preferred non-human interaction facilitated by automated communication. In study 2, confirmatory factor analysis supported the unidimensional structure of the measure and the instrument once again proved to be reliable. Individuals with lower AAC had greater intentions to utilize automated communication, EHRs, and an automated virtual nurse program. AAC is a disposition that predicts significant variance in intentions and comfort with various automated communication technologies. Avoidance increases with age but may be mitigated by systems that allow participants to opt-out or immediately interact with a live person.


Regulation of alkane oxidation in Pseudomonas putida.
We have studied the appearance of whole-cell oxidizing activity for n-alkanes and their oxidation products in strains of Pseudomonas putida carrying the OCT plasmid. Our results indicate that the OCT plasmid codes for inducible alkane-hydroxylating and primary alcohol-dehydrogenating activities and that the chromosome codes for constitutive oxidizing activities for primary alcohols, aliphatic aldehydes, and fatty acids. Mutant isolation confirms the presence of an alcohol dehydrogenase locus on the OCT plasmid and indicated the presence of multiple alcohol and aldehyde dehydrogenase loci on the P. putida chromosome. Induction tests with various compounds indicate that inducer recognition has specificity for chain length and can be affected by the degree of oxidation of the carbon chain. Some inducers are neither growth nor respiration substrates. Growth tests with and without a gratuitous inducer indicate that undecane is not a growth substrate because it does not induce alkane hydroxylase activity. Using a growth test for determining induction of the plasmid alcohol dehydrogenase it is possible to show that heptane induces this activity in hydroxylase-negative mutants. This suggests that unoxidized alkane molecules are the physiological inducers of both plasmid activities.


An evaluation of the CHO/HGPRT mutation assay involving suspension cultures and soft agar cloning: results for 33 chemicals.
The Chinese hamster ovary cell assay (CHO), which measures forward mutation of the HGPRT locus, is used in several laboratories for the detection of mutagens. A procedure involving treatment of CHO cells in suspension culture and mutant selection in soft agar cloning has been developed (Oberly TJ, Bewsey BJ, Probst GS (1987): Mutat Res 182:99-111). In order to evaluate the effectiveness of these modifications, 33 chemicals representing six chemical classes were tested, and the results were compared to findings obtained in other tests for genotoxicity at Lilly Research Laboratories (LRL). A positive response was obtained with 21 chemicals, all of which are recognized mutagens. Of the 12 compounds that produced negative results, 4 were considered to be mutagens and/or carcinogens. Twelve of the compounds mentioned in this report have been previously tested in the CHO/HGPRT assay by other laboratories, and the results showed strong agreement between laboratories. These findings support the conclusion that the use of suspension cultures and soft agar cloning in the CHO assay provides a sensitive test for the identification of mutagens and is a viable alternative to the traditional monolayer procedure of O'Neill et al. (O'Neill JP, Couch DB, Machanoff R, San Sebastian JR, Brimer PA, Hsie AW (1977): Mutat Res 45:103-109).


Preliminary Assessment of the Interoperability Maturity of Healthcare Digital Services vs Public Services of Other Sectors.
The development of electronic services for healthcare presents challenges related to the effective cooperation of systems and stakeholders in a highly regulated environment. Assessing the interoperability maturity of the provided services helps to identify interoperability issues in public administration. This paper presents a typical healthcare digital service: the inpatient admission in a public hospital in Greece. The Interoperability Maturity Model (IMM) is applied to assess its maturity, identify improvement priorities, and compare it with digital services of the healthcare sector. An analysis is also performed to compare a group of fourteen healthcare digital public services with sixty-seven public services of other sectors in the country. The IMM is a useful tool to facilitate awareness raising and priority setting concerning interoperability in public administration. What is discovered, through this preliminary assessment, is that healthcare digital services seem to have higher overall interoperability maturity than those of other sectors in Greece.


Genetic and environmental sources of variation in physical fitness.
The technique of path analysis was used to assess inherited and environmental variance components in physical fitness indicators measured in 1630 subjects from 375 families of French descent living in the greater Québec city area. For that purpose, submaximal power output (PWC150/kg), muscular endurance, muscular strength, reaction time and movement time were evaluated during a visit of the family to the laboratory. Inter-class correlations in various types of relatives were computed from scores adjusted for linear and non-linear effects of age and sex by a regression procedure (Y = age + sex + (age X sex) + age2). Correlations were then used in the path analytic BETA model which allows the partition of transmissible variance (t2) into genetic (h2) and cultural (b2) components. Results indicated that t2 accounted for 18% (movement time) to 63% (muscular strength) of the phenotypic variance. The contribution of genetic factors was found to be negligible for PWC150/kg and movement time, and accounted for about 20% of the phenotypic variance for reaction time and muscular endurance and 30% for muscular strength, while non-transmissible variance (1 - t2) accounted for 37% (muscular strength) to 82% (movement time) of the phenotypic variance. These results suggest that biological variation observed in the physical fitness level of a healthy population is mainly associated with non-transmissible environment factors and that the contribution of heredity is moderate and clearly lower than previously reported.


Efficacy of repeated intravenous injection of peramivir against influenza A (H1N1) 2009 virus infection in immunosuppressed mice.
The efficacy of intravenous peramivir against influenza A (H1N1) 2009 virus infection was evaluated in mice in which the immune system was suppressed by cyclophosphamide (CP) treatment. The mortality rate of the vehicle control group was 100%, and the mice lost 20% of their body weight on average by day 13 postinfection (p.i.). Repeated administration of peramivir (40 mg/kg of body weight once a day, given intravenously for 20 days), starting at 1 h p.i., significantly reduced mortality, body weight loss, viral titers, and cytokine production in infected mice compared with results for administration of vehicle (P < 0.01). In addition, repeated administration of peramivir, starting at 24 h, 48 h, or 72 h p.i., also resulted in increases in survival rates and reduction of viral titers in the lungs (P < 0.01). The mean days to death (MDD) of the vehicle group was 14.5 days, while in the groups treated with peramivir starting at 24 h, 48 h, and 72 h p.i., the MDDs were >23.0, 20.9, and 21.8 days, respectively. In comparison, repeated administration of oseltamivir phosphate (5 mg/kg twice a day, given orally for 20 days), starting at 24 h, 48 h, and 72 h p.i., also significantly prevented body weight loss, whereas no significant differences in mortality rates and viral titers in the lungs were observed compared with results for the vehicle group. These data indicated that repeated administration of peramivir was effective in promoting the survival and reducing virus replication in immunosuppressed mice infected with influenza A (H1N1) 2009 virus.


[Health care quality as perceived by the users of an emergency unit in Rome].
This study is aimed at assessing health care quality within the St. Eugenio Emergency Unit in Rome. The survey covers the months of March, June and November 2000. Patients were given about 9 thousand forms to fill before and after their access. Only 4% of them got to the hospital by ambulance and as many as 85% were immediately discharged after the exam. Their expectations were centred primarily on the health staff's professional skills, whereas their retroactive judgment focused on the poor quality of support services (parking lots, directional signs, waiting time), thus neglecting the very professional skills they previously considered as a priority.


Early Screening of Balkan Endemic Nephropathy.
Balkan endemic nephropathy (BEN) is a chronic irreversible interstitial sclerosis, for which over the last 25 years, chronic exposure to aristolochic acid from the contaminated cereal seeds has been considered the most likely cause. The aim of our research is to reevaluate trends of disease and to try to obtain new information about practical implementing of in-field screening of BEN, and to find indicators or a reliable biomarker for an early detection of the disease, especially for in field conditions. Study was conducted in two phases (two groups of respondents). The first group related to respondents with BEN and microalbuminuria in the family. After filling out the questionnaire and following the consent of the respondents, their medical records were taken, and they were subjected to clinical examination and laboratory tests as well as to abdominal ultrasound and urinary tract examination. For a long time, the disease is asymptomatic, with no hypertension, anemia or disturbed glucoregulation. Only A1M values were increased in the second group (16.22 mg), whereas A1M/CrUrine value was normal in both groups. Renal function in form of creatinine clearence and size of kidneys were in their referent values. The early stages of the disease are nonspecific, with no hypertension and disturbed glucoregulation, with normal renal function and blood count. The kidney size was in referent values. The only reliable symptom in the early stage of the renal disease was microalbuminuria.


