Subtalar fusion for pes valgus in cerebral palsy: results of a modified technique in the setting of single event multilevel surgery.
We studied the use of cortico-cancellous circular allograft combined with cannulated screw fixation for the correction of dorsolateral peritalar subluxation in a series of children with bilateral spastic cerebral palsy undergoing single event multilevel surgery. Forty-six children who underwent bilateral subtalar fusion between January 1999 and December 2004 were retrospectively reviewed. Gait laboratory records, Gross Motor Function Classification System (GMFCS) levels, Functional Mobility Scale (FMS) scores, and radiographs were reviewed. The surgical technique used an Ollier type incision with a precut cortico-cancellous allograft press-fit into the prepared sinus tarsi. One or two 7.3 mm fully threaded cancellous screws were used to fix the subtalar joint. Radiographic analysis included preoperative and postoperative standing lateral radiographs measuring the lateral talocalcaneal angle, lateral talo-first metatarsal angle, and navicular cuboid overlap. Fusion rate was assessed with radiographs >12 months after surgery. The mean patient age was 12.9 years (range, 7.8 to 18.4 y) with an average follow-up of 55 months. Statistically significant improvement postoperatively was found for all 3 radiographic indices: lateral talocalcaneal angle, mean improvement 20 degrees (95% CI, 17.5-22.1; P<0.001); lateral talo-first metatarsal angle, mean improvement 21 degrees (95% CI, 19.2-23.4; P<0.001); and navicular cuboid overlap, mean improvement 29% (95% CI, 25.7%-32.6%; P<0.001). FMS improved across all patients, with Gross Motor Function Classification System III children experiencing a 70% improvement across all 3 FMS distances (5, 50, and 500 m). All 3 radiographic measures improved significantly (P<0.001). Fusion was achieved in 45 patients and there were no wound complications. With this study, we demonstrate significant improvement in radiographic segmental alignment and overall function outcome with this modified subtalar fusion technique. We conclude that this technique is an effective complement for children with dorsolateral peritalar subluxation undergoing single event multilevel surgery. Level IV.


Mycobacterium smegmatis PafBC is involved in regulation of DNA damage response.
Two genes, pafB and pafC, are organized in an operon with the Pup-ligase gene pafA, which is part of the Pup-proteasome system (PPS) present in mycobacteria and other actinobacteria. The PPS is crucial for Mycobacterium tuberculosis resistance towards reactive nitrogen intermediates (RNI). However, pafB and pafC apparently play only a minor role in RNI resistance. To characterize their function, we generated a pafBC deletion in Mycobacterium smegmatis (Msm). Proteome analysis of the mutant strain revealed decreased cellular levels of various proteins involved in DNA damage repair, including recombinase A (RecA). In agreement with this finding, Msm ΔpafBC displayed increased sensitivity to DNA damaging agents. In mycobacteria two pathways regulate DNA repair genes: the LexA/RecA-dependent SOS response and a predominant pathway that controls gene expression via a LexA/RecA-independent promoter, termed P1. PafB and PafC feature winged helix-turn-helix DNA binding motifs and we demonstrate that together they form a stable heterodimer in vitro, implying a function as a heterodimeric transcriptional regulator. Indeed, P1-driven transcription of recA was decreased in Msm ΔpafBC under standard conditions and induction of recA expression upon DNA damage was strongly impaired. Taken together, our data indicate an important regulatory function of PafBC in the mycobacterial DNA damage response.


Where are tomorrow's specialists?
To determine the extent to which New Zealand's future specialists are likely to be graduates of this country's medical schools. Forward projections were made on the basis of information from: (1) Medical Council annual reports recording additions to the Register of Specialists between July 1 1990 and June 30 1994, (2) Medical Council annual questionnaire data relating to New Zealand doctors qualifying in 1971-85, (3) Medical Directories of Australia, Canada, UK and USA, (4) selected Australasian specialist colleges on the number of registered trainees in New Zealand, and (5) Medical School data on New Zealand graduating classes since 1971. Forty percent of the new specialists registered in New Zealand between 1 July 1990 and 30 June 1994 were graduates of overseas medical schools. Future projections suggest that this percentage is likely to increase. Major determinants of New Zealand specialist numbers are (1) the proportion of specialist New Zealand graduates (38%) not working in this country, and (2) the sex ratio of future graduating classes--proportionately fewer women (38%) than men (56%) specialise. Graduates of this country's medical schools are likely to supply approximately half of New Zealand's future specialists.


Gingival squamous cell carcinoma masquerading as an aphthous ulcer.
Gingival squamous cell carcinoma (GSCC) is an uncommon condition of the oral cavity. It is seldom associated with classic risk factors of oral cancer and shows a predilection for females. It's close clinical resemblances to various lesions of the oral cavity may make it go unnoticed. This may lead to diagnosis at advanced stages and coupled with the proximity to underlying alveolar bone may result in subsequent morbidity and mortality. A case of GSCC camouflaged as an aphthous ulcer in a middle aged woman is presented. The article highlights the importance of early diagnosis resulting in conservative treatment approaches.


Mapping of magnesium and of different protein fragments in sea urchin teeth via secondary ion mass spectroscopy.
Mature portions of sea urchin are comprised of a complex array of reinforcing elements yet are single crystals of high and very high Mg calcite. How a relatively poor structural material (calcite) can produce mechanically competent structures is of great interest. In teeth of the sea urchin Lytechinus variegatus, we recorded high-resolution secondary ion mass spectrometry (SIMS) maps of Mg, Ca ,and specific amino acid fragments of mineral-related proteins including aspartic acid (Asp). SIMS revealed strong colocalization of Asp residues with very high Mg. Demineralized specimens showed serine localization on membranes between crystal elements and reduced Mg and aspartic acid signals, further emphasizing colocalization of very high Mg with ready soluble Asp-rich protein(s). The association of Asp with nonequilibrium, very high magnesium calcite provides insight to the makeup of the macromolecules involved in the growth of two different composition calcites and the fundamental process of biomineralization.


A stage-specific functional role of the leucine zipper transcription factor c-Maf in lung Th2 cell differentiation.
The transcription factor c-Maf controls IL-4 gene expression in CD4(+) T cells, and its expression is up-regulated in human asthmatic airways after allergen challenge. In the present study, we addressed the role of c-Maf in asthma by studying transgenic (Tg) mice overexpressing c-Maf in CD4(+) T cells under the control of the CD2 promoter. As shown, lung CD4(+) T cells of c-maf-Tg mice produced more IL-5 at the early stage (day 2) of culture in the presence of IL-4 than wild-type control cells. Consistently, c-maf-Tg mice spontaneously showed increased IL-5 expression and eosinophils in the bronchial alveolar lavage fluid (BALF) and activated IL-5 signal transduction via Raf-1 and Ras in lung eosinophils. Finally, IL-13 was suppressed in the BALF of c-maf-Tg mice and in supernatants of Tg lung CD4(+) T cells cultured in the presence of IL-2. Consistently, retroviral overexpression of c-Maf suppressed IL-13 production in developing lung Th2 cells. In summary, c-Maf induces IL-5 production in lung CD4(+) T cells at an early stage, but along with IL-2 suppresses IL-13 production in differentiating lung Th2 cells, thereby explaining the finding that overexpression of c-Maf does not cause airway hyperresponsiveness, a hallmark feature of asthma.


Structure and ligand-based design of mTOR and PI3-kinase inhibitors leading to the clinical candidates VS-5584 (SB2343) and SB2602.
Phosphoinositide 3-kinases (PI3Ks) and the mammalian target of rapamycin (mTOR) act as critical effectors in a commonly deregulated cell signaling pathway in human cancers. The abnormal activation of the PI3K/mTOR pathway has been shown to play a role in initiation, progression, and metastasis of human tumors. Being one of the most frequently activated pathways in cancer, much effort has been directed toward inhibition of the PI3K/mTOR pathway as a novel oncology therapy. Previous work by a number of groups has revealed several selective PI3K and dual mTOR/PI3K inhibitors. However, there are few reports of therapeutic agents with a pan-PI3K/mTOR inhibitory profile within a narrow concentration range. We therefore initiated a drug discovery project with the aim of discovering dual mTOR/PI3K inhibitors which would equipotently inhibit the 4 isoforms of PI3K, α, β, γ, and δ, and mTOR a compelling profile for powerful blockage of the PI3K/mTOR pathway. A pharmacophore model was generated and used for designing a series of novel compounds, based on a purine scaffold, which potently inhibited mTOR and PI3Ks. These compounds contained a phenol headgroup essential for binding to the target proteins. Early efforts concentrated on finding replacements for the phenol as it was rapidly conjugated resulting in a short half-life in vivo. Compounds with a variety of headgroups were docked into the PI3Kα and mTOR ATP-binding sites, and aminopyrimidine and aminopyrazine were found to make excellent phenol replacements. Further structure guided optimization of side chains in the 8- and 9-positions of the purine resulted in potent inhibitors with good PKDM properties. As the PI3 kinases play a role in insulin signaling, it is believed that targeting mTOR selectively may give the benefit of blocking the AKT-pathway while avoiding the potential side effects associated with PI3K inhibition. As a result we designed a further series of selective mTOR kinase inhibitors. The project was successfully concluded by progressing both a dual mTOR/PI3K inhibitor, SB2343, and a selective mTOR inhibitor, SB2602, into preclinical development. SB2343 has since entered phase 1 clinical development as VS-5584.


Characteristics of intoxicated trauma patients.
Of 1320 patients who were hospitalized for injuries, a total of 315 were known to be intoxicated with alcohol at the time of trauma. A retrospective chart review was performed to determine which biopsychosocial markers correlated with increasing severity of alcohol use disorders in a sample of 184 (58.4%) of these 315 patients. Markers associated with increased severity were: an increased mean corpuscular volume (MCV; p = 0.007), previous legal problems (p = 0.023), previous alcohol rehabilitation (p < 0.001), previous attendance at self-help meetings (p < 0.001), admitting to having an alcohol problem (p < 0.001), and a willingness to change drinking behavior (p < 0.001). Routine toxicology screening tests, simple questions about previous alcohol or drug abuse treatment, and direct questions about the patient's own perception of the severity of disease and readiness to change drinking behavior can identify many victims of major trauma who could potentially benefit from a referral for alcohol rehabilitation.


