[Directional preponderance of nystagmus].
The presence of directional preponderance in the peripheral and central vestibular disorders and the relation of its phenomenon to the definitive etiological factors, spontaneous nystagmus, positional nystagmus and the role of lateralization of directional preponderance were described. Directional preponderance is helpful to distinguish between peripheral and central lesions. The direction of this phenomenon is significant in the supratentorial CNS disturbances. In the peripheral lesions it is possible to estimate the progression of the disease. The coexistence of the directional preponderance, spontaneous nystagmus and positional nystagmus has the diagnostic value in neurootology.


Cerebrofacial venous anomalies, sinus pericranii, ocular abnormalities and developmental delay.
The clinical implications of venous cerebrovascular maldevelopment remain poorly understood. We report on the association of cerebrofacial venous anomalies (including sinus pericranii), ocular abnormalities and mild developmental delay in two children. In addition, one child had a seizure disorder. Complex cerebrofacial slow-flow vascular anomalies may herald an underlying developmental aberration affecting the cerebrofacial and orbital regions.


Mix & Match versus bilateral trifocal and bilateral extended-depth-of-focus intraocular lenses implantation. The spline curves battle.
To compare the postoperative vision acuity curves following three pseudophakic presbyopic correction techniques. Department of Ophthalmology, University Hospital of Alexandroupolis, Alexandroupolis, Greece. Prospective, randomized, comparative trial. Stage 2 LOCS-III Cataract patients populated three study groups: a) Premium Monovision Group who received the Panoptix intraocular lens (IOL) in the recessive eye and the Vivity IOL in the dominant one, b) Bilateral Trifocal Group who received bilaterally the Panoptix IOL, and, c) Bilateral xEDOF Group who received bilaterally the Vivity IOL. Postoperative bilateral uncorrected vision acuity (UVA) was measured at 25.5, 28, 33, 40, 50, 66, 100, 200 and 300cm distances. Spline curve fitting was attempted and areas of the curves (AOC) and Curvatures k were calculated. All patients responded to the NEI-VFQ-25 questionnaire. 90 patients populated equally the three groups. Premium monovision and bilateral trifocal implantation delivered similar visual acuity (all AOC p>0.05); however the trifocal patients suffered from vision acuity drops in certain distance ranges as expressed in negative curvature values. Bilateral xEDOF patients demonstrated worse near vision acuity (p<0.05). Premium monovision patients reported better scores in NEI-VFQ 25 (p=0.03) and in the near activities (p=0.02) and distant activities subscales (p=0.04). All surgical options provide impressive outcomes. Premium monovision seems to deliver the best results.


POPULATION FREQUENCY OF REPEAT EXPANSIONS INDICATES INCREASED DISEASE PREVALENCE ESTIMATES ACROSS DIFFERENT POPULATIONS.
Repeat expansion disorders (REDs) are a devastating group of predominantly neurological diseases. Together they are common, affecting 1 in 3,000 people worldwide with population-specific differences. However, prevalence estimates of REDs are hampered by heterogeneous clinical presentation, variable geographic distributions, and technological limitations leading to under-ascertainment. Here, leveraging whole genome sequencing data from 82,176 individuals from different populations we found an overall carrier frequency of REDs of 1 in 340 individuals. Modelling disease prevalence using genetic data, age at onset and survival, we show that REDs are up to 3-fold more prevalent than currently reported figures. While some REDs are population-specific, e.g. Huntington's disease type 2, most REDs are represented in all broad genetic ancestries, including Africans and Asians, challenging the notion that some REDs are found only in European populations. These results have worldwide implications for local and global health communities in the diagnosis and management of REDs both at local and global levels.


[Rituximab (Mabthera)--treatment of rheumatoid arthritis patients with inadequate response to TNF inhibitors--when to change therapy?].
B cells play a critical role in the pathogenesis of rheumatoid arthritis. Recently, a number of biological agents that target B cells have been tested as therapies for these conditions. Of this group of agents, the first in clinical use has been rituximab, a chimeric monoclonal antibody that depletes B cells by binding to the CD20 cell-surface antigen. 25-40% of patients treated with a TNF inhibitor fail to achieve adequate response. A treatment response is inadequate if low disease activity or remission is not achieved. Treatment of patients with inadequate response to TNF inhibitors represents a challenge. What are the options? Switch to another anti-TNFalpha agent or initiate treatment with a biological agent with a different mechanism of action? In patients with persistent active disease despite anti-TNFalpha therapy, treatment with rituximab may be more effective than switching to another anti-TNFalpha.


Trophic Transfer of Halogenated Organic Pollutants in a Wetland Food Web: Insights from Compound-Specific Nitrogen Isotope of Amino Acids and Food Source Analysis.
A trophic position (TP) model (TPmix model) that simultaneously considered trophic discrimination factor and βGlu/Phe variations was developed in this study and was first applied to investigate the trophic transfer of halogenated organic pollutants (HOPs) in wetland food webs. The TPmix model characterized the structure of the wetland food web more accurately and significantly improved the reliability of TMF compared to the TPbulk, TPAAs, and TPsimmr models, which were calculated based on the methods of stable nitrogen isotope analysis of bulk, traditional AAs-N-CSIA, and weighted βGlu/Phe, respectively. Food source analysis revealed three interlocking food webs (kingfisher, crab, and frogs) in this wetland. The highest HOP biomagnification capacities (TMFmix) were found in the kingfisher food web (0.24-82.0), followed by the frog (0.08-34.0) and crab (0.56-11.7) food webs. The parabolic trends of TMFmix across combinations of log KOW in the frog food web were distinct from those of aquatic food webs (kingfisher and crab), which may be related to differences in food web composition and HOP bioaccumulation behaviors between aquatic and terrestrial organisms. This study provides a new tool to accurately study the trophic transfer of contaminants in wetlands and terrestrial food webs with diverse species and complex feeding relationships.


Self-Reported Dietary Supplement Use Is Reproducible and Relatively Valid in the Cancer Prevention Study-3 Diet Assessment Substudy.
Dietary supplement use is common, particularly among cancer survivors and those at increased risk for cancer. The objectives of this study were to assess 1-year test-retest reproducibility of dietary supplement use reported via food frequency questionnaire (FFQ-1 vs FFQ-2) and relative validity in comparison to repeated 24-hour dietary recalls (FFQ-2 vs DRs). This ancillary study was conducted within a large prospective cohort, the American Cancer Society's Cancer Prevention Study-3. Between 2015 and 2016, 684 participants in the United States (64% women; 62% non-Hispanic White, 23% non-Hispanic Black, and 15% Hispanic) completed two FFQs and up to six unannounced telephone interviewer-administered DRs over 1 year as part of the Cancer Prevention Study-3 Diet Assessment Substudy. FFQs queried current multivitamin-mineral supplement (≥10 components) use, frequency and dose (range) for seven supplements taken individually or as part of a complex (individual/complex) including calcium, vitamins D, C, and E, folic acid, fish oil, and glucosamine. DRs allowed exact reporting of supplement frequency and dose. Weighted κ statistics were used to evaluate reproducibility between FFQ-1 and FFQ-2 and Spearman correlation coefficients assessed agreement between supplemental nutrient amounts assessed by FFQ-2 and the average of DRs. Just more than half of the participants reported taking multivitamin-mineral supplements on the baseline FFQ. Kappa statistics for the comparison of categorical responses between FFQ-1 and FFQ-2 were 0.67 for multivitamin-mineral supplements. Kappas for individual/complex supplements ranged from 0.47 for folic acid to 0.74 for vitamin D, with a mean of 0.64. Results were similar between men and women. Spearman correlation coefficients comparing FFQ-2 with the average of DRs (validity) for nutrient intakes from all sources ranged from 0.65 (fish oil for women) to 0.77 (vitamin D for men and calcium for women); results were similar among men and women. These findings suggest the FFQ used in Cancer Prevention Study-3 has good reproducibility over 1 year and yields estimates comparable to a more detailed assessment for commonly consumed dietary supplements.


A consumer perspective on the family agenda.
The point of view of a mental health researcher who was diagnosed with bipolar disorder when her four children were young is applied to several of the other articles in this section. She comments on various aspects of work with families in which one member has a serious mental illness, raising and discussing issues relevant to consumers, as well as to family members.


Complexity of the human T lymphocyte-specific cell surface antigen T3.
A human T lymphocyte cell surface antigen T3 was found to be involved in several functions that were specific for the cells that express this marker on their surface. We show here that several glycoproteins were found in the immunoprecipitates prepared with a monoclonal reagent anti-T3. In addition to the major glycoprotein complex of 20 kd, glycoproteins of 25 to 28 kd, 37 kd, and 44 kd were detected in immunoprecipitates. The charge heterogeneity of the 20 kd and 25 to 28 kd proteins was caused by variable sialic acid content. The 20-kd T3 glycoprotein carried several "complex-type" and endoglycosidase-H-sensitive sugar moieties. We found that the 20-kd protein could be labeled with 125I-iodonaphthylazide, a reagent that reacts with hydrophobic areas of proteins.


Indomethacin induces differential effects on in vitro endochondral ossification depending on the chondrocyte's differentiation stage.
Heterotopic ossification (HO) is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. Heterotopic ossifications are described to develop via endochondral ossification and standard treatment is administration of indomethacin. It is currently unknown how indomethacin influences heterotopic ossification on a molecular level; therefore, we aimed to determine whether indomethacin might influence heterotopic ossification via impairing the chondrogenic phase of endochondral ossification. Progenitor cell models differentiating in the chondrogenic lineage (ATDC5, primary human bone marrow stem cells and ex vivo periosteal agarose cultures) were treated with increasing concentrations of indomethacin and a decrease in gene- and protein expression of chondrogenic and hypertrophic markers (measured by RT-qPCR and immunoblotting) as well as decreased glycosamino-glycan content (by alcian blue histochemistry) was observed. Even when hypertrophic differentiation was provoked, the addition of indomethacin resulted in decreased hypertrophic marker expression. Interestingly, when mature chondrocytes were treated with indomethacin, a clear increase in collagen type 2 expression was observed. Similarly, when ATDC5 cells and bone marrow stem cells were pre-differentiated to obtain a chondrocyte phenotype and indomethacin was added from this time point onward, low concentrations of indomethacin also resulted in increased chondrogenic differentiation. Indomethacin induces differential effects on in vitro endochondral ossification, depending on the chondrocyte's differentiation stage, with complete inhibition of chondrogenic differentiation as the most pronounced action. This observation may provide a rational behind the elusive mode of action of indomethacin in the treatment of heterotopic ossifications. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:847-857, 2017.