IXDB, an X chromosome integrated database (update).
Chromosome specific databases are an important research tool as they integrate data from different directions, such as genetic and physical mapping data, expression data, sequences etc. They supplement the genome-wide repositories in molecular biology, such as GenBank, Swiss-Prot or OMIM, which usually concentrate on one type of information. The Integrated X Chromosome Database (IXDB, http://ixdb.mpimg-berlin-dahlem.mpg.de/) is a repository for physical mapping data of the human X chromosome and aims at providing a global view of genomic data at a chromosomal level. We present here an update of IXDB which includes schema extensions for storing submaps and sequence information, additional links to external databases, and the integration of an increasing number of physical and transcript mapping data. The gene data was completely updated according to the approved gene symbols of the HUGO Nomenclature Committee. IXDB receives over 1000 queries per month, an indication that its content is valuable to researchers seeking mapping data of the human X chromosome.


The Drosophila chk2 gene loki is essential for embryonic DNA double-strand-break checkpoints induced in S phase or G2.
Cell cycle checkpoints are signal transduction pathways that control the order and timing of cell cycle transitions, ensuring that critical events are completed before the occurrence of the next cell cycle transition. The Chk2 family of kinases is known to play a central role in mediating the cellular responses to DNA damage or DNA replication blocks in various organisms. Here we show through a phylogenetic study that the Drosophila melanogaster serine/threonine kinase Loki is the homolog of the yeast Mek1p, Rad53p, Dun1p, and Cds1 proteins as well as the human Chk2. Functional analyses allowed us to conclude that, in flies, chk2 is involved in monitoring double-strand breaks (DSBs) caused by irradiation during S and G2 phases. In this process it plays an essential role in inducing a cell cycle arrest in embryonic cells. Our results also show that, in contrast to C. elegans chk2, Drosophila chk2 is not essential for normal meiosis and recombination, and it also appears to be dispensable for the MMS-induced DNA damage checkpoint and the HU-induced DNA replication checkpoint during larval development. In addition, Drosophila chk2 does not act at the same cell cycle phases as its yeast homologs, but seems rather to be involved in a pathway similar to the mammalian one, which involves signaling through the ATM/Chk2 pathway in response to genotoxic insults. As mutations in human chk2 were linked to several cancers, these similarities point to the usefulness of the Drosophila model system.


Increased Risk of Osteoporotic Fracture in Patients with Autoimmune Hepatitis.
Few large-scale studies have been published regarding the association between autoimmune hepatitis (AIH) and risk of osteoporotic fracture. This study aimed to determine the risk of developing an osteoporotic fracture in patients with AIH. We used claims data from the Korean National Health Insurance Service (NHIS) between 2007 and 2020. Patients with AIH (n = 7,062) were matched with controls (n = 28,122) based on age, sex, and duration of follow-up using a ratio of 1:4. Osteoporotic fractures included fractures of the vertebrae, hip, distal radius, and proximal humerus. The incidence rate (IR) and incidence rate ratio (IRR) of osteoporotic fracture were compared between the two groups, and their associated factors were evaluated. During a median follow-up period of 5.4 years, 712 osteoporotic fractures occurred in patients with AIH with an IR of 17.5 per 1,000 person-years. Patients with AIH had a significantly higher risk of osteoporotic fractures than matched controls, with an IRR of 1.24 (95% confidence intervals, 1.10-1.39, P<0.01) in the multivariable analysis. Female sex, older age, history of stroke, presence of cirrhosis, and use of glucocorticoids were associated with an increased risk of osteoporotic fractures. In the two-year landmark analysis, longer duration of glucocorticoid exposure was associated with an incremental increased risk of osteoporotic fracture. Patients with AIH had an increased risk of osteoporotic fracture compared to controls. Presence of cirrhosis and long-term use of glucocorticoids further adversely affected osteoporotic fracture in patients with AIH.


The effect of a fish oil enriched diet on oxygen toxicity and lipid peroxidation in mice.
Mice were fed a chow diet or diets enriched in fish oil, sunflower oil or beef tallow for 3 weeks. Fatty acid analysis was carried out in samples of plasma, brain and lungs from these animals and large changes were found in plasma and lungs with relatively small dietary-induced changes in brain tissue. Bleeding times were increased very significantly in the fish oil group, and slightly increased in the sunflower oil group. Endogenous lipid peroxidation (measured as thiobarbituric acid reactive substances) was unchanged in lung and brain, but lung tissue from fish oil fed mice produced more lipid peroxides in vitro during incubation at 37 degrees than those of other dietary groups. Mice fed the four different diets were exposed to hyperbaric oxygen at 618, 585 and 515 kPa and convulsive activity and lung damage was recorded. No dietary-induced alterations in susceptibility to oxygen toxicity were found.


A gain-of-function sodium channel β2-subunit mutation in painful diabetic neuropathy.
Diabetes mellitus is a global challenge with many diverse health sequelae, of which diabetic peripheral neuropathy is one of the most common. A substantial number of patients with diabetic peripheral neuropathy develop chronic pain, but the genetic and epigenetic factors that predispose diabetic peripheral neuropathy patients to develop neuropathic pain are poorly understood. Recent targeted genetic studies have identified mutations in α-subunits of voltage-gated sodium channels (Navs) in patients with painful diabetic peripheral neuropathy. Mutations in proteins that regulate trafficking or functional properties of Navs could expand the spectrum of patients with Nav-related peripheral neuropathies. The auxiliary sodium channel β-subunits (β1-4) have been reported to increase current density, alter inactivation kinetics, and modulate subcellular localization of Nav. Mutations in β-subunits have been associated with several diseases, including epilepsy, cancer, and diseases of the cardiac conducting system. However, mutations in β-subunits have never been shown previously to contribute to neuropathic pain. We report here a patient with painful diabetic peripheral neuropathy and negative genetic screening for mutations in SCN9A, SCN10A, and SCN11A-genes encoding sodium channel α-subunit that have been previously linked to the development of neuropathic pain. Genetic analysis revealed an aspartic acid to asparagine mutation, D109N, in the β2-subunit. Functional analysis using current-clamp revealed that the β2-D109N rendered dorsal root ganglion neurons hyperexcitable, especially in response to repetitive stimulation. Underlying the hyperexcitability induced by the β2-subunit mutation, as evidenced by voltage-clamp analysis, we found a depolarizing shift in the voltage dependence of Nav1.7 fast inactivation and reduced use-dependent inhibition of the Nav1.7 channel.


Clinico-pathological profile of sinonasal masses: an experience in national ear care center Kaduna, Nigeria.
The presence of a mass in the nose and paranasal sinuses may seem to be a simple problem; however it raises many questions about the differential diagnosis. The aim of this study is to evaluate the clinico-pathological profile of sinonasal masses in our environmentThis is a retrospective analytical review of all the patients with sinonasal masses that presented to the national ear care center, Kaduna over a six year (2003-2008) period. Their biodata, clinical profile and histological diagnoses were analyzed. A total of 76 patients were analyzed, age range 5 to 64 yrs with a mean age of 33.3 yr median and modal age of 35.00 (SD = 13.1 +/- 1.5). Majority of the patients were in the age groups 21-50 yrs. There were 34 male and 42 female with M: F ratio of 1:1.2. The main presenting symptoms are nasal blockage 97.4% and rhinorrhea 94.7%. It was bilateral in 34 (44.7%), left side in 24(31.6%) and right side in 18(23.7%) patients. The commonest clinical diagnoses were simple nasal polyp 47(61.8%) and antrochoanal polyp 10(13.2%). About 59 (77.6%) were benign, 2 (2.6%) were malignant and 15 (19.7%) were lost to follow up. The commonest histological diagnosis is simple inflammatory nasal polyp in 28 (36.8%) patients and the least was nasal capillary hemangioma 2 (2.6%). About 55(72.4%) patients had surgical treatment. Nasal obstruction and rhinorrhea are the commonest symptoms of presentation, simple inflammatory nasal polyp is still the commonest histological pattern seen in our environment, and surgery is still the best modality of treatment for benign tumor thus the need for advocacy for early recognition and referral to the ENT surgeon.


Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies.
Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. To examine the association between job strain and body mass index (BMI) in a large adult population. We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). A total of 86 429 participants were of normal weight (BMI 18.5-24.9 kg m(-2) ), 2149 were underweight (BMI < 18.5 kg m(-2) ), 56 572 overweight (BMI 25.0-29.9 kg m(-2) ) and 13 523 class I (BMI 30-34.9 kg m(-2) ) and 3073 classes II/III (BMI ≥ 35 kg m(-2) ) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.00-1.25], obese class I (odds ratio 1.07, 95% CI 1.02-1.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.01-1.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a 'U'-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a population level.