Value of BRAF V600E in High-Risk Thyroid Nodules with Benign Cytology Results.
Limitations of ultrasound-guided fine-needle aspiration include nondiagnostic, indeterminate cytology and false-negative results. The BRAF V600E mutation is a specific biomarker for papillary thyroid carcinoma. This study aimed to investigate the additional diagnostic role of the BRAF V600E mutation in high-risk thyroid nodules with benign cytology results. A total of 787 high-risk nodules in 720 patients underwent ultrasound-fine-needle aspiration. A subsequent BRAF V600E mutation test was performed on thyroid nodules with benign cytology. Final pathology confirmed thyroid nodules with benign cytology that were positive for the BRAF V600E mutation. Ultrasound was performed on thyroid nodules with benign cytology results that were negative for the BRAF V600E mutation. Fine-needle aspiration was repeated on thyroid nodules with enlarged size or changed ultrasound features. Among the 787 nodules, 292 thyroid nodules had benign cytology results with 256 nodules negative for the BRAF V600E mutation and 36 nodules positive for the BRAF V600E mutation. Thirty-one nodules positive for the BRAF V600E mutation were confirmed malignant, and 5 nodules were confirmed benign by pathology. Fine-needle aspiration was repeated on 11 enlarged thyroid nodules with benign cytology findings that were negative for the BRAF V600E mutation. The results of repeat fine-needle aspiration were 4 benign nodules, 2 follicular neoplasms or suspected follicular neoplasms, 3 suspected malignancies, and 2 malignant nodules. Among the 36 thyroid nodules positive for the BRAF V600E mutation, 25 (69.4%) had ≥2 suspicious ultrasound features and 11 (30.6%) nodules had 1 suspicious ultrasound feature. The BRAF V600E mutation test can detect papillary thyroid carcinomas that might be missed by fine-needle aspiration. We recommend that fine-needle aspiration be routinely accompanied by the BRAF V600E mutation test in high-risk thyroid nodules with ≥2 suspicious ultrasound features.


Molecular genetic analysis of a patient with hereditary nonpolyposis colorectal cancer syndrome.
Hereditary nonpolyposis colorectal cancer types I and II constitute approximately 5% to 10% of the cases of colorectal cancer annually. Recognition of its clinical features and identification of affected families are imperative for appropriate medical and surgical management. Furthermore, molecular analysis can be performed in such families because the DNA mismatch repair genes have been identified as being mutated, thereby leading to microsatellite instability. We describe a 33-year-old woman with ovarian, uterine, and colorectal cancer, whose family, on close examination, had features consistent with hereditary nonpolyposis colorectal cancer. The patient had evidence of microsatellite instability in her colon cancer.


Molecular Biomarkers: their significance and application in marine pollution monitoring.
This paper presents an overview of the significance of the use of molecular biomarkers as diagnostic and prognostic tools for marine pollution monitoring. In order to assess the impact of highly persistent pollutants such as polychlorinated biphenyls (PCB), polychlorinated dibenzo-dioxins (PCDD), polychlorinated dibenzo-furans (PCDF), polynuclear aromatic hydrocarbons (PAH), tributyltin (TBT) and other toxic metals on the marine ecosystem a suite of biomarkers are being extensively used worldwide. Among the various types of biomarkers, the following have received special attention: cytochrome P4501A induction, DNA integrity, acetylcholinesterase activity and metallothionein induction. These biomarkers are being used to evaluate exposure of various species of sentinel marine organisms (e.g. mussels, clams, oysters, snails, fishes, etc.) to and the effect of various contaminants (organic xenobiotics and metals) using different molecular approaches [biochemical assays, enzyme linked immuno-sorbent assays (ELISA), spectrophotometric, fluorometric measurement, differential pulsed polarography, liquid chromatography, atomic absorption spectrometry]. The induction of the biotransformation enzyme, cytochrome P4501A in fishes (Callionymus lyra, Limanda limanda, Serranus sp., Mullus barbatus) and mussels (Dreissena polymorpha) by various xenobiotic contaminants such as PCBs, PAHs, PCDs is used as a biomarker of exposure to such organic pollutants. The induction of cytochrome P4501A is involved in chemical carcinogenesis through catalysis of the covalent bonding of organic contaminants to a DNA strand leading to formation of DNA adduct. Measurement of the induction of cytochrome P4501A in terms of EROD (7-ethoxy resorufin O-deethylase) activity is successfully used as a potential biomarker of exposure to xenobiotic contaminants in marine pollution monitoring. In order to assess the impact of neurotoxic compounds on marine environment the evaluation of acetylcholinesterase activity in marine organisms is used as a biomarker of exposure to neurotoxic agents such as organophosphorus, carbamate pesticides etc. Metallothioneins (MTs) are induced by toxic metals such as Cd, Hg, and Cu by chelation through cysteine residues and are used in both vertebrates and invertebrates as a biomarker of metal exposure. The measurement of the levels of DNA integrity in marine organisms such as Sea stars (Asterias rubens) from the North Sea and the marine snails (Planaxis sulcatus) from the Arabian Sea along the Goa coast exposed to environmental xenobiotic contaminants clearly indicated the extent and the nature of pollution at the sampling sites along coastal environment.


Size Controllable, Transparent, and Flexible 2D Silver Meshes Using Recrystallized Ice Crystals as Templates.
Ice templates have been widely utilized for the preparation of porous materials due to the obvious advantages, such as environmentally benign and applicable to a wide range of materials. However, it remains a challenge to have controlled pore size as well as dimension of the prepared porous materials with the conventional ice template, since it often employs the kinetically not-stable growing ice crystals as the template. For example, there is no report so far for the preparation of 2D metal meshes with tunable pore size based on the ice template, although facile and eco-friendly prepared metal meshes are highly desirable for wearable electronics. Here, we report the preparation of 2D silver meshes with tunable mesh size employing recrystallized ice crystals as templates. Ice recrystallization is a kinetically stable process; therefore, the grain size of recrystallized ice crystals can be easily tuned, e.g., by adding different salts and changing the annealing temperature. Consequently, the size and line width of silver meshes obtained after freeze-drying can be easily adjusted, which in turn varied the conductivity of the obtained 2D silver film. Moreover, the silver meshes are transparent and display stable conductivity after the repeated stretching and bending. It can be envisioned that this approach for the preparation of 2D conducting films is of practical importance for wearable electronics. Moreover, this study provides a generic approach for the fabrication of 2D meshes with a controllable pore size.


Evaluation of lymphoid cell populations in cytology specimens using flow cytometry and polymerase chain reaction.
Differential diagnosis between lymphomas and reactive lymphoid proliferations often requires ancillary techniques and morphologic evaluation. Flow cytometry (FCM) and polymerase chain reaction (PCR) can aid the detection of monoclonal B-cell populations. In the present study, the sensitivity and specificity of these two methods in the study of cytology specimens were compared. Eighty-six cytologic specimens from 81 patients (lymph nodes, solid organs, and body cavities) were evaluated. These specimens were taken from three groups of patients: those who underwent an initial evaluation for suspected lymphoma; those who were previously diagnosed with B-cell lymphoma and were now evaluated for possible disease recurrence; and those who were diagnosed with a nonhematologic malignancy. Histologic diagnosis was available for 51 samples. All samples were tested by FCM for the detection of monoclonality using kappa:lambda ratio and for clonal immunoglobulin heavy chain (IgH) gene rearrangements using a single-round PCR after cytologic evaluation. Tissue morphology, FCM and PCR results, and clinical findings in specimens without histologic diagnosis were correlated. Histologic evaluation (N = 51) revealed 44 specimens with B-cell malignancy. Twenty of the 44 lymphoma specimens (45%) were accurately diagnosed in cytologic smears, 18 (41%) were classified as suspicious of lymphoma, and 6 (14%) were diagnosed as reactive. FCM had superior sensitivity compared with PCR (77% vs. 64%). Fifty-six percent of specimens with B-cell malignancy were FCM+/PCR+, 23% were FCM+/PCR-, 14% were FCM-/PCR+, and 7% were FCM-/PCR-. The combined use of FCM and PCR resulted in a diagnosis of B-cell lymphoma in 41 (93%) of 44 B-cell lymphoma specimens and increased the sensitivity of fine needle aspiration by 48%. Both FCM and PCR aid in the diagnosis of lymphoid lesions in cytology specimens, and both can detect monoclonal B-cell populations that may be interpreted in cytology smears as reactive, even by experienced cytologists. Although FCM had higher sensitivity than PCR test in the present study, their combined use should be considered because of a relatively large number of specimens that were detected as monoclonal only with PCR.


Radiofrequency tissue volume reduction: suggested treatment for lymphatic malformation.
Lymphatic malformation is a benign congenital lesion but is often challenging to deal with. Complete excision is its treatment of choice. It has a high rate of recurrence, since a complete excision is difficult, and it may cause cosmetic or functional defect. Radiofrequency tissue volume reduction (RTVR) is used for the treatment of sleep-disordered breathing and other areas of surgery. A case of cervical lymphatic malformation reported here is effectively treated by radiofrequency without scar or any complication.


Metastasis of ocular and flank implants of the 13762NF mammary adenocarcinoma in syngeneic rats.
Solid fragments of a syngeneic tumor of low immunogenicity were implanted on the anterior surface of the iris or posterior surface of the cornea in young Fischer 344 rats. Growth and metastasis of these implants were examined and compared with those occurring following sc tumor implantation in the flank. Corneal implants did not grow well or metastasize. Iridial implants grew well, and tumor typically filled the eye within a few weeks. If tumor-filled eyes were left intact, all rats died or became moribund 7-9 weeks later. Metastasis was seen in the lungs (11/11), cervical lymph nodes (7/11), body wall (5/11), heart (4/11), kidney (4/11), and liver (3/11). Removal (enucleation) of tumor-filled eyes prior to spread to the orbit prevented the development of overt metastatic disease for 1-2 years (11/11). When healthy enucleated rats were necropsied 0 days to 26 weeks post enucleation, small nodules were seen in the lung (9/13), liver (3/13), or spleen (1/13). Nodules were not seen in rats that had been housed in our animal facility for 1-2 years (16/16), had eye surgery with tumor implanted on the posterior surface of the cornea (6/6), or had been subjected to the surgical procedures of corneal implantation and enucleation (3/3). When tumors were implanted sc, rats died after 6-7 weeks. Metastasis was seen in the lung (12/12), lymph nodes (12/12), spleen (1/12), and liver (1/12). Removal of very small flank tumors failed to prevent animals from dying 7-8 weeks later with pulmonary and lymph node metastasis (10/10). In summary, iridial implantation resulted in an altered pattern of metastasis. Animals that had iridial implants and enucleation failed to develop overt metastatic disease and had small nodules in the lung, liver, or spleen.


