A unique method of retention for gum stripper- a case report.
Successful restoration of partially edentulous situations, especially kennedy's class-I, II &IV requires lot of contemporary and conventional treatment approaches. Semi precision attachments play a major role in retention of clinically challenging partially edentulous situation. Attachment retained partial dentures can be one of the successful treatment option in prosthdontics. This article presents a unique technique of retaining gum stripper using semi precision attachments.


Cutting the second order chords during mitral valve repair.
The chordae tendinae connect the papillary muscles (PMs) to the mitral valve. While the first-order chordae serve to secure the leaflets to maintain valve closure and prevent mitral valve prolapse, the second-order chordae are believed to play a role in maintaining normal left ventricle size and geometry. The PMs, from where the chordae tendinae originate, function as shock absorbers that compensate for the geometric changes of the left ventricular wall. The second-order chordae connect the PMs to both trigons under tension. The tension distributed towards the second-order chordae has been demonstrate to be more than threefold that in their first-order counterpart. Cutting the second-order chordae puts all the tension on the first-order chordae, which are then closer to their rupture point. However, it has been experimentally demonstrated that the tension at which the first-order chordae break is 6.8 newtons (N), by far higher than the maximal tension reached, that is 0.4 N. Even if the clinical reports have been favorable, the importance of cutting the second-order chordae to recover curvature of the anterior leaflet and increase the coaptation length between the mitral valve leaflets has been slowly absorbed by the surgical world. Nevertheless, there are progressive demonstrations that chordal tethering affects the anterior leaflet not only in secondary, but also in primary mitral regurgitation, having a not negligible role in the long-term outcome of mitral repair.


Recovery and distribution of Ascaris suum superimposed on a Schistosoma japonicum infection in pigs.
The aim of this study was to examine the effect of a primary patent Schistosoma japonicum infection on the establishment and location of a superimposed Ascaris suum infection in pigs. The study comprised two experiments each containing two groups of pigs. In the first experiment, 7 pigs were injected intramuscular (i.m.) with 800 S. japonicum cercariae and inoculated with 1,000 A. suum eggs 11 weeks post primary infection (ppi) and 8 pigs were inoculated with 1,000 A. suum eggs at the time of challenge infection. In the second experiment, 7 pigs were injected i.m. with 1,100 S. japonicum cercariae and inoculated with 1,000 A. suum eggs 16 weeks ppi and 8 pigs were inoculated with 1,000 A. suum eggs at the time of challenge infection. All pigs were slaughtered 10 days after the A. suum challenge infection. The number of white spots caused by A. suum on the surface of the liver was significantly lower in the groups with primary infections of S. japonicum compared with the control groups. However, the present experiments did not demonstrate any effect of a primary S. japonicum infection on the total recovery and distribution of an A. suum challenge infection.


Adhesive Escherichia coli in inflammatory bowel disease and infective diarrhoea.
The clinical features of ulcerative colitis and Crohn's disease are similar to those of infections of the bowel, although their cause is uncertain. Many bacteria that cause intestinal diseases adhere to the gut mucosa, and adhesion of pathogenic Escherichia coli is resistant to D-mannose. The adhesive properties of isolates of E coli were assessed by assay of adhesion to buccal epithelial cells with mannose added. The isolates were obtained from patients with inflammatory bowel diseases (50 with a relapse of ulcerative colitis, nine with ulcerative colitis in remission, 13 with Crohn's disease, and 11 with infectious diarrhoea not due to E coli) and 22 controls. The median index of adhesion to buccal epithelial cells (the proportion of cells with more than 50 adherent bacteria) for E coli from patients with ulcerative colitis in relapse was significantly higher (43%) than that for controls (5%) and patients with infectious diarrhoea (14%). The index was not significantly different among isolates from patients with ulcerative colitis in relapse, Crohn's disease (53%), and ulcerative colitis in remission (30%). If an index of adhesion of greater than 25% is taken as indicating an adhesive strain 86% of isolates of E coli from patients with inflammatory bowel disease were adhesive compared with 27% from patients with infective diarrhoea and none from controls. The adhesive properties of the isolates from patients with inflammatory bowel disease were similar to those of pathogenic intestinal E coli, raising the possibility that they may have a role in the pathogenesis of the condition; the smaller proportion of adhesive isolates in patients with infective diarrhoea due to other bacteria suggests that the organism may be of primary importance rather than arising secondarily.