Full-length phrenic nerve transfer as the treatment for brachial plexus avulsion injury to restore wrist and finger extension.
The functional restoration of wrist and finger extension after complete brachial plexus avulsion injury remains an unsolved problem. We conducted a prospective study to elucidate a new method for resolving this injury. Six patients with complete brachial plexus avulsion injury underwent a new surgical procedure in which the full-length phrenic nerve was transferred to the medial portion of the radial nerve at the level of the latissimus dorsi insertion via endoscopic thoracic surgery. In 5 patients, extensor carpi ulnaris and extensor carpi radialis strength recovered to Medical Research Council grade ≥M3, and in 4 patients extensor digitorum strength recovered to ≥M3. Neurotization of phrenic nerve to the medial portion of the radial nerve at the level of latissimus dorsi insertion is a feasible means of restoring wrist and finger extension in cases of complete brachial plexus avulsion injury.


An Outline of Data Aggregation Security in Heterogeneous Wireless Sensor Networks.
Data aggregation processes aim to reduce the amount of exchanged data in wireless sensor networks and consequently minimize the packet overhead and optimize energy efficiency. Securing the data aggregation process is a real challenge since the aggregation nodes must access the relayed data to apply the aggregation functions. The data aggregation security problem has been widely addressed in classical homogeneous wireless sensor networks, however, most of the proposed security protocols cannot guarantee a high level of security since the sensor node resources are limited. Heterogeneous wireless sensor networks have recently emerged as a new wireless sensor network category which expands the sensor nodes' resources and capabilities. These new kinds of WSNs have opened new research opportunities where security represents a most attractive area. Indeed, robust and high security level algorithms can be used to secure the data aggregation at the heterogeneous aggregation nodes which is impossible in classical homogeneous WSNs. Contrary to the homogeneous sensor networks, the data aggregation security problem is still not sufficiently covered and the proposed data aggregation security protocols are numberless. To address this recent research area, this paper describes the data aggregation security problem in heterogeneous wireless sensor networks and surveys a few proposed security protocols. A classification and evaluation of the existing protocols is also introduced based on the adopted data aggregation security approach.


Defective assembly and trafficking of mutant HERG channels with C-terminal truncations in long QT syndrome.
Mutations in the human ether-a-go-go-related gene (HERG) cause long QT syndrome type 2 (LQT2). HERG encodes a voltage-gated potassium channel consisting of four subunits. Tetrameric assembly is required for the formation of functional HERG channels. In the present work, we studied the role of assembly in HERG channel dysfunction of LQT2 mutations Q725X and R1014X, both of which cause truncations of the C-terminus of HERG channels. When expressed in HEK293 cells, Q725X did not generate HERG current, while R1014X generated HERG current with markedly reduced amplitude. Western blot analysis showed that both mutations caused defective trafficking of HERG channel proteins. Using sucrose gradient centrifugation we showed that wild type HERG and R1014X formed a tetrameric structure, whereas Q725X was expressed as a monomer. When coexpressed with wild type HERG, R1014X, but not Q725X, caused dominant negative suppression of wild type HERG current. Coimmunoprecipitation experiments showed that the lack of dominant negative effect by Q725X was due to failure of mutant subunits to coassemble with wild type subunits. These results suggest that the Q725X mutation causes HERG channel dysfunction by disruption of tetrameric assembly of HERG channels. In contrast, the R1014X mutation is capable of forming tetrameric structure, and it causes HERG channel dysfunction by defective trafficking of the mutant protein.


Bcl-2/bax mRNA expression ratio as prognostic factor in low-grade urinary bladder cancer.
Apoptotic cell death represents an important mechanism for the precise regulation of cell numbers, and a defence mechanism against tumoral cell. bcl-2 and bax genes are known to be involved in the control of apoptotic pathways; in particular, the ratio between bcl-2 and bax represents a cell rheostat that is able to predict a cell's response toward life or death to an apoptotic stimulus. In the present study we investigated the role of bcl-2 and bax gene expression in a panel of 37 low-grade tumours of the urinary bladder, and correlated the expression of these genes to the prognosis of patients in a follow-up of more than one year. We found that levels of bax expression higher than bcl-2 in bladder tumours well correlates to a better outcome for patients. Early relapses are much more frequently observed in those patients whose tumours express more bcl-2 than bax mRNA. We conclude that the bcl-2/bax expression ratio may be considered as a marker for disease progression in low grade bladder tumours, independently of clinical staging and histological grading.


Circadian analysis of mononuclear cells in the rat following pinealectomy and superior cervical ganglionectomy.
The role of the pineal gland and adrenocorticosteroids in circadian rhythmicity of immune function was investigated in Sprague-Dawley rats that either had been pinealectomized (PX) or had undergone superior cervical ganglionectomy (SCGX), which functionally denervates the pineal. For both experiments, conducted between August and October, rats were entrained to a 10-h light:14-h dark cycle and fed ad libitum. The circadian rhythm in monocytes (ANOVA, p less than .01 for Control + Sham + PX samples) tended to parallel that of plasma corticosteroid levels (ANOVA, p less than .01) with the peak during early dark and the nadir at early light. In comparison, suppressor/cytotoxic T cells and B cells tended to be more frequent during early light with minimum levels during early dark (ANOVA, p less than .05 and .01, respectively, for Control + Sham + PX samples). Natural killer (NK) activity in control animals varied significantly (ANOVA, p less than .05) over the light:dark cycle with peak activity during early dark in the SCGX experiment, but was only slightly elevated during late dark in the PX experiment. PX animals exhibited increased frequency of NK cells, but only in samples collected during the day (t test, p less than .05). This effect was not observed in sham-operated PX controls and in SCGX animals. Neither PX nor SCGX had a significant (ANOVA) effect on plasma corticosterone levels. These observations in the rat are consistent with findings in mice and humans that corticosteroids play an important general role in circadian rhythmicity of immune functions. In contrast, the present study suggests that pineal gland influence of immune function(s) is more specific and that pineal gland interaction with NK cells has a circadian component.


Income is not an equalizer: health development inequities by ethnoracial backgrounds in California kindergartners.
Early childhood health development is positively associated with income, but the strength of this relationship with ethnoracial background remains unclear. This study examined the extent of health development inequities among California kindergarteners based on ethnoracial backgrounds and neighborhood-level income. This cross-sectional study assessed health development inequities by analyzing neighborhood-level income, ethnoracial background, and health development data for California kindergarteners. Student-level data (n = 106,574) were collected through teacher report between 2010-2020 across 52 school districts and 964 schools. Student addresses were geocoded and linked to American Community Survey neighborhood income levels. Health development was measured using the Early Development Instrument, a population-level measure which includes physical health and well-being, social competence, emotional maturity, language and cognitive development, and communication skills and general knowledge domains. Outcomes included being "on-track" in each domain as well as overall health development. Using a Generalized Estimation Equation with a log-link function, while accounting for interactions between ethnoracial background, income, and income-squared, we found significant health development inequities by ethnoracial background and neighborhood-level income. Regarding overall health development, as well as the physical, social and emotional domains, Black students had a lower likelihood of being on-track compared to the weighted average across income levels, whereas Asian students surpassed the weighted average. White students exhibited the steepest slope, and at the lowest income levels, their health development scores were akin to their Black and Hispanic/Latino/a low-income counterparts but resembled their Asian counterparts at higher income levels. For the general knowledge and communication domain, white students consistently had the highest likelihood of being on-track, while Hispanic/Latino/a students had the lowest likelihood across all income levels. This study examines health development inequities among California kindergarteners in diverse communities. Our analysis shows that the relationship between neighborhood-level income and kindergartners' health development varies by domain and is weaker for students of color. Given the scarcity of population-level data on health development outcomes, these analyses offer valuable insights for identifying ecosystems necessitating support in promoting equitable early childhood health development.