Entomobacter blattae gen. nov., sp. nov., a new member of the Acetobacteraceae isolated from the gut of the cockroach Gromphadorhina portentosa.
A novel bacterium designated G55GPT and pertaining to the family Acetobacteraceae was isolated from the gut of the Madagascar hissing cockroach Gromphadorhina portentosa. The Gram-negative cells were rod-shaped and non-motile. The complete 16S rRNA sequence of the strain G55GPT showed the highest pairwise similarity to Gluconacetobacter johannae CFN-Cf-55T (95.35 %), suggesting it represents a potential new genus of the family Acetobacteraceae. Phylogenetic analysis based on 16S rRNA gene and 106 orthologous housekeeping protein sequences revealed that G55GPT forms a monophyletic clade with the genus Commensalibacter, which thus far has also been isolated exclusively from insects. The G55GPT genome size was 2.70 Mbp, and the G+C content was 45.4 mol%, which is lower than most acetic acid bacteria (51-68 mol%) but comparable to Swingsia samuiensis AH83T (45.1 mol%) and higher than Commensalibacter intestini A911T (36.8 mol%). Overall genome relatedness indices based on gene and protein sequences strongly supported the assignment of G55GPT to a new genus within the family Acetobacteraceae. The percentage of conserved proteins, which is a useful metric for genus differentiation, was below 54 % when comparing G55GPT to type strains of acetic acid bacteria, thus strongly supporting our hypothesis that G55GPT is a member of a yet-undescribed genus. The fatty acid composition of G55GPT differed from that of closely related acetic acid bacteria, particularly given the presence of C19 : 1 ω9c/ω11c and the absence of C14 : 0 and C14 : 0 2-OH fatty acids. Strain G55GPT also differed in terms of metabolic features such as its ability to produce acid from d-mannitol, and its inability to produce acetic acid from ethanol or to oxidize glycerol to dihydroxyacetone. Based on the results of combined genomic, phenotypic and phylogenetic characterizations, isolate G55GPT (=LMG 31394T=DSM 111244T) is considered to represent a new species in a new genus, for which we propose the name Entomobacter blattae gen. nov., sp. nov.


Acquired auto-anti D in a patient with myelodysplastic syndrome.
Modification of blood group in the course of malignant haemopathy in an aged patients is described. To our knowledge, this is the first published case describing the appearance of autoantibody due to anti-D in a patient with Rh typing DCcee who has myelodysplastic syndrome in transition to acute leukaemia. We present a patient who developed acquired autoantibody to Rh locus as co-phenomenon of myelodysplastic syndrome in transition to acute leukaemia.


New Insights into the Penetration Depth of Sulfuric Acid and Leaching Effect in the Sulfuric Acid Curing-Leaching Process of Vanadium-Bearing Stone Coal.
In the process of sulfuric acid curing-leaching vanadium-bearing stone coal, the curing effect is very important. The main purpose of this study is to capture the difference in the curing effect between coarse and fine stone coal, with a V2O5 content of 0.88%. In this work, the effects of various factors such as sulfuric acid concentration, curing time, curing temperature, and different agents for curing on the leaching efficiency of vanadium were investigated by the comparison of the two size fractions. The results showed that the leaching efficiency of vanadium was 87.65% under the optimum curing conditions of 25 wt % sulfuric acid, curing time of 8 h, and curing temperature of 130 °C. It was clearly found that, under the same curing condition, the curing effect of fine stone coal was better than that of coarse stone coal. The penetration part of stone coal particles by sulfuric acid was loose, while the non-penetration part was dense after acid curing. Moreover, the penetration depth of sulfuric acid into the particles was mainly 0.5-0.7 mm on average. There was more sericite/illite in coarse leaching residues, which were mostly dense and hard carbonaceous siliceous slate. Thus, sulfuric acid was difficult to penetrate into and reach the interior of the particle, which resulted in that the leaching efficiency of coarse vanadium-bearing stone coal ore was lower than that of fine vanadium-bearing stone coal ore.


Preparation and medical outcomes of Nepalese staff and porters compared with foreign nationals on the Annapurna trekking circuit.
This cross-sectional study investigates preparedness and medical problems in Nepalese staff and porters compared with foreign nationals trekking at altitude in the Nepal Himalaya. 331 Nepalese and 338 foreign nationals in 61 trekking groups were surveyed over 4 weeks on the Annapurna trekking circuit. Foreign nationals reported that 92% of trekking groups received altitude illness information and carried a medical kit. However, fewer than 30% knew the evacuation insurance status of the Nepalese staff and porters on their trek, 39% would not pay for an ill Nepalese national's helicopter evacuation, and 41% reported insufficient resources to carry an individual. Medical problems occurred in 44% of groups. A significantly higher proportion of Nepalese staff and porters were evacuated compared with foreign nationals. No significant differences in Nepalese and foreign national preparation were found between groups with and without medical problems. Medical problems were commonly encountered, yet many groups lacked resources to evacuate someone dangerously ill. Foreign and Nepalese nationals have a duty of care towards each other; recognizing that preparedness relies not only on a first aid kit, but also on knowledge of acclimatization and individuals' insurance is an important part of health and safety for individuals trekking at altitude.


Studies on the Synthesis, Photophysical and Biological Evaluation of Some Unsymmetrical Meso-Tetrasubstituted Phenyl Porphyrins.
Abstract: We designed three unsymmetrical meso-tetrasubstituted phenyl porphyrins for further development as theranostic agents for cancer photodynamic therapy (PDT): 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (P2.2), Zn(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Zn(II)2.2) and Cu(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Cu(II)2.2). The porphyrinic compounds were synthesized and their structures were confirmed by elemental analysis, FT-IR, UV-Vis, EPR and NMR. The compounds had a good solubility in polar/nonpolar media. P2.2 and, to a lesser extent, Zn(II)2.2 were fluorescent, albeit with low fluoresence quantum yields. P2.2 and Zn(II)2.2 exhibited PDT-acceptable values of singlet oxygen generation. A "dark" cytotoxicity study was performed using cells that are relevant for the tumor niche (HT-29 colon carcinoma cells and L929 fibroblasts) and for blood (peripheral mononuclear cells). Cellular uptake of fluorescent compounds, cell viability/proliferation and death were evaluated. P2.2 was highlighted as a promising theranostic agent for PDT in solid tumors considering that P2.2 generated PDT-acceptable singlet oxygen yields, accumulated into tumor cells and less in blood cells, exhibited good fluorescence within cells for imagistic detection, and had no significant cytotoxicity in vitro against tumor and normal cells. Complexing of P2.2 with Zn(II) or Cu(II) altered several of its PDT-relevant properties. These are consistent arguments for further developing P2.2 in animal models of solid tumors for in vivo PDT.


Discomfort improvement for critically ill patients using electronic relaxation devices: results of the cross-over randomized controlled trial E-CHOISIR (Electronic-CHOIce of a System for Intensive care Relaxation).
To assess the impact of different electronic relaxation devices on common stressful patient symptoms experienced in intensive care unit (ICU). Sixty critically ill patients were enrolled in four relaxation sessions using a randomized cross-over design: standard relaxation (TV/radio), music therapy (MUSIC-CARE©), and two virtual reality systems using either real motion pictures (DEEPSEN©) or synthetic motion pictures (HEALTHY-MIND©). The goal was to determine which device was the best to reduce overall patient discomfort intensity (0-10 Numeric Rating Scale (NRS); primary endpoint). Secondary endpoints were specific stressful symptoms (pain, anxiety, dyspnea, thirst, and lack of rest feeling) and stress response measured by Analgesia/Nociception Index (ANI). Multivariate mixed-effect analysis was used, taking into account patient characteristics and multiple measurements. Fifty patients followed the full research protocol, and ten patients did at least one research planned session of relaxation. HEALTHY-MIND© was associated with a significant decrease in overall discomfort, the primary endpoint (median NRS = 4[2-6] vs. 2[0-5]; p = 0.01, mixed-effect model), accompanied by a significant decrease in stress response (increase in ANI, secondary endpoint; p < 0.01). Regarding other secondary endpoints, each of the two virtual reality systems was associated with a decrease in anxiety (p < 0.01), while HEALTHY-MIND© was associated also with a decrease in pain (p = 0.001) and DEEPSEN© with a decrease in lack of rest (p = 0.01). Three incidents (claustrophobia/dyspnea/agitation) were reported among 109 virtual reality sessions. Cybersickness was rare (NRS = 0[0-0]). Electronic relaxation therapy is a promising, safe, and effective non-pharmacological solution that can be used to improve overall discomfort in alert and non-delirious ICU patients. Its effectiveness depends on technical characteristics (virtual reality using a synthetic imagined world versus a real world or music therapy alone without virtual reality), as well as the type of symptoms.


Increasing the thermal storage capacity of a phase change material by encapsulation: preparation and application in natural rubber.
Existing encapsulated organic phase change materials (PCM) usually contain a shell material that possesses a poor heat storage capacity and so results in a lowered latent heat storage density of the encapsulated PCM compared to unencapsulated PCM. Here, we demonstrate the use of a novel microencapsulation process to encapsulate n-eicosane (C20) into a 2:1 (w/w) ratio blend of ethyl cellulose (EC):methyl cellulose (MC) to give C20-loaded EC/MC microspheres with an increased heat storage capacity compared to the unencapsulated C20. Up to a 29 and 24% increase in the absolute enthalpy value during crystallization and melting were observed for the encap-C20/EC/MC microparticles with a 9% (w/w) EC/MC polymer content. The mechanism that leads to the increased latent heat storage capacity is discussed. The blending of the water-dispersible C20-loaded EC/MC microspheres into natural rubber latex showed excellent compatibility, and the obtained rubber composite showed not only an obvious thermoregulation property but also an improved mechanical property.


