Sensitivity analysis and methodological choices on health-related impoverishment estimates in Cambodia, 2009-17.
The measurement of health expenditure-related impoverishment as a proxy of financial risk protection is regularly used as an indicator of progress towards universal health coverage. However, the use of this indicator is greatly sensitive to analysts' choices and data sources, making comparisons across time and countries challenging. We report the results of a sensitivity analysis of critical methodological choices in estimating health-related financial impoverishment in Cambodia from 2009 to 2017. We include the following in our analysis: the construction and data sources for consumption aggregates and out-of-pocket health estimates; the use of international and national absolute and relative poverty thresholds (defined by the share of household food consumption); time and regional price adjustment methods and index sources. Marginal changes substantially affected estimates at the national and regional levels among households. In most cases, the choice of poverty thresholds and temporal and regional deflators had a significant effect. An increase of 0.01 USD in the average daily per capita poverty line resulted in relative increases in impoverished incidences of 2.90-2.62% for 2009 and 3.06-2.95% for 2014. From 2013 onwards, estimates for impoverishment in rural areas based on median food consumption were often significantly higher than estimates using official poverty lines. The high sensitivity of the impoverishment indicator cautions against its use in assessing health-related financial hardship and protection, especially with low and absolute poverty lines. In the context of low- and middle-income countries, assessing financial hardship in relative terms by using measures such as catastrophic health expenditure, complemented with research on coping strategies and their socio-economic effects on households, may be more conducive to policymaking goals and progress towards achieving universal health coverage.


[Triamcinolone-assisted vitrectomy in the treatment of recurrent retinal detachment due to myopic macular hole].
To report the use of triamcinolone-assisted vitrectomy to assess the cause of vitrectomy failure in the treatment of retinal detachment due to myopic macular hole. We report the cases of three myopic patients presenting with recurrent retinal detachment due to macular hole after initial vitrectomy treatment with posterior vitreous detachment, a systematic attempt at membrane peeling, and gas injection (SF6). No retinal traction or tear other than the macular hole was observed. The recurrence of retinal detachment was treated with vitrectomy and intraoperative use of triamcinolone, which demonstrated persistent posterior hyaloid and thin and strongly adherent membrane remnants in each case. Anatomic success was obtained after peeling these structures. Intraoperative use of triamcinolone reduces the risk of overlooking hyaloid or membrane remnants during vitrectomy for the treatment of myopic retinal detachment. Transparent remnants of posterior hyaloid and membranes were visualized by triamcinolone-assisted vitrectomy. They could lead to traction on the retina and explain the failure of the initial vitrectomy. Anatomic success was obtained after peeling these structures.


Femtosecond midinfrared study of the photoinduced Wolff rearrangement of diazonaphthoquinone.
Time-resolved vibrational femtosecond spectroscopy is employed to investigate the photoinduced Wolff rearrangement reaction of diazonaphthoquinone (DNQ) dissolved in different solvents (methanol and water). DNQ is an important compound in commercial Novolak photoresists. Upon photoexcitation the ketene intermediate appears within 300 fs, indicating that the ketene is formed in a very fast concerted process involving N(2) loss and rearrangement. The strong shift of the vibrational band, assigned to the ketene by density functional theory calculations and experimental infrared spectra, toward higher wavenumbers is attributed to vibrational cooling. The relaxation time depends on the solvent (10 ps in methanol and 3 ps in water). However, the spectroscopic data show that the indirect ketene formation via a carbene intermediate might also be involved in the reaction process contributing to the ketene formation on the 10 ps time scale.


Transforming somatic mutations of mammalian target of rapamycin kinase in human cancer.
Mammalian target of rapamycin (mTOR) is a serine-threonine kinase that acts downstream of the phosphatidylinositol 3-kinase signaling pathway and regulates a wide range of cellular functions including transcription, translation, proliferation, apoptosis, and autophagy. Whereas genetic alterations that result in mTOR activation are frequently present in human cancers, whether the mTOR gene itself becomes an oncogene through somatic mutation has remained unclear. We have now identified a somatic non-synonymous mutation of mTOR that results in a leucine-to-valine substitution at amino acid position 2209 in a specimen of large cell neuroendocrine carcinoma. The mTOR(L2209V) mutant manifested marked transforming potential in a focus formation assay with mouse 3T3 fibroblasts, and it induced the phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eukaryotic translation initiation factor 4E-binding protein 1 in these cells. Examination of additional tumor specimens as well as public and in-house databases of cancer genome mutations identified another 28 independent non-synonymous mutations of mTOR in various cancer types, with 12 of these mutations also showing transforming ability. Most of these oncogenic mutations cluster at the interface between the kinase domain and the FAT (FRAP, ATM, TRRAP) domain in the 3-D structure of mTOR. Transforming mTOR mutants were also found to promote 3T3 cell survival, and their oncogenic activity was sensitive to rapamycin. Our data thus show that mTOR acquires transforming activity through genetic changes in cancer, and they suggest that such tumors may be candidates for molecularly targeted therapy with mTOR inhibitors.


Relationship between gender, bone mineral density, and disc degeneration in the lumbar spine: a study in elderly subjects using an eight-level MRI-based disc degeneration grading system.
The study cohort comprised 196 females and 163 males. Lumbar spine bone mineral density (BMD) and magnetic resonance imaging (MRI) were acquired. Females had more severe disc degeneration than males. Lumbar spine lower BMD was associated with less severe disc degeneration. Lumbar disc spaces were more likely to be narrower when vertebral BMD was higher. The purpose of this paper is to study the relationship between gender, BMD, and disc degeneration in the lumbar spine. The study cohort comprised 196 females and 163 males (age range 67-89 years) with no age difference between the two groups. Lumbar spine BMD was measured with dual X-ray densitometry, and MRI was acquired at 1.5 T. A subgroup of 48 males had additional lumbar vertebral quantitative computerized tomography densitometry. Lumbar disc degeneration was assessed using a MRI-based eight-level grading system. Female subjects had more severe disc degeneration than male subjects. After removing age effect, a positive trend was observed between T-score and severity of lumbar disc degeneration. This was significant in female subjects while not significant in male subjects. Lumbar disc spaces were more likely to be narrowed when vertebral BMD was higher. These observations were more significant in the midlumbar region (L3/4 and L4/5) and less so at the thoracolumbar junction. Female subjects tended to have slightly more severe lumbar disc degeneration than male subjects. Lower lumbar spine BMD was associated with less severe disc degeneration.


Optimized needle shape reconstruction using experimentally based strain sensors positioning.
Needles are tools that are used daily during minimally invasive procedures. During the insertions, needles may be affected by deformations which may threaten the success of the procedure. To tackle this problem, needles with embedded strain sensors have been developed and associated with navigation systems. The localization of the needle in the tissues is then obtained in real time by reconstruction from the strain measurements, allowing the physician to optimize its gesture. As the number of strain sensors embedded is limited in number, their positions on the needle have a great impact on the accuracy of the shape reconstruction. The main contribution of this paper is a novel strain sensor positioning method to improve the reconstruction accuracy. A notable feature of our method is the use of experimental needle insertion data, which increases the relevancy of the resulting sensor optimal locations. To the best of the author's knowledge, no experimentally based needle sensor positioning method has been presented yet. Reconstruction validations from clinical data show that the localization accuracy of the needle tip is improved by almost 40% with optimal locations compared with equidistant locations when reconstructing with two sensor triplets or more. Graphical Abstract Improvement of the reconstruction accuracy of a deformed needle shape by using experimental data to position strain sensors.


Degradation of streptococcal cell wall antigens in vivo.
Specific chemical modification of group A polysaccharide antigen to the A-variant structure was demonstrated in the lymphoid organs of mice by autoradiography by use of radioantibodies specific for these structures. Both antigenic moieties persisted and were still discerned 10 weeks after injection of the group A cell wall. In rabbit skin, the group A specificity was altered after a prolonged period. Unlike the situation for the mouse, polysaccharide A was not converted to A-variant structure, but another specificity common to both polysaccharides persisted at the site of injection. Mucopeptide, separated from the polysaccharide of group A cell walls, was eliminated from the site of injection in rabbit skin between 4 and 8 hr after injection. Group D streptococcal cell walls were also rapidly eliminated from tissue, and were no longer detectable 8 hr after injection into rabbit skin or 24 hr after injection into mice. The rapid degradation of these structures was correlated with their susceptibility to lysozyme in vitro and was in contrast to the prolonged persistence of group A cell walls, which were completely resistant to egg white lysozyme. This persistence in tissue correlated with the capacity of group A cell wall fragments to induce a chronic inflammatory process, whereas the isolated mucopeptide or group D cell walls produced only an acute necrotoxic reaction.


Methyl orange adsorption from aqueous solutions on 3D hierarchical PbS/ZnO microspheres.
In this study, three-dimensional (3D) hierarchical PbS/ZnO heterojunction microspheres were successfully fabricated by combining a facile hydrothermal method and an improved successive ionic-layer adsorption and reaction (SILAR). As an adsorbent for the first time, the adsorption activities for the methyl orange (MO) of the prepared 3D hierarchical PbS/ZnO heterojunction microspheres were investigated. By optimizing the loading of PbS nanoparticles (NPs), the 3D hierarchical PbS/ZnO heterojunction microspheres show enhanced adsorption ability for MO with a high removal rate of more than 91% and a maximum adsorption capacity of 159 mg g-1 at equilibrium time within less than 40 min. The kinetics, thermodynamics, and isotherm investigations for the adsorption process of MO over the 3D hierarchical PbS/ZnO heterojunction microspheres experimentally demonstrate that the adsorption process follows a pseudo-second-order model with the nature of spontaneous and endothermic and is well fitted with the normal Langmuir isotherm model. Based on the comparative investigations and the experimental results of kinetics, thermodynamics, and isotherm studies, a reasonable adsorption mechanism of MO over the 3D hierarchical PbS/ZnO heterojunction microspheres was proposed. This work not only describes a new semiconductor heterojunction adsorbent but also offers a new idea for the fabrication of other semiconductor heterojunction adsorbents.