Cancer mortality in Italy, 1993.
Data and statistics are presented on cancer death certification for 1993 in Italy, updating previous publications covering the period 1955-1992. Data for 1993 subdivided into 30 cancer sites are presented in 8 tables, including age- and sex-specific absolute and percentage frequencies of cancer deaths, and crude, age-specific and age-standardized rates, at all ages and truncated for the 35-64 year age group. Age-adjusted death certification rates (on the world standard population) for all neoplasms declined from 189.8 in 1992 (and a peak of 199.2 in 1986) to 187.8/100,000 males in 1993, and remained stable around 100,000 females. The favorable trends were even larger in middle and younger age males, but not in children below age 15, whose overall age-standardized cancer mortality rates increased for the fourth subsequent year. Lung cancer was the leading site of cancer mortality, with over 30,900 deaths. For the fifth subsequent year, its rates in males declined, to reach 56.0/100,000. The decline in lung cancer rates is now established in Italian males and is substantial in middle age, whereas the rise in female lung cancer rates seems to have leveled off over the last few years. Rates for other major cancer sites (intestines, stomach, female breast, prostate, pancreas, leukemias and lymphomas) were stable, but some decrease was apparent also in 1993 for Hodgkin's disease. Italian cancer mortality rates in 1993 were moderately favorable in males, due to the leveling of the tobacco-related epidemic, whereas no appreciable change was registered in females. The persisting unfavorable trends in childhood cancer mortality should be investigated.


Trends in Mortality of Acute Pulmonary Embolism.
Despite substantial advances in the diagnosis and management, pulmonary embolism (PE) continues to be a significant cause of mortality. In this article, we provide a concise overview of the evolution of worldwide mortality trends related to PE. Despite the data being derived mainly from observational studies, there is a clear trend toward decreasing mortality over time from PE. Whether this truly represents a treatment effect or is more related to increased diagnosis of small PEs is not fully clear. Modern approaches to PE management such as the PE response teams have the potential to further reduce the mortality from PE.


Clinical features of Creutzfeldt-Jakob disease with V180I mutation.
The authors describe the clinical features of Creutzfeldt-Jakob disease (CJD) with the causative point mutation at codon 180. The symptoms never started with visual or cerebellar involvement. The patients showed slower progression of the disease compared with sporadic CJD. They never showed periodic sharp and wave complexes in EEG. MRI demonstrated remarkable high-intensity areas with swelling in the cerebral cortex except for the medial occipital and cerebellar cortices. These characteristic MRI findings are an important clue for an accurate premortem diagnosis.


Overlapping roles of the Rous sarcoma virus Gag p10 domain in nuclear export and virion core morphology.
Nucleocytoplasmic shuttling of the Rous sarcoma virus (RSV) Gag polyprotein is an integral step in virus particle assembly. A nuclear export signal (NES) was previously identified within the p10 domain of RSV Gag. Gag mutants containing deletions of the p10 NES or mutations of critical hydrophobic residues at positions 219, 222, 225, or 229 become trapped within the nucleus and exhibit defects in the efficiency of virus particle release. To investigate other potential roles for Gag nuclear trafficking in RSV replication, we created viruses bearing NES mutant Gag proteins. Viruses carrying p10 mutations produced low levels of particles, as anticipated, and those particles that were released were noninfectious. The p10 mutant viruses contained approximately normal amounts of Gag, Gag-Pol, and Env proteins and genomic viral RNA (vRNA), but several major structural defects were found. Thin-section transmission electron microscopy revealed that the mature particles appeared misshapen, while the viral cores were cylindrical, horseshoe-shaped, or fragmented, with some particles containing multiple small, electron-dense aggregates. Immature virus-like particles produced by the expression of Gag proteins bearing p10 mutations were also aberrant, with both spherical and tubular filamentous particles produced. Interestingly, the secondary structure of the encapsidated vRNA was altered; although dimeric vRNA was predominant, there was an additional high-molecular-weight fraction. Together, these results indicate that the p10 NES domain of Gag is critical for virus replication and that it plays overlapping roles required for the nuclear shuttling of Gag and for the maintenance of proper virion core morphology.


Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: new evidence for panselective evolution.
Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA), the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x²9) was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.


Fatty acid-binding protein activities in bovine muscle, liver and adipose tissue.
Subcutaneous adipose tissue, sternomandibularis muscle and liver were obtained from steers immediately postmortem. Muscle strips and adipose tissue snips were incubated with 0.75 mM [1-14C]palmitate and 5 mM glucose. Muscle strips esterified palmitate at the rate of 2.5 nmol/min per gram tissue, which was 30% of the rate observed for adipose tissue. Fatty acid-binding protein activity was measured in 104,000 x g supernatant fractions of liver, muscle and adipose tissue homogenates. Muscle and adipose tissue fractions bound 840 and 140 pmol [1-14C]palmitoyl-CoA per gram tissue, respectively. Fatty acid-binding protein activity was greater in adipose tissue than in muscle when data were expressed per milligram protein (35 vs. 13 pmol palmitoyl-CoA bound per milligram of soluble protein, respectively). Fatty acid binding-protein activity was correlated with the rate of palmitate esterification within each tissue. Liver contained the highest fatty acid-binding protein activity (13,000 pmol palmitoyl-CoA bound per gram tissue and 215 pmol palmitoyl-CoA bound per milligrams soluble protein).


Potential production of sterigmatocystin on country-cured ham.
In laboratory media, 10 of 16 isolates of Aspergillus versicolor from country-cured ham were capable of producing sterigmatocystin. Three of these isolates were tested and found to produce sterigmatocystin on country-cured ham after 14 days of incubation at 20 or 28 C.


Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell migration.
The p21-activated protein kinases (Paks) regulate cellular proliferation, differentiation, transformation, and survival through multiple downstream signals. Paks are activated directly by the small GTPases Rac and Cdc42 and several protein kinases including Akt and PDK-1. We found that Akt phosphorylated and modestly activated Pak1 in vitro. The major site phosphorylated by Akt on Pak1 mapped to serine 21, a site originally shown to be weakly autophosphorylated on Pak1 when Cdc42 or Rac activates it. A peptide derived from the region surrounding serine 21 was a substrate for Akt but not Pak1 in vitro, and Akt stimulated serine 21 phosphorylation on the full-length Pak1 much better than Rac did. The adaptor protein Nck binds Pak near serine 21, and its association is regulated by phosphorylation of this site. We found that either treatment of Pak1 in vitro with Akt or coexpression of constitutively active Akt with Pak1 reduced Nck binding to Pak1. In HeLa cells, green fluorescent protein-tagged Pak1 was concentrated at focal adhesions and was released when Akt was cotransfected. A peptide containing the Nck binding site of Pak1 fused to a portion of human immunodeficiency virus Tat to allow it to enter cells was used to test the functional importance of Nck/Pak binding in Akt-stimulated cell migration. This Tat-Nck peptide reduced Akt-stimulated cell migration. Together, these data suggest that Akt modulates the association of Pak with Nck to regulate cell migration.


Generation and probing of 3D helical lattices with tunable helix pitch and interface.
We propose a method for generation of tunable three-dimensional (3D) helical lattices with varying helix pitch. In order to change only the lattice helix pitch, a periodically varying phase along the propagation direction is added to the central beam - one of the interference beams for lattice construction. The phase periodicity determines the helix pitch, which can be reconfigured at ease. Furthermore, a helical lattice structure with an interface (domain wall) is also achieved by changing the phase structure of the lateral beams, leading to opposite rotating direction (helicity) on different sides of the interface. When a Gaussian beam is used to probe the bulk lattice, it can evolve into a spiral beam with its helicity varying in accordance with that of the lattice. Probing along the interface with two dipole-like optical beams leads to unusual propagation dynamics, depending on the phase and size of the two beams. This approach could be further explored for studies of nonlinear interface solitons and topological interface states. In addition, the helical lattices may find applications in dynamical multi-beam optical tweezers.


[Effect of miR-22 Targeting FMNL2 on Cell Migration and Apoptosis in Childhood Acute Myeloid Leukemia].
To investigate the effect of miR-22 targeting formin-like protein 2 (FMNL2) on the migration and apoptosis of childhood acute myeloid leukemia (AML) cells. Peripheral blood samples from 11 children with AML, 10 children with immune thrombocytopenia, human AML cell lines TF-1a, HL-60, THP-1 and human bone marrow stromal cells HS-5 were used as the research objects. UniCel DxH 800 automatic hematology analyzer detected platelet count, hemoglobin, and white blood cell count in peripheral blood samples, and RT-qPCR detected miR-22 expression in peripheral blood samples and AML cells. HL-60 cells were transfected with LipofectamineTM 2000 kit, the experiments were divided into seven groups: blank (no cells transfected), miR-NC, miR-22 mimics, si-NC, si-FMNL2 , miR-22 mimics+OE-NC and miR-22 mimics+OE-FMNL2 . RT-qPCR was used to detect the expression of miR-22 in each group. Transwell was used to detect cell migration. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter gene detection experiments verified the targeting relationship between miR-22 and FMNL2 . Western blot was used to detect the expression of FMNL2 protein. Compared with the control group, the number of leukocytes in the peripheral blood of children with AML was significantly increased (P <0.001), while the concentration of hemoglobin and the number of platelets were significantly decreased P <0.001). The expression level of miR-22 in peripheral blood of children with AML was significantly lower than that in control group (P <0.001). Compared with HS-5 cells, the expression levels of miR-22 in TF-1a, HL-60, and THP-1 cells were significantly decreased (P <0.05), and in HL-60 cells was the lowest. Therefore, HL-60 cells were selected for subsequent experiments. Up-regulation of miR-22 or silencing of FMNL2 could reduce the number of migrating cells and increase apoptosis rate (P <0.05). MiR-22 targeted and negatively regulated the expression of FMNL2 . FMNL2 overexpression reversed the effects of up-regulated miR-22 on migration and apoptosis of HL-60 cells. MiR-22 can inhibit the migration and promote apoptosis of HL-60 cells by down regulating the expression of FMNL2 .


