Epidemiology of renal stones in a middle-aged male population.
The natural history of upper urinary tract stones has been studied retrospectively in 49-50 year-old men in an urban population. The prevalence of stones in 2322 men was found to be 13.7%, with the highest incidence of onset of the disease during fifth decade. Recurrences had occurred in 42% of all cases, the frequency increasing with observation time. On some occasion 23% of the patients had been admitted to hospital and 12.3% had been operated on, 94.5% of all stones passed spontaneously. A family history of kidney stones was significantly more common in stone patients than in healthy controls, and patients with a family history of stones were more prone to early and repeated recurrences. It is suggested that the raised incidence of stone disease in some families may be attributed to environmental rather than genetic factors. This could be of importance for prophylaxis. Analysis of hospital admission rates supported previous findings of a steady rise in stone incidence. The advantages of population studies for comparative analyses are pointed out.


Total synthesis and antimicrobial activity of +/--laurelliptinhexadecan-1-one and +/--laurelliptinoctadecan-1-one.
The structures previously assigned to (+)-laurelliptinhexadecan-1-one (1a) and (+)-laurelliptinoctadecan-1-one (1b) from Cocculus orbiculatus (L.) DC. (Menispermaceae) have been confirmed by total synthesis of the racemic alkaloids. The key step of the synthesis involved formation of ring C of the aporphines by a radical-intiated cyclisation. Both (+/-)-laurelliptinhexadecan-1-one (1a) and (+/-)-laurelliptinoctadecan-1-one (1b) were inactive against Staphylococcus aureus ATCC25932, Escherichia coli ATCC10536 and Candida albicans ATCC90028.


An antisense oligonucleotide targeting the growth hormone receptor inhibits neovascularization in a mouse model of retinopathy.
We have demonstrated that a 2'-O-methoxyethyl modified antisense oligonucleotide against the mouse growth hormone (GH) receptor (GHr) reduces GH binding and serum insulin-like growth factor-1 in normal mice. We tested whether this systemically delivered antisense oligonucleotide could inhibit neovascularization in mice with oxygen induced retinopathy (OIR). OIR was induced in C57BL/6 mice by housing them in 75% oxygen across postnatal days (P)7 to 12 followed by five days in room air. Shams were in room air from P0-17. GHr antisense oligonucleotide, ATL 227446, was administered by early (P7, 8, 9, 11, 13, 15, and 17) or late (P12-16) intervention at doses of 5, 10, 20, and 30 mg/kg. Other mice were treated with either vehicle (saline), the somatostatin analog octreotide (20 mg/kg/bi-daily), or control oligonucleotides ATL 261303 (at 20 mg/kg by late and early intervention) or ATL 260120 (at 20 and 30 mg/kg by early intervention only). Blood vessel profiles were counted in 3 mm paraffin sections of inner retina. OIR increased blood vessel profiles by 2.5 fold compared to shams. In OIR, early intervention GHr antisense oligonucleotide ATL 227446 reduced blood vessel profiles at higher doses including 10 mg/kg, and 30 mg/kg resulted in the greatest reduction (38%). In OIR, late intervention with all doses of GHr antisense oligonucleotide ATL 227446 reduced blood vessel profiles to a similar extent, and the highest dose resulted in a 26% reduction compared to OIR. Octreotide reduced blood vessel profiles in OIR mice by 26%. In OIR, ATL 261303 had no effect on blood vessel profiles, while 30 mg/kg ATL 260120 reduced blood vessel profiles by 18%. Systemically delivered antisense oligonucleotides directed against the GHr are a potential novel treatment for ocular neovascularization related disorders.


Cardiac Imaging and Management of Prosthetic Valve Candida Parapsilosis Endocarditis.
Fungal infective endocarditis is a rare and serious form of endocarditis associated with severe morbidity and mortality. The greatest propensity for infection can be found in patients with implanted prosthetic valves, implanted cardiac devices, and intravenous drug use. We present a case of a 45-year-old male with a prior bioprosthetic mitral valve who was diagnosed with Candida parapsilosis endocarditis. Computed tomography imaging of the abdomen was significant for splenic infarcts, and transesophageal echocardiography demonstrated a 1.23 cm x 0.55 cm lesion and 1.02 cm x 0.545 cm lesion on the bioprosthetic valve. The patient was subsequently treated with Amphotericin B and life-long Fluconazole. This case highlights the imaging findings and treatment of a rare disease process.


Medical marijuana laws and workplace fatalities in the United States.
The aim of this research was to determine the association between legalizing medical marijuana and workplace fatalities. Repeated cross-sectional data on workplace fatalities at the state-year level were analyzed using a multivariate Poisson regression. To date, 29 states and the District of Columbia have legalized the use of marijuana for medicinal purposes. Although there is increasing concern that legalizing medical marijuana will make workplaces more dangerous, little is known about the relationship between medical marijuana laws (MMLs) and workplace fatalities. All 50 states and the District of Columbia for the period 1992-2015. Workplace fatalities by state and year were obtained from the Bureau of Labor Statistics. Regression models were adjusted for state demographics, the unemployment rate, state fixed effects, and year fixed effects. Legalizing medical marijuana was associated with a 19.5% reduction in the expected number of workplace fatalities among workers aged 25-44 (incident rate ratio [IRR], 0.805; 95% CI, .662-.979). The association between legalizing medical marijuana and workplace fatalities among workers aged 16-24, although negative, was not statistically significant at conventional levels. The association between legalizing medical marijuana and workplace fatalities among workers aged 25-44 grew stronger over time. Five years after coming into effect, MMLs were associated with a 33.7% reduction in the expected number of workplace fatalities (IRR, 0.663; 95% CI, .482-.912). MMLs that listed pain as a qualifying condition or allowed collective cultivation were associated with larger reductions in fatalities among workers aged 25-44 than those that did not. The results provide evidence that legalizing medical marijuana improved workplace safety for workers aged 25-44. Further investigation is required to determine whether this result is attributable to reductions in the consumption of alcohol and other substances that impair cognitive function, memory, and motor skills.


Dehalogenation of iodinated X-ray contrast media in a bioelectrochemical system.
Iodinated X-ray contrast media (ICM) are only to a limited extent removed from conventional wastewater treatment plants, due to their high recalcitrance. This work reports on the cathodic dehalogenation of the ICM iopromide in a bioelectrochemical system (BES), fed with acetate at the anode and iopromide at the cathode. When the granular graphite cathode potential was decreased from -500 to -850 mV vs standard hydrogen electrode (SHE), the iopromide removal and the iodide release rates increased from 0 to 4.62 ± 0.01 mmol m(-3) TCC d(-1) and 0 to 13.4 ± 0.16 mmol m(-3) TCC d(-1) (Total Cathodic Compartment, TCC) respectively. Correspondingly, the power consumption increased from 0.4 ± 1 to 20.5 ± 3.3 W m(-3) TCC. The Coulombic efficiency of the iopromide dehalogenation at the cathode was less than 1%, while the Coulombic efficiency of the acetate oxidation at the anode was lower than 50% at various granular graphite cathode potentials. The results suggest that iopromide could be completely dehalogenated in BESs when the granular graphite cathode potential was controlled at -800 mV vs SHE or lower. This finding was further confirmed using mass spectrometry to identify the dehalogenated intermediates and products of iopromide in BESs. Kinetic analysis indicates that iopromide dehalogenation in batch experiments can be described by a first-order model at various cathode potentials. This work demonstrates that the BESs have a potential for efficient dehalogenation of ICM from wastewater or environmental streams.


Context Is Everything: Harmonization of Critical Food Microbiology Descriptors and Metadata for Improved Food Safety and Surveillance.
Globalization of food networks increases opportunities for the spread of foodborne pathogens beyond borders and jurisdictions. High resolution whole-genome sequencing (WGS) subtyping of pathogens promises to vastly improve our ability to track and control foodborne disease, but to do so it must be combined with epidemiological, clinical, laboratory and other health care data (called "contextual data") to be meaningfully interpreted for regulatory and health interventions, outbreak investigation, and risk assessment. However, current multi-jurisdictional pathogen surveillance and investigation efforts are complicated by time-consuming data re-entry, curation and integration of contextual information owing to a lack of interoperable standards and inconsistent reporting. A solution to these challenges is the use of 'ontologies' - hierarchies of well-defined and standardized vocabularies interconnected by logical relationships. Terms are specified by universal IDs enabling integration into highly regulated areas and multi-sector sharing (e.g., food and water microbiology with the veterinary sector). Institution-specific terms can be mapped to a given standard at different levels of granularity, maximizing comparability of contextual information according to jurisdictional policies. Fit-for-purpose ontologies provide contextual information with the auditability required for food safety laboratory accreditation. Our research efforts include the development of a Genomic Epidemiology Ontology (GenEpiO), and Food Ontology (FoodOn) that harmonize important laboratory, clinical and epidemiological data fields, as well as existing food resources. These efforts are supported by a global consortium of researchers and stakeholders worldwide. Since foodborne diseases do not respect international borders, uptake of such vocabularies will be crucial for multi-jurisdictional interpretation of WGS results and data sharing.


The hydrodynamics of DNA electrophoretic stretch and relaxation in a polymer solution.
Theories of DNA electrophoretic separations generally treat the DNA as a free draining polymer moving in an electric field at a rate that depends on the effective charge density of the molecule. Separations can occur in sieving media ranging from ultradilute polymer solutions to tightly cross-linked gels. It has recently been shown that DNA is not free-draining when both electric and nonelectric forces simultaneously act on the molecule, as occurs when DNA collides with a polymer during electrophoretic separations. Here we show that a semidilute polymer solution screens the hydrodynamic interaction that results from the application of these forces. Fluorescently labeled DNA tethered at one end in a semidilute solution of hydroxyl-ethyl cellulose stretch more in an electric field than they stretch in free solution, and approach free-draining behavior. The steady stretching behavior is predicted without adjustable parameters by a theory developed by Stigter using a hydrodynamic screening length found from effective medium theory. Data on the relaxation of stretched molecules after the electric field is removed agree with the Rouse model prediction, which neglects hydrodynamic interactions. The slowest relaxation time constant, tau(R), scales with chain length as tau(R) approximately L(1.9+/-0.17) when analyzed by the data collapse method, and as tau(R) approximately L(2.17+/-0.17) when analyzed by multiexponential fit.