The fast Padé transform in magnetic resonance spectroscopy for potential improvements in early cancer diagnostics.
The convergence rates of the fast Padé transform (FPT) and the fast Fourier transform (FFT) are compared. These two estimators are used to process a time-signal encoded at 4 T by means of one-dimensional magnetic resonance spectroscopy (MRS) for healthy human brain. It is found systematically that at any level of truncation of the full signal length, the clinically relevant resonances that determine concentrations of metabolites in the investigated tissue are significantly better resolved in the FPT than in the FFT. In particular, the FPT has a better resolution than the FFT for the same signal length. Moreover, the FPT can achieve the same resolution as the FFT by using twice shorter signals. Implications of these findings for two-dimensional magnetic resonance spectroscopy as well as for two- and three-dimensional magnetic resonance spectroscopic imaging are highlighted. Self-contained cross-validation of all the results from the FPT is secured by using two conceptually different, equivalent algorithms (inside and outside the unit-circle), that are both valid in the entire complex frequency plane. The difference between the results from these two variants of the FPT is indistinguishable from the background noise. This constitutes robust error analysis of proven validity. The FPT shows promise in applications of MRS for early cancer detection.


Angiotensin-converting enzyme inhibitory activity and antioxidant properties of Nepeta crassifolia Boiss & Buhse and Nepeta binaludensis Jamzad.
This article reports phytochemical and biological studies on Nepeta binaludensis and Nepeta crassifolia. Both species were investigated for their angiotensin-converting enzyme (ACE) inhibitory activity and antioxidant properties through three in vitro models [2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assay]. Aerial parts were extracted with methanol and partitioned between water and subsequently n-hexane, ethyl acetate and n-butanol. N. binaludensis methanol extract exerted significantly higher reducing power (1.9 μM Fe(II)/g) than did the positive control butylhydroxytoluene (63.2 μM Fe(II)/g) in FRAP assay. The highest DPPH radical scavenging activity was found for N. crassifolia, with IC50 values of 9.6 and 12.1 µg/mL for ethyl acetate and n-butanol fractions, respectively. n-Butanol fraction of both species showed the highest ACE inhibitory activity, with IC50 values of 59.3 and 81.7 µg/mL for N. binaludensis and N. crassifolia, respectively. Phytochemical investigations resulted in the isolation of ursolic acid, oleanolic acid, apigenin, luteolin and ixoroside. Apigenin-7-O-glucoside, 8-hydroxycirsimaritin and cirsimaritin were furthermore identified in N. crassifolia ethyl acetate-soluble fraction. Nepetanudoside B was isolated from the n-butanol fraction of N. binaludensis.


Driving under the influence of drugs other than alcohol.
This paper illustrates different aspects of the problem of driving under the influence of medicine and is based on a survey carried out in 1976 on three groups of drivers: (a) drivers consuming prescription drugs and alcohol; (b) drivers consuming prescription drugs only; and (c) drivers consuming alcohol only. Traffic accidents and traffic accident risks are approximately equal for all three groups, although the author points out that the frequency of traffic accidents and traffic accident risks involving prescription drug intoxicated drivers is probably larger than indicated by the study, as the sample was drawn from persons suspected of drunken driving. The author recommends epidemiological studies of the problem which would be facilitated if the law permitted blood and urine samples to be taken from any driver stopped on the road. He also suggests that formation of interdisciplinary groups to investigate specific aspects of the problem and closer co-operation between interested countries.


Ultra-Sensitive C-Reactive Protein (US-CRP) in Patients With Periodontal Disease and Risk of Acute Myocardial Infarction.
The purpose of this study was to determine if the US-CRP values associated with periodontal disease are risk markers for Acute Myocardial Infarction (AMI) and to determine if the US-CRP levels associated with recent AMI are higher in patients with Periodontal disease. In order to meet the goal of the study, a case control study design was conducted. The analysis sample consisted of 401 adults (30 - 75 years old), living in Bogota D.C., Colombia, from the Hospital Universitario San Ignacio, the Faculty of Dentistry at the Pontificia Universidad Javeriana, and the Fundacion Cardio Infantil. Patients with current infections, antibiotic use in the last 3 months, periodontal treatment at least six months before the baseline of this study, mouth ulcerations caused by any type of prosthesis, candidiasis, stomatitis, or less than 7 teeth in mouth were excluded. Periodontal examination for the case group and the control group was conducted by three previously calibrated examiners. Periodontal disease was diagnosed by the presence of bleeding on probing and attachment loss. The Chronic Periodontitis diagnosis was confirmed with these clinical signs, according to the 1999 Armitage classification. The assessment of the US-CRP was performed using the IMMULITE method containing one monoclonal and one polyclonal anti-CRP antibody. This method provides a measurement range of 0.1 - 500 mg/L. Statistical analysis of variables was performed with OR and confidence intervals. A multivariate analysis was performed to determine the association between the US-CRP increase, periodontal disease and acute myocardial infarction, adjusting for smoking and other confounding factors identified in the analysis. The study population was constituted by 401 patients, 56.1% (225) males, with a mean age of 52.6. When groups were compared it was observed that, in those patients with AMI and chronic severe or moderate periodontitis, 24.2% had HDL-C values lower than 40 mg/dl, 78.8% had LDL-C values higher than 100 mg/dl, 55.2% had triglycerides over 150 mg/dl, and US-CRP over 2 mg/L in 53.3%. Periodontal disease (moderate, severe, and chronic periodontal disease) may increase the risk of Acute Myocardial Infarction (AMI) by increasing the US-CRP levels.


Multiple myeloma in Niger Delta, Nigeria: complications and the outcome of palliative interventions.
Multiple myeloma (MM) is one of the hematological malignancies that require palliative care. This is because of the life-threatening nature and the suffering associated with the illness. The aim of this study is to bring to the fore the complications experienced by people living with MM in the Niger-Delta region of Nigeria and the outcome of various palliative interventions. This was a 10-year multi-center retrospective study of 26 patients diagnosed and managed in three major centers in the Niger-Delta region of Nigeria from January 2003 to December 2012. Information on the clinical, laboratory, radiological data, and palliative treatment was obtained at presentation and subsequently at intervals of 3 months until the patient was lost to follow-up. The mean duration from onset of symptoms to diagnosis was 13.12 months (95% CI, 6.65-19.58). A total of 16 (61.5%), eight (30.8%), and two subjects (7.7%) presented in Durie-Salmon (DS) stages III, II, and I, respectively. The complications presented by patients at diagnoses included bone pain (84.6%), anemia (61.5%), nephropathy (23.1%), and hemiplegia (35%). All the patients received analgesics, while 50.0% received blood transfusion, 56.7% had surgery performed, 19% had hemodialysis, and 3.8% received radiotherapy. A total of 10 (38%) patients benefited from bisphosphonates (BPs). A total of 57.6% of patients were on melphalan-prednisone (MP) double regimen, while 19% and 8% patients were on MP-thalidomide and MP-bortezomib triple regimens, respectively. A total of 3.8% of patients at DS stage IIIB disease had autologous stem-cell transplantation (ASCT). Only 7.6% of the myeloma patients survived up to 5 years post diagnosis. The overall mean survival interval was 39.7 months (95% CI, 32.1-47.2). Late diagnosis and inadequate palliative care account for major complications encountered by MM patients in the Niger-Delta region of Nigeria. This could be responsible for the poor prognostic outcome and low survival interval of MM individuals in this region. There is, therefore, a need to improve the quality of palliative care received by myeloma patients in this region. This is achievable via provision of relevant and affordable health care facilities for diagnosis and treatment of the disease.


Increased Hair Cortisol Concentrations in Patients With Progressive Keratoconus.
To investigate hair cortisol concentration (HCC), a biochemical correlate of chronic psychological stress, and its relationship to the progression of keratoconus. Eighty-six participants were included in this prospective observational study (32 patients with progressive keratoconus, 32 patients with stable keratoconus, and 22 healthy controls). Hair cortisol concentrations were determined from 3-cm hair strands collected near the scalp from patients and controls as an index of cumulative cortisol secretion during the 3-month period prior to hair sampling. In addition, self-reported chronic stress was assessed using the Trier Inventory for the Assessment of Chronic Stress screening scale. Patients with progressive keratoconus exhibited higher hair cortisol concentrations (mean value: 29.11 pg/mg; 95% confidence interval [CI]: 22.13 to 38.28) than patients with stable keratoconus (mean value: 15.88 pg/mg; 95% CI: 12.25 to 20.65; P = .007) and healthy controls (mean value: 16.98 pg/mg; 95% CI: 12.30 to 23.44; P = .049). There were no significant differences in hair cortisol concentrations between healthy controls and patients with stable keratoconus (P = .991). Group differences were not affected by relevant covariates (body mass index, age, or sex). This study shows that increased hair cortisol concentration seems to be associated with the progression of keratoconus. There are a variety of causes of increased hair cortisol concentration. [J Refract Surg. 2017;33(6):383-388.].


[Surveillance of West Nile fever in horses in the Czech Republic from 2011 to 2013].
The West Nile virus (WNV) is an important mosquito-borne flavivirus occurring around the world. Occasionally found in Central Europe, the virus spread massively through whole Hungary between 2008 and 2009. The aim of our study was to determine the recent prevalence of the WNV infection in horses in the Czech Republic. Overall, 2349 serum samples, collected from healthy unvaccinated adult horses in the Czech Republic between 2011 and 2013, were tested. A commercially available competitive ELISA kit (cELISA) was used for this purpose and positive samples were confirmed by virus neutralisation tests using WNV and tick-borne encephalitis virus (TBEV). Altogether 271 of 2348 samples (11.5%) were positive by cELISA. Confirmatory VNT revealed 16 WNV positive samples, 11 of which had titres from 8 to 1024; VNTs with TBEV were negative. Three samples had antibodies against both viruses and the WNV antibody titres were less than or equal to the TBEV antibody titres. A cross reactivity of flaviviruses might have had an impact on the results, but in samples with similar WNV and TBEV titres, co-infection with both pathogens cannot be ruled out either. VNT antibody titres in two horses were inconclusive (cut-off titre 4). The place of birth and transfers (if any) were checked for each WNV seropositive horse. Five WNV positive/TBEV negative samples (0.2%) came from five administrative regions (South Bohemian, Karlovy Vary, Central Bohemian, South Moravian, and Moravian-Silesian) and the respective animals were never moved to a foreign country. Four of these horses never left the farm. Other six WNV positive/TBEV negative horses were imported to the Czech Republic from North America or Central and West Europe and therefore, it is not possible to tell unambiguously whether their infection is autochthonous or imported. The results of the present study confirm that WNV antibodies occur sporadically in horses in the Czech Republic. WNV was found to circulate in different parts of the Czech Republic and not only in the South of Moravia.