Genome-wide identification of R-SNARE gene family in upland cotton and function analysis of GhVAMP72l response to drought stress.
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (R-SNAREs) mainly promoted the assembly of the SNARE complex to drive the final membrane fusion step of membrane transport. Previous research on R-SNAREs has mainly focused on development and growth and has rarely been involved in abiotic stress, especially in cotton. Here, we performed a comprehensive analysis of R-SNARE genes in upland cotton. In total, 51 Gh-R-SNARE genes across six phylogenetic groups were unevenly distributed on 21 chromosomes. Cis elements related to plant growth and response to abiotic stress responses were found in the promoter region of Gh-R-SNAREs. Nine Gh-R-SNARE genes were obviously upregulated under drought stress conditions by RNA-seq and qRT-PCR analysis. Among them, GhVAMP72l might be the key candidate gene contributing to drought stress tolerance in cotton by virus-induced gene silencing (VIGS) assay. These results provide valuable insights for the functional analysis of cotton R-SNAREs in response to drought stress and highlight potential beneficial genes for genetic improvement and breeding in cotton.


Extracorporeal removal of lipids by dextran sulfate cellulose adsorption.
Extracorporeal removal of low-density lipoprotein (LDL) cholesterol by dextran sulfate adsorption is indicated in patients with diet and drug resistant hyper-cholesterolemia to prevent or to regress coronary heart disease. Plasma separation is the first step in the process, followed by adsorption of LDL cholesterol and lipoprotein (a) (Lp[a]) to negatively charged dextran sulfate covalently bound to cellulose beads. The reduction per treatment in LDL cholesterol is 65-75% and in Lp(a) 40-60%. In most patients one treatment per week is sufficient to reduce mean LDL to 100-150 mg/dl. Minor side effects occur in 2-6% of treatments. Major side effects are rare. In uncontrolled studies long-term treatment was associated with inhibition of progression and induction of regression of coronary artery disease. LDL apheresis by dextran sulfate may increase blood perfusion of some tissues, and preliminary results indicate a beneficial effect on therapy resistant nephrotic syndrome with hypercholesterolemia.


A dynamic simulation of bisphenol A dosimetry in neuroendocrine organs.
Bisphenol A (BPA) is a known xenoestrogen with similar properties to 17beta-estradiol. BPA and estrogen are hydrophobic compounds, and this affects the pharmacokinetics of both compounds in mammals. In a previous study we measured the distribution of BPA in female F344 rats exposed to oral doses of 0.1, 10 and 100 mg/kg. The results showed distribution to target neuroendocrine organs at all doses tested. Using these results, we developed a pharmacokinetic model to predict the dynamic uptake and excretion of BPA by various routes of exposure (po, iv, sc, ip). The model was able to simulate the entire time course (48 h) following various routes of exposure in rats over the dose ranges tested. The model indicated that the ultimate tissue uptake of BPA was established by the rapid initial transfer of free BPA into tissues. After free BPA enters the systemic circulation, metabolism and excretion reactions cause a relatively short duration and rapid decline. This period is followed by a slower long-term decline characteristic of BPA's biphasic pharmacokinetics. Plasma protein and tissue binding reactions established the long-term half-life of BPA in the body. Route differences in tissue uptake were directly related to the competition between transfer and binding reactions during the absorption phase.


Synthesis and antiproliferative activities of novel piscidinol a derivatives as potential anticancer agents.
Piscidinol A (1), a major compound isolated from Aphanamixis polystachya, showed modest anticancer activity against cancer cell lines. Subsequently, a series of analogues were synthesised by modification of the key structural functionalities of this high yield natural product and assessed for their anticancer potential against various cancer cell lines. Among the tested derivatives, the compounds 6e and 6i are significantly reduced the cell viability at 5.38 and 5.02 µM against DU145 prostate cancer cells, respectively. Additionally, both the compounds arrested the cell cycle at S phase and induced the late apoptosis in DU145 cells. Together, the results demonstrated that the compounds 6e and 6i could be a promising lead for the development of anticancer agents against DU145 and well worth further investigation aiming to generate potential anticancer agents.


Toward non-toxic antifouling: synthesis of hydroxy-, cinnamic acid-, sulfate-, and zosteric acid-labeled poly[3-hydroxyalkanoates].
The side-chain double bonds of bacterial poly[3-hydroxyalkanoate-co-3-hydroxyalkenoate] (PHAE, 1) were transformed into thioether bonds (derivative 2) via the radical addition reaction of 11-mercapto-1-undecanol. The terminal hydroxy functionalities of derivative 2 were subsequently esterified with cinnamic acid (derivative 3), sulfatized with ClSO(3)H (derivative 4), or coupled with tert-butyldimethylsilyl-protected coumaric acid, to give, after deprotection with tetrabutylammonium fluoride (derivative 5) followed by sulfatization, p-(sulfooxy) cinnamic acid- (zosteric acid) labeled PHAE (derivative 6). The reactions proceeded with good yields and little side reactions, which was confirmed with (1)H NMR and GPC experiments. These functionalized polyesters are currently investigated as environmentally friendly coatings to protect surfaces from biofouling.


Polarizing white light interferometry for phase measurements using two simultaneous interferograms.
Our research introduces a design for a polarization phase-shifting white light interferometric system (PPS-WLIS) that operates in a transmissive mode for measuring the slope phase of transparent objects. It comprises a cyclic path interferometer (lateral shear interferometer) coupled with a multiplexing Michelson interferometer. The system uses polarization to produce two parallel interferograms with polarization modulated with relative shifts simultaneously. To determine the optical phase, we used a two-step algorithm for phase demodulation that does not necessitate precise phase shifts, making the system more straightforward to operate. As a result, we could observe variations in the object associated with optical phase changes. Furthermore, our method simplifies the phase-shift interferometry process by requiring only one capture, making it an effective way to examine objects at dynamic events. As an illustration, we demonstrated the temperature measurement generated by a section of a candle flame.


The use of the World Guidelines for Falls Prevention and Management's risk stratification algorithm in predicting falls in The Irish Longitudinal Study on Ageing (TILDA).
the aim of this study was to retrospectively operationalise the World Guidelines for Falls Prevention and Management (WGFPM) falls risk stratification algorithm using data from The Irish Longitudinal Study on Ageing (TILDA). We described how easy the algorithm was to operationalise in TILDA and determined its utility in predicting falls in this population. participants aged ≥50 years were stratified as 'low risk', 'intermediate' or 'high risk' as per WGFPM stratification based on their Wave 1 TILDA assessments. Groups were compared for number of falls, number of people who experienced one or more falls and number of people who experienced an injury when falling between Wave 1 and Wave 2 (approximately 2 years). 5,882 participants were included in the study; 4,521, 42 and 1,309 were classified as low, intermediate and high risk, respectively, and 10 participants could not be categorised due to missing data. At Wave 2, 17.4%, 43.8% and 40.5% of low-, intermediate- and high-risk groups reported having fallen, and 7.1%, 18.8% and 18.7%, respectively, reported having sustained an injury from falling. the implementation of the WGFPM risk assessment algorithm was feasible in TILDA and successfully differentiated those at greater risk of falling. The high number of participants classified in the low-risk group and lack of differences between the intermediate and high-risk groups may be related to the non-clinical nature of the TILDA sample, and further study in other samples is warranted.


Comparison of ethanol absorption during continuous and intermittent flow irrigation in transurethral resection.
Transurethral resection of the prostate was performed using intermittent-flow bladder irrigation (n = 50), or by continuous-flow irrigation, using a suprapubic trocar (n = 50). The irrigant solution contained 1.5% glycine +1% ethanol and fluid absorption was measured from the ethanol content of the expired breath. Fluid absorption was significantly lower in patients receiving continuous-flow irrigation (p less than 0.007) although major absorption occurred in one of these patients. The immediate detection of absorption with the ethanol method allowed us to stop one of the operations performed with intermittent bladder irrigation, at which 2 l of fluid had been absorbed in 20 min. With correction for the amount of removed prostatic tissue, there were no differences in operation time or blood loss between the two types of irrigation.


[Diagnosis of increased thrombotic tendency with chromogenic substrates].
In 185 patients suffering from increased thrombotic tendency and in 40 healthy individuals, the following parameters were assayed by the aid of chromogenic substrates: antithrombin III, plasminogen, immediate and total antiplasmin. Furthermore, the vascular activator of plasminogen and the spontaneous aggregation of platelets were examined by other methods. Alterations of plasmatic parameters which are likely to cause an increased thrombotic tendency were detected in 10% of all cases. In patients suffering from arterial thrombotic manifestations hyperactive platelets were found in 42%.


Atomic force microscopy study for supermolecular microstructures in side-chain liquid crystalline polymer films.
Atomic force microscopy (AFM) is employed to study the supermolecular microstructures of disclinations and inversion walls in thin films of a smectic side-chain liquid crystalline polymer. Two-dimensional nanostripes are formed in thin films when the material enters the smectic phase. A possible mechanism for their formation is also suggested. The stripes run parallel to the local director and thus decorate the overall patterns of nematic director around the disclinations and inversion walls. Three patterns involving radial, spiral, and circular supermolecular microstructures of a positive disclination with s = +1 and one hyperbolic pattern of a negative disclination with s = -1 are observed. The cores of all these microstructures exhibit circular dark centers in AFM height images. It is found that the specific configurations of a pair of (+1, -1) disclinations form during the late stage of annihilation and inversion walls always separate a pair of (+1, +1) disclinations. The analysis on the director fields around disclinations and inversion walls shows that the bend and splay elastic constants are of the same order of magnitude in the side-chain liquid crystalline polymer.