Neutrophil-to-lymphocyte ratio as a potential biomarker in predicting influenza susceptibility.
Human population exposed to influenza viruses exhibited wide variation in susceptibility. The ratio of neutrophils to lymphocytes (NLR) has been examined to be a marker of systemic inflammation. We sought to investigate the relationship between influenza susceptibility and the NLR taken before influenza virus infection. We investigated blood samples from five independent influenza challenge cohorts prior to influenza inoculation at the cellular level by using digital cytometry. We used multi-cohort gene expression analysis to compare the NLR between the symptomatic infected (SI) and asymptomatic uninfected (AU) subjects. We then used a network analysis approach to identify host factors associated with NLR and influenza susceptibility. The baseline NLR was significantly higher in the SI group in both discovery and validation cohorts. The NLR achieved an AUC of 0.724 on the H3N2 data, and 0.736 on the H1N1 data in predicting influenza susceptibility. We identified four key modules that were not only significantly correlated with the baseline NLR, but also differentially expressed between the SI and AU groups. Genes within these four modules were enriched in pathways involved in B cell-mediated immune responses, cellular metabolism, cell cycle, and signal transduction, respectively. This study identified the NLR as a potential biomarker for predicting disease susceptibility to symptomatic influenza. An elevated NLR was detected in susceptible hosts, who may have defects in B cell-mediated immunity or impaired function in cellular metabolism, cell cycle or signal transduction. Our work can serve as a comparative model to provide insights into the COVID-19 susceptibility.


The Effect of Route of Administration and Vehicle on the Pharmacokinetics of THC and CBD in Adult, Neonate, and Breastfed Sprague-Dawley Rats.
Introduction: Basic pharmacokinetic (PK) and pharmacodynamic models of the phytocannabinoids Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are critical for developing translational models of exposure and toxicity. The neonatal period is a particularly important time to study the effects of cannabinoids, yet there are few studies of cannabinoid PKs by different routes such as direct injection or breast milk ingestion. To study this question, we have developed a translationally relevant rodent model of perinatal cannabinoid administration by measuring plasma levels of THC and CBD after different routes and preparations of these drugs. Materials and Methods: Adult animals and pups were injected with THC or CBD either intraperitoneally or subcutaneously, and plasma was analyzed by liquid chromatography-tandem mass spectrometry to measure cannabinoid levels collected at specified intervals. We also tested the effect of preparation of the drug using an oil-based vehicle (sesame oil) and an aqueous vehicle (Tween). Finally, we measured the plasma levels of cannabinoids in neonatal pups that were transmitted through breast milk after intraperitoneal injection to nursing dams. Results: We observed differences in the PK profiles of cannabinoids in adults and neonatal pups that were dependent on the route of administration and type of vehicle. Cannabinoids prepared in aqueous vehicle, injected intraperitoneally, resulted in a high peak in plasma concentration, which rapidly decreased. In contrast, subcutaneous injections using sesame oil as a vehicle resulted in a slow rise and low plateau in plasma concentration. Intraperitoneal injections with sesame oil as a vehicle resulted in a slower rise compared with aqueous vehicle, but an earlier and higher peak compared with subcutaneous injection. Finally, the levels of THC and CBD that were similar to direct subcutaneous injections were measured in the plasma of pups nursing from intraperitoneally injected dams. Conclusions: The route of administration and the preparation of the drug have important and significant effects on the PK profiles of THC and CBD in rats. These results can be used to create different clinically relevant exposure paradigms in pups and adults, such as short high-dose exposure or a low-chronic exposure, each of which might have significant and varying effects on development.


Sn-centred icosahedral Rh carbonyl clusters: synthesis and structural characterization and 13C-{103Rh} HMQC NMR studies.
The reaction of [Rh7(CO)16]3- with SnCl(2).2H2O in a 1 : 1 molar ratio under N2 results in the formation of the new heterometallic cluster, [Rh12Sn(CO)27]4-, in very high yield (ca. 86%). Further controlled additions of SnCl(2).2H2O, or solutions of HCl, or [RhCl(COD)]2, give [Rh12(mu-Cl)2Sn(CO)23]4-. Similarly, addition of HBr to [Rh12Sn(CO)27]4- gives the related cluster [Rh12(mu-Br)2Sn(CO)23]4-. Notably, if the addition of SnCl(2).2H2O to [Rh12Sn(CO)27]4- is carried out under a CO atmosphere, the reaction takes a different course and leads to the formation of the new cluster, [Rh12Sn(mu3-RhCl)(CO)27]4-. All the above clusters have been shown by single-crystal X-ray diffraction studies to have a metal framework based on an icosahedron, which is centred by the unique Sn atom. Their chemical reactivity and 13C-{103Rh} HMQC NMR spectroscopic characterization are also reported.


Bayesian phylogeny of sucrose transporters: ancient origins, differential expansion and convergent evolution in monocots and dicots.
Sucrose transporters (SUTs) are essential for the export and efficient movement of sucrose from source leaves to sink organs in plants. The angiosperm SUT family was previously classified into three or four distinct groups, Types I, II (subgroup IIB), and III, with dicot-specific Type I and monocot-specific Type IIB functioning in phloem loading. To shed light on the underlying drivers of SUT evolution, Bayesian phylogenetic inference was undertaken using 41 sequenced plant genomes, including seven basal lineages at key evolutionary junctures. Our analysis supports four phylogenetically and structurally distinct SUT subfamilies, originating from two ancient groups (AG1 and AG2) that diverged early during terrestrial colonization. In both AG1 and AG2, multiple intron acquisition events in the progenitor vascular plant established the gene structures of modern SUTs. Tonoplastic Type III and plasmalemmal Type II represent evolutionarily conserved descendants of AG1 and AG2, respectively. Type I and Type IIB were previously thought to evolve after the dicot-monocot split. We show, however, that divergence of Type I from Type III SUT predated basal angiosperms, likely associated with evolution of vascular cambium and phloem transport. Type I SUT was subsequently lost in monocots along with vascular cambium, and independent evolution of Type IIB coincided with modified monocot vasculature. Both Type I and Type IIB underwent lineage-specific expansion. In multiple unrelated taxa, the newly-derived SUTs exhibit biased expression in reproductive tissues, suggesting a functional link between phloem loading and reproductive fitness. Convergent evolution of Type I and Type IIB for SUT function in phloem loading and reproductive organs supports the idea that differential vascular development in dicots and monocots is a strong driver for SUT family evolution in angiosperms.


Marine protected communities against biological invasions: A case study from an offshore island.
Biological invasions are a major threat to the world's biota and are considered a major cause of biodiversity loss. Therefore, world marine policy has recognized the need for more marine protected areas (MPAs) as a major tool for biodiversity conservation. The present work experimentally evaluated how protected communities from an offshore island can face the settlement and/or expansion of nonindigenous species (NIS). First, NIS colonization success in marine protected and marina communities was compared by deploying PVC settling plates at the Garajau MPA and Funchal marina (SW Madeira Island). Then, the settling plates from the MPA were transferred to Funchal marina to test their resistance to NIS invasion under high levels of NIS pressure. Results indicated that the structure and composition of fouling communities from the MPA differed from those collected in the marina. Interestingly, communities from the protected area showed lower NIS colonization success, suggesting some degree of biotic resistance against NIS invasion.


Use of a Cross-Sectional Survey in the Adult Population to Characterize Persons at High-Risk for Chronic Obstructive Pulmonary Disease.
Rationale/Objective: The Behavioral Risk Factor Surveillance System (BRFSS) health survey has been used to describe the epidemiology of chronic obstructive pulmonary disease (COPD) in the US. Through addressing respiratory symptoms and tobacco use, it could also be used to characterize COPD risk. Four US states added questions to the 2015 BRFSS regarding productive cough, shortness of breath, dyspnea on exertion, and tobacco duration. We determined COPD risk categories: provider-diagnosed COPD as self-report, high-risk for COPD as ≥10 years tobacco smoking and at least one significant respiratory symptom, and low risk was neither diagnosed COPD nor high risk. Disease burden was defined by respiratory symptoms and health impairments. Data were analyzed using multiple logistic regression models with age as a covariate. Among 35,722 adults ≥18 years, the overall prevalence of COPD and high-risk for COPD were 6.6% and 5.1%. Differences among COPD risk groups were evident based on gender, race, age, geography, tobacco use, health impairments, and respiratory symptoms. Risk for disease was seen early where 3.75% of 25⁻34 years-old met high-risk criteria. Longer tobacco duration was associated with an increased prevalence of COPD, particularly >20 years. Seventy-nine percent of persons ≥45 years-old with frequent shortness of breath (SOB) reported having or being at risk of COPD, reflecting disease burden. These data, representing nearly 18% of US adults, indicates those at high risk for COPD share many, but not all of the characteristics of persons diagnosed with the disease and demonstrates the value of the BRFSS as a tool to define lung health at a population level.


[The comparative analysis of medical demographic situation in the Uralskii economic district].
The evaluation of medical demographic situation in Kurganskaia, Chelyabinskaia and Orenburgskaia oblasts of the Uralskii economic district was implemented. On the territory of all studied subjects dynamics of decreasing of population size is observed. The evaluation of number of divorces per 1 000 marriages established tendency of increasing of number of divorces in all mentioned oblasts. During examined period, level of morbidity increased in the Kurganskaia and Chelyabinskaia oblasts and decreased in the Orenburgskaia oblast. In 2015 the leading cause of mortality ofpopulation of able-bodied age was external factors in the Chelyabinskaia and Kurganskaia oblasts and diseases of blood circulation system in the Orenburgskaia oblast.


A case of symptomatic granular cell tumor of the sellar region with large calcification.
We report here a rare case of symptomatic granular cell tumor (GCT) of the sellar region with a large calcification. A 70-year-old woman presented with a sellar mass, accompanied by bitemporal hemianopia. The patient was diagnosed preoperatively as having a craniopharyngioma or a pituitary adenoma, because of the large calcification. The patient underwent surgical tumor resection via endoscopic trans-sphenoidal surgery and was diagnosed pathologically as having GCT. The patient's postoperative course was uneventful and her visual field disturbance improved soon after the operation. We briefly discuss the pathological discrimination of GCT and other sellar tumors, since there are many unclear points concerning this rare tumor.