Identification and evaluation of quantitative trait loci underlying resistance to multiple HG types of soybean cyst nematode in soybean PI 437655.
We performed QTL analysis for SCN resistance in PI 437655 in two mapping populations, characterized CNV of Rhg1 through whole-genome resequencing and evaluated the effects of QTL pyramiding to enhance resistance. Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is one of the most serious pests of soybean worldwide. PI 437655 has broader resistance to SCN HG types than PI 88788. The objectives of this study were to identify quantitative trait loci (QTL) underlying SCN resistance in PI 437655, and to evaluate the QTL for their contribution to SCN resistance. Two F6:7 recombinant inbred line populations, derived from cv. Williams 82 × PI 437655 and cv. Hutcheson × PI 437655 crosses, were evaluated for resistance to SCN HG types 184.108.40.206 (PA2), 0 (PA3), 220.127.116.11.7 (PA14), and 184.108.40.206.5.6.7 (LY2). The 1,536 SNP array was used to genotype the mapping populations and construct genetic linkage maps. Two significant QTL were consistently mapped on chromosomes (Chr.) 18 and 20 in these two populations. One QTL on Chr. 18, which corresponds to the known Rhg1 locus, contributed resistance to SCN HG types 184.108.40.206, 0, 18.104.22.168.7, and 188.8.131.52.5.6.7 (PA2, PA3, PA14, and LY2, respectively). Copy number variation (CNV) analysis by whole-genome resequencing showed that PI 437655 and PI 88788 had similar CNV at the Rhg1 locus. The QTL on Chr. 20 contributed resistance to SCN HG types 220.127.116.11.7 (PA14) and 184.108.40.206.5.6.7 (LY2). Evaluation of both QTL showed that pyramiding of Rhg1 and the QTL on Chr. 20 significantly improved the resistance to SCN HG types 220.127.116.11.7 (PA14) and 22.214.171.124.5.6.7 (LY2) in both populations. Our studies provided useful information for deploying PI 437655 as a donor for SCN resistance in soybean breeding through marker-assisted selection.


Movement of C-compounds from Maternal Tissue into Maize Seeds Grown in Vitro.
Uptake from nutrient media into the cob and translocation of various (14)C-compounds from maternal tissue (cob) into developing maize seeds was examined by using caryopsis cultures. Based on relative (14)C concentrations in the cob and the endosperm, it was concluded that the relative efficiencies of movement of amino acids (leucine, phenylalanine, proline), vitamins (thiamine HCl, nicotinic acid), and nucleic acid bases (adenine, thymine) from the cob to the endosperm were 11 to 250 times lower than that of sucrose. Thiamine was unique in that it was concentrated in the embryo at a level that was almost 10 times higher than in the endosperm. The absence of auxotrophic mutants requiring an organic supplement in higher plants (other than thiamine auxotrophs) may be explained by inadequate translocation of these essential metabolites into the mutant zygotes (embryos) to enable their development to mature seeds.


Efficient Active Learning by Querying Discriminative and Representative Samples and Fully Exploiting Unlabeled Data.
Active learning is an important learning paradigm in machine learning and data mining, which aims to train effective classifiers with as few labeled samples as possible. Querying discriminative (informative) and representative samples are the state-of-the-art approach for active learning. Fully utilizing a large amount of unlabeled data provides a second chance to improve the performance of active learning. Although there have been several active learning methods proposed by combining with semisupervised learning, fast active learning with fully exploiting unlabeled data and querying discriminative and representative samples is still an open question. To overcome this challenging issue, in this article, we propose a new efficient batch mode active learning algorithm. Specifically, we first provide an active learning risk bound by fully considering the unlabeled samples in characterizing the informativeness and representativeness. Based on the risk bound, we derive a new objective function for batch mode active learning. After that, we propose a wrapper algorithm to solve the objective function, which essentially trains a semisupervised classifier and selects discriminative and representative samples alternately. Especially, to avoid retraining the semisupervised classifier from scratch after each query, we design two unique procedures based on the path-following technique, which can remove multiple queried samples from the unlabeled data set and add the queried samples into the labeled data set efficiently. Extensive experimental results on a variety of benchmark data sets not only show that our algorithm has a better generalization performance than the state-of-the-art active learning approaches but also show its significant efficiency.


Transient Changes in Hepatic Physiology That Alter Bilirubin and Bile Acid Transport May Explain Elevations in Liver Chemistries Observed in Clinical Trials of GGF2 (Cimaglermin Alfa).
GGF2 is a recombinant human neuregulin-1β in development for chronic heart failure. Phase 1 clinical trials of GGF2 were put on hold when transient elevations in serum aminotransferases and total bilirubin were observed in 2 of 43 subjects who received single doses of GGF2 at 1.5 or 0.378 mg/kg. However, aminotransferase elevations were modest and not typical of liver injury sufficient to result in elevated serum bilirubin. Cynomolgus monkeys administered a single 15 mg/kg dose of GGF2 had similar transient elevations in serum aminotransferases and bilirubin as well as transient elevations in serum bile acids. However, no hepatocellular necrosis was observed in liver biopsies obtained during peak elevations. When sandwich-cultured human hepatocytes were treated with GGF2 for up to 72 h at concentrations approximately 0.8-fold average plasma Cmax for the 0.378 mg/kg dose, no cytotoxicity was observed. Gene expression profiling identified approximately 50% reductions in mRNAs coding for bilirubin transporters and bile acid conjugating enzymes, as well as changes in expression of additional genes mimicking the interleukin-6-mediated acute phase response. Similar gene expression changes were observed in GGF2-treated HepG2 cells and primary monkey hepatocytes. Additional studies conducted in sandwich-cultured human hepatocytes revealed a transient and GGF2 concentration-dependent decrease in hepatocyte bile acid content and biliary clearance of taurocholate without affecting biliary taurocholate efflux. Taken together, these data suggest that GGF2 does not cause significant hepatocellular death, but transiently modifies hepatic handling of bilirubin and bile acids, effects that may account for the elevations in serum bilirubin observed in the clinical trial subjects.


Bladder conservation treatment in the elderly population: results and prognostic factors of muscle-invasive bladder cancer.
To report the long-term results of bladder conservation strategies in elderly patients with muscle-invasive bladder cancer and evaluate the different factors affecting locoregional control and patient survival. We reviewed the records of 39 elderly patients aged 70 or older, treated with curative intent with radiotherapy, with or without chemotherapy after transurethral resection of bladder for T2-T4aN0 carcinoma of the bladder. Twenty-seven men and 12 women were identified with a median age of 78 (range 70-87). Sixteen of the patients had a previous history of superficial bladder cancer. Twenty-five patients had T2 lesions, 13 patients had T3 lesions, and 1 patient had T4a lesion. The majority of patients were unsuitable for surgery because of medical reasons (67%), whereas the others refused radical cystectomy (33%). Patients were treated with radical radiation therapy with or without chemotherapy. At a median follow-up time of 35.5 months for patients at risk, the 5-year overall survival is 28.9% for all stages, 31.9% for T2 lesions, and 26.8% for T3-T4a lesions. Significant prognostic factors for overall survival on univariate analysis were performance status and age. Five-year cause-specific survival is 37.5% for all stages, 41.5% for T2 lesions, and 34.7% for T3-T4a lesions. No significant prognostic factors for cause-specific survival were indentified on univariate analysis. Toxicity was acceptable. Younger age and good performance status were favorable prognostic factors for overall survival. Bladder conservation strategies achieved satisfactory results and were well-tolerated in this elderly population with invasive bladder cancer.


Predictive Factors Associated with Complications after Laparoscopic Distal Pancreatectomy.
Although laparoscopic distal pancreatectomy (LDP) has become more popular, the postoperative complication rate remains high. We sought to identify the risk factors for post-LDP complications. We examined 1227 patients who underwent LDP between March 2005 and December 2015 at a single large-volume center. We used logistic regression for the analysis. The overall (13.2%) and major (3.3%) complication rates were determined. Postoperative pancreatic fistula was the most frequent complication, and 58 patients (4.7%) had clinically significant (grade B) pancreatic fistulas. No 90-day mortality was recorded. Long operative time (≥200 min), large estimated blood loss (≥320 mL), LDP performed by an inexperienced surgeon (<50 cases), and concomitant splenectomy were identified as risk factors for overall complications using a logistic regression model. For major complications, male sex (p = 0.020), long operative time (p = 0.005), and LDP performed by an inexperienced surgeon (p = 0.026) were significant predictive factors. Using logistic regression analysis, surgery-related factors, including long operative time and LDP performed by an inexperienced surgeon, were correlated with overall and major complications of LDP. As LDP is a technically challenging procedure, surgery-related variables emerged as the main risk factors for postoperative complications. Appropriate patient selection and sufficient surgeon experience may be essential to reduce the complications of LDP.


[A case of Legionnaires' infection with meningeal irritation and abnormal cerebrospinal fluid].
A 60-year-old man was admitted to our hospital because of fever and mental status change. Neurological examination showed meningeal irritation and frontal sign. Cerebrospinal fluid (CSF) examination showed mild pleocytosis and elevated protein. Laboratory findings showed hyponatremia, elevated liver enzymes and creatine phosphokinase, and positive Legionella pneumophila antigen in urine. The chest computed tomographic scans showed consolidation in the left lower lobe lung. We diagnosed Legionnaires' pneumonia and started treatment with levofloxacin. Legionella pneumophila was isolated from culture of the bronchoalveolar lavage fluid, but Legionella culture and polymerase chain reaction in CSF were negative. We hypothesize that Legionella pneumophila could produce nerological symptoms by immune-mediated mechanism associated with elevated IgG index. The neurologist should recognize the presence of the meningo-encephalitis associated with Legionnaires' pneumonia lacking remarkable pulmonary symptoms.


Transient microcircuits formed by subplate neurons and their role in functional development of thalamocortical connections.
Subplate neurons are a transient population of neurons in the brain forming one of the first functional cortical circuits. Past experiments have demonstrated their importance in growth of thalamocortical afferents into the cortical plate and later segregation of thalamocortical afferents. Recently, subplate neurons have been shown to be required for the functional maturation of both thalamocortical connections and mature visual responses in visual cortex. These findings suggest that thalamocortical afferents might not segregate properly in the absence of subplate neurons because the thalamocortical synapse does not mature. Subplate neurons are unique in that they form a circuit that appears to promote synaptic scaling and maturation. Although the precise contribution of subplate neurons within the context of cortical development is unknown, they might play an early role in providing thalamic input to cortex that then interacts with learning rules governing synaptic strengthening at the thalamocortical synapse. Because they appear to play multiple key roles at different stages of development, subplate neurons might also play a role in the pathology of developmental disorders, such as epilepsy and schizophrenia.