Human monoclonal antibody against Rh(D) antigen: partial characterization of the Rh(D) polypeptide from human erythrocytes.
A human monoclonal anti-Rh(D) antibody produced by an Epstein-Barr virus (EBV)-transformed B-cell line (IgG1(lambda), clone H2D5D2) has been purified on protein A-Sepharose column and used for binding studies and immune precipitation of the blood group rhesus (Rh) antigens. Scatchard plot analyses show that the 125I-labeled antibody (iodo-gen procedure), binds to 1.09 X 10(5), 0.43 X 10(5), and 0.32 X 10(5) antigen sites on each D--/D--, R2R2 and R1R1 RBC, respectively, with an association constant of approximately 0.6 X 10(8) mol/L-1. Immune precipitation studies indicate also that the Rh(D) antigen of the Rh(D)-positive RBCs is carried by a 29 kd polypeptide as deduced from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). No material could be precipitated from Rh(D)-negative or Rhnull RBCs. These results indicate that the monoclonal and the polyclonal human anti-Rh(D) behave similarly. A sample (Blo., presumed genotype R2r or R0R2) showing an increased number of antigen sites (0.76 X 10(5)/cell) and a high binding constant (5.7 X 10(8) mol/L-1) was used, as well as D--/D-- RBCs, for further purification of the 29-kd component. Extraction by Triton X-100 (0.1% to 5%) of the immune complexes formed between the membrane-bound Rh(D) antigens and the monoclonal antibody as well as a direct quantitative estimate of the 29-kd component, suggest that the Rh(D) polypeptide is loosely bound to the skeleton, since less than or equal to 80% can be solubilized from the membrane. In similar conditions, glycophorin A showed a slight association with the Triton-insoluble residue, whereas glycophorin B was easily and completely extracted. In contrast, both the minor RBC sialoglycoproteins, glycophorin C and glycoprotein gamma, remained predominantly bound to the membrane skeleton. The purified Rh(D) polypeptide obtained from Blo. and D--/D-- RBCs by immunoprecipitation and preparative gel electrophoresis was homogenous as judged by SDS-PAGE. Amino acid composition indicated that the Rh(D) protein contained sulfhydryl groups which are essential for biological activity.


Gene therapy for human immunodeficiency virus infection: genetic antiviral strategies and targets for intervention.
Gene therapeutic strategies for the treatment of human immunodeficiency virus type 1 (HIV-1) infection have received increased attention due to lack of chemotherapeutic drugs or vaccines that show long-term efficacy in vivo. An emerging group, referred to here as "genetic antivirals," is reviewed. Genetic antivirals are defined as DNA or RNA elements that are transferred into cells and affect their intracellular targets either directly, or after expression as RNA or proteins. They include antisense oligonucleotides, ribozymes, RNA decoys, transdominant mutants, toxins, and immunogens. They offer the possibility to target simultaneously multiple sites in the HIV genome, thereby minimizing the production of resistant viruses. We review the molecular mechanisms of genetic antivirals, their HIV molecular targets, and discuss issues concerning their application as anti-HIV agents.


A retrospective study on surgical repair of the Achilles tendon.
The authors have found in their study of eight cases that ruptured Achilles tendon occurred most often in nonconditioned, obese individuals in their third decade. These individuals often participate in sports requiring sustained, rapid acceleration. After injuries, the Lindholm technique with modification yielded satisfactory results in their patients, although none returned to full preoperative athletic activity.


[Criteria for intensive treatment of hepatic coma].
Results observed over a period of two years in the intensive care of hepatic coma at the University of Genova surgical pathology department are briefly surveyed. A set of practical suggestions is offered for the management of patients whose prognosis is not open to change by the administration of conventional forms of treatment. A critical appraisal of the results achieved is presented along with the general series.


Correlations between echo-encephalographic and computer tomographic measures of third and lateral ventricle size in children and adults.
Accuracy of echo-encephalography (EVG) was assessed by comparison with computer-tomography (CT) in a material of 49 children aged 2 weeks to 15.5 years and 158 adults aged 17 to 83 years. Third ventricle width could be measured on EVG in all the patients, and the correlations with CT values were excellent both in children and adults (r = 0.89 and r = 0.94, respectively). Lateral ventricle echoes could be recorded in 43 children (87.7%) and in 95 adults (60.1%). There were very good correlations between lateral ventricle size estimated as LVI (lateral ventricle index on EVG) and BI (body index on CT) both in children and adults (r = 0.84 and r = 0.86, respectively). In adults, a fairly large proportion (46.3%) of the patients where lateral ventricle echoes could be recorded, apparently had essentially normal ventricle systems, although there was evidence that these echoes could be recorded more easily from widened ventricles.


Draft Genome Sequence of Corynebacterium pseudotuberculosis Strain PA05 Isolated from an Ovine Host in Pará State, Brazil.
We report here the draft genome sequence of Corynebacterium pseudotuberculosis PA05, isolated from an ovine host in Pará State, Brazil. C. pseudotuberculosis is an etiological agent of diseases with veterinary and medical importance. The genome contains 2,435,137 bp, a G+C content of 52.2%, 2,295 coding sequences, five pseudogenes, 53 tRNAs, and six rRNAs.


[Results of refractive surgery in hyperopic and combined astigmatism].
The refractive surgery includes a lot of procedures for changing the refraction of the eye to obtain a better visual acuity with no glasses or contact lenses. LASIK is the most commonly performed laser refractive surgery today. The goal is to present the postoperative evolution of the refraction and visual acuity after LASIK for Mixed and Hyperopic Astigmatism. The results show that LASIK is safe and predictible if we have well performed interventions and well-selected patients.


Effect of orlistat on weight regain and cardiovascular risk factors following a very-low-energy diet in abdominally obese patients: a 3-year randomized, placebo-controlled study.
To investigate the efficacy of orlistat on the maintenance of weight loss over 3 years following a major weight loss induced by very-low-energy diet (VLED) in obese patients with metabolic risk factors such as dyslipidemia, impaired fasting glucose, and diet-treated type 2 diabetes. Initially, weight loss was induced by an 8-week VLED (600-800 kcal/day) in 383 patients with a mean BMI of 37.5 kg/m(2) (range 30.0-45.2). Those who lost > or = 5% of their body weight (309 of 383 patients) were then randomized to receive lifestyle counseling for 3 years together with either orlistat 120 mg t.i.d. or matching placebo capsules. Primary end points were the maintenance of > or = 5% weight loss after 3 years. Additionally, differences in the development of type 2 diabetes between orlistat and placebo were analyzed. The VLED induced a mean weight loss of 14.4 +/- 2.0 kg among the subsequently randomized patients. The mean weight gain after 3 years was lower with orlistat than with placebo (4.6 +/- 8.6 vs. 7.0 +/- 7.1 kg; P < 0.02). The number of participants who achieved > or =5% weight loss also favored orlistat (67 vs. 56%; P = 0.037). Waist circumference was significantly more reduced in the orlistat group (P < 0.05), but no other differences in the risk factors were observed between the two groups. The incidences of new cases of type 2 diabetes were significantly reduced in the orlistat group (8 cases out of 153 subjects) versus placebo (17 cases out of 156 subjects) (P = 0.041). The addition of orlistat to lifestyle intervention was associated with maintenance of an extra 2.4 kg weight loss after VLED for up to 3 years in obese subjects. The combination of orlistat and lifestyle intervention was associated with a reduced occurrence of type 2 diabetes.


Development of an N-Terminal BRD4 Bromodomain-Targeted Degrader.
Targeted protein degradation is a powerful induced-proximity tool to control cellular protein concentrations using small molecules. However, the design of selective degraders remains empirical. Among bromodomain and extra-terminal (BET) family proteins, BRD4 is the primary therapeutic target over family members BRD2/3/T. Existing strategies for selective BRD4 degradation use pan-BET inhibitors optimized for BRD4:E3 ubiquitin ligase (E3) ternary complex formation, but these result in residual inhibition of undegraded BET-bromodomains by the pan-BET ligand, obscuring BRD4-degradation phenotypes. Using our selective inhibitor of the first BRD4 bromodomain, iBRD4-BD1 (IC50 = 12 nM, 23- to 6200-fold intra-BET selectivity), we developed dBRD4-BD1 to selectively degrade BRD4 (DC50 = 280 nM). Notably, dBRD4-BD1 upregulates BRD2/3, a result not observed with degraders using pan-BET ligands. Designing BRD4 selectivity up front enables analysis of BRD4 biology without wider BET-inhibition and simplifies designing BRD4-selective heterobifunctional molecules, such as degraders with new E3 recruiting ligands or for additional probes beyond degraders.


Treating high-rate stereotyped behaviours in children.
High-rate stereotyped behaviour is typically displayed by children who present with some form of sensory or intellectual handicap. This paper reviews the available knowledge on the treatment of the disorder and suggests specific intervention guidelines.


Accuracy of Linking VR-12 and PROMIS Global Health Scores in Clinical Practice.
To examine the accuracy of general health cross-walk tables in a clinical sample of patients with spine disorders. Published tables (Schalet BD, Rothrock NE, Hays RD, et al. Linking physical and mental health summary scores from the Veterans RAND 12-Item Health Survey (VR-12) to the PROMIS(®) Global Health Scale. J Gen Intern Med 2015;30:1524-30) link scores from the Veterans RAND 12-Item Health Survey (VR-12) to the 10-Item Patient-Reported Outcome Measurement Information System (PROMIS), a global health scale metric for both mental (GMH) and physical (GPH) summary scores. We assessed the accuracy of administered PROMIS and VR-12 scores with scores predicted by cross-walks in 4606 adult patients seen in a spine clinic from October 2015 to 2016. Accuracy of linking scores was evaluated using Pearson correlation, intraclass correlation coefficients, and mean and SD of score differences. Bland-Altman plots were used to graphically assess the levels of agreement. The consistency in scores' discrimination across levels of pain severity, depression, and other patient characteristics was assessed. Bootstrap methods estimated linking precision across varying sample sizes. Actual and cross-walked PROMIS scores showed moderate correlation (ICC(3,1): GMH 0.73; GPH 0.81), with Bland-Altman plots suggesting smaller differences between scores in patients with lower and higher general health. Significant discrimination between patient subgroups was demonstrated reliably by both actual and estimated scores. Bootstrapped resamples indicated adequate precision for 200 patients (95% confidence interval for mean difference: GMH -1.38 to 0.60; GPH 0.39 to 1.93). VR-12 and PROMIS global health scores can be accurately linked within a sample of patients with spine disorders; nevertheless, bias is high and precision is low for linking on the patient level. Linked scores at the group level for more than 200 patients can be used in comparative effectiveness research and for comparing results across studies.


Utility of Genomic Assessment of Blood-Derived Circulating Tumor DNA (ctDNA) in Patients with Advanced Lung Adenocarcinoma.
Purpose: Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes.Experimental Design: Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next-generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications.Results: Seventy-two patients (82%) had ≥1 ctDNA alteration(s); among these, 75% carried alteration(s) potentially actionable by FDA-approved (61.1%) or experimental drug(s) in clinical trials (additional 13.9%). The most frequent alterations were in the TP53 (44.3% of patients), EGFR (27.3%), MET (14.8%), KRAS (13.6%), and ALK (6.8%) genes. The concordance rate for EGFR alterations was 80.8% (100% vs. 61.5%; ≤1 vs. >1 month between ctDNA and tissue tests; P = 0.04) for patients with any detectable ctDNA alterations. Twenty-five patients (28.4%) received therapy matching ≥1 ctDNA alteration(s); 72.3% (N = 16/22) of the evaluable matched patients achieved stable disease ≥6 months (SD) or partial response (PR). Five patients with ctDNA-detected EGFR T790M were subsequently treated with a third generation EGFR inhibitor; all five achieved SD ≥ 6 months/PR. Patients with ≥1 alteration with ≥5% variant allele fraction (vs. < 5%) had a significantly shorter median survival (P = 0.012).Conclusions: ctDNA analysis detected alterations in the majority of patients, with potentially targetable aberrations found at expected frequencies. Therapy matched to ctDNA alterations demonstrated appreciable therapeutic efficacy, suggesting clinical utility that warrants future prospective studies. Clin Cancer Res; 23(17); 5101-11. ©2017 AACR.