Temporal Sequencing of Physical Activity Change Constructs within the Transtheoretical Model.
Studies support the Transtheoretical Model's (TTM) ability to describe behavior change processes and guide interventions; however, the temporal sequencing of constructs is less understood. This cohort study tested five sequences to identify TTM construct changes related to physical activity. A random sample provided baseline data (n=689; 63% female; M age (SD)=47(17); 37% white), with 401 participants providing 24-month data, at six-month intervals. Structural equation models revealed processes to cognitions to stage (AIC=29313.093, BIC=29514.883, CFI=0.999, RMSEA=0.006, SRMR=0.026); processes to stage to cognitions (AIC=27788.651, BIC=27973.268, CFI=0.978, RMSEA=0.024, SRMR=0.038), self-efficacy/temptations to processes to decisional balance to stage (AIC=13914.771, BIC=14031.169, CFI=0.981, RMSEA=0.018, SRMR=0.034), and stage to processes to cognitions (AIC=22048.324, BIC=22212.986, CFI=0.976, RMSEA=0.026, SRMR=0.029) all fit well. However, cognitions to processes to stage did not fit the data well (AIC=10353.555, BIC=10444.179, CFI=0.937, RMSEA=0.038, SRMR=0.035). Integrating results revealed a cyclical model so that intervention efforts should focus on processes to change cognitions related to barrier self-efficacy and decisional balance, which then lead to change in stage and then renew focus on the processes.


η(6) -Arene-Zirconium-PNP-Pincer Complexes: Mechanism of Their Hydrogenolytic Formation and Their Reactivity as Zirconium(II) Synthons.
The cyclometalated monobenzyl complexes [(Cbzdiphos(R) -CH)ZrBnX] 1 (iPr) Cl and 1 (Ph) I reacted with dihydrogen (10 bar) to yield the η(6) -toluene complexes [(Cbzdiphos(R) )Zr(η(6) -tol)X] 2 (iPr) Cl and 2 (Ph) I (cbzdiphos=1,8-bis(phosphino)-3,6-di-tert-butyl-9H-carbazole). The arene complexes were also found to be directly accessible from the triiodide [(Cbzdiphos(Ph) )ZrI3 ] through an in situ reaction with a dibenzylmagnesium reagent and subsequent hydrogenolysis, as exemplified for the η(6) -mesitylene complex [(Cbzdiphos(Ph) )Zr(η(6) -mes)I] (3 (Ph) I). The tolyl-ring in 2 (iPr) Cl adopts a puckered arrangement (fold angle 23.3°) indicating significant arene-1,4-diido character. Deuterium labeling experiments were consistent with an intramolecular reaction sequence after the initial hydrogenolysis of a Zr-C bond by a σ-bond metathesis. A DFT study of the reaction sequence indicates that hydrogenolysis by σ-bond metathesis first occurs at the cyclometalated ancillary ligand giving a hydrido-benzyl intermediate, which subsequently reductively eliminates toluene that then coordinates to the Zr atom as the reduced arene ligand. Complex 2 (Ph) I was reacted with 2,6-diisopropylphenyl isocyanide giving the deep blue, diamagnetic Zr(II) -diisocyanide complex [(Cbzdiphos(Ph) )Zr(CNDipp)2 I] (4 (Ph) I). DFT modeling of 4 (Ph) I demonstrated that the HOMO of the complex is primarily located as a "lone pair on zirconium", with some degree of back-bonding into the C≡N π* bond, and the complex is thus most appropriately described as a zirconium(II) species. Reaction of 2 (Ph) I with trimethylsilylazide (N3 TMS) and 2 (iPr) Cl with 1-azidoadamantane (N3 Ad) resulted in the formation of the imido complexes [(Cbzdiphos(R) )Zr=NR'(X)] 5 (iPr) Cl-NAd and 5 (Ph) I-NTMS, respectively. Reaction of 2 (iPr) Cl with azobenzene led to N-N bond scission giving 6 (iPr) Cl, in which one of the NPh-fragments is coupled with the carbazole nitrogen to form a central η(2) -bonded hydrazide(-1), whereas the other NPh-fragment binds to zirconium acting as an imido-ligand. Finally, addition of pyridine to 2 (iPr) Cl yielded the dark purple complex [(Cbzdiphos(iPr) )Zr(bpy)Cl] (7 (iPr) Cl) through a combination of CH-activation and C-C-coupling. The structural data and UV/Vis spectroscopic properties of 7 (iPr) Cl indicate that the bpy (bipyridine) may be regarded as a (dianionic) diamido-type ligand.


Quantitative characterization of gold nanoparticles by size-exclusion and hydrodynamic chromatography, coupled to inductively coupled plasma mass spectrometry and quasi-elastic light scattering.
The physicochemical characterization of nanoparticles (NPs) is of paramount importance for tailoring and optimizing the properties of these materials as well as for evaluating the environmental fate and impact of the NPs. Characterizing the size and chemical identity of disperse NP sample populations can be accomplished by coupling size-based separation methods to physical and chemical detection methods. Informed decisions regarding the NPs can only be made, however, if the separations themselves are quantitative, i.e., if all or most of the analyte elutes from the column within the course of the experiment. We undertake here the size-exclusion chromatographic characterization of Au NPs spanning a six-fold range in mean size. The main problem which has plagued the size-exclusion chromatography (SEC) analysis of Au NPs, namely lack of quantitation accountability due to generally poor NP recovery from the columns, is overcome by carefully matching eluent formulation with the appropriate stationary phase chemistry, and by the use of on-line inductively coupled plasma mass spectrometry (ICP-MS) detection. Here, for the first time, we demonstrate the quantitative analysis of Au NPs by SEC/ICP-MS, including the analysis of a ternary NP blend. The SEC separations are contrasted to HDC/ICP-MS (HDC: hydrodynamic chromatography) separations employing the same stationary phase chemistry. Additionally, analysis of Au NPs by HDC with on-line quasi-elastic light scattering (QELS) allowed for continuous determination of NP size across the chromatographic profiles, circumventing issues related to the shedding of fines from the SEC columns. The use of chemically homogeneous reference materials with well-defined size range allowed for better assessment of the accuracy and precision of the analyses, and for a more direct interpretation of results, than would be possible employing less rigorously characterized analytes.


Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques.
On the cusp of widespread permeation of nanomedicine, academia, industry, and government have invested substantial financial resources in developing new ways to better treat diseases. Materials have unique physical and chemical properties at the nanoscale compared with their bulk or small-molecule analogs. These unique properties have been greatly advantageous in providing innovative solutions for medical treatments at the bench level. However, nanomedicine research has not yet fully permeated the clinical setting because of several limitations. Among these limitations are the lack of universal standards for characterizing nanomaterials and the limited knowledge that we possess regarding the interactions between nanomaterials and biological entities such as proteins. In this review, we report on recent developments in the characterization of nanomaterials as well as the newest information about the interactions between nanomaterials and proteins in the human body. We propose a standard set of techniques for universal characterization of nanomaterials. We also address relevant regulatory issues involved in the translational process for the development of drug molecules and drug delivery systems. Adherence and refinement of a universal standard in nanomaterial characterization as well as the acquisition of a deeper understanding of nanomaterials and proteins will likely accelerate the use of nanomedicine in common practice to a great extent.


Palliation of pancreatic neoplasms.
Pancreatic adenocarcinoma accounts for 80% of pancreatic tumours. The majority are unresectable at diagnosis and only 10% of patients survive to 1 year. Therefore, selection of appropriate palliative procedures for jaundice, gastric outlet obstruction or pain is a vitally important aspect of the management of these patients. Overall survival is equivalent following surgical or non-surgical palliation of biliary obstruction. Operative biliary bypass is a more major intervention but is associated with longer relief of symptoms and fewer readmissions compared to non-operative procedures. Prognostic factors such as histopathology, presence of metastatic disease and C reactive protein levels may allow better prediction of survival, therefore aiding selection of the most appropriate palliative techniques.


Implementation and evaluation of a paediatric nurse-driven sedation protocol in a paediatric intensive care unit.
Optimal sedation and analgesia is a challenge in paediatric intensive care units (PICU) because of difficulties in scoring systems and specific metabolism inducing tolerance and withdrawal. Excessive sedation is associated with prolonged mechanical ventilation and hospitalisation. Adult and paediatric data suggest that goal-directed sedation algorithms reduce the duration of mechanical ventilation. We implemented a nurse-driven sedation protocol in a PICU and evaluated its impact. We conducted a before and after protocol implementation study in a population of children aged 0-18 years who required mechanical ventilation for at least 24 h between January 2013 and March 2015. After the protocol implementation in January 2014, nurses managed analgesia and sedation following an algorithm that included the COMFORT behaviour scale (COMFORT-B). Duration of mechanical ventilation was the primary outcome; secondary outcomes were total doses and duration of medications, PICU length of stay, incidence of ventilator-associated pneumonia, and occurrence of withdrawal symptoms. Pre-post analysis followed with segmented regression analysis of interrupted time series was used to assess the effect of protocol. A total of 200 children were analysed, including 107 before implementation and 93 children after implementation of the protocol. After implementation of the protocol, the total number of COMFORT-B scores per day of mechanical ventilation significantly increased from 3.9 ± 2.5 times during the pre-implementation period to 6.6 ± 3.5 times during the post-implementation period (p < 10-3). Mean duration of mechanical ventilation tended to be lower in the post-implementation period (8.3 ± 7.3 vs 6.6 ± 5.6 days, p = 0.094), but changes in either the trend per trimester from pre-implementation to post-implementation (p = 0.933) or the immediate change after implementation (p = 0.923) were not significant with segmented regression analysis. No significant change between pre- and post-implementation was shown for total dose of sedatives, withdrawal symptoms, agitation episodes, or unplanned endotracheal extubations. These results were promising and suggested that implementation of a nurse-driven sedation protocol in a PICU was feasible. Evaluation of sedation and analgesia was better after the protocol implementation; duration of mechanical ventilation and occurrence of withdrawal symptoms tended to be reduced.