Evidence for a homogeneous lateral distribution of lipids in a bacterial membrane. A photo cross-linking approach using anthracene as a photoactivable group.
A new photo cross-linking method has been developed for the study of the lateral distribution of lipids in natural membranes, which uses anthracene as a photoactivable group. This method, which rests on the potentiality of anthracene to form covalently bound dimers upon irradiation around 340-380 nm has been applied to the membrane lipids (dimannosyl diacylglycerol, phosphatidylglycerol, phosphatidylinositol) of the bacterium Micrococcus luteus. These glyco- and phospholipids were anthracene labelled by metabolically incorporating the synthetic 9-(2-anthryl)nonanoic acid. The following sequential procedure was used: dimerization of the anthracene-labelled lipids in the membrane by irradiation of the intact cells at 360 nm; extraction of the lipids and thin-layer chromatography in the first dimension to separate the various lipid dimers from the monomers; partial dedimerization of the lipid dimers by illumination of the chromatogram at around 250-280 nm; chromatography in the second dimension to separate the native lipid monomers from the corresponding residual lipid dimers. On account of the occurrence of the 3 hetero dimers phosphatidylglycerol-dimannosyl diacylglycerol, phosphatidylinositol-dimannosyl diacylglycerol and phosphatidylglycerol-phosphatidylinositol after irradiating the cells, it is concluded that in this bacterial membrane, dimannosyl diacylglycerol, phosphatidylglycerol and phosphatidylinositol are homogeneously distributed.


Involuntary weight loss and the nonhealing wound: the role of anabolic agents.
Endocrine responses to trauma result in a net catabolic state and exaggerated hepatic gluconeogenesis, with losses in lean body mass that can compromise wound healing. With proper nutrition, reduction of stress, resistance exercise, and the addition of certain anabolic agents, lean body mass can be restored and wound healing promoted.


Conjunctival amelanotic melanoma--a case report.
Conjunctival melanoma is a relatively rare malignancy. It is presented as pigmented nodule in any area of conjunctiva, amelanotic tumors are pink with smooth appearance. The authors describe an amelanotic melanoma of the conjunctiva in an 82-year-old female patient. Cytological, histopathological and immunohistochemical studies revealed an invasive amelanotic melanoma exhibiting S-100 and MART-1 positivity. The patient undervent surgical and chemotherapy treatment and three years after the initial treatment is in the terminal stage of metastatic disease. Absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is crucial for early recognition and appropriate management.


In situ XAS and XRPD parametric rietveld refinement to understand dealumination of Y zeolite catalyst.
Dealumination of NH(4)-Y zeolite during steaming to 873 K was investigated with in situ, time-dependent, synchrotron radiation XRPD and in situ Al K-edge XAS. Water desorption is complete at 450 K, and ammonium decomposition occurs between 500 and 550 K. Only a small fraction of Al(3+) species (5%) leaves the framework during heating from 710 to 873 K; these species occupy site I' inside the sodalite cage. This fraction increases up to 8% in the first 50 min at 873 K and remains constant for the following 70 min isotherm and during the high-temperature part of the cooling experiment. During cooling from 500 to 450 K, the electron density at site I' increases suddenly, corresponding to a fraction of 30-35% of the total Al, confirmed by ex situ (27)Al MAS solid-state NMR. At that temperature, in situ Al K-edge XAS indicates a change in Al coordination of a large fraction of Al, and thermogravimetric (TG) data show the first water molecules start to repopulate the pores. Such molecules drive the dislodgment of most of the Al from the zeolitic framework. Our data indicate that considerable structural collapse caused by steaming does not occur at the highest temperature; however, defects form, which lead to significant migration of framework Al(3+) to extraframework positions, which occurs only as water is able to enter the pores again, that is, at much lower temperature. Contrary to general opinion, these results demonstrate that zeolite dealumination is not primarily a high-temperature process. The standard Rietveld refinement approach failed to identify extraframework Al species. These new results were obtained by adopting the innovative parametric refinement [J. Appl. Crystallogr. 2007, 40, 87]. Treating all of the XRPD patterns collected during the evolution of temperature as one unique data set significantly reduces the overall number of optimized variables and, thus, their relative correlation, and finally results in a more reliable estimate of the optimized parameters. Our results contribute to a better understanding of the phenomena involved on the atomic scale in the preparation of ultrastable Y zeolites (USY). USY are employed in fluid catalytic cracking (FCC), which is the most important conversion process in petroleum refineries to convert the high-boiling hydrocarbon fractions of petroleum crude oils to more valuable products like gasoline and olefinic gases.


Survey of Hfe Gene C282Y Mutation in Turkish Beta-Thalassemia Patients and Healthy Population: A Preliminary Study.
This study was planned in order to determine the effect of C282Y mutation in development of secondary hemochromatosis in beta-thalassemia patients and to determine the prevalence and allele frequency of this mutation in a healthy control group. Eighty-seven children and young adults (46 males and 41 females; mean age: 15.6±6.1 years, range: 3-30 years) with beta-thalassemia major (BTM) and 13 beta-thalassemia intermedia (BTI) patients (6 males and 7 females; mean age: 19.6±3.5 years, range: 13-26 years) were included in the study. The control group comprised 100 healthy blood donors. Neither heterozygous nor homozygous HFE gene C282Y mutation was detected in patients with BTM or BTI, or in control group. The C282Y mutation, which is supposed to be responsible for the majority of hereditary hemochromatosis, was not found to have a role in the development of hemochromatosis in beta-thalassemia patients and was not detected in a healthy Turkish population. However, research on larger cohorts of individuals is required in order to determine the exact prevalence of the HFE gene mutation in Turkish populations from diverse ethnic origins and whether it would have an impact on iron loading in thalassemic populations.


Endoscopic management of obstruction due to an acquired bronchial web.
Bronchial webs are thin, membrane-like diaphragms that may obstruct the airway. Several congenital cases have been reported. Though rare, the true incidence of these lesions is probably underestimated because many of them are unrecognized. The case of a 71-year-old woman with an acquired bronchial web causing right main stem bronchus obstruction that went unrecognized for 47 years post-trauma is reported. The lesion was successfully treated using rigid bronchoscopy with laser therapy, balloon dilation and stent placement. This is the first reported case of an acquired bronchial web formation. It is also the first reported case that was successfully treated with this technique.


Birth weight and childhood growth in daughters of women with irregular menstrual cycles.
Menstrual irregularity has been associated with insulin resistance, type 2 diabetes mellitus and markers of metabolic dysfunction. This study aimed to determine whether irregular menstrual cycles (MCs) in reproductive-age women are associated with the weight of their daughters at birth and growth up to age five. We studied 4863 pregnant women with menstrual history data in a prospective cohort, recruited from the Kaiser Health Plan (1959-1966). Serial measures of their daughters' weight and height were abstracted from medical records. We used analysis of covariance, stratified by maternal body mass index, to explore the association between maternal MC and infant birth weight (BW). We included 4774 daughters in a repeated measures analysis to compare the effect of maternal MC on childhood weight through age five. Daughters of non-obese women with irregular MC had a statistically significant lower BW compared to daughters of women with regular MC; this difference was notably amplified among obese women. The daughters' weights were not statistically different when growth was assessed from birth to five years. We conclude that daughters of obese women with irregular MC, in particular, had significantly lower BW compared to daughters of women with regular MC, which did not persist over five years of follow-up.


A conserved heptapeptide restrains the activity of the yeast heat shock transcription factor.
In yeast, expression of heat shock genes is regulated by a factor (HSF) which binds constitutively to DNA, but activates transcription efficiently only after heat shock. We have compared the HSFs from Saccharomyces cerevisiae and Kluyveromyces lactis. Both factors contain an activation domain whose activity is masked at low temperature, but the amino acid sequences of these activators are unrelated. Masking requires the evolutionarily conserved DNA binding and oligomerization domains, as well as a short conserved element close to the activator. Although this element contains potential phosphorylation sites, they are not required for induction. We suggest that the conserved element binds either to the structural core of the protein or to another polypeptide, holding the activator in an inactive configuration, and that high temperatures disrupt this interaction. Our results emphasize the importance of global protein structure in the regulation of transcription factor activity.


Repeatability and agreement of corneal thickness measurements by three methods of pachymetry in small incision lenticule extraction eyes.
Background: The accurate evaluation of corneal thickness (CT) post small incision lenticule extraction (SMILE) is clinically relevant to reduce the risk of complications. We aimed to analyze repeatability and agreement of central corneal thickness (CCT), thinnest corneal thickness (TCT), and mid-peripheral corneal thickness (MPCT) measurements using Scheimpflug imaging, anterior segment swept-source optical coherence tomography (AS-SS-OCT, CASIA 1000, Tomey), and ultrasound pachymetry (USP, SP-3000, Tomey) in eyes with previous SMILE. Methods: Ninety-one eyes of 91 patients were included. Within-subject standard deviation (Sw), test-retest repeatability (TRT), intraclass correlation coefficient (ICC), and coefficient of variation (CoV) were used to evaluate repeatability. Agreement was assessed by repeat-measurement analysis of variance and Bland-Altman analysis. Results: The above three instruments revealed that Sw was <5.91 µm, CoV was <1.08%, TRT was <16.38 µm, and ICC was >0.94. The 95% limits of agreement were relatively narrow and Bland-Altman plots were more concentrated at the CCT, at the TCT, and at the CT2mm. However, it was shown to be wide at the CT5mm. Conclusions: The three devices provide good repeatability of CT measurements in patients who undergone SMILE. Agreement between measurements at the CCT, TCT, and CT2mm were high, but measurement agreements among CT5mm revealed poor agreement.


COSMO-RS-Based Descriptors for the Machine Learning-Enabled Screening of Nucleotide Analogue Drugs against SARS-CoV-2.
Chemical similarity-based approaches employed to repurpose or develop new treatments for emerging diseases, such as COVID-19, correlates molecular structure-based descriptors of drugs with those of a physiological counterpart or clinical phenotype. We propose novel descriptors based on a COSMO-RS (short for conductor-like screening model for real solvents) σ-profiles for enhanced drug screening enabled by machine learning (ML). The descriptors' performance is hereby illustrated for nucleotide analogue drugs that inhibit the ribonucleic acid-dependent ribonucleic acid polymerase, key to viral transcription and genome replication. The COSMO-RS-based descriptors account for both chemical reactivity and structure, and are more effective for ML-based screening than fingerprints based on molecular structure and simple physical/chemical properties. The descriptors are evaluated using principal component analysis, an unsupervised ML technique. Our results correlate with the active monophosphate forms of the leading drug remdesivir and the prospective drug EIDD-2801 with nucleotides, followed by other promising drugs, and are superior to those from molecular structure-based descriptors and molecular docking. The COSMO-RS-based descriptors could help accelerate drug discovery for the treatment of emerging diseases.