Comparing genome scans among species of the stickleback order reveals three different patterns of genetic diversity.
Comparing genome scans among species is a powerful approach for investigating the patterns left by evolutionary processes. In particular, this offers a way to detect candidate genes that drive convergent evolution. We compared genome scan results to investigate if patterns of genetic diversity and divergence are shared among divergent species within the stickleback order (Gasterosteiformes): the threespine stickleback (Gasterosteus aculeatus), ninespine stickleback (Pungitius pungitus), and tubesnout (Aulorhynchus flavidus). Populations were sampled from the southern and northern edges of each species' range, to identify patterns associated with latitudinal changes in genetic diversity. Weak correlations in genetic diversity (F ST and expected heterozygosity) and three different patterns in the genomic landscape were found among these species. Additionally, no candidate genes for convergent evolution were detected. This is a counterexample to the growing number of studies that have shown overlapping genetic patterns, demonstrating that genome scan comparisons can be noisy due to the effects of several interacting evolutionary forces.


Nursing as vocation.
In this article the author argues that nursing is best understood as a vocational occupation. Using Blum's model of vocations it is argued that such occupations are socially expressed within practices embodying traditions, norms and a range of meanings: industrial, social, personal and moral. Vocational workers are those who identify in certain ways with these traditions, norms and meanings. One problem with the vocational model, as it has historically applied to nursing, is that it has been articulated through concepts of motherhood. Nursing was a vocation precisely because the character of the nurse was identified as feminine. The author argues that the vocational model for nursing can be conceptually disentangled from its identification with ideals of motherhood and femininity. It is nursing work and the identification with the moral and social meaning of nursing that give nursing its vocational status, not the feminized character of the nurse.


Role of equilibrium associations on the hydrogen atom transfer from the triethylborane-methanol complex.
The triethylborane-methanol system used in radical deoxygenation and dehalogenation processes has been investigated. Unambiguous evidence for the formation of a complex between triethylborane and methanol is provided. It was shown that the complexation process is exothermic (ΔH° ≈ -7.6 kcal mol(-1)) while being entropically disfavored (ΔS° ≈ -24 cal mol(-1) K(-1)). This study demonstrates that only very small quantities of complex (1-2%) are present in most of the reported conditions used in dehalogenation and deoxygenation processes. Recalculating the rate constant for the hydrogen transfer to a secondary alkyl radical with this concentration suggests a value in the 10(6) M(-1) s(-1) range for the complex itself, indicating a much more important activation of the O-H bond than previously thought. The importance of solvent effects is also highlighted. The formation of a larger amount of complex by the addition of methanol is accompanied by its deactivation via hydrogen bonding. These observations open new opportunitites for the future preparation of more effective hydrogen atom donors involving borane complexes.


Study of external low irradiation dose effects on induction of chromosome aberrations in Pisum sativum root tip meristem.
The effects of low doses of ionizing radiation have been a matter of important debate over the last few years. The point of discussion concerns the validity of the linear dose-response extrapolation for low doses, used by international organizations, to establish radio-protection norms. Here, we contributed to this discussion by investigating the induction of chromosome aberrations by low to moderate doses ranging from 0 to 10 Gy in root meristem cells of 6-day-old Pisum plantlets. After acute irradiation of plantlets by a (60)Co source, the percentage of root tip meristem cells displaying chromosome aberrations was estimated immediately after irradiation and after 20 h recovery time. The dose-effect curves show non-linear responses, especially in the low dose range (0- 1 Gy), which is of particular interest. After 20 h of recovery, a steep increase of aberrations was observed for cells exposed to 0.4 Gy, followed by a plateau for doses until 1 Gy. There was an irradiation effect on plant growth during the first and second generations, showing the persistence of cell division anomalies as a long term effect of acute irradiation. This result suggests the induction of a genomic instability. Our results, in agreement with some obtained in animals, show rather non-linear dose-effect responses, with notably higher biological effects of low doses than expected.


The Quality of My Life questionnaire: the minimal clinically important difference for pediatric rheumatology patients.
To determine parent-child agreement for the Quality of My Life (QoML) questionnaire. To establish construct validity of the QoML questionnaire. To determine the minimal clinically important difference (MCID) for the Quality of Life (QOL) and Health-Related Quality of Life (HRQOL) scales. A total of 136 families of children with inflammatory arthritis were interviewed. The QoML questionnaire was completed for the child's current state of health, and under 2 hypothetical scenarios, where (1) there is a hypothetical small improvement, and (2) there is a hypothetical small deterioration in health. The differences between the original QOL and HRQOL scores and hypothetical improvement and deterioration scores, respectively, were calculated to give MCID scores. In total, 131 families completed the questionnaires. Intraclass correlation coefficients for parent proxy report and patient self-report of the QOL and HRQOL were 0.63 and 0.40, respectively. Correlations of QOL with pain and disease severity were moderately negative (r = -0.55 and -0.56, respectively, p < 0.0001). Correlations of HRQOL with pain and disease severity were strongly negative (r = -0.66 and r = -0.68, respectively, p < 0.0001). The MCID for improvement on the QOL was 7 mm, and for the HRQOL 11 mm. The MCID for deterioration in QOL was -33 mm, and for HRQOL -38 mm. The QoML questionnaire demonstrated fair parent-child agreement and good convergent construct validity. MCID scores will enable clinicians to interpret QoML questionnaire results in a clinically meaningful way.


[Hibernoma of the forearm].
Hibernomas are rare benign tumours originating from the brown fat found in the foetus and animals that hibernate. In most cases they present as a slowly growing painful mass situated in those regions where this type of fat persists in the adult. We report a case of hibernoma of the forearm, which is an unusual localization, and we review the diagnostic and therapeutic aspects of this of tumour whose main differential diagnosis is liposarcoma.


[Biomechanical and clinical interpretation of firearm wounds. General problems. VI. Propedeutic ABC of terminal ballistics].
Any lengthy and properly structured propedeutic ABC of terminal ballistics must necessarily embrace a comparison between the two main protagonists of gunshot wounds. It is almost a specular, yet distorted image of the ritual act consumed by the larger mammals, not proud of their mutual aggression, but the conformation between mechanics and biology, or between kilogram-metres and life. The two types of physical entity brought together through the unique agency of a new language--both biological and mechanical, but necessarily halting and inadequate--stand out like two parallel lines opposite one another, displaying their respective profiles and most intimate structures. One can take this as far as the biological paradox of the clash between the dimension of power and the chance quality of life.


Clinical and pathological significance of myeloid differentiation factor 88 expression in human hepatocellular carcinoma tissues.
The innate immune system, which includes toll-like receptor (TLR) signaling, plays an important role in inflammation and oncogenesis. Although TLR common adaptor myeloid differentiation factor 88 (MyD88) is known to have multiple effects on carcinogenesis, the role of MyD88 in hepatocarcinogenesis remains unknown. In this study, MyD88 expression was examined in 105 samples of human hepatocellular carcinoma (HCC) tissue by immunohistochemistry, Western blot, and quantitative reverse-transcriptase polymerase chain reaction methods. The relationships between MyD88 expression and clinical and pathological parameters were analyzed. The results showed that attenuated expression of MyD88 in HCC tissue tumor cells was significantly related to hepatitis B virus infection, large tumor size, positive vascular invasion, and intrahepatic metastasis (P < 0.05). Western blot analysis of MyD88 protein in nine normal livers and 28 HCCs showed gender disparity (P < 0.01, P < 0.05), and attenuated expression in cirrhotic livers (P < 0.05). Low expression of MyD88 mRNA was evident in HCCs with vascular invasion (P < 0.01). In contrast to previous reports, these results suggest that attenuated expression of MyD88 in HCC is associated with tumor progression.


Transient carcinoembryonic antigen (CEA) elevations following resection of colorectal cancer: a limitation in the use of serial CEA levels as an indicator for second-look surgery.
In a previous study, other investigators recommended second-look surgery for colorectal cancer primarily on the basis of plasma carcinoembryonic antigen (CEA) rises and prepared a nomogram for ready recognition of these "significant" increases. We found 25 patients whose CEA levels met the recommended criteria for significance; however, in 9 of these patients the rises were transient. Eight had no clinical evidence of recurrent cancer and they might have had negative second-look surgery had this been done because of CEA rises alone. The use of the CEA nomogram merely eliminated laboratory variation as a cause of the CEA rise. It did not, however, rule out biologic causes of CEA rises, other than that of cancer, especially benign liver disease. We were unable to differentiate benign from malignant rises on the basis of CEA changes alone. Preoperative CEA values helped to separate the two rises. Transient rises usually began earlier. Malignant CEA rises were more likely to be exponential. The rate of rise alone did not discriminate between the two rises. Thus, although serial CEA levels were helpful in making the decision for reexploration, they did not substitute for complete clinical assessment.


High expression of long non-coding RNA CCAT2 indicates poor prognosis of gastric cancer and promotes cell proliferation and invasion.
Numerous studies have demonstrated that long non-coding RNAs (lncRNAs) have many biological functions and play crucial roles in various human cancers, including cancer development, metastasis and prognosis of cancer patients. CCAT2, a novel long non-coding RNA, has been identified as correlating with several different types of cancers. However, the role of lncRNA CCAT2 in gastric cancer (GC) patients is unknown. The purpose of our research was to investigate the function and prognostic significance of lncRNA CCAT2 expression in GC patients. Expression of lncRNA CCAT2 was examined in 208 paired normal and cancerous gastric tissues. Molecular and cellular techniques were used to explore the biological function of lncRNA CCAT2 in GC cells. Kaplan-Meier method and Cox proportional hazards model were used to analyze the prognostic significance of lncRNA CCAT2 expression. The results showed that lncRNA CCAT2 was upregulated in GC tissues (P=0.000), and positively correlated with TNM stage (P=0.029), lymphatic invasion (P=0.042) and nervous invasion (P=0.024) in GC patients. Furthermore, we also found that high expression of lncRNA CCAT2 was an unfavorable prognostic factor in GC patients. Silencing of lncRNA CCAT2 inhibits gastric cancer cell proliferation and invasion. lncRNA CCAT2 may serve as a tumor promoter and a new predictive prognostic factor for human gastric cancer.


Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury.
The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H2S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H2S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12 ml/kg for 6 h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H2S. In addition, phosphorylation of the signaling protein Akt was induced by H2S. In contrast, inhibition of Akt by LY294002 during ventilation reestablished lung damage, neutrophil influx, and proinflammatory cytokine release despite the presence of H2S. Moreover, the ability of H2S to induce the antioxidant glutathione and to prevent ROS production was reversed in the presence of the Akt inhibitor. Here, we provide the first evidence that H2S-mediated Akt activation is a key step in protection against VILI, suggesting that Akt signaling limits not only inflammatory but also detrimental oxidative processes that promote the development of lung injury.


Comparison between wavefront-derived refraction and auto-refraction.
This study aimed to compare objective refractive errors and keratometry measurements obtained using the Nidek OPD-Scan II aberrometer/topographer and Topcon KR 8900 autorefractokeratometer. The right eye medical records of 176 patients aged 18-35 years who were admitted to our clinic as refractive surgery candidates were tested for refractive status and keratometry measurements with a Nidek OPD-Scan II aberrometer/topographer and a standard table-top autorefractokeratometer (Topcon KR 8900) before and after the induction of cycloplegia. Patients who had undergone any eye surgery and had hereditary, ectatic, or acquired corneal pathology were excluded. Refractive data were compared as spheres, cylinders, spherical equivalents, and power vectors before and after the induction of cycloplegia. Flat and steep keratometry (K1-K2) readings were recorded in diopters (D) and axis degrees, respectively, for each eye. The spherical, cylindrical, spherical equivalence, J0-J45 vector values and K1-K2 readings (D, axis) between the two devices were statistically significant before and after the induction of cycloplegia (p<0.05). Bland-Altman analysis identified mean differences (95%CI of limits of agreement) of 0.77 (-0,57 to 2,11) in sphere, 0.74 (-0,54 to 2,01) in spherical equivalent, -0,07 (-0,41 to 0,26) in J0 vector, 0,06 (-0,31 to 0,43) in J45 vector, -0,16 (-0,66 to 0,33) in K1, -0,23 (-0,79 to 0,33) in K2 values before induction of cycloplegia. The refractive and keratometry results of the Nidek OPD Scan II system and Topcon KR 8900 standard table-top autorefractokeratometer are not interchangeable in healthy adult population before and after induction of cycloplegia.


Multidrug Resistant Invasive Nontyphoidal Salmonella Isolated from and Masquerading Healed Tubercular Constrictive Pericarditis and Study of Virulence Markers.
Among the infectious causes of pericarditis are various bacteria, viruses, fungal and parasitic infections. The course disease may progress to a chronic constrictive pattern especially with tubercular etiology. Non-typhoidal Salmonella has rarely been reported as a cause of pericarditis. We describe here a case from which the pericardial fluid from an old case of tubercular pericarditis sent for culture to microbiology laboratory grew a Salmonella typhimurium. We studied the antibiotic resistance pattern, phage type and virulence factors playing a role in the invasive nature of the pathogen since no such study from pericardial fluid was found in the literature. The isolate was sensitive only to cephalosporins and it was untypable. It showed amplification for five fimbrial operons, three colonization factors, and other genes (pef operon), gog B(Gifsy-1 encoded effector), sseI (Gifsy-2 encoded effector), sodC ( the periplasmic [copper and zinc Cu, Zn ]-superoxide dismutase) & sopE (a guanine nucleotide exchange factors). The present case highlights the need for early detection of the exact causative agent and serovar in management, the likelihood of a different etiological agent other than the original to be kept in mind for timely management and the highly resistant pattern of non-typhoidal Salmonella (NTS) limiting the therapeutic options as in our case to only cephalosporins. The genes encoded from the NTS might be required for invasive cardiac manifestation in humans.


Survival of patients with multiple sclerosis in Denmark: a nationwide, long-term epidemiologic survey.
We estimated survival probability and excess death rates for patients with MS on the basis of data from the Danish Multiple Sclerosis Registry, which includes virtually all patients diagnosed with MS in Denmark (population, five million) since 1948. We reviewed and reclassified all case records according to standardized diagnostic criteria. By linkage to the Danish Central Population Registry, we lost to follow-up only 25 patients who had emigrated. The median survival time from onset of the disease was 28 years in men (compared with 40 years in the matched general male population) and 33 years in women (versus 46 years). The median survival time from diagnosis was 22 years in men (versus 37 years) and 28 years in women (versus 42 years). The excess death rate between onset and follow-up (observed deaths per 1,000 person-years minus the expected number of deaths in a matched general population) was 14.3 in men, which was significantly higher than in women (12.0). Excess mortality increased with age at onset of MS in people of each sex. The 10-year excess death rate has decreased significantly in recent decades. Excess mortality was highest in cases with cerebellar symptoms at onset.


A study of methanol transport/uptake by a methanol-utilizing bacterium L3 in a batch bioreactor.
Two novel, nitrogen-limited and oxygen-limited, perturbed transient experiments were performed to examine the presence of active transport of methanol and study the effect on methanol uptake by a methanol-utilizing bacterium, L3, in a batch bioreactor. Transient limitations of both ammonium ions and O(2) in batch cultures were found to cause methanol leakages out of the cells, suggesting the presence of an active transport of methanol in L3. Such experimental results were used to indirectly estimate the intracellular levels of methanol during a batch growth of L3. The results of our analysis indicate that the intracellular methanol level is high and show an increasing trend during the unbalanced phase, but falls to a constant low level in the balanced phase of a typical batch growth(8) of L3. A simple modelling analysis suggests that a four-parameter "pump-and-extrusion" model could be used to adequately describe the transport of methanol between the extra cellular and intracellular phases of batch cultures of L3.


Suicide attempts and completions on medical-surgical and intensive care units.
Studies of inpatient suicide attempts and completions on medical-surgical and intensive care units are rare, and there are no large studies in the United States. We reviewed 50 cases, including 45 suicide attempts and 5 completed suicides, that occurred on medical surgical or intensive care units in the Veterans Health Administration between December 1, 1999 and December 31, 2012. The method, location, and the root causes of the events were categorized. The most common methods included cutting with a sharp object, followed by overdose and hanging. Root causes included problems with communication of risk, need for staff education in suicide assessment, and the need for better treatment for depressed and suicidal patients on medical units. Based on these results, we made our recommendations for managing suicidal patients on medical-surgical and intensive care units, including improved education for staff, standardized communication about suicide risk, and clear management protocols for suicidal patients.


'Competent to practise'?
The concept of competence to practise and the possibility of introducing a scheme of continuous assessment into the qualifying Diploma are currently being investigated within the profession. Ways in which these might be operated are discussed.


Microarray analysis of differentially expressed genes and their functions in omental visceral adipose tissues of pregnant women with vs. without gestational diabetes mellitus.
Increasing evidence has shown that insulin resistance in omental visceral adipose tissue (OVAT) is a characteristic of gestational diabetes mellitus (GDM). The present study aimed to identify differentially expressed genes (DEGs) and their associated functions and pathways involved in the pathogenesis of GDM by comparing the expression profiles of OVATs obtained from pregnant Chinese women with and without GDM during caesarian section. A total of 935 DEGs were identified, including 450 downregulated and 485 upregulated genes. In the gene ontology category cellular components, the DEGs were predominantly associated with functions of the extracellular region, while receptor binding was predominant in the molecular function category and biological process terms included antigen processing and presentation, extracellular matrix organization, positive regulation of cell-substrate adhesion, response to nutrients and response to dietary excess. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed and a functional interaction network was constructed. Functions of downregulated genes included antigen processing and presentation as well as cell adhesion molecules, while those of upregulated genes included transforming growth factor (TGF)-β-signaling, focal adhesion, phosphoinositide-3 kinase-Akt-signaling, P53 signaling, extracellular matrix-receptor interaction and regulation of actin cytoskeleton pathway. The five main pathways associated with GDM were antigen processing and presentation, cell adhesion molecules, Type 1 diabetes mellitus, natural killer cell-mediated cytotoxicity and TGF-β signaling. These pathways were included in the KEGG pathway categories of 'signaling molecules and interaction', 'immune system' and 'inflammatory response', suggesting that these processes are involved in GDM. The results of the present study enhanced the present understanding of the mechanisms associated with insulin resistance in OVATs of GDM.


Specific language impairment in Italian: the first steps in the search for a clinical marker.
Recent studies of children with specific language impairment (SLI) have identified language measures that seem quite accurate in distinguishing preschool-age children with SLI from their normally developing peers. However, the studies have focussed exclusively on English, and it is clear from the literature that the SLI profile varies between languages. This paper reports on three studies designed to assess the utility of particular language measures for Italian. In the first two studies, it was found that a composite measure based on the use of definite singular articles and third-person plural inflections showed good sensitivity and specificity in distinguishing Italian-speaking children with SLI from their typically developing peers. The third study showed that the same composite can be applied successfully to individual cases of SLI. Some of the additional steps needed to evaluate this composite measure are discussed.


A call for consultants.
There is a consensus that reform will create a boon for consultants. Many organizations have already brought in consultants to help formulate new strategies; but how do you find the right one?