Adipose-Derived Stromal Vascular Fraction/Xenohybrid Bone Scaffold: An Alternative Source for Bone Regeneration.
Adipose tissue-derived stem cells (ASCs) are a promising tool for the treatment of bone diseases or skeletal lesions, thanks to their ability to potentially repair damaged tissue. One of the major limitations of ASCs is represented by the necessity to be isolated and expanded through in vitro culture; thus, a strong interest was generated by the adipose stromal vascular fraction (SVF), the noncultured fraction of ASCs. SVF is a heterogeneous cell population, directly obtained after collagenase treatment of adipose tissue. In order to investigate and compare the bone-regenerative potential of SVF and ASCs, they were plated on SmartBone®, a xenohybrid bone scaffold, already used in clinical practice with successful results. We showed that SVF plated on SmartBone, in the presence of osteogenic factors, had better osteoinductive capabilities than ASCs, in terms of differentiation into bone cells, mineralization, and secretion of soluble factors stimulating osteoblasts. Indeed, we observed an increasing area of new tissue over time, with and without OM. These data strongly support an innovative idea for the use of adipose SVF and bone scaffolds to promote tissue regeneration and repair, also thanks to an easier cell management preparation that allows a potentially larger use in clinical applications.


Recent structural and mechanistic insights into endplate acetylcholine receptors.
Voluntary movement mediated by skeletal muscle relies on endplate acetylcholine receptors (AChR) to detect nerve-released ACh and depolarize the muscle fiber. Recent structural and mechanistic studies of the endplate AChR have catalyzed a leap in our understanding of the molecular steps in this chemical-to-electrical transduction process. Studies of acetylcholine binding protein (AChBP) give insight into ACh recognition, the first step in activation of the AChR. An atomic structural model of the Torpedo AChR at a resolution of 0.4 nm, together with single-ion channel recording methods, allow tracing of the link between the agonist binding event and gating of the ion channel, as well as determination of how the channel moves when it opens to allow flow of cations. Structural models of the human AChR enable precise mapping of disease-causing mutations, while studies of the speed with which single AChR channels open and close cast light on pathogenic mechanisms.


[Risk factors of atherosclerosis in young people].
Factor analysis was used to study an association of risk factors of atherosclerosis (AS) in student during their study. These factors were shown to be rather evident just at the age of 17-22 years. The correlation matrixes in male and female students are described by a mixed number of factors and the factors differ themselves in the internal structure, magnitude, and correlation signs. Young men were ascertained to be more susceptible to stresses and to have more abnormal lipid metabolism. The risk of AS is much higher just in young men. It is concluded that male sex is a major potential risk factor of this disease. Accordingly, rational hygienic and demographic strategy must be aimed primarily at maintaining the health status of men as the most susceptible social sector.


Dihexanoylphosphatidylethanolamine: effect of head group charge on rates of alkaline and phospholipase A2 catalyzed hydrolyses.
Dihexanoylphosphatidylethanolamine (DiC6-PE) was prepared by phospholipase D catalyzed transphosphatidylation of dihexanoylphosphatidylcholine (DiC6-PC). Below the critical micellar concentration the pKa of the amino group is 9.4 +/- 0.05. The critical micellar concentration of the zwitterionic species is 5.3 +/- 0.2 mM, while that of the anionic species is 11.0 +/- 0.05 mM. Based on the pH dependence of the rate of hydroxide ion catalyzed hydrolysis, the second order rate constant for hydrolysis of the zwitterionic species is 0.70 +/- 0.021 s-1 M-1, while that for the anionic species is 0.040 +/- 0.011 s-1 M-1. The pH-dependence of phospholipase A2 catalyzed hydrolysis at substrate concentrations below the critical micellar concentration shows that the zwitterionic species is the preferred substrate, and the anionic species is either a competitive inhibitor of the hydrolysis of the zwitterionic species or poor substrate. DiC6-PE is hydrolyzed by C. adamanteus at about 1% the rate of DiC6-PC.


Change in binge eating and binge eating disorder associated with migration from Mexico to the U.S.
Exposure to Western popular culture is hypothesized to increase risk for eating disorders. This study tests this hypothesis with respect to the proposed diagnosis of binge eating disorder (BED) in an epidemiological sample of people of Mexican origin in Mexico and the U.S. Data come from the Mexico National Comorbidity Survey, National Comorbidity Survey Replication, and National Latino and Asian American Survey (N = 2268). Diagnoses were assessed with the WMH-CIDI. Six groups were compared: Mexicans with no migrant family members, Mexicans with at least one migrant family member, Mexican return-migrants, Mexican-born migrants in the U.S., and two successive generations of Mexican-Americans in the U.S. The lifetime prevalence of BED was 1.6% in Mexico and 2.2% among Mexican-Americans. Compared with Mexicans in families with migrants, risk for BED was higher in US-born Mexican-Americans with two U.S.-born parents (aHR = 2.58, 95% CI 1.12-5.93). This effect was attenuated by 24% (aHR = 1.97, 95% CI 0.84-4.62) with adjustment for prior-onset depressive or anxiety disorder. Adjustment for prior-onset conduct disorder increased the magnitude of association (aHR = 2.75, 95% CI 1.22-6.20). A similar pattern was observed for binge eating. Among respondents reporting binge eating, onset in the U.S. (vs. Mexico) was not associated with prevalence of further eating disorder symptoms. Migration from Mexico to the U.S. is associated with an increased risk for BED that may be partially attributable to non-specific influences on internalizing disorders. Among respondents reporting binge eating in either country, similar levels of further symptoms were endorsed, suggesting some cross-cultural generalizability of criteria.


Comparative ratios of carcinoma of the vagina and cervix in different population groups.
A retrospective study of squamous carcinoma of the vagina at Baragwanath Hospital over a period of 20 years shows that the incidence of this condition is much lower than that reported in other series. In addition, the ratio of primary carcinoma of the vagina to that of the cervix is much lower than in comparable studies. The age distribution, aetiology and the sexual characteristics of the Black population are discussed.


Characteristics of internet addiction/pathological internet use in U.S. university students: a qualitative-method investigation.
Studies have identified high rates and severe consequences of Internet Addiction/Pathological Internet Use (IA/PIU) in university students. However, most research concerning IA/PIU in U.S. university students has been conducted within a quantitative research paradigm, and frequently fails to contextualize the problem of IA/PIU. To address this gap, we conducted an exploratory qualitative study using the focus group approach and examined 27 U.S. university students who self-identified as intensive Internet users, spent more than 25 hours/week on the Internet for non-school or non-work-related activities and who reported Internet-associated health and/or psychosocial problems. Students completed two IA/PIU measures (Young's Diagnostic Questionnaire and the Compulsive Internet Use Scale) and participated in focus groups exploring the natural history of their Internet use; preferred online activities; emotional, interpersonal, and situational triggers for intensive Internet use; and health and/or psychosocial consequences of their Internet overuse. Students' self-reports of Internet overuse problems were consistent with results of standardized measures. Students first accessed the Internet at an average age of 9 (SD = 2.7), and first had a problem with Internet overuse at an average age of 16 (SD = 4.3). Sadness and depression, boredom, and stress were common triggers of intensive Internet use. Social media use was nearly universal and pervasive in participants' lives. Sleep deprivation, academic under-achievement, failure to exercise and to engage in face-to-face social activities, negative affective states, and decreased ability to concentrate were frequently reported consequences of intensive Internet use/Internet overuse. IA/PIU may be an underappreciated problem among U.S. university students and warrants additional research.