Virulence-associated plasmids in Rhodococcus equi.
Twenty-three strains of Rhodococcus equi from independent clinical cases were analyzed for the presence of virulence plasmid DNA. Of the clinical isolates, 19 contained an 85-kb plasmid and the remaining 4 contained a 90-kb plasmid. All of the isolates expressed 15- to 17-kDa antigens and were virulent in mice. Restriction enzyme and Southern blot analyses showed large regions of DNA homology between the 85- and 90-kb virulence plasmids. It was concluded tentatively that there are at least two virulence plasmids in R. equi and that they have a common origin.


Complete nose coverage to prevent airborne contamination via nostrils is unnecessary.
Besides an atraumatic procedure, aseptic techniques during surgery have been suggested to have a positive impact on the predictability of osseointegration. To avoid an infection of the surgical field, coverage of the face of the patient (drapes) and nose (surgical mask, drape and plastic film) were advocated in order to reduce airborne infections and to prevent a contact contamination of instruments and gloves. Such a coverage, however, increases the feeling of claustrophobia when local anaesthesia is used and can lead to hypoxemia. The aim of the present study was to investigate whether the expired air via the nostrils could contribute to the contamination of the oral surgical field. Test blood agar plates were installed for 30 min under the nose of volunteers lying on a surgical table; once with full coverage of their nostrils, as indicated above, and once without. Simultaneously, control plates were installed on a table besides the patient to measure the basic contamination from the environment. All plates were incubated both aerobically and anaerobically. The number of colony forming units (c.f.u.) recorded on test plates after aerobic and anaerobic incubation were surprisingly low, with a mean score of 2.7 and 5.0 c.f.u. for the uncovered situation, and 2.5 and 3.3 c.f.u. for the covered situation, respectively. The control plates were infected by a nearly comparable number of bacteria (means ranging from 2.2 to 3.2). These findings indicate that covering nostrils by a mask and sterile adhesive plastic film is not essential in avoiding airborne microbial contamination. However, the use of a meshed nose guard to prevent contact with the highly contaminated nasal skin is highly recommended.


Bubble growth within the skin by rectified diffusion might play a significant role in sonophoresis.
Low frequency ultrasound has successfully been used for enhancing transdermal transport of a variety of different molecules. This phenomenon is referred to as sonophoresis. Several attempts have been made to investigate the enhancing mechanism in order to modulate the overall process. In this study we assess whether rectified diffusion is a process that occurs within the skin, which could eventually lead to channeling and thereby to transdermal sonophoresis. The model presented in this paper is based on the following postulate: gas bubbles are randomly distributed within the lipid bilayers of the stratum corneum (SC). As the skin is subjected to ultrasound, gas bubbles grow by rectified diffusion. During this period, bubbles may merge with the outer or inner boundaries of the SC, or merge with neighboring bubbles. Eventually, channels are created, allowing drugs to easily penetrate through the most significant barrier to transdermal delivery, the SC. As a result, transdermal transport rate is enhanced. In this work, a mathematical model has been formulated, in which permeability enhancement of the SC is linked to channels, possibly created by means of rectified diffusion. Sonophoresis may result from various mechanisms that act in synergy. The present model predicts that rectified diffusion might be one of the factors that lead to sonophoresis during ultrasound treatment.


[Therapy delays among women with diagnosed breast cancer and chosen sociodemographic factors].
Up to now, there have been very few studies concerning delay issues in the treatment of breast cancer in Poland. The aim of the study was to determine the time and causes of delay in the treatment of women diagnosed with breast cancer and the importance of demographic and social factors on the occurrence of delays in the implementation of therapy. The study was conducted in 2015-2016 in the Podkarpackie Oncology Centre in Brzozów for a group of 231 women. The time criterion of the delays in the treatment of women suffering from breast cancer was more than 1 month from the first oncological consultation to therapy initiation. The diagnostic poll method and medical documentation analysis were used. Research tools included a survey questionnaire and research protocol. The collected material was subjected to the statistical analysis using the χ2 test. The values of p < 0.05 were considered statistically significant. Delays were noted in 62.8% of the study participants and the mean delay time took 12.6 weeks. The main causes of the delays were: fear that the diagnosis would be confirmed, long waiting time for specialist investigations and their results, age, marital status and professional activity. No statistically significant correlation was found between profession, education level and the place of residence with therapy delays. Delays in the treatment of breast cancer patients were noted in the majority of study participants. A correlation was observed between the delays and chosen sociodemographic factors. Med Pr. 2019;70(1):89-98.


Brachytherapy and breast cancer.
Brachytherapy has been an important component of radiation therapy for breast cancer. It played a historical role in the development of breast-conserving techniques for early-stage breast cancer. The primary use for brachytherapy in this setting has been to deliver a localized boost dose of radiation to the lumpectomy bed after whole breast radiation therapy. In recent years, there has been less utilization of brachytherapy as a boost technique. This is predominantly related to wider availability of electrons for delivering a boost dose. Another significant factor for the decline is the controversy of whether routine boosting of the tumor bed is necessary for all early-stage breast cancer patients after conservative surgery and whole breast radiation therapy. Despite this, brachytherapy is still the preferred boost technique in certain subsets of patients. Newer applications of brachytherapy for the treatment of breast cancer have emerged and have shown promise. For early-stage breast cancer, these include brachytherapy as the sole radiation modality after lumpectomy and in combination with local excision as an alternative to mastectomy for treatment of local recurrences after conservative surgery and radiation therapy. In selected locally advanced cases of breast cancer, brachytherapy has been used as part of a technique that attempts breast conservation. At this time, these newer uses of brachytherapy for the treatment of breast cancer remain investigational.


Valence tautomeric transitions of three one-dimensional cobalt complexes.
Three novel complexes, namely, [Co(III)(3,5-DBCat)(3,5-DBSq)(bpe)]·2CH3CN·2H2O (1·S), [Co(III)(3,5-DBCat)(3,5-DBSq)(azpy)]·2CH3CN·2H2O (2·S), and [Co(II)(3,5-DBSq)2(bpb)][Co(III)(3,5-DBCat)(3,5-DBSq)(bpb)]0.5·2CH3CN·2H2O (3·S), were synthesized and characterized by valence tautomeric (VT) X-ray diffraction and magnetic measurements [where 3,5-DBCatH2 = 3,5-di-tert-butyl-catechol, 3,5-DBSqH = 3,5-di-tert-butyl-semiquinone, bpe = trans-bis(4-pyridyl)ethylene, azpy = trans-4,4'-azopyridine, and bpb = 1,4-bis(4-pyridyl)benzene]. The three complexes have similar one-dimensional chain structure building from bidentate-bridging pyridine ligands and planar 3,5-DBCat/3,5-DBSq-fixed Co(II/III) entities. Complexes 1·S and 2·S could retain the crystallinity during desolvation, and the crystal structures of 1 and 2 were therefore able to be determined. Only when 1·S and 2·S desolvated above 310 K did the magnetic susceptibilities × temperatures values of the two complexes rise sharply, and then thermally induced complete, one-step VT transitions for 1 and 2 were available and repeatable. Complex 3·S showed an incomplete, one-step VT transition independent of solvent molecules. Among these complexes, only 1 was sensitive to photoexcitation at low temperature, its photoinduced metastable state relaxed with temperature-independent behavior at low temperature range (5-10 K) and with thermally assisted behavior at high temperature range (above 20 K), respectively.


[Value of direct radiographic enlargement (DIMA) in early detection of rheumatic inflammatory lesions. Comparative evaluation with high resolution conventional imaging technique].
Rheumatological joint disorders were examined with mammographic film-screen combinations and high-definition microfocal magnification radiography. Our objective was to evaluate the potentials of magnification radiography in diagnosing arthritis by means of interobserver and ROC analysis. The microfocal X-ray unit had a spot size of 20-130 microns; 5-fold magnification was performed. Digital luminescence radiography was employed; digital image processing included simulation of conventional technique and edge enhancement. Eighty radiographs were obtained with conventional and magnification technique. All films were analyzed by five readers. Anatomical and pathological structures were evaluated. The percentage of uncertain findings in magnification radiography was lower compared to conventional radiographs (14% to 26%); in 8% (compared to 19%) the diagnosis of erosions was uncertain. Additionally ROC analysis was carried out. Magnification radiography was significantly (p < 0.03) better than the conventional films.


[Isomeric derivatives of lupinine and epilupinine--organophosphorus inhibitors of cholinesterases].
The isomeric-structure analysis data of anticholinesterase action of organophosphorous inhibitors with similar structure help in the search of specific effectors and detection of differences in reactivity of various animals' enzymes. This study compared the data of efficacy in respect of 4 mammal and 5 arthropoda cholinesterase preparations for 26 quinolizidine inhibitors, which molecules contain both the isomeric unbranched and branched alkoxyl radicals in the phosphoryl group, and the epimeric lupinine and epilupinine derivatives in the leaving group. The changes in the alkoxyl radical structure of inhibitor molecules act on their efficacy only with respect to the mammal enzymes ("group" inhibitor specificity). The differences between lupinine and epilupinine derivatives were revealed. Highly specific inhibitors of different enzymes were detected among the tested compounds.


Heinz-body hemolytic anemia associated with phenazopyridine and sulfonamide.
A 27-year-old white woman developed Heinz-body hemolytic anemia following multiple courses of oral phenazopyridine and trimethoprim-sulfamethoxazole. Her diagnosis was supported by the finding of bite cells on peripheral blood smear. The patient's rapid recovery and reversal of abnormal laboratory parameters were consistent with an acquired hemolytic disorder. This case should sensitize the clinician to the development of drug-induced oxidative hemolysis, its clinical features, and its reversibility. It is also important that the clinician recognize those drugs capable of causing this disorder and appreciate the methods available to establish the diagnosis.