Cesarean section rates in Turkey 2018-2023: Overview of national data by using Robson ten group classification system.
Cesarean section (CS) rates continue to rise globally because of various factors. Medically unnecessary cesarean operations have no benefit to the mother or child's health. Since the World Health Organization (WHO) has determined that the acceptable CS rate should not be more than 10-15%, it also stated the use of a classification system to compare different patient groups and facilities. Turkey has the highest CS rates globally and has been rising over the years. This study aims to assess CS rates between 2018 and 2023 using National Health Data and to analyze them according to the Robson classification system and WHO reference values to discuss possible measures against increasing rates. In this study, we assessed the rates of CSs between 2018 and 2023; the CS rate including all 5-years and analysis of CS rates for each Robson group as advocated by WHO. Also, another assessment was done of the facilities where the CSs were applied (Public, private, or university hospitals). The total number of births recorded between 2018 and2023 was 6.161.976. The overall CS rate was 57.55%. The number of total CS operations was 3.546.049. The primary CS rate was 28.83% (N:1.776.503). Significant differences were observed between the public and private centers for each Robson group. The CS rates of Groups 1-4 are obviously higher than expected. The CSs of these groups cumulatively affect the rates of other groups. Nulliparous women have CSs mostly in private hospitals. There is a need for improvements in the health system in this regard for better maternal and child health.


Salivary lactate and 8-isoprostaglandin F2α as potential non-invasive biomarkers for monitoring heart failure: a pilot study.
Heart failure (HF) is a cardiovascular disease affecting about 26 million people worldwide costing about $100 billons per year. HF activates several compensatory mechanisms and neurohormonal systems, so we hypothesized that the concomitant monitoring of a panel of potential biomarkers related to such conditions might help predicting HF evolution. Saliva analysis by point-of-care devices is expected to become an innovative and powerful monitoring approach since the chemical composition of saliva mirrors that of blood. The aims of this study were (i) to develop an innovative procedure combining MEPS with UHPLC-MS/MS for the simultaneous determination of 8-isoprostaglandin F2α and cortisol in saliva and (ii) to monitor lactate, uric acid, TNF-α, cortisol, α-amylase and 8-isoprostaglandin F2α concentrations in stimulated saliva samples collected from 44 HF patients during their hospitalisation due to acute HF. Limit of detection of 10 pg/mL, satisfactory recovery (95-110%), and good intra- and inter-day precisions (RSD ≤ 10%) were obtained for 8-isoprostaglandin F2α and cortisol. Salivary lactate and 8-isoprostaglandin F2α were strongly correlated with NT-proBNP. Most patients (about 70%) showed a significant decrease (a factor of 3 at least) of both lactate and 8-isoprostaglandin F2α levels at discharge, suggesting a relationship between salivary levels and improved clinical conditions during hospitalization.


Osteolytic phaeohyphomycosis caused by Phialemonium obovatum.
Phialemonium obovatum was found to be the cause of nosocomial osteomyelitis in a 41-year-old man after sustaining a nonpenetrating injury to his lumbar and cervical region. Histologic examination of fragments of disk and bone from L3-4 hemilaminectomy showed multiple fragments of fibrocartilage with focal necrosis, chronic inflammation, and granulation tissue formation. Sections stained with Gomori's methenamine silver procedure showed multiple fungal elements in necrotic areas consisting of irregularly branched, hyaline septate hyphae having swollen cells, and occasional yeastlike cells. The use of Fontana-Masson silver stain showed the presence of melanin in cells walls and septa of the hyphae. Phialemonium obovatum was isolated when the ground tissue from disk and bone from L3-4 was cultured on biphasic brain-heart infusion medium. Colonies were moist, off-white to ochraceous with a characteristic green, diffusible pigment on the reverse side. The isolate grew well up to 40 degrees C. It formed characteristic adelophialides without conspicuous collarettes and basal septa and produced smooth, one-celled, hyaline, and obovate conidia.


Development of radicicol analogues.
Radicicol, a macrocyclic antibiotic produced by fungi, was originally isolated many years ago, and was described as tyrosine kinase inhibitor. We also rediscovered radicicol as an inhibitor of signal transduction of oncogene products, such as K-ras and v-Src, using yeast and mammalian cell-based assays. In a study of mechanisms of action, it was revealed that radicicol depletes the Hsp90 client signaling molecules in cells, and thus inhibit the signal transduction pathway. In addition, direct binding of radicicol to the N-terminal ATP/ADP binding site of Hsp90 was shown, and thus radicicol has been recognized as a structurally unique antibiotic that binds and inhibits the molecular chaperone Hsp90. Although radicicol itself has little or no activity in animals because of instability in animals, its oxime derivatives showed potent antitumor activities against human tumor xenograft models. Hsp90 client proteins were depleted and apoptosis was induced in the tumor specimen treated with radicicol oxime derivatives. Taken together, these results suggest that the antitumor activity of radicicol oxime derivatives is mediated by binding to Hsp90 and destabilization of Hsp90 client proteins in the tumor. Among Hsp90 clients, we focused on ErbB2 and Bcr-Abl as examples of important targets of Hsp90 inhibitors. Radicicol oxime showed potent antitumor activity against ER negative/ErbB2 overexpressing breast cancer and Bcr-Abl expressing CML. Putative mechanisms of action and future directions of radicicol oxime against these kinds of tumor are discussed.


Assessment of condom use among Bolivian truck drivers through the lens of social cognitive theory.
This study demonstrates that Bolivian long distance truck drivers are a high risk population of HIV infection and transmission, supporting other global studies involving truck drivers and their high risk. The aims of this investigation were to estimate the prevalence of high risk behaviors and to identify predictors of condom use in this population. Analysis was completed on survey results from 246 male truckers (aged 18-67). About one in three of the truck drivers (30%) reported having had a sexually transmitted infection sometime in their past. More than half (56%) reported having sex with casual partners. Other risks involved unprotected anal sex. Age and two social cognitive constructs (outcome expectations and perceived social norms) predicted condom use from logistic regression analysis. The authors discuss the need for expanded HIV/sexually transmitted infection prevention programs that incorporate social cognitions.


Genome-wide SNP identification in multiple morphotypes of allohexaploid tall fescue (Festuca arundinacea Schreb).
Single nucleotide polymorphisms (SNPs) provide essential tools for the advancement of research in plant genomics, and the development of SNP resources for many species has been accelerated by the capabilities of second-generation sequencing technologies. The current study aimed to develop and use a novel bioinformatic pipeline to generate a comprehensive collection of SNP markers within the agriculturally important pasture grass tall fescue; an outbreeding allopolyploid species displaying three distinct morphotypes: Continental, Mediterranean and rhizomatous. A bioinformatic pipeline was developed that successfully identified SNPs within genotypes from distinct tall fescue morphotypes, following the sequencing of 414 polymerase chain reaction (PCR) - generated amplicons using 454 GS FLX technology. Equivalent amplicon sets were derived from representative genotypes of each morphotype, including six Continental, five Mediterranean and one rhizomatous. A total of 8,584 and 2,292 SNPs were identified with high confidence within the Continental and Mediterranean morphotypes respectively. The success of the bioinformatic approach was demonstrated through validation (at a rate of 70%) of a subset of 141 SNPs using both SNaPshot™ and GoldenGate™ assay chemistries. Furthermore, the quantitative genotyping capability of the GoldenGate™ assay revealed that approximately 30% of the putative SNPs were accessible to co-dominant scoring, despite the hexaploid genome structure. The sub-genome-specific origin of each SNP validated from Continental tall fescue was predicted using a phylogenetic approach based on comparison with orthologous sequences from predicted progenitor species. Using the appropriate bioinformatic approach, amplicon resequencing based on 454 GS FLX technology is an effective method for the identification of polymorphic SNPs within the genomes of Continental and Mediterranean tall fescue. The GoldenGate™ assay is capable of high-throughput co-dominant SNP allele detection, and minimises the problems associated with SNP genotyping in a polyploid by effectively reducing the complexity to a diploid system. This SNP collection may now be refined and used in applications such as cultivar identification, genetic linkage map construction, genome-wide association studies and genomic selection in tall fescue. The bioinformatic pipeline described here represents an effective general method for SNP discovery within outbreeding allopolyploid species.


Geographically-based approaches to the integration of health promotion into health systems: a comparative study of two Health Action zones in the UK.
Health Action Zones (HAZs) were introduced in the UK in the late 1990s as a whole system approach to public health and health care. Resources were targeted in historically deprived subregional units of England. Based on process evaluations undertaken in their fourth year of operation, the approaches taken by two HAZs were compared. Each had different histories of intersectoral cooperation and strategic approaches to integration. Both operated in a rapidly changing policy and organizational environment. This undermined attempts to sustain a consistent vision and eventually led to the demise of HAZs as subregional units. The approaches chosen by these two HAZs to integrate health promotion into health systems cannot be divorced from the political, historical and geographical contexts in which they were initiated. What the experiences of the two HAZs demonstrate is that while subregions and localities can potentially benefit from a whole systems perspective, there are deep-seated structural problems that constrain progress. Their experience demonstrates that context is of key importance in understanding the outcomes of any intervention aimed at promoting health.


Physiological age-related changes: cross-sectional and longitudinal studies.
Physiological age-related changes were investigated by cross-sectional and longitudinal studies. The data of the study were derived from volunteers admitted to the Gerontology Center in Budapest. In the follow-up study 864 subjects took part, and in the cross-sectional study 2,281 individuals. The 20-year longitudinal study and the cross-sectional examination showed that from a clinical standpoint the most important observation is that several biochemical data do not change with age. No changes were found in the values in erythrocyte sedimentation, hemoglobin, hematocrit, serum total protein, albumin, liver function, glucose, creatinine, triglyceride, and HDL-cholesterol levels. Changes were observed in the levels of HDL-cholesterol, immunoglobulins, rheumatoid factors, antinuclear factors, morphology of lymphocytes, serum TSH and T3 concentration, and systolic blood pressures.


A laboratory model of canine leishmaniasis: the inoculation of dogs with Leishmania infantum promastigotes from midguts of experimentally infected phlebotomine sandflies.
Twenty-five dogs (beagles) were infected with Leishmania infantum by the intradermal inoculation of an estimated 5-8,000 metacyclic promastigotes harvested from the midguts of 320 experimentally infected P. perniciosus. Details are given of the methods of infecting the flies and harvesting the parasites. All dogs developed small, self-healing chancres at the sites of inoculation. Parasites were isolated from lymph nodes, bone marrow or spleen of 21 dogs, 12 of which developed signs of disease and raised IFAT litres to Leishmania. Nine of the 21 remained healthy over a five-year observation period. Six of the nine were shown to have a cell mediated immune response to Leishmania. No parasites were isolated from four of the 25 dogs, two of which had a demonstrable cell mediated immunity and another had low transitory IFAT titres. The fourth had chancres at the sites of inoculation. The results show that dogs can be readily infected with promastigotes from the midguts of sandflies. However, a high proportion develop a cell mediated immunity and show on signs of disease. It is suggested that serological surveys of dogs for canine leishmaniasis reveal neither the true prevalence of infection nor the intensity of transmission. The efficacy of controlling human visceral leishmaniasis caused by L. infantum by destroying seropositive dogs is questioned.