Structural basis for the autoinhibition of the C-terminal kinase domain of human RSK1.
p90 ribosomal S6 kinases (RSKs) respond to various mitogen stimuli and comprise two distinct protein kinase domains. The C-terminal kinase domain (CTKD) receives signal from ERK1/2 and adopts an autoinhibitory mechanism. Here, the crystal structure of human RSK1 CTKD is reported at 2.7 Å resolution. The structure shows a standard kinase fold, with the catalytic residues in the ATP-binding cleft orientated in optimal conformations for phosphotransfer. The inactivation of the CTKD is conferred by an extra α-helix (αL), which occupies the substrate-binding groove. In combination with previous knowledge, this structure indicates that activation of RSK1 involves the removal of αL from the substrate-binding groove induced by ERK1/2 phosphorylation.


Americium Inhalational Exposure with Successful Chelation Therapy.
Americium is a man-made metal produced in very small quantities in nuclear reactors. Americium-241 is one of the radioactive isotopes of americium and has commercial applications, including use in smoke detectors. This is a case report of an occupational inhalation of americium-241, treated with both effective external decontamination and the use of diethylenetriamine pentaacetate to promote decorporation. This experience is significant because of the potential for americium or similar radionuclides to be used in "dirty" bombs or other radiological dispersion devices to cause large-scale radioactive contamination.


The AtRAD21.1 and AtRAD21.3 Arabidopsis cohesins play a synergistic role in somatic DNA double strand break damage repair.
The RAD21 cohesin plays, besides its well-recognised role in chromatid cohesion, a role in DNA double strand break (dsb) repair. In Arabidopsis there are three RAD21 paralog genes (AtRAD21.1, AtRAD21.2 and AtRAD21.3), yet only AtRAD21.1 has been shown to be required for DNA dsb damage repair. Further investigation of the role of cohesins in DNA dsb repair was carried out and is here reported. We show for the first time that not only AtRAD21.1 but also AtRAD21.3 play a role in somatic DNA dsb repair. Comet data shows that the lack of either cohesins induces a similar high basal level of DNA dsb in the nuclei and a slower DNA dsb repair kinetics in both cohesin mutants. The observed AtRAD21.3 transcriptional response to DNA dsb induction reinforces further the role of this cohesin in DNA dsb repair. The importance of AtRAD21.3 in DNA dsb damage repair, after exposure to DNA dsb damage inducing agents, is notorious and recognisably evident at the phenotypical level, particularly when the AtRAD21.1 gene is also disrupted. Our data demonstrates that both Arabidopsis cohesin (AtRAD21.1 and AtRAD21.3) play a role in somatic DNA dsb repair. Furthermore, the phenotypical data from the atrad21.1 atrad21.3 double mutant indicates that these two cohesins function synergistically in DNA dsb repair. The implications of this data are discussed.


A Liquid-Metal-Enabled Versatile Organic Alkali-Ion Battery.
Despite the high specific capacity and low redox potential of alkali metals, their practical application as anodes is still limited by the inherent dendrite-growth problem. The fusible sodium-potassium (Na-K) liquid metal alloy is an alternative that detours this drawback, but the fundamental understanding of charge transport in this binary electroactive alloy anode remains elusive. Here, comprehensive characterization, accompanied with density function theory (DFT) calculations, jointly expound the Na-K anode-based battery working mechanism. With the organic cathode sodium rhodizonate dibasic (SR) that has negligible selectivity toward cations, the charge carrier is screened by electrolytes due to the selective ionic pathways in the solid electrolyte interphase (SEI). Stable cycling for this Na-K/SR battery is achieved with capacity retention per cycle to be 99.88% as a sodium-ion battery (SIB) and 99.70% as a potassium-ion battery (PIB) for over 100 cycles. Benefitting from the flexibility of the liquid metal and the specially designed carbon nanofiber (CNF)/SR layer-by-layer cathode, a flexible dendrite-free alkali-ion battery is achieved with an ultrahigh areal capacity of 2.1 mAh cm-2 . Computation-guided materials selection, characterization-supported mechanistic understanding, and self-validating battery performance collectively promise the prospect of a high-performance, dendrite-free, and versatile organic-based liquid metal battery.


Clinical significance of taurodontism.
In an attempt to determine the clinical significance of taurodontism, two reports of cases of patients with the anomaly have been presented. It seems that the taurodont form does not interfere with routine operative procedures, but it is suggested that the morphology might hamper the location of orifices and could create difficulties in instrumentation and obturation in endodontic treatment. It is hoped that other cases involving the treatment of taurodont teeth will be reported to aid in determining the clinical significance of the anomaly for other areas of dentistry.


Thiobarbituric acid reactive substances are increased in the subcutaneous fat tissue of patients with end-stage renal disease.
Patients with end-stage renal disease are thought to be in a highly peroxidative state, based on studies showing decreased serum antioxidant activity and increased peroxidative products. In this study we confirm these findings by examining lipid peroxidation in subcutaneous fat tissue in uraemia. Twenty-seven subcutaneous fat samples were taken from patients with end-stage renal disease when they underwent intervention for arteriovenous fistula for haemodialyis or for catheter insertion for continuous ambulatory peritoneal dialysis. The control samples were taken from 11 patients with normal renal function and without any history of renal disease who had surgical interventions. Lipid peroxides were measured as thiobarbituric acid reactive substance. The concentration of thiobarbituric acid reactive substances in subcutaneous fat tissue in the patients with end-stage renal disease is 1.223 +/- 0.636 nmol/mg fat tissue (mean +/- SD) whereas the level in the control group is 0.097 +/- 0.054 nmol/mg fat tissue. A comparison of the two groups by Student's t test revealed a highly significant difference (P < 0.001). This study supports the finding of a severe peroxidative state in patients with end-stage renal disease.


Perioperative administration of selective cyclooxygenase-2 inhibitors for postoperative pain management in patients after total knee arthroplasty.
Total knee arthroplasty (TKA) is associated with considerable postoperative pain. The relative analgesic efficacy and adverse effect profile of perioperative use of selective cyclooxygenase-2 (COX-2) inhibitors for patients undergoing TKA are unclear. This is a systematic review and meta-analysis of all randomized controlled trials evaluating perioperative administration of COX-2 inhibitors for TKA. Eight studies that had enrolled a total of 571 patients were identified. There was a statistical significance in postoperative pain scores (0-24 hours: P = .0007, 24-48 hours: P = .01, 48-72 hours: P < .0001), opioid consumption (P = .006), active range of motion (P = .002), itching (P = .005), and postoperative nausea/vomiting (P = .003) between groups. There was no difference in blood loss during the first 24 hours after operation between groups. The efficacy of perioperative administration of selective COX-2 inhibitors to reduce postoperative pain and opioid consumption after TKA is validated. Furthermore, it has important outcome benefits after TKA.


Tobacco assessment in actively accruing National Cancer Institute Cooperative Group Program Clinical Trials.
Substantial evidence suggests that tobacco use has adverse effects on cancer treatment outcomes; however, routine assessment of tobacco use has not been fully incorporated into standard clinical oncology practice. The purpose of this study was to evaluate tobacco use assessment in patients enrolled onto actively accruing cancer clinical trials. Protocols and forms for 155 actively accruing trials in the National Cancer Institute's (NCI's) Clinical Trials Cooperative Group Program were evaluated for tobacco use assessment at enrollment and follow-up by using a structured coding instrument. Of the 155 clinical trials reviewed, 45 (29%) assessed any form of tobacco use at enrollment, but only 34 (21.9%) assessed current cigarette use. Only seven trials (4.5%) assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and 0.6% during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco status assessment was higher in lung/head and neck trials as well as phase III trials, but there was no difference according to year of starting accrual or cooperative group. Most actively accruing cooperative group clinical trials do not assess tobacco use, and there is no observable trend in improvement over the past 8 years. Failure to incorporate standardized tobacco assessments into NCI-funded Cooperative Group Clinical Trials will limit the ability to provide evidence-based cessation support and will limit the ability to accurately understand the precise effect of tobacco use on cancer treatment outcomes.


Clinical Utility of Mobocertinib in the Treatment of NSCLC - Patient Selection and Reported Outcomes.
Mobocertinib is an oral tyrosine kinase inhibitor (TKI) that selectively targets epidermal growth factor receptor exon 20 insertion (EGFRex20ins) mutations. It is a structural analog of the third-generation TKI osimertinib, which targets EGFR T790M mutant non-small cell lung cancer (NSCLC); however, mobocertinib gains selectivity for EGFRex20ins mutants over wild type (WT) by interacting with the C790 gatekeeper residue of EGFR. This is accomplished via a carboxylated isopropyl ester moiety at the C5-position of mobocertinib's central pyrimidine core. In Phase 1/2 dose-escalation and dose-expansion studies, mobocertinib was found to have an investigator-confirmed overall response rate (ORR) of 56% (9/16; 95% CI: 30-80%) and 25% (3/12; 95% CI: 5-57%) in patients without and with baseline brain metastasis, respectively. Median investigator-assessed progression-free survival (mPFS) was 10.2 months (95% CI: 5.6 - not reached) and 3.7 months (95% CI: 1.8-15.9) in patients without and with baseline brain metastasis, respectively. A third phase evaluated patients who had received pre-treatment with platinum-based chemotherapy (PPP) and included an extension cohort (EXCLAIM cohort) which evaluated patients treated previously with 1 or 2 lines of therapy. An Independent Review Committee (IRC) found both cohorts to have similar outcomes in terms of ORR, median time to response, mPFS, and disease progression or death. The treatment-emergent adverse events (TEAE) related to mobocertinib are similar to other EGFR inhibitors and are predominately gastrointestinal (eg diarrhea, nausea, vomiting) and cutaneous (eg rash). In September 2021, the FDA granted accelerated approval for mobocertinib in the treatment of patients with locally advanced or metastatic NSCLC with EGFRex20ins mutation whose disease progressed while on platinum-based chemotherapy. The present review describes data that led to the approval of mobocertinib.


CD8 T-cell subsets and viral load in the cerebrospinal fluid of therapy-naive HIV-infected individuals.
Central nervous system involvement is common in HIV infection. We determined the relationship between T-cell subsets and viral load in the cerebrospinal fluid (CSF) of therapy-naive, asymptomatic HIV-infected individuals. A shift from naive to effector-memory CD8 T cells was observed in the CSF of HIV-infected individuals compared with controls. The HIV load strongly correlated with CD8 T cells in CSF. Effector-memory CD8 T cells were positively and effector CD8 T cells were negatively associated with viral replication in CSF.


Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B (RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen.
The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces. Downstream signaling triggered by costimulatory molecule ligation results in reciprocal DC and T cell activation and survival, which predisposes to enhanced T cell-mediated immune responses. In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses. We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs. These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens. Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival. These results have generic implications for improved tumor Ag-expressing DC vaccines, and specific implications for a DC-based vaccine approach for human papillomavirus 16-associated cervical carcinoma.


Molnupiravir Does Not Induce Mutagenesis in Host Lung Cells during SARS-CoV-2 Treatment.
As SARS-CoV-2 continues to evolve and spread with the emergence of new variants, interest in small molecules with broad-spectrum antiviral activity has grown. One such molecule, Molnupiravir (MOV; other names: MK-4482, EIDD-2801), a ribonucleoside analogue, has emerged as an effective SARS-CoV-2 treatment by inducing catastrophic viral mutagenesis during replication. However, there are growing concerns as MOV's potential to induce host DNA mutagenesis remains an open question. Analysis of RNA-seq data from SARS-CoV-2-infected MOV-treated golden hamster lung biopsies confirmed MOV's efficiency in stopping SARS-CoV-2 replication. Importantly, MOV treatment did not increase mutations in the host lung cells. This finding calls for additional mutation calls on host biopsies from more proliferative tissues to fully explore MOV's hypothesized mutagenic risk.


Pseudo-templated transcription by Escherichia coli RNA polymerase at a mutant promoter.
A G----T mutation at the start-point of transcription of the phage P22 sar promoter (sar + 1T) causes a novel defect in promoter clearance by Escherichia coli RNA polymerase (RNAP) in vitro. Under standard transcription conditions, in the presence of high concentrations of all four NTPs, the predominant products from this promoter are poly(U) chains of varying length. Because the mutation creates a run of four T: A base-pairs from - 1 to +3 (TGTT----TTTT), we propose that synthesis of poly(U) is pseudo-templated by the A4 stretch on the template strand. G----A and G----C mutations at position +1 do not cause pseudo-templated transcription. Several molecules of poly(U) are produced and released per sar+1T promoter-polymerase complex without dissociation of RNAP from the template DNA. The exponential relationship between yield and size of individual poly(U) species indicates that there is a constant probability that another U residue will be added to the nascent chain. Presumably, pseudo-templated transcription occurs by a slippage (stuttering) mechanism like that proposed to explain certain kinds of RNA editing in eukaryotic viral mRNAs.


Blockade of K+ contractures in skeletal muscle by opioid drugs: a nonstereospecific effect.
The effect of several opioid drugs was tested on the K+ contractures in frog's skeletal muscle. These contractures are produced by the entrance of extracellular Ca2+ ions via the voltage-dependent, slow Ca2+ channels located in the T tubules. Morphine and other opioid agonists in concentrations ranging from 10(-10) to 10(-5) M inhibited K+ contractures. The stereoisomers, dextrorphan and levorphanol, were found to have identical potency in inhibiting high K+ contractures, suggesting that this was a nonstereospecific blockade of voltage-dependent calcium channels by the opioid drugs despite the low effective drug concentrations. In agreement with this conclusion it was found that the inhibition of K+ contractures by the opioids was not antagonized by naloxone. It also was observed using a sucrose gap apparatus that these opioid drugs in concentrations used to block the high K+ contractures did not reduce the K+-induced membrane depolarization. Raising the bathing solution Ca2+ concentration from 1.08 to 5 mM produced a reversal of the opioid-induced block of K+ contractures. Finally it was shown that while opioids completely blocked K+ contractures, they did not produce any effect on caffeine contractures showing that opioids do not deplete intracellular Ca2+ stores or inhibit the release of Ca2+ from intracellular sarcoplasmic reticulum stores. It was concluded that several opioid drugs in very low concentrations block K+ contractures in frog's skeletal muscle by a nonstereospecific block of voltage-dependent slow calcium channels.


Relationships between transport conditions and welfare outcomes during commercial long haul transport of cattle in North America.
The objective of the present study was to document the relationships between selected welfare outcomes and transport conditions during commercial long haul transport of cattle (≥400 km; 6,152 journeys; 290,866 animals). Surveys were delivered to transport carriers to collect information related to welfare outcomes including the number of dead, non-ambulatory (downer) and lame animals during each journey. Transport conditions surveyed included the length of time animals spent on truck, ambient temperature, animal density, shrinkage, loading time, cattle origin, season, experience of truck drivers, and vehicle characteristics. Overall 0.012% of assessed animals became lame, 0.022% non-ambulatory and 0.011% died onboard. Calves and cull cattle were more likely to die and become non-ambulatory during the journey, feeders intermediate, and fat cattle appeared to be the most able to cope with the stress of transport (P ≤ 0.01). The likelihood of cattle becoming non-ambulatory, lame, or dead increased sharply after animals spent over 30 h on truck (P < 0.001). The likelihood of animal death increased sharply when the midpoint ambient temperature fell below -15°C (P = 0.01) while the likelihood of becoming non-ambulatory increased when temperatures rose above 30°C (P = 0.03). Animals that lost 10% of their BW during transport had a greater (P < 0.001) likelihood of dying and becoming non-ambulatory or lame. Animals were more likely to die at smaller space allowances (P < 0.05), particularly at allometric coefficients below 0.015 (P = 0.10), which occurred more frequently in the belly and deck compartments of the trailers, and also at high space allowances in the deck (allometric coefficients > 0.035). The proportion of total compromised animals decreased with more years of truck driving experience (P < 0.001). Mortality was greater in cattle loaded at auction markets compared with feed yards and ranches (P < 0.01). Cull cattle, calves and feeders appear to be more affected by transport based on the likelihood of becoming non-ambulatory and dying within a journey. Most important welfare concerns during long distance transport include the total journey duration, too low or high space allowances, too high or too low ambient temperature, and the experience of the truck drivers.


Multiporous Supramolecular Microspheres for Artificial Photosynthesis.
Artificial photosynthesis shows a promising potential for sustainable supply of nutritional ingredients. While most studies focus on the assembly of the light-sensitive chromophores to 1-D architectures in an artificial photosynthesis system, other supramolecular morphologies, especially bioinspired ones, which may have more efficient light-harvesting properties, have been far less studied. Here, MCpP-FF, a bioinspired building block fabricated by conjugating porphyrin and diphenylalanine, was designed to self-assemble into nanofibers-based multiporous microspheres. The highly organized aromatic moieties result in extensive excitation red-shifts and notable electron transfer, thus leading to a remarkable attenuated fluorescence decay and broad-spectrum light sensitivity of the microspheres. Moreover, the enhanced photoelectron production and transfer capability of the microspheres are demonstrated, making them ideal candidates for sunlight-sensitive antennas in artificial photosynthesis. These properties induce a high turnover frequency of NADH, which can be used to produce bioproducts in biocatalytic reactions. In addition, the direct electron transfer makes external mediators unnecessary, and the insolubility of the microspheres in water allows their easy retrieval for sustainable applications. Our findings demonstrate an alternative to design new platforms for artificial photosynthesis, as well as a new type of bioinspired, supramolecular multiporous materials.


Health of resettled Iraqi refugees --- San Diego County, California, October 2007-September 2009.
In recent years, Iraqi refugees have been resettling in the United States in large numbers, with approximately 28,000 arrivals during October 2007-September 2009 (federal fiscal years [FYs] 2008 and 2009). All refugees undergo a required medical examination before departure to the United States to prevent importation of communicable diseases, including active tuberculosis (TB), as prescribed by CDC Technical Instructions. CDC also recommends that refugees receive a more comprehensive medical assessment after arrival, which typically occurs within the first 90 days of arrival. To describe the health profile of resettled Iraqi refugees, post-arrival medical assessment data were reviewed for 5,100 Iraqi refugees who underwent full or partial assessments at the San Diego County refugee health clinic during FYs 2008 and 2009. Among 4,923 screened refugees aged >1 year, 692 (14.1%) had latent tuberculosis infection (LTBI); among 3,047 screened adult refugees aged >18 years, 751 (24.6%) were classified as obese; and among 2,704 screened adult refugees, 410 (15.2%) were hypertensive. Although infectious illness has been the traditional focus of refugee medical screening, a high prevalence of chronic, noninfectious conditions that could lead to serious morbidity was observed among Iraqi refugees. Public health agencies should be aware of the potentially diverse health profiles of resettling refugee groups. Medical assessment of arriving refugee populations, with timely collection and review of health data, enables early detection, treatment, and follow-up of conditions, and can help public health agencies develop and set priorities for population-specific health interventions and guidelines.


[A pharmacokinetic study of diffusion in adenomatous prostatic tissue of an intravenous bolus of cefamandole].
Twenty-three patients undergoing transurethral resection of the prostate for benign prostatic hypertrophy received antibiotic prophylaxis with a second generation cephalosporin, cefamandole, administered by a single IV bolus of 2.5 g. A pharmacokinetic study was performed on blood and resection chips collected at regular intervals. Cefamandole penetrates rapidly into the prostate without any saturation threshold. It diffuses less extensively and persists for a shorter period in elderly subjects, but penetrates to an identical degree regardless of the volume of the adenoma. The prostatic concentration was always higher than the minimal inhibitory concentration for the bacteria generally encountered, except for pseudomonas. The pharmacokinetic study of cefamandole therefore demonstrated that an IV bolus of 2.5 g is perfectly suitable for antibiotic prophylaxis prior to prostatic resection.


Effects of temperature and novobiocin on the expression of calf prochymosin gene and on plasmid copy number in recombinant Escherichia coli.
Escherichia coli strain HB101 harboring an expression plasmid bearing calf prochymosin gene under the control of the tac promoter was grown in the presence of IPTG with or without novobiocin at 28 and 40 degrees C, respectively. The differential rates of synthesis of prochymosin inclusions, and, for comparison, of beta-lactamase and beta-galactosidase, as well as plasmid copy number, were determined during the first hours of steady state growth. At 28 degrees C the induced expression of prochymosin gene was almost blocked. Addition of novobiocin did not alleviate this effect. In fact, it strengthened it, and we conclude that both these additive inhibitory effects are a consequence of the decrease in negative superhelical tension of plasmid DNA to an insufficient level. At 40 degrees C the differential rate of prochymosin synthesis was markedly enhanced. Since the copy number of the expression plasmid increased approximately to the same extent, we conclude that an increase in gene dose is the cause. The stimulation of cloned heterologous gene expression at 40 degrees C and inhibition at 28 degrees C may be conveniently used in biotechnological-scale cultivations of some recombinant bacteria.