[Interaction of gag polyprotein-precursors p55 and p48 with p160gag-pol during formation of virus-like particles of HIV-1 with recombinant strains of vaccinia virus].
The polypeptide composition of HIV-I virus-like particles produced by CV-I cells during mono- and coinfection with recombinant vaccinia virus (rVV) strains containing the whole (p55) and carboxyterminal truncated (p48) gag genes and gag-pol sequence is studied. In monoinfection both the gag-strains actively produced virus-like particles consisting of non-processed p55Gag and p48Gag polyprotein without p6 domain. In case of a coinfection of the cells with one of these strains and the rVV producing p160Gag-Pol polyprotein the virus-like particles consisted of p24 protein and a negligible amount of non-processed Gag precursors. The share of p24 protein increased in proportion to the duration of coinfection and decreased with a reduction of multiplicity of infection with rVV carrying p160Gag-Pol. Hence, the absence of p6 domain does not influence the processing of Gag proteins during virus-like particles assembly and budding. In contrast to the natural systems of HIV-I development, in the rVV expression system the p6Gag domain virtually does not contribute to reactions between Gag and Gag-Pol precursors and to the particles' morphogenesis.


HER2 fragmentation and breast cancer stratification.
HER2 is a tyrosine kinase receptor whose overexpression in breast cancers correlates with poor prognosis. A subset of HER2-positive tumors also expresses a series of HER2 fragments, collectively known as p95HER2. These fragments are emerging as a valuable biomarker for this subset of patients, who have a particularly poor prognosis.


Unravelling the diversity of grapevine microbiome.
Vitis vinifera is one of the most widely cultivated fruit crops with a great economic impact on the global industry. As a plant, it is naturally colonised by a wide variety of both prokaryotic and eukaryotic microorganisms that interact with grapevine, having either beneficial or phytopathogenic effects, who play a major role in fruit yield, grape quality and, ultimately, in the evolution of grape fermentation and wine production. Therefore, the objective of this study was to extensively characterize the natural microbiome of grapevine. Considering that the majority of microorganisms are uncultivable, we have deeply studied the microflora of grapevine leaves using massive parallel rDNA sequencing, along its vegetative cycle. Among eukaryotic population the most abundant microorganisms belonged to the early diverging fungi lineages and Ascomycota phylum, whereas the Basidiomycota were the least abundant. Regarding prokaryotes, a high diversity of Proteobacteria, Firmicutes and Actinobacteria was unveiled. Indeed, the microbial communities present in the vineyard during its vegetative cycle were shown to be highly structured and dynamic. In all cases, the major abundant microorganisms were the yeast-like fungus Aureobasidium and the prokaryotic Enterobacteriaceae. Herein, we report the first complete microbiome landscape of the vineyard, through a metagenomic approach, and highlight the analysis of the microbial interactions within the vineyard and its importance for the equilibrium of the microecosystem of grapevines.


TNF-α involvement in insulin resistance induced by experimental scorpion envenomation.
Scorpion venom induces systemic inflammation characterized by an increase in cytokine release and chemokine production. There have been few experimental studies assessing the effects of scorpion venom on adipose tissue function in vivo. To study the adipose tissue inflammation (ATI) induced by Androctonus australis hector (Aah) venom and to assess possible mechanisms of ATI, mice (n = 6, aged 1 month) were injected with Aah (0.45 mg/kg), toxic fraction of Aah (FTox-G50; 0.2 mg/kg) or saline solution (control). Inflammatory responses were evaluated by ELISA and cell sorting analyses in adipose tissue 45 minutes and 24 hours after injection. Quantitative real-time PCR was used to assess the regulation of genes implicated in glucose uptake. The titers of selected inflammatory cytokines (IL-1β, IL-6 and TNF-α) were also determined in sera and in insulin target tissues. The serum concentration of IL-1β rose 45 minutes after envenomation and returned to basal level after 24 hours. The pathophysiological effects of the venom after 24 hours mainly involved M1-proinflammatory macrophage infiltration in adipose tissue combined with high titers of IL-1β, IL-6 and TNF-α. Indeed, TNF-α was strongly induced in both adipose tissue and skeletal muscle. We studied the effects of Aah venom on genes implicated in insulin-stimulated glucose uptake. Insulin induced a significant increase in the expression of the mRNAs for hexokinase 2 and phosphatidylinositol 3-kinase in both skeletal muscle and adipose tissue in control mice; this upregulation was completely abolished after 24 hours in mice envenomed with Aah or FTox-G50. Our findings suggest that Aah venom induces insulin resistance by mechanisms involving TNF-α-dependent Map4k4 kinase activation in the adipose tissue.


Prediction of tricyclic antidepressant response: a critical review.
This article reviews all the prospective, double-blind controlled studies that have evaluated the prediction of response to imipramine hydrochloride and amitriptyline hydrochloride in depressed patients. Despite widely divergent methodologies, an attempt is made to extract clinically useful conclusions from these data. Critiques of each study and the criteria used in their evaluation are presented, with suggestions for future research included. The predictors of positive response to imipramine and amitriptyline are as follows: upper socioeconomic class, insidious onset, anorexia, weight loss, middle and late insomnia, and psychomotor disturbance. The predictors of poor response are the following: neurotic, hypochondriacal, and hysterical traits, multiple prior episodes, and delusions. Pretreatment urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels may some day be useful in predicting to which of these two tricyclic antidepressants a patient will respond.


Computer vision syndrome and associated factors among medical and engineering students in chennai.
Almost all institutions, colleges, universities and homes today were using computer regularly. Very little research has been carried out on Indian users especially among college students the effects of computer use on the eye and vision related problems. The aim of this study was to assess the prevalence of computer vision syndrome (CVS) among medical and engineering students and the factors associated with the same. A cross-sectional study was conducted among medical and engineering college students of a University situated in the suburban area of Chennai. Students who used computer in the month preceding the date of study were included in the study. The participants were surveyed using pre-tested structured questionnaire. Among engineering students, the prevalence of CVS was found to be 81.9% (176/215) while among medical students; it was found to be 78.6% (158/201). A significantly higher proportion of engineering students 40.9% (88/215) used computers for 4-6 h/day as compared to medical students 10% (20/201) (P < 0.001). The reported symptoms of CVS were higher among engineering students compared with medical students. Students who used computer for 4-6 h were at significantly higher risk of developing redness (OR = 1.2, 95% CI = 1.0-3.1,P = 0.04), burning sensation (OR = 2.1,95% CI = 1.3-3.1, P < 0.01) and dry eyes (OR = 1.8, 95% CI = 1.1-2.9, P = 0.02) compared to those who used computer for less than 4 h. Significant correlation was found between increased hours of computer use and the symptoms redness, burning sensation, blurred vision and dry eyes. The present study revealed that more than three-fourth of the students complained of any one of the symptoms of CVS while working on the computer.


Regulation of competence development and sugar utilization in Haemophilus influenzae Rd by a phosphoenolpyruvate:fructose phosphotransferase system.
Changes in intracellular cAMP concentration play important roles in Haemophilus influenzae, regulating both sugar utilization and competence for natural transformation. In enteric bacteria, cAMP levels are controlled by the phosphoenolpyruvate:glycose phosphotransferase system (PTS) in response to changes in availability of the preferred sugars it transports. We have demonstrated the existence of a simple PTS in H. influenzae by several methods. We have cloned the H. influenzae ptsI gene, encoding PTS Enzyme I; genome analysis locates it in a pts operon structurally homologous to those of enteric bacteria. In vitro phosphorylation assays confirmed the presence of functional PTS components. A ptsI null mutation reduced fructose uptake to 1% of the wild-type rate, and abolished fructose fermentation even when exogenous cAMP was provided. The ptsI mutation also prevented fermentation of ribose and galactose, but utilization of these cAMP-dependent sugars was restored by addition of cAMP. In wild-type cells the non-metabolizable fructose analogue xylitol prevented fermentation of these sugars, confirming that the fructose PTS regulates cAMP levels. Development of competence under standard inducing conditions was reduced 250-fold by the ptsI mutation, unless cells were provided with exogenous cAMP. Competence is thus shown to be under direct nutritional control by a fructose-specific PTS.