[Physiological and pathophysiological investigations on neuronal mechanisms of locomotion in the cats (author's transl)].
Electromyographic investigation was carried out on the cats in order to analyse the neuronal mechanisms of locomotive movements. 1. When normal unrestrained cats walked gastrocnemius muscle, an extensor, began the activities 77.4 +/- 12.1 msec prior the stance phase. This evidence shows that locomotive movement is preprogrammed in the central nervous system. 2. When hemisection was applied to the spinal cord, reciprocal activities in the antagonistic muscles disappeared for several days. However, the reciprocity resumed again eventually. 3. When two hemisections on both sides were applied at different levels of the spinal cord at intervals of more than 30 days, the cat could not stand for 20-30 days after the second hemisection, but eventually could stand. The reciprocity between the antagonistic muscles were greatly disturbed in many cases. 4. In several cases placing reaction could not be elicited in the two hemisected cats. The possible roles of descending tracts in locomotion were discussed.


Toward 3D reconstruction of outdoor scenes using an MMW radar and a monocular vision sensor.
In this paper, we introduce a geometric method for 3D reconstruction of the exterior environment using a panoramic microwave radar and a camera. We rely on the complementarity of these two sensors considering the robustness to the environmental conditions and depth detection ability of the radar, on the one hand, and the high spatial resolution of a vision sensor, on the other. Firstly, geometric modeling of each sensor and of the entire system is presented. Secondly, we address the global calibration problem, which consists of finding the exact transformation between the sensors' coordinate systems. Two implementation methods are proposed and compared, based on the optimization of a non-linear criterion obtained from a set of radar-to-image target correspondences. Unlike existing methods, no special configuration of the 3D points is required for calibration. This makes the methods flexible and easy to use by a non-expert operator. Finally, we present a very simple, yet robust 3D reconstruction method based on the sensors' geometry. This method enables one to reconstruct observed features in 3D using one acquisition (static sensor), which is not always met in the state of the art for outdoor scene reconstruction. The proposed methods have been validated with synthetic and real data.


PITX1 plays essential functions in cancer.
PITX1, also known as the pituitary homeobox 1 gene, has emerged as a key regulator in animal growth and development, attracting significant research attention. Recent investigations have revealed the implication of dysregulated PITX1 expression in tumorigenesis, highlighting its involvement in cancer development. Notably, PITX1 interacts with p53 and exerts control over crucial cellular processes including cell cycle progression, apoptosis, and chemotherapy resistance. Its influence extends to various tumors, such as esophageal, colorectal, gastric, and liver cancer, contributing to tumor progression and metastasis. Despite its significance, a comprehensive review examining PITX1's role in oncology remains lacking. This review aims to address this gap by providing a comprehensive overview of PITX1 in different cancer types, with a particular focus on its clinicopathological significance.


Alteration of acetylcholine receptor and acetylcholinesterase metabolism by actinomycin D in cultured muscle cells.
Actinomycin D (ACT-D), an inhibitor of transcription, was added to chick muscle cultures to study its effect on the synthesis of acetylcholine receptor (ACHR) and acetylcholinesterase (ACHE, EC 220.127.116.11). Doses of ACT-D (1.85-18.5 nM), which inhibited uridine incorporation up to 80%, increased ACHR, ACHE, and creatine kinase (CK, EC 220.127.116.11) levels without affecting general cell protein. Degradation of ACHR was slower in ACT-D treated cultures than controls, resulting in a twofold increase in receptor half-life. Uridine incorporation was inhibited by ACT-D in both mononucleated cells and myotubes and [3H]uridine nuclear grain distribution were shifted to values lower than controls. The results indicate that posttranscriptional effects of ACT-D increase levels of ACHR, ACHE, and CK and that decreased degradation could account for the increase in the number of surface ACH receptors.


Adsorptive Water Removal from Dichloromethane and Vapor-Phase Regeneration of a Molecular Sieve 3A Packed Bed.
The drying of dichloromethane with a molecular sieve 3A packed bed process is modeled and experimentally verified. In the process, the dichloromethane is dried in the liquid phase and the adsorbent is regenerated by water desorption with dried dichloromethane product in the vapor phase. Adsorption equilibrium experiments show that dichloromethane does not compete with water adsorption, because of size exclusion; the pure water vapor isotherm from literature provides an accurate representation of the experiments. The breakthrough curves are adequately described by a mathematical model that includes external mass transfer, pore diffusion, and surface diffusion. During the desorption step, the main heat transfer mechanism is the condensation of the superheated dichloromethane vapor. The regeneration time is shortened significantly by external bed heating. Cyclic steady-state experiments demonstrate the feasibility of this novel, zero-emission drying process.


Interferon-β and Interferon-γ Are Weak Inhibitors of Ebola Virus in Cell-Based Assays.
Previous studies have demonstrated little efficacy of interferons (IFNs) in animal models of Ebola virus disease. However, these studies were limited to a small number of type I IFNs and, during the most recent outbreak of Ebola virus, questions regarding the suitability of the animal models to evaluate IFNs were raised. To address the potential that anti-Ebola virus activity was overlooked, type I and type II IFNs (α-2a, α-2b, -β, -γ, and -universal) were tested in a variety of cell types (Vero E6, Huh 7 cells, and human macrophages). IFNs are weak inhibitors of Ebola virus Makona in these cell lines.


Review of hazards to female reproductive health in veterinary practice.
OBJECTIVE To review publications that address female reproductive health hazards in veterinary practice, summarize best practices to mitigate reproductive risks, and identify current knowledge gaps. DESIGN Systematized review. SAMPLE English-language articles describing chemical, biological, and physical hazards present in the veterinary workplace and associations with adverse reproductive outcomes or recommendations for minimizing risks to female reproductive health. PROCEDURES Searches of the CAB abstracts database were performed in July 2012 and in May 2015 with the following search terms: veterinarians AND occupational hazards and vets.id AND occupational hazards.sh. Searches of the PubMed database were conducted in November 2012 and in May 2015 with the following medical subject heading terms: occupational exposure AND veterinarians; anesthetics, inhalation/adverse effects AND veterinarians; risk factors AND pregnancy AND veterinarians; pregnancy outcome AND veterinarians; and animal technicians AND occupational exposure. Two additional PubMed searches were completed in January 2016 with the terms disinfectants/toxicity AND female AND fertility/drug effects and veterinarians/psychology AND stress, psychological. No date limits were applied to searches. RESULTS 4 sources supporting demographic trends in veterinary medicine and 118 resources reporting potential hazards to female reproductive health were identified. Reported hazards included exposure to anesthetic gases, radiation, antineoplastic drugs, and reproductive hormones; physically demanding work; prolonged standing; and zoonoses. CONCLUSIONS AND CLINICAL RELEVANCE Demographic information suggested that an increasing number of women of reproductive age will be exposed to chemical, biological, and physical hazards in veterinary practice. Information on reproductive health hazards and minimizing risk, with emphasis on developing a safety-focused work culture for all personnel, should be discussed starting in veterinary and veterinary technical schools and integrated into employee training.


Comprehensive treatment approach for bilateral idiopathic condylar resorption and anterior open bite with customized lingual braces and total joint prostheses.
This case report describes the successful treatment of a 14-year-old girl with severe bilateral idiopathic condylar resorption and resultant mandibular retrusion, increased overjet, and anterior open bite. The nonextraction treatment plan included (1) aligning and leveling the teeth in both arches, (2) performing Le Fort I maxillary osteotomy, bilateral condylectomy, and mandibular joint replacement, and (3) postsurgical correction of the malocclusion. The orthodontic treatment was initiated with the use of custom lingual appliances followed by orthognathic surgery planned with virtual surgical planning. Patient-fitted and customized temporomandibular joint implants were designed and manufactured based on the patient's stereolithic bone anatomic model. Treatment was concluded with detailed orthodontic finishing. Optimum esthetic and functional results were achieved with the cooperation of 2 specialties and the use of state-of-the-art technology.


Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-90 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity.
One factor that is critical to the potential effectiveness of radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. Stability in vivo depends on the condition that both the chelate linkage and radiolabeling procedures not alter antibody specificity and biodistribution. In addition, synthesis and selection of the chelating agent is critical for each radiometal in order to prevent inappropriate release of the radiometal in vivo. In the present study, we compare the in vivo stability of seven radioimmunoconjugates that use different polyaminocarboxylate chelating agents to complex yttrium-88 to the mouse anti-human interleukin-2 receptor monoclonal antibody, anti-Tac. Chelate linkage and radiolabeling procedures did not alter the immunospecificity of anti-Tac. In order to assess whether yttrium was inappropriately released from the chelate-coupled antibody in vivo, iodine-131-labeled and yttrium-88 chelate-coupled antibodies were simultaneously administered to the same animals to correlate the decline in yttrium and radioiodinated antibody activity. The four stable yttrium-88 chelate-coupled antibodies studied displayed similar iodine-131 and yttrium-88 activity, indicating minimal elution of yttrium-88 from the complex. In contrast, the unstable yttrium-88 chelate-coupled antibodies had serum yttrium-88 activities that declined much more rapidly than their iodine-131 activities, suggesting loss of the radiolabel yttrium-88 from the chelate. Furthermore, high rates of yttrium-88 elution correlated with deposition in bone. Four chelating agents emerged as promising immunotherapeutic reagents: isothiocyanate benzyl DTPA and its derivatives 1B3M, MX, and 1M3B. All four isothiocyanate agents showed prolonged yttrium-88 vascular survival which was essentially identical to that of their iodine-131 activity with only minimum accumulation (1.4-1.8%/g) of the yttrium-88 injected dose into bone. Thus, these four chelating agents were very stable in vivo and suitable for yttrium-monoclonal antibody radioimmunotherapy.