Analysis of lung cancer risk factors from medical records in Ethiopia using machine learning.
Cancer is a broad term that refers to a wide range of diseases that can affect any part of the human body. To minimize the number of cancer deaths and to prepare an appropriate health policy on cancer spread mitigation, scientifically supported knowledge of cancer causes is critical. As a result, in this study, we analyzed lung cancer risk factors that lead to a highly severe cancer case using a decision tree-based ranking algorithm. This feature relevance ranking algorithm computes the weight of each feature of the dataset by using split points to improve detection accuracy, and each risk factor is weighted based on the number of observations that occur for it on the decision tree. Coughing of blood, air pollution, and obesity are the most severe lung cancer risk factors out of nine, with a weight of 39%, 21%, and 14%, respectively. We also proposed a machine learning model that uses Extreme Gradient Boosting (XGBoost) to detect lung cancer severity levels in lung cancer patients. We used a dataset of 1000 lung cancer patients and 465 individuals free from lung cancer from Tikur Ambesa (Black Lion) Hospital in Addis Ababa, Ethiopia, to assess the performance of the proposed model. The proposed cancer severity level detection model achieved 98.9%, 99%, and 98.9% accuracy, precision, and recall, respectively, for the testing dataset. The findings can assist governments and non-governmental organizations in making lung cancer-related policy decisions.


Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh.
Chronic exposure to arsenic is associated with cancer and hypertension. Growing evidence suggests that altered methylation in long interspersed nuclear element-1 (LINE-1) is involved in many types of disorders, including cardiovascular disease. Here we evaluated the association between arsenic exposure and LINE-1 methylation levels, especially in relation to blood pressure (BP). A total of 236 subjects (175 from arsenic-endemic areas and 61 from a non-endemic area) in rural Bangladesh were recruited. The subjects' arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by inductively coupled plasma mass spectroscopy. The subjects' LINE-1 methylation levels were determined by pyrosequencing. The average LINE-1 methylation levels of the subjects living in the arsenic-endemic areas were significantly (p < 0.01) lower than those of the subjects living in the non-endemic area. In a sex-stratified analysis, the arsenic exposure levels in female but not male subjects showed a significant inverse association with LINE-1 methylation levels before (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) and after (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) adjustment for age, body mass index and smoking. Analyses examining interactions among arsenic levels, BP and LINE-1 methylation showed that arsenic-related elevated levels of BP were associated with LINE-1 hypomethylation. Our findings demonstrated that chronic exposure to arsenic was inversely associated with LINE-1 methylation levels in blood leukocyte DNA and this was more pronounced in females than males; in addition, the decreased levels of LINE-1 methylation might be involved in the arsenic-induced elevation of BP.


Effect of Comorbidities on the Infection Rate and Severity of COVID-19: Nationwide Cohort Study With Propensity Score Matching.
A vaccine against COVID-19 has been developed; however, COVID-19 transmission continues. Although there have been many studies of comorbidities that have important roles in COVID-19, some studies have reported contradictory results. This study was conducted using real-world data from COVID-19 patients in South Korea and aimed to investigate the impact of patient demographics and comorbidities on the infection rate and severity of COVID-19. Data were derived from a nationwide South Korean COVID-19 cohort study with propensity score (PS) matching. We included infected individuals who were COVID-19-positive between January 1, 2020, and May 30, 2020, and PS-matched uninfected controls. PS matching was performed to balance the baseline characteristics of each comorbidity and to adjust for potential confounders, such as age, sex, Charlson Comorbidity Index, medication, and other comorbidities, that were matched with binary variables. The outcomes were the confirmed comorbidities affecting the infection rate and severity of COVID-19. The endpoints were COVID-19 positivity and severe clinical outcomes of COVID-19 (such as tracheostomy, continuous renal replacement therapy, intensive care unit admission, ventilator use, cardiopulmonary resuscitation, and death). The COVID-19 cohort with PS matching included 8070 individuals with positive COVID-19 test results and 8070 matched controls. The proportions of patients in the severe group were higher for individuals 60 years or older (severe clinical outcomes for those 60 years or older, 16.52%; severe clinical outcomes for those of other ages, 2.12%), those insured with Medicaid (Medicaid, 10.81%; other insurance, 5.61%), and those with disabilities (with disabilities, 18.26%; without disabilities, 5.07%). The COVID-19 infection rate was high for patients with pulmonary disease (odds ratio [OR] 1.88; 95% CI 1.70-2.03), dementia (OR 1.75; 95% CI 1.40-2.20), gastrointestinal disease (OR 1.74; 95% CI 1.62-1.88), stroke (OR 1.67; 95% CI 1.23-2.27), hepatobiliary disease (OR 1.31; 95% CI 1.19-1.44), diabetes mellitus (OR 1.28; 95% CI 1.16-1.43), and cardiovascular disease (OR 1.20; 95% CI 1.07-1.35). In contrast, it was lower for individuals with hyperlipidemia (OR 0.73; 95% CI 0.67-0.80), autoimmune disease (OR 0.73; 95% CI 0.60-0.89), and cancer (OR 0.73; 95% CI 0.62-0.86). The severity of COVID-19 was high for individuals with kidney disease (OR 5.59; 95% CI 2.48-12.63), hypertension (OR 2.92; 95% CI 1.91-4.47), dementia (OR 2.92; 95% CI 1.91-4.47), cancer (OR 1.84; 95% CI 1.15-2.94), pulmonary disease (OR 1.72; 95% CI 1.35-2.19), cardiovascular disease (OR 1.54; 95% CI 1.17-2.04), diabetes mellitus (OR 1.43; 95% CI 1.09-1.87), and psychotic disorders (OR 1.29; 95% CI 1.01-6.52). However, it was low for those with hyperlipidemia (OR 0.78; 95% CI 0.60-1.00). Upon PS matching considering the use of statins, it was concluded that people with hyperlipidemia could have lower infection rates and disease severity of COVID-19.


In the clinic. Type 2 diabetes.
It is nearly impossible to be a practicing internist in the United States and have a day of clinical work pass without encountering at least 1 patient with type 2 diabetes. Currently, over 20 million Americans and over 150 million worldwide have type 2 diabetes. Models estimate that this number will nearly double by the year 2050 so that about one third of adult Americans will have the disease. This In the Clinic feature includes answers to these and other practical, clinical questions... What are the diagnostic criteria for type 2 diabetes in nonpregnant adults? Should we screen for type 2 diabetes? Can we prevent type 2 diabetes? What should the initial evaluation of patients with newly diagnosed type 2 diabetes include? What measures do U.S. stakeholders use to evaluate the quality of care for patients with type 2 diabetes? Only ACP members and individual subscribers can access the electronic features of In the Clinic. Non-subscribers who wish to access this issue of In the Clinic can elect "Pay for View." Subscribers can receive 1.5 category 1 CME credits by completing the CME quiz that accompanies this issue of In the Clinic. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians' Information and Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing division and with assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult www.acponline.org, http://pier.acponline.org, and other resources referenced within each issue of In the Clinic.


The chemotherapy of rodent malaria.XLIII. Indolo (3,2-c) quinoline-N-oxides.
A number of novel indolo (3,2-c) quinoline-N-oxides possess antimalarial activity. One of the series, compound CM 6606, has a superior blood schizontocidal action against drug-sensitive Plasmodium berghei in the mouse to that of chloroquine, although it is not fully active against strains highly resistant to chloroquine or mefloquine. It also shows some tissue schizontocidal (causal prophylactic) and gametocytocidal action in mice infected with P. yoelii nigeriensis. The structure activity of this chemical series and the possibility that CM 6606 functions through an active metabolite are discussed.


[Genotyping of hepatitis B virus by restriction enzyme analysis].
Hepatitis B is one of the most common infectious diseases in the world, and 350 million people have been estimated to be chronic hepatitis B virus carriers world-wide. Hepatitis B virus (HBV) has been classified into 8 genotypes (A-H) based on an intergroup divergence of 8% or more in the complete nucleotide sequence. Different genotypes of the hepatitis B virus may influence the clinical outcome of the disease. HBV genotyping method using restriction fragment length polymorphism (RFLP) can reliably identify genotypes. HBV genotyping with S gene sequence is consistent with genetic analysis using the full genomic sequences. The aim of this study was to determine the genotypes of HBV by using restriction fragment length polymorphism (RFLP) method in the region of Elazig. A total of 127 HBV-DNA positive patients (74 male, 53 female) were included in the study. Semi-nested polymerase chain reaction (PCR) was performed to amplify the specific parts of HBV S gene. In the first step, 685 base paired (bp) region was amplified by sense primer HBMF1 and anti-sense primer HBMR2, while in the second step 485 bp region was amplified by using inner-sense primer HBMF2 and anti-sense primer HBMR2. PCR products were then digested by the restriction enzymes, Alwl, Earl, Hphl, Ncil and NlalV. The RFLP assay indicated that genotype D was the only detected type in our samples. In conclusion, genotype D is the predominant type among hepatitis B patients in our region. RFLP is considered to be an easy and useful method for genotyping HBV strains.


[Efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome].
Objective: To evaluate the efficacy of CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves in the treatment of Meige syndrome. Methods: The Clinical data of 56 patients with Meige syndrome in the Department of Pain Medicine, Affiliated Hospital of Jiaxing University from June 2019 to January 2023 were retrospectively analyzed [19 males and 37 females, aged 42-76 (58.6±8.3) years], including 51 cases of blepharospasm, 3 cases of oromandibular dystonia and 2 cases of blepharospasm concomitant with oromandibular dystonia. CT-guided partial radiofrequency ablation of bilateral responsible cranial nerves was performed on different types of Meige syndrome. And the efficacy and complications of the technique were observed. Results: Fifty-one patients with blepharospasm Meige syndrome underwent CT-guided radiofrequency of facial nerve through bilateral stylomastoid foramen punctures, the symptoms of blepharospasm disappeared completely, leaving bilateral mild and moderate facial paralysis symptoms. Three patients with oral-mandibular dystonia underwent CT-guided radiofrequency therapy by bilateral foramen ovale puncture of mandibular branches of trigeminal nerve, masticatory muscle spasm disappeared, the patients had no difficulty opening the mouth, and the skin numbness in bilateral mandibular nerve innervation area was left. Two cases of Meige syndrome with blepharospasm concomitant with oromandibular dystonia were treated by radiofrequency of facial nerve and mandibular branch of trigeminal nerve, and all symptoms disappeared. The patients were followed up for 1-44 months after the operation, and the symptoms of mild and moderate facial paralysis disappeared at (3.2±0.8) months after the operation, but the numbness did not disappear. Three patients with blepharospasm recurred at the 14, 18 and 22 months after the operation, respectively, while the rest cases did not recur. Conclusions: According to different types of Meige syndrome, CT-guided partial radiofrequency ablation of responsible cranial nerves can effectively treat the corresponding type of Meige syndrome. The complications are only mild and moderate facial paralysis which can be recovered, and/or skin numbness in the mandibular region.