Further evaluation of the efficacy of contamination removal from bone surfaces.
Studies of low copy number (LCN) and degraded DNA are prone to contamination from exogenous DNA sources that in some cases out-compete endogenous DNA in PCR amplification, thus leading to false positives and/or aberrant results. Particularly problematic is contamination that is inadvertently deposited on the surfaces of bones through direct handling. Whereas some previous studies have shown that contamination removal is possible by subjecting samples to sodium hypochlorite prior to DNA extraction, others caution that such treatment can destroy a majority of the molecules endogenous to the sample. To further explore this topic, we experimentally contaminated ancient northern fur seal (Callorhinus ursinus) ribs with human DNA and treated them with sodium hypochlorite to remove that contamination. Our findings are consistent with previous studies that found sodium hypochlorite to be highly efficient (~81-99%) at contamination removal; however, there emerged no treatment capable of removing 100% of the contamination across all of the experiments. Moreover, the ability to estimate the degree of damage to endogenous northern fur seal molecules was compromised due to the inherent variability of preserved mtDNA across the bones, and the presence of co-extracted PCR inhibitors.


Older drivers--a complex public health issue.
This article provides estimates of the percentage of seniors who are licensed to operate a motor vehicle. It describes the health characteristics of these license holders and reviews research relating to older drivers. The data are from the cross-sectional file of Statistics Canada's 1996/97 National Population Health Survey. The sample size of respondents aged 65 or older was 13,363, weighted to represent 3.4 million individuals. Supplementary data are from the 1991 Survey of Ageing and Independence, also conducted by Statistics Canada, and from Transport Canada. The percentages of seniors with a license were calculated by age and sex. Percentages by presence of chronic conditions, disabilities and medication use were age-standardized to control for the increasing prevalence of illness at older ages. The percentage of seniors who had a driver's license declined with advancing age. The negative association between disability and license holding was pronounced. The percentage of seniors with a driver's license was also relatively low among those with heart disease, arthritis, stroke or cataracts, and among those who reported taking selected medications in the last month.


Hepatocellular carcinoma and suspected splenic hemangiosarcoma in a potbellied pig.
A 10-year-old, lethargic, potbellied pig presented with signs of abdominal discomfort and a palpable abdominal mass. Laparotomy revealed a 20 cm diameter mass on the spleen and smaller masses on the omentum and liver. After euthanasia and histologic examination of the hepatic mass, the diagnosis was hepatocellular carcinoma.


The role of protein kinase C in T lymphocyte proliferation. Existence of protein kinase C-dependent and -independent pathways.
The mouse cytotoxic T cell clone (CTLL-2) was able to grow in the presence of culture medium supplemented only with transferrin, 2-mercaptoethanol, and recombinant interleukin 2 (IL-2). This lymphokine stimulated the synthesis of DNA in these cells. Similarly, phorbol esters, which activate protein kinase C, induced DNA synthesis in this clone. Furthermore, this later proliferation was not blocked by anti-IL-2 receptor antibodies, which inhibited IL-2-induced proliferation, suggesting that it was not indirectly due to the secretion of IL-2 by the cells. CTLL-2 cells pretreated with high doses of phorbol esters for 48 h down regulated protein kinase C and were depleted of this enzyme. This was shown by: 1) purification and in vitro assay of protein kinase C; 2) the lack of effect of phorbol esters in the stimulation of the Na+/H+ anti-porter which has been directly linked to the activation of protein kinase C. As expected, those protein kinase C-depleted cells no longer synthesized DNA and proliferated in response to phorbol esters. However, they proliferated identically to control cells in response to IL-2. Therefore, our results suggest two different pathways for T cell proliferation, one which involves protein kinase C and the other which does not.


Fluorine uptake in bovine enamel from various treatment agents.
Bovine tooth enamel with a low and uniform fluorine content was used for the study of fluorine uptake by the Micro-Acid-Drop enamel biopsy technique from different treatment agents commonly used in Sweden. The fluorine concentration in the enamel was also measured after an exposure of the treated test surfaces in artificial saliva for 90 minutes. Sodium fluoride 0.2% and 2%, ferric aluminum fluoride solution and Duraphat varnish showed a high uptake of fluorine in the enamel with the highest concentration in the surface layer. Fluor Protector and the toothpastes showed a considerably lower fluorine uptake. After immersion in artificial saliva of the specimens, the concentration of fluorine in the enamel decreased.


Impact of Roadway Stormwater Runoff on Microbial Contamination in the Receiving Stream.
Stormwater runoff from roadways has increasingly become a regulatory concern for water pollution control. Recent work has suggested roadway stormwater runoff as a potential source of microbial pollutants. The objective of this study was to determine the impact of roadway runoff on the microbiological quality of receiving streams. Microbiological quality of roadway stormwater runoff and the receiving stream was monitored during storm events with both cultivation-dependent fecal bacteria enumeration and cultivation-independent high-throughput sequencing techniques. Enumeration of total coliforms as a measure of fecal microbial pollution found consistently lower total coliform counts in roadway runoff than those in the stream water, suggesting that roadway runoff was not a major contributor of microbial pollutants to the receiving stream. Further characterization of the microbial community in the stormwater samples by 16S ribosomal RNA gene-based high-throughput amplicon sequencing revealed significant differences in the microbial composition of stormwater runoff from the roadways and the receiving stream. The differences in microbial composition between the roadway runoff and stream water demonstrate that roadway runoff did not appear to have a major influence on the stream in terms of microbiological quality. Thus, results from both fecal bacteria enumeration and high-throughput amplicon sequencing techniques were consistent that roadway stormwater runoff was not the primary contributor of microbial loading to the stream. Further studies of additional watersheds with distinct characteristics are needed to validate these findings. Understanding gained in this study could support the development of more effective strategies for stormwater management in sensitive watersheds.


A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis.
Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein-protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K-AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible "dangerous liaison" between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.


Challenges and Strategies for Inpatient Diabetes Management in Older Adults.
Adults older than 65 years of age are the fastest growing segment of the U.S. population. Aging is also one of the most important risk factors for diabetes, and about one-third of all individuals with diabetes are in this age-group. Older people with diabetes are more likely to have comorbidities such as hypertension, ischemic heart disease, chronic kidney disease, and cognitive impairment, which lead to higher rates of hospital admissions compared with individuals without diabetes. Professional organizations have recommended patient-centric individualized glycemic reduction approaches, with an emphasis on potential harms of intensive glycemic control and overtreatment in older adults. Insulin therapy remains a mainstay of diabetes management in the inpatient setting regardless of patients' age; however, there is uncertainty about optimal glycemic targets during the hospital stay. Increasing evidence supports selective use of dipeptidyl peptidase-4 inhibitors, alone or in combination with low-dose basal insulin, in older noncritically ill patients with mild to moderate hyperglycemia. This article reviews the prevalence, diagnosis, and monitoring of, and the available treatment strategies for, diabetes among elderly patients in the inpatient setting.


Objective evaluation of plantar hyperhidrosis after sympathectomy.
The aim of the present study was to prospectively, randomly, blindly, and objectively investigate how surgery affects plantar sudoresis in patients with palmar and plantar hyperhidrosis over a one-year period using a sudorometer (VapoMeter). From February 2007 to May 2009, 40 consecutive patients with combined palmar hyperhidrosis and plantar hyperhidrosis underwent video-assisted thoracic sympathectomy at the T3 or T4 ganglion level (15 women and 25 men, with a mean age of 25 years). Immediately after the operation and during the one-year follow-up, all of the patients were free from palmar hyperhidrosis episodes. Compensatory hyperhidrosis of varying degrees was observed in 35 (87.5%) patients after one year. Only two (2.5%) patients suffered from severe compensatory hyperhidrosis. There was a large initial improvement in plantar hyperhidrosis in 46.25% of the cases, followed by a progressive regression of that improvement, such that only 30% continued to show this improvement after one year. The proportion of patients whose condition worsened increased progressively (from 21.25% to 47.50%), and the proportion of stable patients decreased (32.5% to 22.50%). This was not related to resection level; however, a lower intensity of plantar hyperhidrosis prior to sympathectomy correlated with worse evolution. Patients with palmar hyperhidrosis and plantar hyperhidrosis who underwent video-assisted thoracic sympathectomy to treat their palmar hyperhidrosis exhibited good initial improvement in plantar hyperhidrosis, which then decreased to lesser degrees of improvement over a one-year period following the surgery. For this reason, video-assisted thoracic sympathectomy should not be performed when only plantar hyperhidrosis is present.


The risk of HIV and HCV infections among injection drug users in northeast India.
Injection drug users (IDUs) and their associated risk behavior are responsible for driving the human immunodeficiency virus (HIV) epidemic in northeast India. So a group of IDUs from two northeastern states (Mizoram and Nagaland) of India were studied to find the prevalence of HIV, co-infection with hepatitis C virus (HCV), hepatitis B virus (HBV), and associated risk behaviors. Out of the 400 IDUs enrolled, 398 consented for HIV, HCV, and hepatitis B surface antigen (HbsAg) test. Of them, 10.8% were HIV-1 antibody positive, 47.8% had HCV antibody, and 3.8% had detectable HBsAg. Among the HIV infected subjects, 79.1% were co-infected with HCV and 6.9% had triple infection. Heroin users showed a higher association with HIV (OR = 7.3, 95% CI: 2.5-21.5, p=0.0003) and HCV infection (OR = 7.6, 95% CI: 3.5-16.6, p<0.0001) than Spasmo-proxyvon (dextropropoxyphene, a synthetic opiod analgesic). In summary, apart from the known risk variables among IDUs, type of injecting drugs also influences the HIV/HCV transmission pattern among the IDUs.


[Travassosius rufus (Trichostrongylidae)--new for Poland nematode of beavers and comments about helminthfauna of these animals].
Two females of beaver from north-east Poland were necropsied. Moreover, 15 samples of feaces were examinated. Both necropsied beavers were infected with 46 and 362 specimens of trematode Stichorchis subtriquetrus (RUDOLPHI 1814). In stomach of one beaver were found 2800 specimens of nematode Travassosius rufus Khalil, 1922. It was the first registration of this species in Poland. Coproscopical examination showed eggs of S. subtriquetrus in all 15 fecal samples and eggs T. rufus in 5 samples.