[Free endogenous aminoacids in perfused intestine in rats (author's transl)].
The intestinal content of free aminoacids from endogenous origin is studied by perfusion through the small intestine of rats under the influence of several factors, pancreatic and biliary secretions, the addition of L-glutamic acid at two different concentrations to the perfusion liquid either with the pancreatic and biliary secretion or without them. The conclusion is reached that the pancreatic juice contributes significantly to the intestinal amount of free aminoacids; the addition of L-glutamic acid to the perfusion liquid under the fixed experimental conditions decreases the amount of free amino acids transfered by active mechanisms in the intestinal contents. This effect shows a certain selective preference to the essential aminoacids against the non-essential aminoacids. Such effect is not observed, however when the pancreatic secretion is not present in the intestinal contents.


Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial.
GH is often used to treat children with idiopathic short stature despite the lack of definitive, long-term studies of efficacy. We performed a randomized, double-blind, placebo-controlled trial to determine the effect of GH on adult height in peripubertal children. Subjects (n = 68; 53 males and 15 females), 9-16 yr old, with marked, idiopathic short stature [height or predicted height < or = -2.5 sd score (SDS)] received either GH (0.074 mg/kg) or placebo sc three times per week until they were near adult height. At study termination, adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr. Adult height was greater in the GH-treated group (-1.81 +/- 0.11 SDS, least squares mean +/- sem) than in the placebo-treated group (-2.32 +/- 0.17 SDS) by 0.51 SDS (3.7 cm; P < 0.02; 95% confidence interval, 0.10-0.92 SDS). A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS. Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS (0.52 SDS; 3.8 cm; P < 0.001; 95% confidence interval, 0.22-0.82 SDS) and no important dropout bias. In conclusion, GH treatment increases adult height in peripubertal children with marked idiopathic short stature.


Defect engineering for thermal transport properties of nanocrystalline molybdenum diselenide.
Molybdenum diselenide (MoSe2) is attracting great attention as a transition metal dichalcogenide (TMDC) due to its unique applications in micro-electronics and beyond. In this study, the role of defects in the thermal transport properties of single-layer MoSe2 is investigated using non-equilibrium molecular dynamics (NEMD) simulations. Specifically, this work quantifies how different microstructural defects such as vacancies and grain boundaries (GBs) and their concentration (N) alter the thermal conductivity (TC) of single crystal and nanocrystalline MoSe2. These results show a significant drop in thermal conductivity as the concentration of defects increases. Specifically, point defects lower the TC of MoSe2 in the form of N-β where β is 0.5, 0.48 and 0.36 for VMo, VMo-Se and VSe vacancies, respectively. This study also examines the impact of grain boundaries on the thermal conductivity of nanocrystalline MoSe2. These results suggest that GB migration and stress-assisted twinning along with localized phase transformation (2H to 1T) are the primary factors affecting the thermal conductivity of nanocrystalline MoSe2. Based on MD simulations, TC of polycrystalline MoSe2 increases with the average grain size (d̄) in the form of d̄4.5. For example, the TC of nanocrystalline MoSe2 with d̄ = 11 nm is around 40% lower than the TC of the pristine monocrystalline sample with the same dimensions. Finally, the influence of sample size and temperature is studied to determine the sensitivity of quantitative thermal properties to the length scale and phonon scattering, respectively. The results of this work could provide valuable insights into the role of defects in engineering the thermal properties of next generation semiconductor-based devices.


Thyrotoxic hypokalemic periodic paralysis in a Native American patient: case report and literature review.
To describe a rare case of thyrotoxic hypokalemic periodic paralysis in a half Native American and half African American person. We present a case of a man of Native American descent with thyrotoxic periodic paralysis and review the pertinent literature. In a 53-year-old man with untreated hyperthyroidism, bilateral lower extremity weakness developed as a result of hypokalemia. Two months before admission, the patient had thyroid function test results that were consistent with hyperthyroidism. He also had undergone a thyroid radioiodine uptake study and scan, which demonstrated a diffuse 60% uptake in the thyroid at 24 hours. His symptoms resolved promptly after treatment with potassium, a 3-adrenergic blocking agent, and propylthiouracil. The pathophysiologic features of this disorder have not been entirely elucidated but most likely involve a sudden increase in intracellular shift of potassium and progressive depolarization of the resting membrane potential. Therapy consists of replacing the potassium and treating the cause. Thyrotoxic hypokalemic periodic paralysis, although rare in the Native American and African American population, should be considered in the differential diagnosis of hypokalemia and flaccid paralysis. Timely recognition and prompt treatment can reduce the risk of severe morbidity.


Self-consistent determination of the spike-train power spectrum in a neural network with sparse connectivity.
A major source of random variability in cortical networks is the quasi-random arrival of presynaptic action potentials from many other cells. In network studies as well as in the study of the response properties of single cells embedded in a network, synaptic background input is often approximated by Poissonian spike trains. However, the output statistics of the cells is in most cases far from being Poisson. This is inconsistent with the assumption of similar spike-train statistics for pre- and postsynaptic cells in a recurrent network. Here we tackle this problem for the popular class of integrate-and-fire neurons and study a self-consistent statistics of input and output spectra of neural spike trains. Instead of actually using a large network, we use an iterative scheme, in which we simulate a single neuron over several generations. In each of these generations, the neuron is stimulated with surrogate stochastic input that has a similar statistics as the output of the previous generation. For the surrogate input, we employ two distinct approximations: (i) a superposition of renewal spike trains with the same interspike interval density as observed in the previous generation and (ii) a Gaussian current with a power spectrum proportional to that observed in the previous generation. For input parameters that correspond to balanced input in the network, both the renewal and the Gaussian iteration procedure converge quickly and yield comparable results for the self-consistent spike-train power spectrum. We compare our results to large-scale simulations of a random sparsely connected network of leaky integrate-and-fire neurons (Brunel, 2000) and show that in the asynchronous regime close to a state of balanced synaptic input from the network, our iterative schemes provide an excellent approximations to the autocorrelation of spike trains in the recurrent network.


Identification of functional mutations associated with environmental variance of litter size in rabbits.
Environmental variance (VE) is partly under genetic control and has recently been proposed as a measure of resilience. Unravelling the genetic background of the VE of complex traits could help to improve resilience of livestock and stabilize their production across farming systems. The objective of this study was to identify genes and functional mutations associated with variation in VE of litter size (LS) in rabbits. To achieve this, we combined the results of a genome-wide association study (GWAS) and a whole-genome sequencing (WGS) analysis using data from two divergently selected rabbit lines for high and low VE of LS. These lines differ in terms of biomarkers of immune response and mortality. Moreover, rabbits with a lower VE of LS were found to be more resilient to infections than animals with a higher VE of LS. By using two GWAS approaches (single-marker regression and Bayesian multiple-marker regression), we identified four genomic regions associated with VE of LS, on chromosomes 3, 7, 10, and 14. We detected 38 genes in the associated genomic regions and, using WGS, we identified 129 variants in the splicing, UTR, and coding (missense and frameshift effects) regions of 16 of these 38 genes. These genes were related to the immune system, the development of sensory structures, and stress responses. All of these variants (except one) segregated in one of the rabbit lines and were absent (n = 91) or fixed in the other one (n = 37). The fixed variants were in the HDAC9, ITGB8, MIS18A, ENSOCUG00000021276 and URB1 genes. We also identified a 1-bp deletion in the 3'UTR region of the HUNK gene that was fixed in the low VE line and absent in the high VE line. This is the first study that combines GWAS and WGS analyses to study the genetic basis of VE. The new candidate genes and functional mutations identified in this study suggest that the VE of LS is under the control of functions related to the immune system, stress response, and the nervous system. These findings could also explain differences in resilience between rabbits with homogeneous and heterogeneous VE of litter size.


The health impact of war.
Armed conflict causes an enormous amount of death and disability worldwide. It destroys families, communities and cultures. It diverts scarce resources. It disrupts the societal infrastructure that supports health. It forces people to leave their homes and become internally displaced persons or refugees who have fled to other countries. It violates human rights. It promotes violence as a means to resolve conflicts and it degrades the environment. Armed conflict has an even more profound effect on low- and middle-income countries. Health professionals can play important roles in minimising the adverse consequences of war and in preventing war itself.


Optimization of a multiresidual method for the determination of waterborne emerging organic pollutants using solid-phase extraction and liquid chromatography/tandem mass spectrometry and isotope dilution mass spectrometry.
A high-throughput, liquid chromatography/tandem mass spectrometry (LC/MS-MS) method has been developed for the determination of 51 emerging organic pollutants (EOPs) in environmental waters. The method was validated for the analysis of 38 pharmaceutically active, 10 endocrine disrupting, and three perfluoroalkylated compounds. Method performance parameters, including sample preservatives, pH values used in the solid-phase extraction (SPE), sample storage, sample extract storage time, and matrix effects were discussed in detail for different aquatic matrices, including drinking water, wastewater, and surface water. Isotope-labeled compounds were used as injection internal standards (IIS) or isotope dilution quantitation standards (IDQS) to improve the data quality, investigate the behavior of matrix effects during SPE sample preparation and LC/MS-MS analysis, and to validate isotope dilution mass spectrometric (IDMS) determination of selected compounds. Method detection limits were determined to be in the low ng/L range forthe compounds evaluated. By application of this method to the analysis of effluents and samples downstream of a wastewater treatment plant, more than 35 target EOPs were quantified. We demonstrated method ruggedness by quality control and quality assurance (QC/QA) data, showed that matrix effects were dependent on modes of electrospray ionization, and could not be removed via SPE or cleanup procedures, exerting the same effect to target compounds in both raw and extracted samples. Both 13C- and 2H-labeled IDQS could be added to samples before sample extraction, and their recoveries used to correct matrix effects in LC/MS-MS EOP analyses.