Genome-wide analysis of DNA methylation in bovine placentas.
DNA methylation is an important epigenetic modification that is essential for epigenetic gene regulation in development and disease. To date, the genome-wide DNA methylation maps of many organisms have been reported, but the methylation pattern of cattle remains unknown. We showed the genome-wide DNA methylation map in placental tissues using methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq). In cattle, the methylation levels in the gene body are relatively high, whereas the promoter remains hypomethylated. We obtained thousands of highly methylated regions (HMRs), methylated CpG islands, and methylated genes from bovine placenta. DNA methylation levels around the transcription start sites of genes are negatively correlated with the gene expression level. However, the relationship between gene-body DNA methylation and gene expression is non-monotonic. Moderately expressed genes generally have the highest levels of gene-body DNA methylation, whereas the highly, and lowly expressed genes, as well as silent genes, show moderate DNA methylation levels. Genes with the highest expression show the lowest DNA methylation levels. We have generated the genome-wide mapping of DNA methylation in cattle for the first time, and our results can be used for future studies on epigenetic gene regulation in cattle. This study contributes to the knowledge on epigenetics in cattle.


Signal transduction by inflammatory cytokines.
The mechanisms by which the inflammatory cytokines interleukin-1 and interleukin-6, and tumour necrosis factor alpha activate cellular genes are reviewed. Common usage of some receptors and transcription factors are beginning to emerge, and many offer insights into newer therapeutic options.


Ultrasonication assisted preparation of carbonaceous nanoparticles modified polyurethane foam with good conductivity and high oil absorption properties.
In this work, we report a facile, low cost and time-saving method for the fabrication of compressible, electrically conductive, oil absorptive, cost-effective and flexible polyurethane (PU) foam through ultrasonication induced carbonaceous nanoparticles (CNP) onto flexible PU foam (CNP-PU foam). SEM images showed that the CNP could be firmly anchored onto the PU foam, and made the PU foam surface much rougher. Zero-dimensional carbonaceous nanoparticles were easier to anchor onto the PU foam surface than one-dimensional nanoparticles (e.g., carbon nanotube) or two-dimensional nanoparticles (e.g., graphene oxide). The CNP-PU foam exhibited excellent elasticity and high mechanical durability even when it was subjected to 500 cyclic compression. The CNP-PU foam had excellent absorption of organic solvents up to 121 times the weight of the initial PU foam. In addition, the electrical conductivity of PU foams was considerably increased with the anchoring of CNP onto the matrix. In addition, compression experiments confirmed that the electrical conductivity of CNP-PU foams changed with their compression ratios, thus exhibiting excellent pressure sensitivity. The as-prepared materials have significant potential as oil absorbents, elastic conductors, flexible electrodes, pressure sensors, etc.


Effects of tryptamine antagonists on the anaphylactic contractions of the bovine pulmonary smooth muscles.
Calves were sensitized with horse plasma (H.P.), 0.2 ml/kg, i.v., and H.P. (0.2 ml/kg) in Freund's complete adjuvant, s.c. The latter injection was repeated 1 week later and the animals were killed 10 days after the second injection. Spirally cut strips of pulmonary artery and vein and the trachealis muscle from the sensitized calves contracted to 5-hydroxytryptamine (5-HT) and specific antigen (horse plasma). Antigen-induced contractions of the pulmonary smooth muscles were significantly blocked (P less than 0.05) by the 5-HT antagonists, methysergide and ketanserin. The trachea, however, appeared less sensitive to the antagonists than the pulmonary vessels. The results suggest that 5-HT participates in the pulmonary anaphylactic reactions of cattle and that ketanserin may be useful in suppressing bovine pulmonary hypersensitivities.


Couplet Analysis of Linguistic Topology Using Deep Neural Networks in Cognitive Linguistics.
The work reported here primarily aims to realize the automatic generation of couplets using the linguistic topology of deep neural network (DNN). First, the symmetry, topology, and cognitive linguistics of language are explored to lay a theoretical foundation for subsequent model establishment and analysis. Then, the recurrent neural network (RNN) is employed to build the Seq2Seq model, and Liweng's Guide to Rhyme (an ancient Chinese enlightenment reading material to poetry creation) is imported into the Seq2Seq model as a basic corpus. Eventually, the entire system is implemented automatically on TensorFlow. The system undergoes tests of the five-character quatrain, the seven-character quatrain, the couplet, and the part-of-speech detection. Results demonstrate that both the first and the second lines of the couplet present an excellent correspondence regarding sentences and words. After some famous verses are entered, the second line of the couplet obtained is quite vivid and appropriate. Meanwhile, the results can be generated quickly and meet the requirements on rhyme and couplet matching. This model can input verses according to users' own needs and generate the second line of the couplet quickly, showing good correspondence in words, part-of-speech, and sentence pattern. Because the couplet belongs to Chinese traditional culture, it has a strong local Chinese cultural flavor. The system designed based on computer technology can help people learn and experience the charm of couplets.


Proliferation of human testicular tumours.
Whole tumour perfusion with radioactive DNA precursors reveals that proliferation of human testicular tumours differs widely depending on type and stage of development. In seminomas a homogeneous distribution of proliferating cells at early stages is followed by a shift of the growth fraction to the periphery at advanced stage. Embryonal carcinomas show a chessboard-like pattern of proliferating fractions with high 3H-thymidine labelling indices and short tpot. In mature teratomas proliferation is low. It increases in immature teratocarcinomas. Lack of proliferation is observed in beta-hCG-positive syncytiotrophoblastic cells of choriocarcinomas, the growth fraction being limited to the cytotrophoblastic compartment.


Alternative measures reveal different but low estimates of labour market attachment after severe traumatic brain injury: A nationwide cohort study.
To explore if the definition of labour market attachment (LMA) changes LMA proportions after severe traumatic brain injury (TBI). Cohort study with 5-year follow-up. Patients aged 18-64 years with severe TBI from 2004 to 2012 (n = 637) and matched controls (n = 2497). LMA was defined in three ways. All definitions included patients working with no government benefits. Definition 2 included patients receiving unemployment benefits (LMA-unemployment benefits). Definition 3 included patients receiving supplemental benefits/services such as patients involved in work-activation schemes (LMA supplementary benefits). First week of return to work (RTW), stable LMA first year after RTW and weekly LMA prevalence were calculated. Patients and controls were compared using multivariable conditional logistic regression. LMA unemployment benefits had similar proportions to LMA with no benefits. These estimates were lower than LMA supplemental benefits where 52% attempted to RTW and 31% achieved stable LMA within 2 years. The maximal LMA prevalence (LMA supplementary benefits) decreased from 33 to 30% from years 2 to 5. Adjusted odds ratios were 0.05 and 0.06 for years 1 and 2, and 0.07 for stable LMA in patients compared to controls. LMA proportions differed depending on the definition. Regardless of definition, LMA proportions following severe TBI were low in Denmark.


Designing an anatomical contour titanium 3D-printed oblique lumbar interbody fusion cage with porous structure and embedded fixation screws for patients with osteoporosis.
This study aimed to design an anatomical contour metal three-dimensional (3D)-printed oblique lateral lumbar interbody fusion (OLIF) cage with porous (lattices) structure and embedded screw fixation to enhance bone ingrowth to reduce the risk of cage subsidence and avoid the stress-shielding effect. Finite element (FE) analysis and weight topology optimization (WTO) were used to optimize the structural design of the OLIF cage based on the anatomical contour morphology of patients with osteoporosis. Two oblique embedded fixation screws and lattice design with 65% porosity and average pore size of 750 μm were equipped with the cage structure. The cage was fabricated via metal 3D printing, and static/dynamic compression and compressive-shear tests were performed in accordance with the ASTM F2077-14 standard to evaluate its mechanical resistance. On FE analysis, the OLIF cage with embedded screw model had the most stability, lowest stress values on the endplate, and uniform stress distribution versus standalone cage and fixed with lateral plate under extension, lateral flexion, and rotation. The fatigue test showed that the stiffnesses/endurance limits (pass 5 million dynamic test) were 16,658 N/mm/6000 N for axial load and 19,643 N/mm/2700 N for compression shear. In conclusion, an OLIF cage with embedded fixation screws can be designed by integrating FE and WTO analysis based on the statistical results of endplate morphology. This improves the stability of the OLIF cage to decrease endplate destruction. The complex contour and lattice design of the OLIF cage need to be manufactured via metal 3D printing; the dynamic axial compression and compressive-shear strengths are greater than that of the U.S. Food and Drug Administration (FDA) standard.


Conjunctival bacterial flora in nasolacrimal duct obstruction and its changes after successful dacryocystorhinostomy surgery.
To evaluate the results of conjunctival culture in patients with nasolacrimal duct obstruction (NLDO) and its changes after successful dacryocystorhinostomy surgery. In this prospective study, 71 adult patients with NLDO and 41 age- and sex-matched controls without NLDO were evaluated. The patients were divided in 2 groups based on clinical examination; group A with purulent regurgitation and group B without purulent regurgitation. Dacryocystorhinostomy surgery was performed, and the silicon tube was inserted in patients with upper lacrimal drainage system stenosis and when the lacrimal sac or nasal mucosal flap was inadequate for suitable anastomosis. Before surgery, microbiologic specimens were taken from the conjunctiva. Postoperative conjunctival sampling was continued weekly until the culture became negative or the colony count reached to the range of the control group. There were 38 and 33 patients in groups A and B, respectively. Silicone tube was inserted for 17 patients (23.9%). The culture was positive for bacterial growth in all cases. The conjunctival culture in the control group was positive in 17 eyes (41.4%). The mean count of colonies in a sample unit was 5274 ± 6300, 1167 ± 1504, and 9.5 ± 1.5 for group A, group B, and controls, respectively. The mean time of normalization of specimens was 3.3 ± 1.3 weeks (range 1-7). Pathogenic bacterial growth, higher colony counts, the presence of silicone tube, and purulent regurgitation were significantly associated with longer normalization time (p = 0.007, p = 0.0001, p = 0.0001, and p = 0.01, respectively). This study suggests that after successful dacryocystorhinostomy surgery, a waiting period of 7 weeks is enough for conjunctival bacterial cultures to become negative or reach the level of the normal eyes.


FDG PET imaging for identifying pulmonary hypertension and right heart failure.
Pulmonary arterial hypertension (PAH) is a syndrome characterized by lung vascular intimal lesions, smooth muscle layer hypertrophy, perivascular inflammation, and concomitant right ventricular (RV) remodeling which can ultimately lead to the RV function decline known as RV failure (RVF). A key determining factor for RVF development is the RV metabolic state defined by the level of ischemia and glycolysis which constitute a vicious cycle of hypoxia, metabolic shift from glucose oxidation (GO) to glycolysis, increased RV systolic pressure (RVSP), decreased RV output, and further myocardial ischemia. In this context, 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) has been used for the measurement of glucose uptake (GU) as an indicator of glucose metabolism in the right heart and pulmonary vasculature. The focus of this review is the application of FDG PET modality for assessing PAH severity and clinical outcome.