Anesthetic management of an elderly COVID-19 patient with pulmonary thromboembolism for hip surgery - A case report.
COVID-19 and delayed hip surgery are well-known risk factors for thromboembolism in elderly patients. We report the case of an 88-year-old female patient with COVID-19 and pulmonary thromboembolism (PTE) who underwent delayed hip surgery 21 days after the injury. Heparinization and inferior vena cava filters were used to treat and prevent PTE. Transesophageal echocardiography and extracorporeal membrane oxygenation (ECMO) sheaths were inserted as a precaution in case of emergencies during surgery; the procedure was performed without any specific event. COVID-19-infected patients suffering from a hip fracture have a high risk of thromboembolism, and therefore, require utmost attention for appropriate evaluation and prevention.


Comparative Plasma Pharmacokinetics of Ceftriaxone and Ertapenem in Normoalbuminemia, Hypoalbuminemia, and Albumin Replacement in a Sheep Model.
Optimal concentrations of unbound antimicrobials are essential for a maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare the effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model. The study design was a prospective, three-phase intervention observational study. The subjects were healthy Merino sheep. Eight sheep were subjected to three experimental phases: normoalbuminemia, hypoalbuminemia using plasmapheresis, and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone at 40 mg/kg of body weight and ertapenem at 15 mg/kg were given intravenously. Blood samples were collected at predefined intervals and analyzed using an ultrahigh-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters such as the area under the curve from 0 to 24 h (AUC0-24), plasma clearance (CL), and apparent volume of distribution in the terminal phase (V) were estimated and compared between the phases. The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC0-24 and higher CL of total and unbound concentrations of ceftriaxone than in the other phases, whereas albumin replacement led to higher AUC0-24 and lower CL than in the other phases for both drugs. The V values for total drug concentrations for both drugs were significantly lower with albumin replacement. For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.


Ambient concentrations of total suspended particulate matter and its elemental constituents at the wider area of the mining facilities of TVX Hellas in Chalkidiki, Greece.
To assess ambient air quality at the wider area of TVX Hellas mining facilities, the Total Suspended Particulate matter (TSP) and its content in characteristic elements, i.e., As, Cd, Cu, Fe, Mn, Pb, Zn are being monitored for more than thirty months as part of the established Environmental Monitoring Program. High Volume air samplers equipped with Tissue Quartz filters were employed for the collection of TSP. Analyses were effected after digestion of the suspended particulate with an HNO3-HCl solution and determination of elemental concentrations with an Atomic Absorption Spectroscopy equipped with graphite furnace. The sampling stations were selected to record representatively the existing ambient air quality in the vicinity of the facilities and at remote sites not affected from industrial activities. Monitoring data indicated that the background TSP concentrations ranged from 5-60 microg/m3. Recorded TSP concentrations at the residential sites close to the facilities ranged between 20-100 microg/m3, indicating only a minimal influence from the mining and milling activities. Similar spatial variation was observed for the TSP constituents and specifically for Pb and Zn. To validate the monitoring procedures, a parallel sampling campaign took place with different High Volume samplers at days where low TSP concentrations were expected. The satisfactory agreement (+/- 11%) at low concentrations (50-100 microg/m3) clearly supported the reproducibility of the techniques employed specifically at the critical range of lower concentrations.


Pharmacokinetics of 5-fluorouracil and cyclophosphamide in depression rats.
Efficacy and toxicity of the drug are mainly determined by physicochemical properties and pharmacological effects of its own. In addition, they are also affected by other factors, such as gender, age, genetic character, pathophysiological status, mood states and so on. The paper aims to study whether mood disorder alters drug metabolism process through the pharmacokinetic research on some clinically important anticancer drugs in depression model rats. The depression model rats were built by exposing to chronic unpredicted mild stresses (CUMS) for 8 weeks. 36 female Sprague-Dawley (SD) rats were randomized into model group and control group. In each group, 18 rats were randomized into 2 subgroups: 5-fluorouracil (5-FU) subgroup and cyclophosphamide (CP) subgroup which were given a certain doses of 5-FU and CP. The blood samples were collected at different time points and plasma drug concentration were respectively assayed by high performance liquid chromatography (HPLC) for 5-FU and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for CP. Pharmacokinetic parameters were processed with DAS software. There were significant differences in the pharmacokinetic parameters of 5-FU and CP between in depression model rats group and in the normal control group (p < 0.05), except t1/2alpha (p > 0.05) for CP pharmacokinetics in depression model rats group and in the normal control rats group, with the value of those was 0.07 and 0.09 h. Depression mood disorder might alter drug metabolism process.


Taxonomic status of Harlan's Hawk Buteo jamaicensis harlani (Aves: Accipitriformes).
Since its description in 1830 by Audubon, Harlan's Hawk (taxon harlani) has been considered both as a species (Buteo harlani) (1830-1891 and 1944-1972) and as a subspecies of Red-tailed Hawk (B. jamaicensis harlani) (1891-1944 and 1973 to present). Both decisions making it a subspecies lacked sufficient taxonomic justification, whereas the 1944 decision to consider it a species was supported by convincing arguments. I conducted field and museum work over many years to better understand the morphology and taxonomic status of harlani and how this taxon differs from other taxa currently included in B. jamaicensis. Some hybridization between these taxa has been reported, as has been between many other species of Buteo. The taxon harlani is distinguished from all subspecies of B. jamaicensis in plumage, including the extent of feathering on the tarsus. The species occupies a breeding range parapatric, but with some overlap, to that of B. jamaicensis but occasionally breeds within a large area of the range of the latter in western Canada. It should be considered a full species based on lack of justification for considering it a subspecies, and the many differences between it and B. jamaicensis, which are greater than differences between any two subspecies of diurnal raptor.


Liver sarcoidosis that presented with dysphagia.
We report a case of liver sarcoidosis with dysphagia. Although akinesia of the soft palate, disappearance of the palatal reflex, and pyramidal signs indicated brainstem lesions, brain magnetic resonance imaging showed no lesion and the focus was obscure. Iritis, parotiditis, and hilar lymphadenopathy supported the diagnosis of sarcoidosis. However, lung biopsy was normal. Finally, sarcoidosis was diagnosed by liver biopsy. We speculated that microgranulomas in the brainstem that did not exhibit imaging abnormalities causing the neurological symptoms and that liver biopsy can be an effective diagnostic tool even for cases that presented with neurological signs, but no gastrointestinal symptom.


Metabolic Syndrome, Its Components, and Knee Osteoarthritis: The Framingham Osteoarthritis Study.
Previous studies have suggested that metabolic syndrome is associated with osteoarthritis (OA). However, analyses have often not included adjustment for body mass index (BMI) and have not addressed whether levels of individual metabolic syndrome components are related to OA. This study was undertaken to examine the relationship of metabolic syndrome and its components with radiographic and symptomatic knee OA. Framingham Study subjects were assessed for OA in 1992-1995 and again in 2002-2005. Near the baseline visit, subjects had components of metabolic syndrome assessed. We defined incident radiographic OA as present when a knee without radiographic OA at baseline had a Kellgren/Lawrence grade of ≥2 at follow-up, and defined incident symptomatic OA as present when a knee developed the new combination of radiographic OA and knee pain. After excluding knees with prevalent OA at baseline, we tested the relationship of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria and its components with the risk of incident radiographic OA and symptomatic OA before and after adjusting for BMI using the risk ratio from a binary regression with generalized estimating equations. A total of 991 subjects (55.1% women) with a mean age of 54.2 years were studied, and 26.7% of men and 22.9% of women had metabolic syndrome. Metabolic syndrome and many of its components were associated with both incident radiographic OA and symptomatic OA, but after adjustment for BMI, almost all of these associations became weak and nonsignificant. An association of high blood pressure, especially diastolic pressure, with OA outcomes persisted in both men and women. After adjustment for BMI, neither metabolic syndrome nor its components were associated with incident OA. There may be an association between OA and high blood pressure that needs further study.


Proliferative response of human T lymphocytes to a vaccinal preparation of ribosomes from Streptococcus pyogenes.
The in vitro lymphocyte-activating properties of a ribosomal preparation of Streptococcus pyogenes were investigated. The preparation was mitogenic for human lymphocytes with a peak of 3H-thymidine incorporation occurring after 3-5 days of culture. The response was abolished by removal of CD3-positive cells and by alteration of accessory cells by exposure to L-leucine methyl ester. Most of the cells synthesizing DNA at the end of the culture expressed CD4 or CD8 but not CD20 antigens. No immunoglobulin synthesis was demonstrable. Although the same preparation was shown to be a T-independent polyclonal B-cell activator of murine cells, it preferentially triggers T cells in humans.


Implant-abutment interface design affects fatigue and fracture strength of implants.
Failures of implant-abutment connections are relatively frequent clinical problems. The aim of this study was to evaluate the influence of long-term dynamic loading on the fracture strength of different implant-abutment connections. Six implant systems were tested: two systems with external connections (Brånemark, Compress) and four systems with internal connections (Frialit-2, Replace-Select, Camlog, Screw-Vent). Fracture strength was tested in two subgroups for each system: one subgroup with (dyn) and the other without prior dynamic loading (contr). Each subgroup consisted of eight specimens with standard implant-abutment combinations for single molar crowns. Dynamic loading was performed in a two-axis chewing simulator with 1,200,000 load cycles at 120 N. Median fracture strengths in Newton (N) and 25th and 75th percentiles [in brackets] were: Brånemark: dyn=729 [0;802]/contr=782 [771;811], Frialit-2: dyn=0 [0;611]/contr=887 [798;941], Replace-Select: dyn=1439 [1403;1465]/contr=1542 [1466;1623], Camlog: dyn=1482 [1394;1544]/contr=1467 [1394;1598], Screw-Vent: dyn=0 [0;526]/contr=780 [762;847] and Compress: dyn=818[0;917]/contr=1008 [983;1028]. In some dyn subgroups, failures of the implant-abutment connection occurred already during dynamic loading: three specimens of the Brånemark and Compress groups and six specimens of the Screw-Vent and the Frialit-2 groups failed during dynamic loading. Statistically significant differences (P< or =0.05) in fracture strength could be found between groups with different connection designs. Implant systems with long internal tube-in-tube connections and cam-slot fixation showed advantages with regard to longevity and fracture strength compared with systems with shorter internal or external connection designs.