Spatiotemporal mapping of diffusion dynamics and organization in plasma membranes.
Imaging fluorescence correlation spectroscopy (FCS) and the related FCS diffusion law have been applied in recent years to investigate the diffusion modes of lipids and proteins in membranes. These efforts have provided new insights into the membrane structure below the optical diffraction limit, new information on the existence of lipid domains, and on the influence of the cytoskeleton on membrane dynamics. However, there has been no systematic study to evaluate how domain size, domain density, and the probe partition coefficient affect the resulting imaging FCS diffusion law parameters. Here, we characterize the effects of these factors on the FCS diffusion law through simulations and experiments on lipid bilayers and live cells. By segmenting images into smaller 7 × 7 pixel areas, we can evaluate the FCS diffusion law on areas smaller than 2 µm and thus provide detailed maps of information on the membrane structure and heterogeneity at this length scale. We support and extend this analysis by deriving a mathematical expression to calculate the mean squared displacement (MSDACF) from the autocorrelation function of imaging FCS, and demonstrate that the MSDACF plots depend on the existence of nanoscopic domains. Based on the results, we derive limits for the detection of domains depending on their size, density, and relative viscosity in comparison to the surroundings. Finally, we apply these measurements to bilayers and live cells using imaging total internal reflection FCS and single plane illumination microscopy FCS.


Validation of three breast cancer nomograms and a new formula for predicting non-sentinel lymph node status.
The aim of the study was to evaluate the available breast nomograms (MSKCC, Stanford, Tenon) to predict non-sentinel lymph node metastasis (NSLNM) and to determine variables for NSLNM in SLN positive breast cancer patients in our population. We retrospectively reviewed 170 patients who underwent completion axillary lymph node dissection between Jul 2008 and Aug 2010 in our hospital. We validated three nomograms (MSKCC, Stanford, Tenon). The likelihood of having positive NSLNM based on various factors was evaluated by use of univariate analysis. Stepwise multivariate analysis was applied to estimate a predictive model for NSLNM. Four factors were found to contribute significantly to the logistic regression model, allowing design of a new formula to predict non-sentinel lymph node metastasis. The AUCs of the ROCs were used to describe the performance of the diagnostic value of MSKCC, Stanford, Tenon nomograms and our new nomogram. After stepwise multiple logistic regression analysis, multifocality, proportion of positive SLN to total SLN, LVI, SLN extracapsular extention were found to be statistically significant. AUC results were MSKCC: 0.713/Tenon: 0.671/Stanford: 0.534/DEU: 0.814. The MSKCC nomogram proved to be a good discriminator of NSLN metastasis in SLN positive BC patients for our population. Stanford and Tenon nomograms were not as predictive of NSLN metastasis. Our newly created formula was the best prediction tool for discriminate of NSLN metastasis in SLN positive BC patients for our population. We recommend that nomograms be validated before use in specific populations, and more than one validated nomogram may be used together while consulting patients.


The effectiveness of residential treatment services for individuals with substance use disorders: A systematic review.
Residential treatment is a standard treatment for individuals with severe and complex substance use problems. However, there is limited evidence on best practice approaches to treatment in these settings. This review provides a comprehensive update on the evidence base for residential treatment, and directions for future research and clinical practice. A systematic review of all studies published between January 2013 and December 2018 was conducted. Public health and psychology databases (Medline, CINAHL, PsycARTICLES and PsycINFO) were systematically searched, and forward and backward snowballing were used to identify additional studies. Studies were included if they were quantitative, assessed the effectiveness of residential substance treatment programs for adults, were published in the English language and in peer-reviewed journals. The Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies was used to assess methodological quality. Our search identified 23 studies. Eight were rated as methodologically strong, five as moderate and ten rated as weak. Quality ratings were impacted by attrition at follow-up and research design. Despite limitations, results provide moderate quality evidence for the effectiveness of residential treatment in improving outcomes across a number of substance use and life domains. With caution, results suggest that best practice rehabilitation treatment integrates mental health treatment and provides continuity of care post-discharge. Future research and practice should focus on better collection of outcome data and conducting data linkage of key health, welfare and justice agency administrative data to enhance understanding of risk and recovery trajectories.


High expression of ERCC1, FLT1, NME4 and PCNA associated with poor prognosis and advanced stages in myelodysplastic syndrome.
Myelodysplastic syndrome (MDS) represents a good model for research of prognostic/progression markers due to frequent transformation into acute myeloid leukemia (AML). We analysed expression profiles of 26 MDS and 6 AML patients using cDNA arrays comprising 588 gene probes. The array data were validated in a larger set of 46 patients by qRT-PCR. Data analysis identified differently expressed genes in MDS and the cluster of four genes (ERCC1, FLT1, NME4 and PCNA) whose expression was correlated with MDS subtypes. High expression of these genes was associated with poor prognosis and/or unfavorable outcome. Furthermore, PCNA expression was correlated with peripheral blood blast percentage (r = 0.71, p < 0.05), while the other genes showed non-significant correlation. Our findings demonstrate the progressive up-regulation of the genes along the sequence of 5q-syndrome/RCMD/RAEB/de novo AML, suggesting their association with disease progression.


Treatment with triple combination of atorvastatin, perindopril, and amlodipine in patients with stable coronary artery disease: A subgroup analysis from the PAPA-CAD study.
Background In patients with stable coronary artery disease, aspirin, a statin, and an angiotensin-converting enzyme inhibitor are recommended as first-line agents for secondary prevention. Subgroup analyses of the previously published Hungarian Perindopril plus Amlodipine in PAtients with Coronary Artery Disease (PAPA-CAD) non-interventional trial demonstrated that the addition of the metabolically beneficial, fixed combination of perindopril + amlodipine to atorvastatin further improves the patient's lipid profile. Methods The PAPA-CAD study, a 6-month open-label, prospective, multicenter, observational/non-interventional survey evaluated data accumulated from patients with hypertensive patients with stable coronary artery disease. The herein-reported subgroup analysis was conducted using the findings from those 1130 patients, who were taking atorvastatin in addition to the fixed combination of perindopril + amlodipine at the time of all four study visits (i.e., at baseline and 1, 3, and 6 months later). Results In the subgroup of patients taking atorvastatin as an add-on agent, 82.5% reached the target blood pressure of 140/90 mmHg compared with 78.8% of those not taking a statin. The addition of atorvastatin to the fixed combination of perindopril + amlodipine resulted in further significant improvements of key metabolic parameters. Conclusion This subgroup analysis confirmed that favorable synergism exists among perindopril, amlodipine, and atorvastatin.


Effect of implanted insulin pumps on fluorescein transcapillary escape time in type 1 diabetes mellitus.
To determine whether significant increases in fluorescein transcapillary escape time (FTET) would occur after treatment of patients with type 1 diabetes with insulin delivered intraperitoneally by a surgically implanted pump. Nine patients with type 1 diabetes who were otherwise healthy and had received surgically implanted insulin pumps on a study protocol were recruited to have three measurements of FTET and glycosylated hemoglobin during an 18-month period. Serum fluorescein-albumin binding was measured at the time of the final test. Control FTETs were measured in 46 patients with type 1 diabetes who did not have insulin pumps and in 15 adults without diabetes. In the implanted insulin pump group, 50% of the FTETs were below normal, but no significant longitudinal change in FTETs was noted in eight of the nine study patients. The mean FTETs in the implanted insulin pump group were significantly higher than those of the control patients with diabetes but without insulin pumps (mean, 88 versus 62 seconds; P<0.05) but significantly lower than those of the control subjects without diabetes (88 versus 163 seconds; P<0.001). Four of the nine patients with implanted insulin pumps had normal FTETs on all three studies. This subgroup had used insulin pumps (external + implanted) for significantly longer periods (6.2 versus 2.6 years; P<0.05) than the other five patients. These differences within the implanted pump group did not correlate with differences in glycosylated hemoglobin values or fluorescein-albumin binding; however, the glycosylated hemoglobin levels before insulin pump implantation were significantly lower than those of the other five patients. Three patients with onset of type 1 diabetes before age 10 years had the lowest FTETs. Implanted insulin pumps did not alter FTETs between 6 months and 32 months after pump implantation. Total time on insulin pumps (external and implanted) is associated with normal FTET, and onset of diabetes before age 10 years is associated with abnormal FTET.


Retrotransposons in the development and progression of amyotrophic lateral sclerosis.
Endogenous retrotransposon sequences constitute approximately 42% of the human genome, and mobilisation of retrotransposons has resulted in rearrangements, duplications, deletions, novel transcripts and the introduction of new regulatory domains throughout the human genome. Both germline and somatic de novo retrotransposition events have been involved in a range of human diseases, and there is emerging evidence for the modulation of retrotransposon activity during the development of specific diseases. Particularly, there is unequivocal consensus that endogenous retrotransposition can occur in neuronal lineages. This review addresses our current knowledge of the different mechanisms through which retrotransposons might influence the development of and predisposition to amyotrophic lateral sclerosis.


Cloning and Functional Characterization of Putative Escherichia coli ABC Multidrug Efflux Transporter YddA.
A putative multidrug efflux gene, yddA, was cloned from the Escherichia coli K-12 strain. A drugsensitive strain of E. coli missing the main multidrug efflux pump AcrB was constructed as a host and the yddA gene was knocked out in wild-type (WT) and drug-sensitive E. coliΔacrB to study the yddA function. Sensitivity to different substrates of WT E.coli, E. coliΔyddA, E. coliΔacrB and E. coliΔacrBΔyddA strains was compared with minimal inhibitory concentration (MIC) assays and fluorescence tests. MIC assay and fluorescence test results showed that YddA protein was a multidrug efflux pump that exported multiple substrates. Three inhibitors, ortho-vanadate, carbonyl cyanide m-chlorophenylhydrazone (CCCP), and reserpine, were used in fluorescence tests. Ortho-vanadate and reserpine significantly inhibited the efflux and increased accumulation of ethidium bromide and norfloxacin, while CCCP had no significant effect on YddA-regulated efflux. The results indicated that YddA relies on energy released from ATP hydrolysis to transfer the substrates and YddA is an ABC-type multidrug exporter. Functional study of unknown ATP-binding cassette (ABC) superfamily transporters in the model organism E. coli is conducive to discovering new multidrug resistance-reversal targets and providing references for studying other ABC proteins of unknown function.