Isoform specific differences in phospholipase C beta 1 expression in the prefrontal cortex in schizophrenia and suicide.
Our previous study demonstrated that phospholipase C beta 1 mRNA was down-regulated in Brodmann's area 46 from subjects with schizophrenia. However, phospholipase C beta 1 protein has also been shown to be lower in Brodmann's area 8 and 9 from teenage suicide subjects, creating a potential confound in interpreting the findings in schizophrenia due to the high suicide rate associated with this disorder. To begin to reconcile and consolidate these findings, in this study, we measured mRNA and protein levels of phospholipase C beta 1 variants a and b in Brodmann's area 46 and Brodmann's area 9 from subjects with schizophrenia, many of whom were suicide completers, and determined the diagnostic specificity of observed findings. Consistent with our previous study, levels of phospholipase C beta 1 a and b mRNA, but not protein, were lower in Brodmann's area 46 from subjects with schizophrenia. In Brodmann's area 9, phospholipase C beta 1a protein levels were lower in subjects with schizophrenia, while phospholipase C beta 1b mRNA was higher and protein was lower in those that had died of suicide. Altered protein levels in Brodmann's area 9 appeared to be diagnostically specific, as we did not detect these changes in subjects with bipolar disorder, major depressive disorder or suicide completers with no diagnosis of mental illness. We further assessed the relationship between phospholipase C beta 1 and levels of muscarinic receptors (CHRMs) that signal through this protein, in both human and Chrm knockout mouse central nervous system tissue, and found no strong relationship between the two. Understanding central nervous system differences in downstream effector pathways in schizophrenia may lead to improved treatment strategies and help to identify those at risk of suicide.


Labyrinthine anomalies in trisomy 13 mosaicism.
The temporal bone histopathology of a 2-month-old male with a bilateral cleft palate, cleft lip and polydactylia due to trisomy 13 mosaicism was studied. Anomalies in the ear involved a partial absence of the superior semicircular canal, an abnormally wide lateral semicircular canal, underdeveloped cochlear coils, an abnormally broad modiolus, an undeveloped organ of Corti and an underdeveloped basilar membrane in the basal turn of the cochlea, an unusually wide cochlear aqueduct, and deformed stapedial crura.


Venous pressure-volume relation and calf blood flow determined by changes in posture.
The volume capacity of the venous system in the calves of 70 normal subjects was determined by passive and active changes in posture, using mercury-in-rubber strain gauges. The mean volume capacity was 1.26% (SD 0.39%) at a venous pressure of 0 kPa (o mm Hg) and 2.05% (SD 0.70%) at 1.60 kPa (12 mm Hg). With this method the blood flow in the calves at rest was measured without venous occlusion: 2.84 ml-100 ml-1/min (SD 1.20). During interpolated venous occlusion the mean blood flow was 2.67 ml-100 ml-1/min (SD 1.21). The pressure-volume relation over the pressure range 0 to 9.31 kPa (0 to 70 mm Hg) was determined in seven normal subjects.


Primary esophageal mucosa-associated lymphoid tissue lymphoma: A case report and review of literature.
Mucosa-associated lymphoid tissue (MALT) lymphoma is a low grade malignant B cell lymphoma which occurs mainly in the organs having mucosal layer. Though gastrointestinal tract is the most commonly involved extranodal site, primary esophageal MALT lymphoma is very rare with less than 20 cases reported in literature. A 75-year-old man was referred to our hospital for evaluation of dysphagia. Endoscopy revealed a submucosal tumor located in the middle and lower third of esophagus. CT chest and endoscopic ultrasound revealed a 15.5 × 5.9 × 4.0 cm well circumscribed submucosa esophageal tumor. Test for serum antibody against H. pylori was negative. Due to the large tumor size, patient underwent surgical resection. Histological examination showed a submucosal tumor consisting of multiple nodules of varying sizes with intact covering squamous epithelium. The nodules were mainly composed of diffusely and monoclonal proliferating centrocyte-like or monocyte-like cells. Follicular colonizations were observed without lymphoepithelial lesions. The tumor cells were diffusely positive for CD20, PAX-5, Bcl-2 and follicular dendritic cells were positive for CD21, CD23. Monoclonal gene rearrangement was positive for immunoglobulin heavy chain gene, Kappa light chain gene and Lambda light chain gene. Based on these findings, final diagnosis of esophageal MALT lymphoma was made. At 8 month follow up, no recurrence or metastases was detected. Esophageal MALT lymphoma is a rare disease with definitive diagnosis possible only after histopathological examination. It carries good prognosis due to low malignant potential.


Socioeconomic Status and Cardiovascular Responses to Standardized Stressors: A Systematic Review and Meta-Analysis.
Disparities in cardiovascular health by socioeconomic status (SES) are a pressing public health concern. Hypothesized mechanisms linking low SES to poor health are large cardiovascular responses to and delayed recovery from psychological stress. The current study presents a meta-analysis of the literature on the association of SES with blood pressure and heart rate reactivity to and recovery from acute stress tasks. The PubMed database was searched, and 26 unique studies with relevant data were identified (k = 25 reactivity [n = 14,617], k = 6 recovery [n = 1,324]). Using random-effects models, no significant association between SES and cardiovascular reactivity to stress emerged (r = .008, 95% confidence interval = -.02 to .04), although higher SES was associated with better recovery from stress (r = -.14, 95% confidence interval -.23 to -.05). Stressor type moderated the reactivity effect, wherein higher SES was associated with greater reactivity to cognitive stressors (r = .036, p = .024), not with reactivity to interpersonal stressors (r = -.02, p = .62), but was associated with lower reactivity to tasks with combinations of cognitive, interpersonal, and physical challenges (r = -.12, p = .029). Accounting for publication bias revealed a significant association between SES and reactivity in the opposite direction of hypotheses. Cardiovascular recovery from acute stress, but not reactivity to stress, may be a key pathway between low SES and risk for cardiovascular diseases. Heterogeneity in effect size and direction, challenges related to working across temporal dynamics, and recommendations for future research are discussed.


Acute pancreatitis as initial presentation of acute myeloid leukemia-M2 subtype: A case report.
Direct infiltration of the pancreas by acute myeloid leukemia (AML) with acute pancreatitis (AP) as an initial symptom is extremely rare. Only once in the literature, the leukemia cells in AML have been implicated as the cause of AP. Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes. Severe AP (SAP) progresses rapidly with a high fatality rate. Therefore, it is important to identify the predisposing factors in the early stage of SAP, evaluate the condition, determine prognosis, formulate treatment plans, and prevent a recurrence. Here, we describe a case of SAP due to AML. A 61-year-old man presented to the hospital with fever and persistent abdominal pain. Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia. Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion. The patient had no common etiologies and risk factors for AP, but the concurrent severe thrombocytopenia could not be explained by pancreatitis. Finally, the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis, AML (M2 type based on the French-American-British classifications system). Direct infiltration of the pancrease by acute leukemia, particularly AML cells, is an infrequent cause of AP. Therefore, although AP is a rare extramedullary infiltration characteristic for AML patients, it should be considered when determining the etiology of AP.


Polyethylene Glycol 3350 Changes Stool Consistency and the Microbiome but not Behavior of CD1 Mice.
Polyethylene Glycol 3350 (PEG3350) is a laxative commonly used to treat constipation in children. The Food and Drug Administration has received reports of increased anxiety, aggression, and obsessive--compulsive behaviors in children administered PEG3350. Thus, we assessed whether daily administration of PEG3350 leads to anxiety-like behavior in mice. Outbred CD-1 IGS mice were administered either a high or a low dose of PEG3350 via daily oral gavage for 2 weeks. As a laxative comparison and control, additional mice were given a high or low dose of magnesium citrate or vehicle (water). Weight and stool consistency were assessed after each gavage to determine laxative effectiveness. Anxiety-like behaviors were assessed using light/dark, open field, and elevated plus maze (EPM) tests at baseline, after 2 weeks of daily gavage, and after a 2 week washout in experiment 1, and after 2 weeks of daily gavage in experiment 2. Stool samples were collected for microbiome analysis in experiment 2 at baseline, after 2 weeks of daily gavage, and after 2 weeks washout. PEG3350 and magnesium citrate significantly changed stool consistency, as well as microbiome alpha and beta diversity. Anxiety-like behaviors were not, however, different in mice administered low or high doses of PEG3350 or magnesium citrate. Although changes in stool consistency and the gut microbiome occurred, administration of PEG3350 did not alter anxiety-like behaviors.


Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients.
Anderson-Fabry disease (AFD) is an X-linked condition originating from a deficiency in alpha-galactosidase, a lysosomal enzyme. Multi-organ involvement ensues in early adulthood and vital organs are affected: the kidneys, brain, heart. Several reports however suggest that AFD is underdiagnosed. We screened a kidney transplant population using a two-tier approach. The first tier was the determination of alpha-galactosidase A (AGALA) activity using a dried blood spot on filter paper (DBFP); in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene. From the database of 2328 patients, 1233 subjects met the inclusion criteria. Finally, after informed consent, 673 patients were screened (54.5%-395 women and 278 men). DBFP analysis resulted in a mean AGALA of 2.63 +/- 2.48 micromol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 micromol/L/h, respectively). Eleven patients were subjected to further genetic analysis. In a male patient a pathogenic missense mutation p.Ala143Thr (c.427A>G) was identified. Our results show that the proposed approach can detect AFD patients in a until now seldomly screened high-risk group: kidney transplant patients. We conclude that screening for AFD in high-risk populations is a cost-effective, technically feasible and clinically valuable objective.


Prevalence of radiographic findings consistent with femoroacetabular impingement in military personnel with femoral neck stress fractures.
A femoral neck stress fracture is a serious condition that affects military personnel and endurance athletes. There is increasing evidence that femoroacetabular impingement contributes to significant hip pathology. This study investigates the prevalence of radiographic abnormalities associated with impingement in military personnel treated for femoral neck stress fractures. The radiographs of 69 consecutive soldiers being treated for a femoral neck stress fracture identified on magnetic resonance imaging were reviewed for radiographic signs of femoroacetabular impingement. In the cohort, the average incidence of a crossover sign was 51% (27/53). The incidence of a center edge angle greater than 40° was 47% (25/53). The alpha angle was greater than 50° in 55% (29/53). In conclusion, it appears that young patients with femoral neck stress fractures have a high prevalence of radiographic abnormalities suggestive of hip impingement. Hip impingement may lead to abnormal stress across the femoral neck, predisposing individuals to stress fractures.