Reliability of a multiplex PCR assay for the identification of the major Campylobacter taxa.
The primer pair (C412F/C1228R) constructed previously for the polymerase chain reaction (PCR) identification of the genus Campylobacter using an approximate 800 base pair (bp) 16S rRNA gene target segment proved to be useful for the identification of a total of 49 Campylobacter lari isolates including urease-positive thermophilic Campylobacter (UPTC) organisms (n=25). When the primer pair (CLF/R) developed previously for the PCR identification of C. lari species using an approximate 250 bp glyA segment was employed, 27 C. lari isolates, including all the UPTC isolates, were identified to be PCR-negative (55%). Therefore, this PCR procedure developed for the molecular identification of C. lari was shown to be unreliable for C. lari identification. Nucleotide sequencing analysis clarified the reason(s) why PCR-negative examples occurred in many C. lari isolates, including UPTC isolates. The primer pair target sequences in the C. lari-specific PCR-negative isolates apparently varied at the 3' end region, as compared with C. lari-specific PCR-positive isolates. Thus, the multiplex PCR assay developed previously was shown to be unreliable for the molecular identification of C. lari subspecies organisms.


Tetranuclear platinum phosphido complexes with different structures.
The addition of [NBu4]Br or [NBu4][BH4] to solutions of [Pt4(mu-PPh2)4(C6F5)4(CO)2] yields the complexes [NBu4]2[Pt4(mu-PPh2)4(mu-X)2(C6F5)4] (X=Br, H,) in which the two CO groups have been replaced by two anionic, bridging X ligands. The total valence electron counts are 64 and 60, respectively; thus, complex does not require Pt-Pt bonds, while two metal-metal bonds are present in, as their NMR spectra confirm. Also, the NMR spectra indicate a nonsymmetrical "Pt(mu-PPh2)2Pt(mu-PPh2)(mu-X)Pt(mu-PPh2)(mu-X)Pt" disposition for and. Treatment of with HX (X=Cl, Br) yields the complexes [NBu4]2[Pt4(mu-PPh2)4(mu-H)2(C6F5)3X] (X=Cl, Br,). These complexes react with [Ag(OClO 3)PPh3] with displacement of the halide and formation of [NBu4][Pt4(mu-PPh2)4(mu-H)2(C6F5)3PPh3]. Complexes maintain the same basic skeleton as, with two Pt-Pt bonds. Complex is, however, an isomer of the symmetric [NBu4]2[{(C6F5)2Pt(mu-PPh2)2Pt(mu-Br)}2], which has been prepared by a metathetical process from the well-known [NBu4]2[{(C6F5)2Pt(mu-PPh2)2Pt(mu-Cl)}2]. The comparison of the X-ray structures of and confirms the different disposition of the bridging ligands, and their main structural differences seem to be related to the size of Br- and its position in the skeleton.


"I did not know it was so important to take it the whole time" - self-reported barriers to medical treatment among individuals with asthma.
Asthma is an extensive public health problem and inadequate disease control is not uncommon. Individuals' self-perceived barriers to medical treatment for the entire treatment chain (from seeking care for symptoms to using a medicine) have seldom been studied for chronic diseases such as asthma. The aim of this study was to explore self-perceived barriers to medical treatment among individuals with asthma within the framework of AAAQ (availability, accessibility, acceptability and quality). Individuals with asthma visiting the asthma nurse at a primary health care centre, and who currently had a prescription for anti-asthmatic medicines, were informed about the study. The nurse asked the persons for their consent to be contacted by an interviewer. The interview guide was constructed from the elements of AAAQ exploring self-perceived barriers to asthma treatment. Interviews were conducted in Swedish, English, Arabic and Persian. They were transcribed verbatim and a manifest content analysis was conducted. Fourteen interviews were conducted. There was a large variation in both age and reported number of years with asthma. Self-perceived barriers to asthma treatment were experienced throughout the whole treatment chain. Barriers that emerged were health care accessibility, perceived quality of care, beliefs about medicines, life circumstances, knowledge gap about asthma and medicines, practical obstacles to using medicines, and experiences with treatment. The self-perceived barriers cover all four elements of AAAQ, but there are also some barriers that go beyond those elements (life circumstances and practical obstacles to using medicines). Self-perceived barriers among individuals with asthma cover the whole treatment chain. We want to highlight the inadequate information/education of patients leading to knowledge gaps about both disease and the effect of medicines, and also the perceived unsatisfactory treatment at the PHCC, which could partly be counteracted if patients know what to expect from health care visits.


Ferritin iron minerals are chelator targets, antioxidants, and coated, dietary iron.
Cellular ferritin is central for iron balance during transfusions therapies; serum ferritin is a small fraction of body ferritin, albeit a convenient reporter. Iron overload induces extra ferritin protein synthesis but the protein is overfilled with the extra iron that damages ferritin, with conversion to toxic hemosiderin. Three new approaches that manipulate ferritin to address excess iron, hemosiderin, and associated oxidative damage in Cooley's Anemia and other iron overload conditions are faster removal of ferritin iron with chelators guided to ferritin gated pores by peptides; more ferritin protein synthesis using ferritin mRNA activators, by metal complexes that target mRNA 3D structures; and determining if endocytotic absorption of iron from legumes, which is mostly ferritin, is regulated during iron overload to prevent excess iron entry while providing protein. More of a focus on ferritin features, including protein cage structure, iron mineral, regulatable mRNA, and specific gut absorption properties, will achieve the three novel experimental goals for managing iron homeostasis with transfusion therapies.


Polyphosphate exerts differential effects on blood clotting, depending on polymer size.
Polyphosphate, a linear polymer of inorganic phosphate, is secreted by activated platelets and accumulates in many infectious microorganisms. We recently showed that polyphosphate modulates the blood coagulation cascade at 3 steps: it triggers the contact pathway, it accelerates factor V activation, and it enhances fibrin polymerization. We now report that polyphosphate exerts differential effects on blood clotting, depending on polymer length. Very long polymers (≥ 500mers, such as those present in microorganisms) were required for optimal activation of the contact pathway, while shorter polymers (∼ 100mers, similar to the polymer lengths released by platelets) were sufficient to accelerate factor V activation and abrogate the anticoagulant function of the tissue factor pathway inhibitor. Optimal enhancement of fibrin clot turbidity by polyphosphate required ≥ 250mers. Pyrophosphate, which is also secreted by activated platelets, potently blocked polyphosphate-mediated enhancement of fibrin clot structure, suggesting that pyrophosphate is a novel regulator of fibrin function. In conclusion, polyphosphate of the size secreted by platelets is very efficient at accelerating blood clotting reactions but is less efficient at initiating them or at modulating clot structure. Microbial polyphosphate, which is highly procoagulant, may function in host responses to pathogens.


The contribution of the obturator nerve block in the transurethral resection of bladder tumors.
This study was designed to evaluate the efficacy of local block of the obturator nerve to avoid it's stimulation during transurethral resection (TUR) or tumors localised on the lateral bladder wall. Forty-five patients were studied, in whom the TUR operations were performed under spinal anaesthesia. The patients were divided into two groups: in the first group a local block of the obturator nerve was done, while the second group served as controls, and the stimulation of the nerve was avoided by reduction of the electrocoagulation voltage, incomplete bladder filling and resections of smaller ships. In the first group no stimulation was observed while in 5 patients of the second group was not possible to totally resect the tumor due to the persistent stimulation of the obturator nerve. In conclusion the local block of the obturator nerve is an effective method to avoid it's stimulation, easily performed and without complications.


Dendritic cell-derived exosome-entrapped fluorouracil can enhance its anti-colon cancer effect.
To explore the effectiveness of fluorouracil (FU) entrapped in dendritic cell (DC)-secreted exosomes (DC-Exos) for enhancing its anti-colon cancer effect. DC-Exos were extracted through ultrahigh-speed centrifugation, and the FU-DC-Exos system was constructed using electroporation. Moreover, the influence of FU-DC-Exos on the viability of mouse colon cancer CT26 cells was determined in vitro using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining, and pharmacodynamic evaluation was performed in vivo through TUNEL and hematoxylin-eosin (H&E) staining, with the CT26 tumor-bearing mouse model as the study object. Compared with the control group, FU and DC-Exos groups exhibited a lowered proliferation rate of mouse CT26 colon cancer cells, whereas the apoptosis rate of cells in FU-DC-Exos group differed significantly from FU group. According to the wound healing assay, the migration rate of CT26 cells was reduced in FU and DC-Exos groups, and it was evidently different between FU-DC-Exos group and FU group. Moreover, in vivo experiments revealed that DC-Exos alone exhibited a trend of suppressing tumor growth, and that DC-Exos as carriers not only killed tumor cells alone, but also enhanced the anti-colon cancer effect of FU after entrapment. Exos extracted via ultrahigh-speed centrifugation can be used for the preparation of the drug delivery system of FU-DC-Exos via electroporation, and drug-loaded Exos are able to effectively inhibit the proliferation of tumor cells and induce their apoptosis, exerting an anti-tumor effect.


[Surgical treatment of pulmonary tuberculosis complicated with aspergilloma].
To investigate the surgical indications of pulmonary tuberculosis complicated with aspergilloma , and to reduce postoperative complications. From 1993 to 2010, a total of 51 surgically treated patients in pulmonary tuberculosis complicated with aspergilloma were analyzed retrospectively. The common surgical procedure performed was lobectomy(60.8%), followed by segmentectomy(15.7%), pneumonectomy(9.8%), wedge resection(9.8%). Postoperative non-fatal complications occurred in all patients, the complications (13 cases) included postoperative atelectasis(7.8%), bleeding(5.9%), bronchopleural fistula(5.9%), cardiac arrhythmia and heart failure(2.0%), incisional infection(2.0%). Surgical treatment of pulmonary tuberculosis complicated with aspergilloma is the most effective treatment; pulmonary resection is the treatment of choice when indicated.