Multicenter trial of desirudin for the prophylaxis of thrombosis: an alternative to heparin-based anticoagulation (DESIR-ABLE).
Desirudin, a subcutaneously (SC) administered direct thrombin inhibitor, is indicated for prevention of venous thromboembolic events (VTEs) after total joint replacement surgery. DESIR-ABLE (multicenter trial of desirudin for the prophylaxis of thrombosis: an alternative to heparin-based anticoagulation) was a multicenter, open-label, single-arm study of hospitalized patients requiring VTE protection designed to extend the safety profile for desirudin to include a broad population of perioperative/critically ill patients. The primary end point was major bleeding. A total of 516 patients undergoing major surgery (378, 73%) or who were medically ill with prolonged immobility (138, 27%) were enrolled at 19 centers and received desirudin 15 mg Q12H. Many patients had high-risk features for bleeding and thrombosis such as thrombocytopenia (<100 x 10(9)/mL, n = 50), severe obesity (body mass index >35, n = 145), and renal impairment (creatinine clearance <60 mL/min, n = 292). There were no major bleeds and no VTE-related deaths in this study. The DESIR-ABLE demonstrated the safety of desirudin in critically ill perioperative and medical patients. Trials in specific surgical or medically ill patients are needed to confirm these findings.


Tyrosine/cysteine cluster sensitizing human γD-crystallin to ultraviolet radiation-induced photoaggregation in vitro.
Ultraviolet radiation (UVR) exposure is a major risk factor for age-related cataract, a protein-aggregation disease of the human lens often involving the major proteins of the lens, the crystallins. γD-Crystallin (HγD-Crys) is abundant in the nucleus of the human lens, and its folding and aggregation have been extensively studied. Previous work showed that HγD-Crys photoaggregates in vitro upon exposure to UVA/UVB light and that its conserved tryptophans are not required for aggregation. Surprisingly, the tryptophan residues play a photoprotective role because of a distinctive energy-transfer mechanism. HγD-Crys also contains 14 tyrosine residues, 12 of which are organized as six pairs. We investigated the role of the tyrosines of HγD-Crys by replacing pairs with alanines and monitoring photoaggregation using light scattering and SDS-PAGE. Mutating both tyrosines in the Y16/Y28 pair to alanine slowed the formation of light-scattering aggregates. Further mutant studies implicated Y16 as important for photoaggregation. Mass spectrometry revealed that C18, in contact with Y16, is heavily oxidized during UVR exposure. Analysis of multiple mutant proteins by mass spectrometry suggested that Y16 and C18 likely participate in the same photochemical process. The data suggest an initial photoaggregation pathway for HγD-Crys in which excited-state Y16 interacts with C18, initiating radical polymerization.


Comparative 3-D modeling of tmRNA.
Trans-translation releases stalled ribosomes from truncated mRNAs and tags defective proteins for proteolytic degradation using transfer-messenger RNA (tmRNA). This small stable RNA represents a hybrid of tRNA- and mRNA-like domains connected by a variable number of pseudoknots. Comparative sequence analysis of tmRNAs found in bacteria, plastids, and mitochondria provides considerable insights into their secondary structures. Progress toward understanding the molecular mechanism of template switching, which constitutes an essential step in trans-translation, is hampered by our limited knowledge about the three-dimensional folding of tmRNA. To facilitate experimental testing of the molecular intricacies of trans-translation, which often require appropriately modified tmRNA derivatives, we developed a procedure for building three-dimensional models of tmRNA. Using comparative sequence analysis, phylogenetically-supported 2-D structures were obtained to serve as input for the program ERNA-3D. Motifs containing loops and turns were extracted from the known structures of other RNAs and used to improve the tmRNA models. Biologically feasible 3-D models for the entire tmRNA molecule could be obtained. The models were characterized by a functionally significant close proximity between the tRNA-like domain and the resume codon. Potential conformational changes which might lead to a more open structure of tmRNA upon binding to the ribosome are discussed. The method, described in detail for the tmRNAs of Escherichia coli, Bacillus anthracis, and Caulobacter crescentus, is applicable to every tmRNA. Improved molecular models of biological significance were obtained. These models will guide in the design of experiments and provide a better understanding of trans-translation. The comparative procedure described here for tmRNA is easily adopted for the modeling the members of other RNA families.


Patient perceptions of service quality. Combining the dimensions.
Empirically investigates, using a conjoint methodology, the importance weights given to the attributes of quality for acute care hospital services. The study shows that consumers evaluated the technical dimensions of nursing care, physician care, and outcome as more important than the accommodation functions of hospital care, and there are significant interactions among the technical dimensions. Both sets of dimensions were important and significant, but technical quality evaluations were not influenced by the perceived quality level of the affective attributes. The relative importance of these attributes were quite stable among various subgroups of past patients.


Improving biliary-enteric drainage in primary sclerosing cholangitis: experience with endoscopic methods.
Six jaundiced patients with primary sclerosing cholangitis and a dominant biliary stricture were managed by endoscopic placement of endoprostheses. Five showed considerable improvement within weeks of stenting: their serum bilirubin concentration fell from mean (range) 266 mumol/l (63-681) to 65 mumol/l (10-280) after one month. One patient required a liver transplant at five months because of continued deterioration in hepatic function. Follow up of 12-49 months in the remaining five patients shows sustained biochemical improvement, with repeat cholangiograms indicating doubling of the minimum calibre of the extrahepatic bile duct in four patients and considerable shortening of stricture length in three. Three patients developed sepsis at the time of the initial endoprosthesis insertion: surgical drainage was necessary in one. Endoscopic methods of improving biliary-enteric drainage in jaundiced patients with primary sclerosing cholangitis may be preferable to surgical and percutaneous methods, which may complicate subsequent liver transplantation.


Efficacy of Recent Emissions Controls on Road Vehicles in Europe and Implications for Public Health.
Road traffic is a major source of urban air pollution responsible for substantial premature mortality. Until recently, attention has focussed primarily on exhaust emissions of particulate matter from traffic as a causal factor. From analysis of air quality measurement data from the UK and France, we demonstrate that road traffic exhaust has a far greater impact on concentrations of nitrogen dioxide than of PM2.5. PM2.5 and carbonaceous particle concentrations have been declining appreciably since 2010/11 due to the use of diesel particle filters, but little change is seen in nitrogen dioxide over the period from 1995 to 2015. It is shown that the effect of NO2 from road traffic upon premature mortality was ten-fold greater than that of PM2.5 even before the widespread use of diesel particle filters, and is now considerably larger. The overwhelming contribution of diesel compared to gasoline-fuelled vehicles to emissions of both PM2.5 and NO2 emphasises the importance of further controls on emissions from diesels.


[Women's perceptions on intimate partner violence in Mexico].
To identify personal, cultural, and institutional factors that hinder the solution to domestic violence. In Quintana Roo, Coahuila, and Mexico City, 26 in-depth interviews with women currently suffering from intimate partner violence and others who had already found a solution were carried out, between May and November 2003. Among women's explanations to violence, it was possible to distinguish between causes (non intentional violence) and motives (intentional violence). Associated with these explanations, issues related to tolerance emerge, as well as attribution of responsibility. Moreover, the social ties of the women contribute to the acting out of gender roles and the justification or tolerance of conjugal abuse. The dominant values and norms of gender in society, shared by abused women and the community, are responsible for the perpetuation of intimate partner violence.


Intercalation of proflavine and a platinum derivative of proflavine into double-helical Poly(A).
The equilibria and kinetics of the interactions of proflavine (PR) and its platinum-containing derivative [PtCl(tmen)(2)HNC(13)H(7)(NHCH(2)CH(2))(2)](+) (PRPt) with double-stranded poly(A) have been investigated by spectrophotometry and Joule temperature-jump relaxation at ionic strength 0.1 M, 25 degrees C, and pH 5.2. Spectrophotometric measurements indicate that base-dye interactions are prevailing. T-jump experiments with polarized light showed that effects due to field-induced alignment could be neglected. Both of the investigated systems display two relaxation effects. The kinetic features of the reaction are discussed in terms of a two-step series mechanism in which a precursor complex DS(I) is formed in the fast step, which is then converted to a final complex in the slow step. The rate constants of the fast step are k(1) = (2.5 +/- 0.4) x 10(6) M(-1) s(-1), k(-1) = (2.4 +/- 0.1) x 10(3) s(-1) for poly(A)-PR and k(1) = (2.3 +/- 0.1) x 10(6) M(-1) s(-1), k(-1) = (1.6 +/- 0.2) x 10(3) s(-1) for poly(A)-PRPt. The rate constants for the slow step are k(2) = (4.5 +/- 0.5) x 10(2) s(-1), k(-2) = (1.7 +/- 0.1) x 10(2) s(-1) for poly(A)-PR and k(2) = 9.7 +/- 1.2 s(-1), k(-2) = 10.6 +/- 0.2 s(-1) for poly(A)-PRPt. Spectrophotometric measurements yield for the equilibrium constants and site size the values K = (4.5 +/- 0.1) x 10(3) M(-1), n = 1.3 +/- 0.5 for poly(A)-PR and K = (2.9 +/- 0.1) x 10(3) M(-1), n = 2.3 +/- 0.6 for poly(A)-PRPt. The values of k(1) are similar and lower than expected for diffusion-limited reactions. The values of k(-1) are similar as well. It is suggested that the formation of DS(I) involves only the proflavine residues in both systems. In contrast, the values of k(2) and k(-2) in poly(A)-PRPt are much lower than in poly(A)-PR. The results suggest that in the complex DS(II) of poly(A)-PRPt both proflavine and platinum residues are intercalated. In addition, a very slow process was detected and ascribed to the covalent binding of Pt(II) to the adenine.