Mitigating harmful cyanobacterial blooms in a human- and climatically-impacted world.
Bloom-forming harmful cyanobacteria (CyanoHABs) are harmful from environmental, ecological and human health perspectives by outcompeting beneficial phytoplankton, creating low oxygen conditions (hypoxia, anoxia), and by producing cyanotoxins. Cyanobacterial genera exhibit optimal growth rates and bloom potentials at relatively high water temperatures; hence, global warming plays a key role in their expansion and persistence. CyanoHABs are regulated by synergistic effects of nutrient (nitrogen:N and phosphorus:P) supplies, light, temperature, vertical stratification, water residence times, and biotic interactions. In most instances, nutrient control strategies should focus on reducing both N and P inputs. Strategies based on physical, chemical (nutrient) and biological manipulations can be effective in reducing CyanoHABs; however, these strategies are largely confined to relatively small systems, and some are prone to ecological and environmental drawbacks, including enhancing release of cyanotoxins, disruption of planktonic and benthic communities and fisheries habitat. All strategies should consider and be adaptive to climatic variability and change in order to be effective for long-term control of CyanoHABs. Rising temperatures and greater hydrologic variability will increase growth rates and alter critical nutrient thresholds for CyanoHAB development; thus, nutrient reductions for bloom control may need to be more aggressively pursued in response to climatic changes globally.


Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome.
The human gut microbiota encodes β-glucuronidases (GUSs) that play key roles in health and disease via the metabolism of glucuronate-containing carbohydrates and drugs. Hundreds of putative bacterial GUS enzymes have been identified by metagenomic analysis of the human gut microbiome, but less than 10% have characterized structures and functions. Here we describe a set of unique gut microbial GUS enzymes that bind flavin mononucleotide (FMN). First, we show using mass spectrometry, isothermal titration calorimetry, and x-ray crystallography that a purified GUS from the gut commensal microbe Faecalibacterium prausnitzii binds to FMN on a surface groove located 30 Å away from the active site. Second, utilizing structural and functional data from this FMN-binding GUS, we analyzed the 279 unique GUS sequences from the Human Microbiome Project database and identified 14 putative FMN-binding GUSs. We characterized four of these hits and solved the structure of two, the GUSs from Ruminococcus gnavus and Roseburia hominis, which confirmed that these are FMN binders. Third, binding and kinetic analysis of the FMN-binding site mutants of these five GUSs show that they utilize a conserved site to bind FMN that is not essential for GUS activity, but can affect KM. Lastly, a comprehensive structural review of the PDB reveals that the FMN-binding site employed by these enzymes is unlike any structurally characterized FMN binders to date. These findings reveal the first instance of an FMN-binding glycoside hydrolase and suggest a potential link between FMN and carbohydrate metabolism in the human gut microbiota.


[Study on the value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 and growth differentiation factor-15 in the diagnosis of sepsis: test results from the patients of a multicenter study].
To investigate the diagnostic value of mitochondrial associated protein fumarylacetoacetate domain containing protein 1 (FAHD1) and growth differentiation factor-15 (GDF-15) in sepsis. Based on the database of the whole process of sepsis early warning, diagnosis and treatment management, which was established on the study of sepsis early warning and standardized diagnosis and treatment system, adult patients with suspected infection admitted to the department of critical care medicine of Zhejiang Hospital, Second Affiliated Hospital of Zhejiang University, the First Affiliated Hospital of Sun Yat-Sen University, West China Hospital of Sichuan University, Ningbo First Hospital from May 2014 to October 2015 were enrolled. The basic vital signs, and the main blood routine results, liver and kidney function, blood gas, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score at the time of diagnosis of patients with or without sepsis were analyzed. The preserved serum samples were taken, the levels of procalcitonin (PCT), C-reactive protein (CRP) were detected by electrochemiluminescence method, immunoturbidimetry respectively, and FAHD1 and GDF-15 were detected by enzyme linked immunosorbent assay (ELISA). Univariate and multivariate Logistic regression were used to analyze the risk factors for sepsis diagnose. The indexes' diagnostic efficacy in sepsis were analyzed by receiver operating characteristics curve (ROC curve). A total of 132 patients were enrolled, including 76 cases of sepsis and 56 cases of non-sepsis. Compared with the non-sepsis group, the heart rate in the sepsis group was increased (bpm: 116.4±17.8 vs. 97.4±19.1), while the mean arterial pressure (MAP), platelet count (PLT), arterial partial pressure of oxygen (PaO2) were significantly decreased [MAP (mmHg, 1 mmHg = 0.133 kPa): 65.8±9.7 vs. 74.7±10.3, PLT (×109/L): 120 (69, 204) vs. 163 (117, 239), PaO2 (mmHg): 83.0 (66.6, 108.0) vs. 108.0 (84.4, 130.0), all P < 0.05], direct bilirubin (DBil), serum creatinine (SCr), lactic acid (Lac), APACHE II score and SOFA score were significantly increased [DBil (μmol/L): 13.00 (5.55, 55.31) vs. 6.20 (2.20, 21.90), SCr (μmol/L): 118.00 (70.00, 191.73) vs. 77.20 (59.65, 110.86), Lac (mmol/L): 2.90 (1.50, 4.10) vs. 1.90 (1.20, 2.80), APACHE II score: 20.0 (16.0, 25.0) vs. 16.0 (10.0, 21.0), SOFA score: 12.0 (8.0, 16.0) vs. 8.0 (5.0, 13.0), all P < 0.05]. In addition, the serum levels of FAHD1, GDF-15, PCT and CRP in sepsis group were significantly higher than those in non-sepsis group [FAHD1 (μg/L): 3.96 (2.25, 5.92) vs. 2.47 (1.03, 3.54), GDF-15 (μg/L): 8.46 (4.37, 19.68) vs. 4.32 (1.74, 10.39), PCT (μg/L): 3.79 (1.37, 11.32) vs. 0.42 (0.12, 2.14), CRP (mg/L): 154.43 (61.33, 283.20) vs. 65.95 (28.15, 144.69), all P < 0.01]. Multivariate Logistic regression showed that serum FAHD1 [odds ratio (OR) = 1.135, 95% confidence interval (95%CI) was 1.045-1.234], GDF-15 (OR = 1.090, 95%CI was 1.029-1.155) and CRP (OR = 1.007, 95%CI was 1.002-1.011) were risk factors for sepsis (all P < 0.05). ROC curve analysis of sepsis showed that the areas under ROC curve (AUC) of serum mitochondrial associated proteins FAHD1 and GDF-15 were 0.727 (95%CI was 0.641-0.802) and 0.677 (95%CI was 0.588-0.757), respectively; and the AUC of classical infection indexes PCT and CRP were 0.767 (95%CI was 0.683-0.837) and 0.680 (95%CI was 0.59-0.760), respectively. There was no significant difference between the AUC of mitochondrial associated proteins and classical infection indexes. The combination of FAHD1, GDF-15, PCT and CRP had the largest AUC, which was 0.809 (95%CI was 0.730-0.874), and the sensitivity was 75.00%, and the specificity was 80.00%. Mitochondrial associated protein FAHD1 and GDF-15 are associated with sepsis, and the diagnostic efficiency is improved when combined with PCT and CRP, which might provide experimental basis for screening diagnostic markers of sepsis.


Preferences for sex of children in Thailand: a comparison of husbands' and wives' attitudes.
Findings on sex preference for children from a Thai national survey show substantial differences for men and women. Married women appear to have a weak or moderate preference for sons, coexisting with a desire to have at least one child of each sex. Their husbands' preference for sons is noticeably more pronounced. Son preference is strongest among urban ethnic Chinese men but is also substantial among ethnic Thai men. There is also some evidence that men like to have at least one daughter. The contrasting patterns of sex preferences found for men and women in Thailand suggest that results can be misleading if studies of sex preferences for children are based exclusively on samples of married women.


Cinacalcet-Associated Resolution of Primary Hyperparathyroidism in a Patient With Normal Kidney Function.
Cinacalcet use is associated with risk of hypocalcemia; however, this risk has been mostly demonstrated in patients with chronic kidney disease. In this article, we describe a case of a 59-year-old male with primary hyperparathyroidism (PHPT), hypercalciuria, osteopenia, and normal kidney function who was started on cinacalcet for the management of recurrent hypercalcemia following prior unsuccessful parathyroidectomy. Within 6 months following cinacalcet commencement, he developed symptomatic and biochemical hypocalcemia requiring discontinuation of the medication and initiation of calcium supplementation. Over more than 3 years of follow-up, his calcium supplementation was gradually tapered off and then discontinued. He is presently eucalcemic and euparathyroid off calcium supplements while also demonstrating normalization of hypercalciuria and bone mineral density. These data indicate that our patient has experienced resolution of PHPT after brief exposure to cinacalcet. We recommend that low starting cinacalcet doses should be considered for treatment of hypercalcemia in patients with PHPT who underwent unsuccessful parathyroidectomy along with close clinical and biochemical follow-up.


Self-trapped bidirectional waveguides in a saturable photorefractive medium.
A time-dependent model for the generation of joint waveguides by counterpropagating light beams in photorefractive crystals is introduced. Depending on initial conditions and parameter values, the beams form stable structures or display periodic and irregular dynamics. Steady-state solutions nonuniform in the direction of propagation are found, representing a general class of self-trapped waveguides that include counterpropagating spatial vector solitons as a particular case.