1,3-Benzothia-zole-2(3H)-selone.
The title compound, C(7)H(5)NSSe, is the product of the reaction of 2-chloro-benzothia-zole with sodium hydro-selenide. The mol-ecule is almost planar (r.m.s. deviation = 0.018 Å) owing to the presence of the long chain of conjugated bonds (Se=C-N-C=C-C=C-C=C). The geometrical parameters correspond well to those of the analog N-methyl-benzothia-zole-2(3H)-selone, demonstrating that the S atom does not take a significant role in the electron delocalization within the mol-ecule. In the crystal, mol-ecules form centrosymmetric dimers by means of inter-molecular N-H⋯Se hydrogen bonds. The dimers have a nonplanar ladder-like structure. Furthermore, the dimers are linked into ribbons propagating in [010] by weak attractive Se⋯S [3.7593 (4) Å] inter-actions.


Prostaglandin H synthase-catalyzed ring oxygenation of 2-naphthylamine: evidence for two distinct oxidation pathways.
Previous studies showed that prostaglandin H synthase (PHS) cooxidizes 2-naphthylamine (2-NA) to ring-oxygenated products. These metabolites are atypical for a peroxidase-mediated reaction and are completely different from the polymeric nonoxygenated metabolites of 2-NA that are generated with the model peroxidase horseradish peroxidase (HRP). In this study, we investigated possible explanations for the PHS-catalyzed formation of ring-oxygenated 2-NA metabolites. We found that introduction of a peroxyl radical-generated cosubstrate into the HRP/2-NA system resulted in the formation of the same ring-oxygenated products observed in the PHS/2-NA system. 18O2 incorporation studies were utilized to further characterize the source of oxygen in the ring-oxygenated 2-NA metabolites. The data show that, in the case of PHS, ring oxygenation can occur both by peroxyl radical-mediated attack on 2-NA and by direct transfer of peroxide oxygen from PHS to 2-NA.


Modern or traditional? A study of treatment preference for neuropsychiatric disorders in Botswana.
Subjects in Botswana were asked to state their preference between modern (doctor or nurse) or indigenous (traditional or religious healer) care for three case vignettes of epilepsy, psychosis, and tuberculosis. Nurses, medical patients, and a general village population were studied. Many subjects preferred modern care for all disorders, whilst a small number favoured indigenous treatment only. A significant percentage discriminated between disorders, choosing indigenous care for some and modern for others. Indigenous care was most favoured for epilepsy, and least for tuberculosis. Psychosis took an intermediate position. The size of the discriminating group varied between populations, but the overall pattern of attitudes remained the same. Neither demographic factors nor aetiological beliefs consistently identified those who choose indigenous care.


Long term neurological outcome of herpes encephalitis.
Twenty eight children with herpes simplex encephalitis were followed up for a mean of 5.5 years. Two children died and 26 survived, of whom 16 were left with no neurological sequelae and 10 had persistent neurological sequelae. Mean (SD) Glasgow coma score was significantly lower in the patients with neurological sequelae (7.7 (1.5)) and the patients who died (4.5 (0.7)), compared with the patients without neurological sequelae (11 (1.7)).


The effects of recombinant hirudin on various platelet functions.
The effect of two recombinant hirudins, HBW 023 (Hoechst AG, Frankfurt, FRG) and CGP 39393 [recy(tyr 63)] (Ciba Geigy, Basel, Switzerland) on various platelet functions has been investigated in blood samples of healthy volunteers anticoagulated with hirudin at concentrations of 10, 30, 50 micrograms/ml blood. Spontaneous aggregation was rarely observed in hirudinized platelet-rich plasma (PRP) compared to citrate-PRP. In comparison with citrate-PRP, both hirudins reduced the maximal response to epinephrine, but had no influence on the maximal response to ADP. Both hirudins reduced platelet adhesion to siliconized glass and inhibited platelet spreading compared to citrate-PRP. If hirudin was added to citrate-PRP, platelet count, epinephrine-induced aggregation, platelet spreading and adhesion remained unchanged while the maximal response to ADP increased. If citrate was added to hirudin-PRP, the maximal response to epinephrine as well as platelet spreading and adhesion increased to the extent observed in citrate-PRP. The effects of hirudin on platelet function are more pronounced than those of unfractionated heparin.


Selection of lac gene fusions in vivo: ompR-lacZ fusions that define a functional domain of the ompR gene product.
We describe a simple method for selecting Escherichia coli mutants that carry gene fusions between a cloned gene and lacZ. We test this technique with the ompR gene, which codes for a positive regulatory factor in porin synthesis. A number of OmpR-LacZ hybrid proteins are examined, and several unusual phenotypes associated with these protein fusions are described. Evidence is presented to support the two-domain model for ompR proposed previously (Hall and Silhavy, J. Mol. Biol. 151:1-15). In addition, one of the ompR-lacZ fusions exhibits a dominant OmpR- phenotype. The utility of isolating a series of lacZ gene fusions to any target gene is discussed.


[Seat belt syndrome: a new abdominal pathology].
Between January 1976 and December 1980, 43 patients involved in automobile accidents while wearing passive restraints were treated at l'Hôpital du Sacré-Coeur in Montreal. Thirty-seven showed signs of abdominal trauma and were operated upon. There was a strikingly high incidence of gastrointestinal injury. Thirty-two of the 37 had injury to the bowel or its mesentery. This spectrum of injury is most likely related to the rapid deceleration caused by the restraint with the three-point harness.


Remote magnetic catheter navigation for cavotricuspid isthmus ablation in patients with common-type atrial flutter.
Conventional catheter ablation of cavotricuspid isthmus (CTI)-dependent atrial flutter is a widely applied standard therapy. Remote magnetic catheter navigation (RMN) may provide benefits for different ablation procedures, but its efficacy for CTI ablation has not been evaluated in a randomized, controlled trial. Ninety patients undergoing de novo ablation of atrial flutter were randomly assigned to conventional manual (n=45) or RMN-guided (n=45) CTI ablation with an 8-mm-tip catheter. Complete bidirectional isthmus block was achieved in 84% (RMN) and 91% (conventional catheter ablation) of the cases (P=0.52). RMN was associated with shorter fluoroscopy time (median, 10.6 minutes; interquartile range [IQR], 7.6 to 19.9, versus 15.0 minutes; IQR, 11.5 to 23.1; P=0.043) but longer total radiofrequency application (17.1 minutes; IQR, 8.6 to 25, versus 7.5 minutes; IQR, 3.6 to 10.9; P<0.0001), ablation time (55 minutes; IQR, 28 to 76, versus 17 minutes; IQR, 7 to 31; P<0.0001), and procedure duration (114+/-35 versus 77+/-24 minutes, P<0.0001). Procedure duration in the RMN group did not decrease significantly with case experience. Long-term procedure success, defined as achievement of complete CTI block and freedom from atrial flutter recurrence during 6 months of follow-up, was lower in the RMN group (73% versus 89%, P=0.063). Right atrial angiography after ablation revealed no significant differences between groups in terms of right atrial diameter or CTI length, morphology, and angulation. Furthermore, none of these parameters was predictive for difficult (ablation time >20 minutes) or unsuccessful ablation. RMN-guided CTI ablation is associated with reduced radiation exposure but prolonged ablation and procedure times as compared with conventional catheter navigation. Our findings suggest that ablation lesions produced with an RMN-guided 8-mm catheter are less effective irrespective of CTI anatomy. clinicaltrials.gov Identifier: NCT00560872.


Periodontal regeneration of human intrabony defects with titanium reinforced membranes. A controlled clinical trial.
The purpose of this controlled clinical trial was to compare the clinical efficacy of 3 treatment modalities in the treatment of deep interproximal intrabony defects. Forty-five (45) defects in 45 patients were randomly assigned to 1 of 3 treatment groups by blocking to prognostic variables. The test group was treated with titanium reinforced membranes positioned just apical to the cemento-enamel junction and the modified papilla preservation technique; the second group received conventional expanded polytetrafluoroethylene (ePTFE) barrier membranes applied at the alveolar crest; the third group was treated with an access flap procedure. The groups were well balanced with respect to all prognostic variables. During the 1-year observation period, patients were subjected to a stringent infection control program including: professional tooth cleaning every week for the first 6 weeks (all groups) and in the 4 weeks following membrane removal (guided tissue regeneration groups), then at monthly intervals (all groups). The results indicated that: 1) all treatment modalities resulted in clinical and statistically significant improvements in clinical attachment level (CAL) and probing depths (PD) at 1 year; 2) a significantly greater amount of CAL gain (P = 0.0003, analysis of variance) was observed in the test group (5.3 +/- 2.2 mm) with respect to both the ePTFE group (4.1 +/- 1.8 mm) and the flap control group 2.5 +/- 0.8; 3) in the test group the 1 year CAL (4.7 +/- 1.8 mm) was located more coronally than the baseline position of the interproximal alveolar crest (5.9 +/- 2 mm; P = 0.003, t test).(ABSTRACT TRUNCATED AT 250 WORDS)


A comparison of the effect of refresh plus and bion tears on dry eye symptoms and ocular surface health in myopic LASIK patients.
To compare the effect of artificial tears (0.5% carboxymethylcellulose [CMC] in lactate buffer vs. 0.3% hydroxypropyl methylcellulose and 0.1% dextran in bicarbonate buffer [HPMC]) on the preservation of ocular surface health in postoperative laser in situ keratomileusis (LASIK) patients. Nonrandomized, comparative, retrospective analysis of a clinical database. Patients (n = 519; 985 eyes) had undergone LASIK in a single refractive surgery center performed by a single surgeon using the same LASIK technique (Nidek EC5000 laser and ACS keratome). Patients (n = 254) were given CMC (Refresh Plus/Cellufresh) or HPMC (Bion Tears) four times per day and were evaluated at presurgery, week 2, and months 1, 3, and 6. Included patients were those with complete clinical data through the month I follow-up visit. There were no significant between-group differences in any baseline variable. Following LASIK, fewer CMC patients (n = 111) reported dry eye symptoms than HPMC patients (n = 143) at the week 2 (13.5% vs. 30.8%; P = .001) and month 1 (19.8% vs. 38.5%; P = .001) follow-up visits. CMC patients also had significantly lower mean ocular surface staining scores than HPMC patients at week 2 (0.09 vs. 0.30; P = .015) and month 1 (0.05 vs. 0.28; P = .008). There were no between-group differences in either measure at months 3 or 6 (P < or = .728). CMC was more effective than HPMC in controlling dry eye symptoms and preserving ocular surface health in the immediate postoperative period in myopic post-LASIK patients, possibly due to the greater muco-adhesive properties of CMC. These results warrant further investigation as to the most effective postoperative LASIK lubricant.