[The deformation-strain state of bridgework dentures].
Holographic interferometry was used to study strained deformed status of bridge dentures. The technique of measurements with a small holographic system is described. Dentures made of Cr-Ni steel with a principally new method of crown to intermediate part adhesion were under study, as were other bridge denture designs. The findings evidence that holographic interferometry may be used as a sparing method for checking up the quality of casting and adhesion of abutment crowns and an intermediate part of fixed dentures, as well as the strength of adhesion of the facing material (porcelain, plastic) to the metal base of the denture.


Psychological attitude to self-appraisal of stoma patients: prospective observation of stoma duration effect to self-appraisal.
In recent years, many psychological problems in patients with stomas have been addressed in a number of studies. But there are only a few studies that use objective measures to take into account self-appraisal by patients with permanent or temporary stomas. The aim of this study is to compare the psychological attitude of patients with permanent and temporary stomas and to determine the most appropriate psychological supportive care. Sixty-five patients, who received a stoma between January 2009 and March 2012, were classified into two groups with either permanent or temporary stomas and were observed prospectively. We developed a questionnaire with the aid of a psychiatrist to analyze the grade of psychological attitude of self-appraisal of patients. The questionnaire was categorized into three parts; body image scale, self-esteem scale, and depression scale. Patients responded to the questionnaire 4 weeks after the operation and the answers of each group were compared. Out of 65 patients, 42 received temporary stomas and 23 received permanent stomas. There was no significant mean difference between permanent and temporary stoma patients in the body image scale, the self-esteem scale, and the depression scale. However, patients with a permanent stoma tended to have a worse body image and lower self-esteem on some specific items within the questionnaires. Patients with stomas have negative attitudes toward themselves and some meaningful differences were found between different types of stoma applied. Surgeons should be concerned about postoperative psychological support for patients with stomas.


[Experimental rationale and clinical evaluation of perichondroplasty used in surgery for tuberculosis and nonspecific joint diseases].
Experiments on 77 rabbits studied the specific features of chondrogenesis during different grafting modifications for the perichondrium. The latter was found to have a high chondroplastic potential. The factors predisposing to cartilaginification and inhibiting this process were identified. Experimental positive results of perichondrial arthroplasty, in tuberculous arthritis as well, were achieved. By taking into account the experimental data, original methods for reparative operations used in patients with tuberculosis and nonspecific diseases of the joints were developed in the clinical setting. Their use in 12 patients yielded positive results, suggesting that the above methods are promising and their further study is advisable.


Longitudinal fractures of the condyles of the third metacarpal and metatarsal bones in racehorses: 224 cases (1986-1995).
To determine type, distribution, and radiographic appearance of condylar fractures of the third metacarpal bone (MC-3) or third metatarsal bone (MT-3) in Thoroughbreds (TB), Standardbreds (SB), and Arabians, to assess long-term outcome of horses in which fractures were repaired surgically, and to identify variables associated with prognosis for return to racing. Retrospective study. 224 horses with 233 fractures. Medical records and radiographs obtained before and after treatment were reviewed. Racing performance before and after treatment was determined by reviewing race records. TB were overrepresented and SB were underrepresented, compared with the hospital population. Thoroughbreds had significantly more lateral condylar fractures and significantly more forelimb fractures than did SB. Thoroughbreds were less likely to race after treatment if they had complete, rather than incomplete, lateral condylar fracture or had concurrent proximal sesamoid bone fracture. Convalescent time for TB with medial condylar fractures of MT-3 was significantly longer than that for TB with lateral condylar fractures of MT-3. Horses with condylar fractures of MC-3 and MT-3 that had minimal pathologic changes in the involved joint had a favorable prognosis for returning to racing after surgical treatment. Prognosis for horses with complete condylar fractures, particularly those with substantial pathologic changes in the involved joint, was worse.


[The "cost reimbursement" trial regulation in mandatory health insurance: results of a survey of participants].
Since 1994 seven substitution funds of the German statutory health insurance have offered their mandatorily insured members to choose cost reimbursement in place of benefits in kind for a limited testing period. Participants of the cost reimbursement arrangement are considered private patients and are billed accordingly. However, these bills are only in part reimbursed. This study investigates the expectations participants had with respect to the cost reimbursement arrangement as well as the experiences they made. For this purpose a survey among the participants was carried out using a self-administered questionnaire. Most of the 1390 respondents were satisfied with the cost reimbursement arrangement. Organisational, personal and medical advantages which the majority of participants expected were mostly fulfilled. Especially elderly members chose the cost reimbursement arrangement and often made the experience that their doctors spent more time talking to them. The necessary co-payments had hardly any impact on the positive judgment; most participants had an extra private insurance to close the gap of coverage. The results also show that transparency, control of costs and cost-consciousness of patients are improved by the cost reimbursement method. With respect to the preferences of the insured, the results of this study plead for keeping up the offer of cost reimbursement as an alternative to benefits in kind. However, the influence of sickness funds on the care process as well as the equity of care may be negatively affected.


Orthopaedic trauma clinical research: is 2-year follow-up necessary? Results from a longitudinal study of severe lower extremity trauma.
The ideal length of follow-up for orthopedic trauma research studies is unknown. This study compares 1- and 2-year complications, clinical recovery, and functional outcomes from a large prospective clinical study. Patients (n = 336) with limb threatening unilateral lower extremity injuries were followed at the 12, 24, and 84 months. Major outcomes observed were complications requiring hospital re-admission, fracture and wound healing, attainment of full weight bearing status, return to work, and self-reported functional outcome using the Sickness Impact Profile. The rate of newly observed complications beyond year 1 was small, ranging from 0 to <2%. In addition, 85% to 90% of the clinical recovery outcomes were attained by 1 year, and patients not achieving clinical recovery during the first year had significantly worse functional outcomes. Only 5% of patients returned to work between 1 year and 2 years. Although, a substantial number of patients achieved functional recovery between 1 year and 2 years, of the patients not achieving functional recovery at year 1, 85% of those who would go on to achieve functional recovery during the second year could be predicted using year 1 data. Although long-term follow-up provides a more complete picture of final outcomes and rate of recovery, follow-up beyond 1 year is difficult and expensive. In our study, it accounted for 20% of the total cost. The analysis of our data suggests that 1-year data were sufficient to address our major study hypotheses.


Modern electronic and chemical thermometers used in the axilla are inaccurate.
Rectal and axillary temperatures were measured simultaneously in 83 children using three different thermometer devices providing 166 pairs of results. In the first series consisting of 22 febrile children (44 measurements) and 20 afebrile children (40 measurements), the rectal mercury measurement was compared to an axillary mercury and axillary Tempa-DOT thermometer. The axillary mercury had sensitivity of 14/22 (64%) and specificity of 20/20 (100%) while the Tempa-DOT had sensitivity of 15/22 (68%) and specificity of 19/20 (95%). In the second series comprising 21 febrile children (42 measurements) and 20 afebrile children (40 measurements) the axillary mercury had sensitivity of 11/21 (52%) and specificity of 20/20 (100%) while the electronic thermometer had sensitivity of 10/21 (48%) and specificity of 20/20 (100%). Regardless of the thermometer used, the axilla is a poor alternative to rectal measurements in the diagnosis of fever. Mercury-free thermometers, when used in the axilla are as poor alternatives to rectal measurements as mercury-in-glass thermometers.