Overlapping sets of viral RNAs reflect the array of polypeptides in the EcoRI J and N fragments (map positions 81.2 to 85.0) of the Autographa californica nuclear polyhedrosis virus genome.
In several parts of the Autographa californica nuclear polyhedrosis virus (AcNPV) genome, nested sets of overlapping RNAs with common 3' or 5' termini have been recognized. In the present report, the pattern of viral transcription and the arrangement of viral gene products in the region of 81.2 to 85.0 map units were investigated. In this segment of the AcNPV genome, at least nine size classes of viral RNA were identified which ranged in size from 1.3 kilobases (kb) to 4.6 kb and exhibited common 3' termini. The detailed restriction map and the nucleotide sequence of this part of the AcNPV genome were determined. Computer analyses revealed several open reading frames (ORFs) on the rightward-transcribed strand with potential TATA and CAAT signals preceding many of the potential ORFs and the 5' termini of some of the mapped RNAs. The leftward-transcribed strand was devoid of major ORFs. The presumptive polypeptides encoded by the larger ORFs ranged in size from 11.3 to 55.6 kilodaltons (kDa). The amino acid sequence of the presumptive polypeptide encoded by ORF3, a 33.6-kDa molecule, exhibited an unusual, clustered 16-fold repeat of the dipeptide arginine-serine in a protein that showed an overall preponderance of basic amino acids. The results of in vitro translation experiments with hybrid-selected RNAs homologous to internal subfragments of the 81.2- to 85.0-map-unit region yielded polypeptides of approximately 28, 34 to 36, and 48 to 50 kDa, which were close in size to the lengths of the major ORFs derived from the nucleotide sequence. The localizations of individual size classes of RNAs in the 81.2- to 85.0-map-unit region of the viral genome were determined precisely at the 3' and 5' termini by S1 protection analyses. Within a sequence of eight nucleotides, all RNAs had the same 3' terminus, which lay close to multiple polyadenylation signals. The initiation sites of the nine different RNA size classes were precisely mapped. As the cap sites of the smaller RNAs (less than 1.8 kb) were determined by S1 protection analyses, a multitude of RNA initiation sites became apparent. It was also shown that the different RNA size classes in the 81.2- to 85.0-map-unit region were detectable as early as 2 h and at least until 36 to 48 h after infection. In unselected cytoplasmic RNA, the size classes of viral RNAs specific for the EcoRI J fragment were detectable early as well as late after infection, although at early times the larger RNAs were detectable in smaller amounts.(ABSTRACT TRUNCATED AT 400 WORDS)


Analysis of the interface characteristics of CVD-grown monolayer MoS2 by noise measurements.
We investigated the current-voltage and noise characteristics of two-dimensional (2D) monolayer molybdenum disulfide (MoS2) synthesized by chemical vapor deposition (CVD). A large number of trap states were produced during the CVD process of synthesizing MoS2, resulting in a disordered monolayer MoS2 system. The interface trap density between CVD-grown MoS2 and silicon dioxide was extracted from the McWhorter surface noise model. Notably, generation-recombination noise which is attributed to charge trap states was observed at the low carrier density regime. The relation between the temperature and resistance following the power law of a 2D inverted-random void model supports the idea that disordered CVD-grown monolayer MoS2 can be analyzed using a percolation theory. This study can offer a viewpoint to interpret synthesized low-dimensional materials as highly disordered systems.


The nitroimidazoles as radiosensitizers and cytotoxic agents.
Using hamster cells in culture, the radiosensitizing and cytotoxic properties of 8 electron-affinic drugs have been compared. These include nitrofurans derivatives as well as 2 and 5-nitroimidazoles. Most work has been performed with misonidazole for which it appears that, at 37 degree C, the concentration of drug required to produce a given level of cell killing is inversely proportional to the square of the exposure time. Misonidazole was also compared with X-rays for its ability to produce neoplastic transformations in vitro, using the C3H 10T 1/2 cell line.


A dermal-fat flap for nipple reconstruction.
A refinement in technique for nipple reconstruction utilizing local tissue is described. The operation has been performed on 31 patients who have previously undergone the transverse abdominal island flap breast reconstruction. The longest follow-up is 12 months. Preliminary results appear excellent with desired nipple size and projection.


[Quality of life study in chronic psychotic patients using a day hospital].
This survey concerned 24 adult patients, who are chronic psychotics, living in town and followed by a day hospital team. Their life quality was evaluated with the help of a validated questionnaire, "Subjective Life Quality Profile" ("PQVS"). The same version of this questionnaire was filled in by the patients and their referent nurse, two times, at six month interval. In the mean-time, the service psychiatrist also filled in questionnaires, assessing the psychiatric symptomatology. The main results confirm the reliability of the tool used and the feasibility of this type of survey with a population of chronic psychotics. The results are coherent at six month interval, and the points of view correspond between the patient and this referent. Finally the life quality is less good when the symptomatology quotation is bad. The aim of this work was to give an account of the patient's life, as seen by himself and by the caretakers.


Antigenic relationship among Nocardia asteroides immunotypes.
Culture filtrate antigens from seven Nocardia asteroides immunotypes, and N caviae and N. brasiliensis, were studied by agar gel diffusion using anti-Nocardia sera and immune sera absorbed with cross-reacting antigens. It was found that all seven immunotypes demonstrated specific antigenic determinants. A few immunotypes showed cross-reactivity with other immunotypes. However, this cross-reactivity could be completely removed by absorbing the antibody with the cross-reacting antigen without major change in the reactivity with homologous antigen and antisera. This study clearly demonstrates that the various immunotypes are antigenically distinct, and that for the demonstration of antibody in patients, antigens from various immunotypes are to be used.


Prevalence, serological features, response to treatment and outcome of critical peripheral ischaemia in a cohort of lupus patients.
This study addresses the issue of risk factors and management of critical peripheral ischaemia (CPI) and gangrene in SLE and proposes rituximab as a novel therapy. We conducted a retrospective study of 485 patients with SLE attending a UK tertiary referral centre, followed up over 27 yrs. Demographics, clinical features, serological features, treatment and outcome data were assessed. Seven out of 485 patients (1.4%) had evidence of gangrene or CPI with onset at any stage of SLE disease from presenting feature to 27 yrs after SLE onset, aPL and LAC were over-represented in the CPI patients. All had active SLE at the time of CPI. All seven were treated with intravenous (IV) epoprostenol infusion and aPL-positive patients were anti-coagulated. One patient failed to respond to this treatment and to IV calcitonin gene-related peptide but responded to B-cell depletion therapy using rituximab. Five out of the seven patients suffered digit loss with auto-amputation. CPI is a rare but potentially devastating complication of SLE associated with aPL, LAC and active SLE. B-cell depletion therapy with rituximab may be an option in severe ischaemia not improving with IV epoprostenol.


Differential regulation of cerebral microvascular transcription by single and repetitive hypoxic conditioning.
Systemic conditioning therapeutics afford brain protection at all levels of organization, occurring autonomously for neurons, glia, vascular smooth muscle, and endothelium, which are mediated systemically for the adaptive and innate immune system. The present study was undertaken to examine acute (3 h) and delayed (2 days) gene expression changes in mouse cerebral microvessels following single hypoxic conditioning (HX1) and repetitive hypoxic conditioning (HX9), the latter for which we showed previously to extend focal stroke tolerance from days to months. Microarray (Illumina) analyses were performed on microvessel-enriched fractions of adult mouse brain obtained from the following five groups (naïve; HX1-3h; HX1-2days; HX9-3h; HX9-2days). Differentially expressed genes were analyzed bioinformatically using Ingenuity Pathway Analysis software, with qPCR validating selected up- and down-regulated genes. As expected, some differentially expressed genes were common to more than one treatment or time point, whereas others were unique to treatment or time point. Bioinformatic analyses provided insights into acute (3h) inflammatory and immune signaling pathways that may be differentially activated by HX1 and HX9, with anti-inflammatory and trophic pathways coincident with the ischemia-tolerant phenotype two days after HX1. Interestingly, two days after HX9, microvessels were transcriptionally silent, with only five genes remaining differentially expressed relative to naïve mice. Our microarray findings and bioinformatic analyses suggest that cerebral microvessels from HX1-treated mice exhibit early activation of immune system signaling that is largely suppressed in microvessels from HX9-treated mice. These and other differences between these responses require further study, including at the proteomic level, and with pharmacologic and genetic experiments designed to reveal causality, to reveal further insights into the mechanisms underlying long-lasting stroke tolerance.


Acute radiation effects on cutaneous microvasculature: evaluation with a laser Doppler perfusion monitor.
Laser Doppler perfusion monitoring is a noninvasive technique for measuring blood flow in epidermal microvasculature that makes use of the frequency shift of light reflected from red blood cells. Measurements in patients undergoing radiation therapy show increases in blood flow of ten to 25 times baseline at doses above 50 Gy, and increases are observed with doses as low as 2 Gy. Follow-up measurements show rapid decreases in flow levels after completion of therapy, but levels remain elevated even at 1 year.


Healing of Postextraction Sockets Preserved With Autologous Platelet Concentrates. A Systematic Review and Meta-Analysis.
The true benefit of autologous platelet concentrates (APCs) for enhancing the healing of postextraction sites is still a matter of debate, and in recent years several clinical trials have addressed this issue. The purpose of this study was to determine the effectiveness of an APC adjunct in the preservation of fresh extraction sockets. An electronic search was performed on Medline, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Only controlled clinical trials or randomized clinical trials were included. Selected articles underwent risk-of-bias assessment. The outcomes were complications and adverse events, discomfort and quality of life, bone healing and remodeling assessed by histologic and radiographic techniques, and soft tissue healing. Thirty-three comparative studies were included. Nine articles had a parallel design and 24 had a split-mouth design. Twenty studies were considered to have a low risk of bias and 13 were considered to have a high risk. Overall, 1,193 teeth were extracted from 911 patients. Meta-analysis showed that soft tissue healing, probing depth at 3 months, and bone density at 1, 3, and 6 months were statistically better for the APC group. Qualitative analysis suggested that APCs might be associated with a decrease in swelling and trismus. However, no relevant difference among groups was found for probing depth at 1 month, incidence of alveolar osteitis, acute inflammation or infection, percentage of new bone, and indirect measurement of bone metabolism. APCs should be used in postextraction sites to improve clinical and radiographic outcomes such as bone density and soft tissue healing and postoperative symptoms. The actual benefit of APCs on decreasing pain in extraction sockets is still not quantifiable.


A novel flow cytometric method to assess inflammasome formation.
Inflammasomes are large protein complexes induced by a wide range of microbial, stress, and environmental stimuli that function to induce cell death and inflammatory cytokine processing. Formation of an inflammasome involves dramatic relocalization of the inflammasome adapter protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) into a single speck. We have developed a flow cytometric assay for inflammasome formation, time of flight inflammasome evaluation, which detects the change in ASC distribution within the cell. The transit of ASC into the speck is detected by a decreased width or increased height of the pulse of emitted fluorescence. This assay can be used to quantify native inflammasome formation in subsets of mixed cell populations ex vivo. It can also provide a rapid and sensitive technique for investigating molecular interactions in inflammasome formation, by comparison of wild-type and mutant proteins in inflammasome reconstitution experiments.


Cutaneous adverse reactions of amiodarone.
Dermatological complications of amiodarone are commonly encountered problems in therapy. The incidence in the population of patients with prolonged use of amiodarone reaches nearly 75% according to various sources. Nevertheless, they are often misdiagnosed or overlooked. The aim of this review is to present the current state of knowledge about skin changes induced by amiodarone, including phototoxic and photoallergic reactions, as well as hyperpigmentation. In most cases, the adverse effects are reversible and disappear after discontinuation of the drug. Although the dermatological complications usually do not influence the outcome of the therapy and rarely cause discontinuation of treatment, they have a great impact on patient quality of life.