Changes in benthos associated with mussel (Mytilus edulis L.) farms on the west-coast of Scotland.
Aquaculture, as a means of food production, is growing rapidly in response to an increasing demand for protein and the over-exploitation of wild fisheries. This expansion includes mussels (family Mytilidae) where production currently stands at 1.5 million tonnes per annum. Mussel culture is frequently perceived as having little environmental impact yet mussel biodeposits and shell debris accumulate around the production site and are linked to changes in the benthos. To assess the extent and nature of changes in benthos associated with mussel farming grab and video sampling around seven mussel farms was conducted. Grab samples were analysed for macrofauna and shell-hash content whilst starfish were counted and the shell-hash cover estimated from video imaging. Shell-hash was patchily distributed and occasionally dominated sediments (maximum of 2116 g per 0.1 m(2) grab). Mean shell-hash content decreased rapidly at distances >5 m from the line and, over the distance 1-64 m, decreased by three orders of magnitude. The presence of shell-hash and the distance-from-line influenced macrofaunal assemblages but this effect differed between sites. There was no evidence that mussel farming was associated with changes in macrobenthic diversity, species count or feeding strategy. However, total macrofaunal count was estimated to be 2.5 times higher in close proximity to the lines, compared with 64 m distance, and there was evidence that this effect was conditional on the presence of shell-hash. Starfish density varied considerably between sites but, overall, they were approximately 10 times as abundant close to the mussel-lines compared with 64 m distance. There was no evidence that starfish were more abundant in the presence of shell-hash visible on the sediment surface. In terms of farm-scale benthic impacts these data suggest that mussel farming is a relatively benign way of producing food, compared with intensive fish-farming, in similar environments.


Pathways of cellular efflux and particulate clearance after carbon instillation to the lung.
The pulmonary response to the deposition of carbon particles was investigated to determine the routes of cellular efflux and the mechanisms of particulate clearance. At intervals to 6 months after the intratracheal instillation of 4 mg carbon, the lungs of mice were fixed in situ by perfusion without lavage. Within a few hours, migration of granulocytes into the bronchioles was observed; large numbers of PMNs were not seen in alveoli until 24 h. Associated with the PMN efflux there was transient oedema with no evidence of pulmonary cell necrosis. The number of free macrophages increased in response to the carbon and mononuclear cell migration into alveoli and bronchioles was also observed. The bronchiolar component of the cellular efflux indicates that PMNs and macrophages recovered from the lung by lavage are not entirely of alveolar origin. Whereas most particles, either free or in phagocytic cells, were cleared by the bronchial tree, some transepithelial passage of free particles to the interstitium was observed. Some carbon was found in hilar lymph nodes but overall lymphatic clearance was low.


Microbial Diversity and Metabolite Profile of Fermenting Millet in the Production of Hausa koko, a Ghanaian Fermented Cereal Porridge.
Hausa koko is an indigenous porridge processed from millet in Ghana. The process involves fermentation stages, giving the characteristic organoleptic properties of the product that is produced largely at a small-scale household level and sold as a street food. Like many other indigenous foods, quality control is problematic and depends on the skills of the processor. In order to improve the quality of the product and standardize the process for large-scale production, we need a deeper understanding of the microbial processes. The aim of this study is to investigate the microbial community involved in the production of this traditional millet porridge and the metabolites produced during processing. High-throughput amplicon sequencing was used to identify the bacterial (16S rRNA V4 hypervariable region) and fungal [Intergenic Transcribed Spacer (ITS)] communities associated with the fermentation, while nuclear magnetic resonance (NMR) was used for metabolite profiling. The bacterial community diversity was reduced during the fermentation processes with an increase and predominance of lactobacilli. Other dominant bacteria in the fermentation included Pediococcus, Weissella, Lactococcus, Streptococcus, Leuconostoc, and Acetobacter. The species Limosilactobacillus fermentum and Ligilactobacillus salivarius accounted for some of the diversities within and between fermentation time points and processors. The fungal community was dominated by the genus Saccharomyces. Other genera such as Pichia, Candida, Kluyveromyces, Nakaseomyces, Torulaspora, and Cyberlindnera were also classified. The species Saccharomyces cerevisiae, Stachybotrys sansevieriae, Malassezia restricta, Cyberlindnera fabianii, and Kluyveromyces marxianus accounted for some of the diversities within some fermentation time points. The species S. sansevieria and M. restricta may have been reported for the first time in cereal fermentation. This is the most diverse microbial community reported in Hausa koko. In this study, we could identify and quantify 33 key different metabolites produced by the interactions of the microbial communities with the millet, composed of organic compounds, sugars, amino acids and intermediary compounds, and other key fermentation compounds. An increase in the concentration of organic acids in parallel with the reduction of sugars occurred during the fermentation process while an initial increase of amino acids followed by a decrease in later fermentation steps was observed.


Investigation of plasmid instability in amylase-producing B. subtilis using continuous culture.
Continuous culture was employed to study plasmid instability in an amylase-producing Bacillus subtilis 1A289 that was genetically manipulated. No true steady state could be obtained with 1A289(pEAA)-strain (plasmid)-due to its structural instability, which occurred both with glucose and Maltrin-100 as limiting carbon sources. The plasmid, pEAA (Cm(R), amy(+), i.e., chloramphenicol resistant, amylase positive) degenerated into a smaller plasmid, pEAA1 (CM(R), amy(-)) that was stable. There was a direct correlation between amylase-producing ability and this structural instability since f(amy) (fraction of cells with amylase-producing ability) reached zero at the same time that f (fraction of cells that are resistant to chloramphenicol) reached its maximum level. Since the deletion in pEAA was larger than the original amylase-gene insert, either all of part of the insert is absent from pEAA1. Though on discernible change in 1A289(pHV33), where pHV33 is the vector plasmid, was observed during continuous cultivation, its behavior was different from that of the stable 1A289(pEAA1).


Methadone: dental risks and preventive action.
For some time dentists have successfully promoted the benefits of sugar-free medications. There are now over 180 sugar-free medicines manufactured and prescribed. Methadone, used in the rehabilitation of drug-users, is available as a sugar-free preparation; however, the sugar-based version is most often used. This article examines the content of methadone, explains some of the reasons for prescribing patterns and explores how a multi-disciplinary approach can be used to help methadone users with their rehabilitation and minimize risks to oral health. The wider public health and health policy implications of methadone use are discussed and the available literature reviewed. Dentists are most likely to encounter patients on methadone as a dental emergency and they need to be aware that methadone users are at greater risk of decay and erosion from methadone sugar syrup, as well as perhaps their lifestyle. For dental practitioners, addressing the oral health needs of methadone users can contribute to their general well-being.


The clinical significance of papillitis of the major duodenal papilla.
This study investigated the clinical significance of papillitis of the major duodenal papilla and analyzed the correlation between endoscopic and histologic papillitis in patients with biliary or pancreatic disorders. Eighty-seven patients and 12 healthy control subjects were enrolled. The endoscopic appearance of papillitis was classified by two blinded endoscopists, and biopsy specimens were taken of the papilla. Various factors were prospectively analyzed to identify any relationship with the endoscopic severity of the papillitis. By univariate analysis, a clinically acute inflammatory condition and elevation of serum transaminase levels were significantly associated with moderate and severe endoscopic papillitis (p < 0.05). However, by multivariate analysis, only a clinically acute inflammatory condition was significantly associated with moderate and severe endoscopic papillitis (p < 0.001). The endoscopic severity of papillitis was poorly correlated with monocyte infiltration, but there was a good correlation with neutrophil infiltration. Moderate and severe papillitis were not observed in healthy volunteers. Moderate and severe endoscopic papillitis were significantly more common in patients with biliary or pancreatic disorders plus a clinically acute inflammatory condition, whereas moderate and severe papillitis were not observed in healthy volunteers. Moderate and severe endoscopic papillitis are characteristic of biliary or pancreatic disorders.


Haemodynamic regulation of renal prostaglandin and renin release.
To examine the relationship between renal release of the prostaglandins E2 (PGE2) and I2 (PGI2) and renin during autoregulatory vasodilation, experiments were performed in anaesthetized dogs with denervated kidneys. Autoregulatory vasodilation was induced by reducing renal arterial pressure (RAP) or by raising ureteral pressure in steps. During progressive renal arterial constriction, PGE2 and PGI2 release reached maximal values (10.6 +/- 1.7 for PGE2 and 6.6 +/- 1.1 pmol min-1 for PGI2 release) at RAP of 70-80 mmHg, associated with almost no increase in renin release. By further reduction of RAP, prostaglandin release was not significantly altered, whereas renin release reached maximal values (18.7 +/- 2.4 micrograms AI min-1) when autoregulatory vasodilation was complete at RAP below 55-60 mmHg. During progressive elevation of ureteral pressure, the release of PGE2, PGI2 and renin increased in concert in a curvilinear fashion, reaching maximal values at a ureteral pressure of 85 mmHg. There was no further increase during ureteral occlusion and the plateau values averaged 23.6 +/- 3.7 pmol min-1 for PGE2, 8.0 +/- 1.6 pmol min-1 for PGI2 and 16.6 +/- 3.4 micrograms AI min-1 for renin. We conclude that vascular dilation enhances both prostaglandin and renin release. During reduction of RAP, preglomerular arteries are dilated at higher RAP than are afferent arterioles. Release of prostaglandins synthetized in arteries consequently occurs at higher RAP than release of renin, which is not enhanced until afferent arterioles ultimately dilate at RAP approaching 60 mmHg. In contrast, elevation of ureteral pressure provides nearly uniform enhancement of prostaglandin and renin release, indicating a more uniform dilation of the whole preglomerular vascular tree.