Water transfer via ectomycorrhizal fungal hyphae to conifer seedlings.
Little is known about water transfer via mycorrhizal hyphae to plants, despite its potential importance in seedling establishment and plant community development, especially in arid environments. Therefore, this process was investigated in the study reported in this paper in laboratory-based tripartite mesocosms containing the shrub Arctostaphylos viscida (manzanita) and young seedlings of sugar pine (Pinus lambertiana) and Douglas-fir (Pseudotsuga menziesii). The objectives were to determine whether water could be transported through mycorrhizal symbionts shared by establishing conifers and A. viscida and to compare the results obtained using two tracers: the stable isotope deuterium and the dye lucifer yellow carbohydrazide. Water containing the tracers was added to the central compartment containing single manzanita shrubs. The fungal hyphae were then collected as well as plant roots from coniferous seedlings in the other two compartments to determine whether water was transferred via fungal hyphae. In addition, the length of the hyphae and degree of mycorrhizal colonisation were determined. Internal transcribed spacer-restriction fragment length polymorphism (ITS-RFLP) analysis was used to identify the fungal species involved in dye (water) transfer. Results of the stable isotope analysis showed that water is transferred via mycorrhizal hyphae, but isotopically labelled water was only detected in Douglas-fir roots, not in sugar pine roots. In contrast, the fluorescent dye was transported via mycorrhizal hyphae to both Douglas-fir and sugar pine seedlings. Only 1 of 15 fungal morphotypes (identified as Atheliaceae) growing in the mesocosms transferred the dye. Differences were detected in the water transfer patterns indicated by the deuterium and fluorescent dye tracers, suggesting that the two labels are transported by different mechanisms in the same hyphae and/or that different fungal taxa transfer them via different routes to host plants. We conclude that both tracers can provide information on resource transfer between fungi and plants, but we cannot be sure that the dye transfer data provide accurate indications of water transfer rates and patterns. The isotopic tracer provides more direct indications of water movement and is therefore more suitable than the dye for studying water relations of plants and their associated mycorrhizal fungi.


Comparison of Three Commercial Collagen Mixtures: Quality Characteristics of Marinated Pork Loin Ham.
Various commercial collagen mixtures aimed at improving the quality of meat products are available, but the optimal composition is unclear. This study aimed to compare the functional properties, including physicochemical characteristics and lipid oxidative stability, of loin ham marinated with three commercial collagen mixtures sold as food additives. The addition of collagen mixtures led to significant increases in the moisture content, water holding capacity (WHC), cooking yield, and instrumental tenderness, regardless of the type of collagen mixture. In particular, meat samples containing collagen mixture C showed the highest (p<0.05) WHC and tenderness among all groups. Furthermore, collagen mixture B induced increases (p<0.05) in pH values in both raw and cooked samples. The a* values of samples with collagen mixtures were lower (p<0.05) than those of samples without collagen mixtures. All collagen mixtures effectively improved oxidative stability during 7 days of storage at 4°C. The samples containing collagen mixture B had the lowest lipid oxidation (p<0.05) among groups. These results indicated that collagen mixture C could be used in injection brine to enhance the quality characteristics of meat products, particularly the WHC and tenderness. Collagen mixture A could be used for meat products with high fat contents based on its ability to improve lipid oxidative stability during long-term storage.


The cold-inducible RNA-binding protein-Thioredoxin 1 pathway ameliorates mitochondrial dysfunction and mitochondrial dynamin-related protein 1 level in the hippocampus of aged mice with perioperative neurocognitive dysfunction.
As a multi-disease model, neuroinflammation, mitochondrial dysfunction, and oxidative stress might be involved in the pathogenic process of perioperative neurocognitive dysfunction (PND). Dynamin-related protein 1 (Drp1) could mediate mitochondrial fission and play important roles in mitochondrial dynamic homeostasis and mitochondria function. The Drp1 may be involved in PND development. The cold-inducible RNA-binding protein (Cirbp) could bind to the 3'-UTR of the thioredoxin 1 (Trx1) mRNA, control oxidative stress, and improve mitochondrial function. In this study, we hypothesized that the Cirbp-Trx1 pathway could ameliorate mitochondrial dysfunction and Drp1 levels in PND mice. Differentially expressed genes were screened using the Gene Expression Omnibus (GEO) database GSE95426 and validated using PCR. Eighteen-month-old C57BL/6 mice were subjected to tibial fracture surgery to generate a PND model. Cirbp was upregulated by hippocampal stereotaxic injections of over-Cirbp plasmid according to the manufacturer's instructions for the in vivo DNA transfection reagent. Cirbp expression was measured using western blot (WB) and immunofluorescence (IF). The Morris water maze (MWM) was used to assess cognitive function. After behavioral testing, the hippocampal tissue was extracted to examine changes in mitochondrial Drp1, mitochondrial function, neuroinflammation, and oxidative stress. Differential gene screening showed that Cirbp expression was significantly downregulated (fold change >1.5, p = 0.003272) in the PND model. In this study, we also found that Cirbp protein levels were downregulated, accompanied by an impairment of cognition, a decrease in superoxide dismutase (SOD) activity, and an increase in malondialdehyde (MDA) content, mitochondrial Drp1 levels, neuroinflammation, and apoptosis. Cirbp overexpression increased Trx1 protein levels and reversed the damage. However, this protective effect was abolished by PX-12 treatment with a Trx1 inhibitor. The Cirbp-Trx1 pathway may regulate mitochondrial dysfunction and mitochondrial Drp1 expression in the hippocampus of PND mice to ameliorate cognitive dysfunction.


What CO2 well gases tell us about the origin of noble gases in the mantle and their relationship to the atmosphere.
Study of commercially produced volcanic CO2 gas associated with the Colorado Plateau, USA, has revealed substantial new information about the noble gas isotopic composition and elemental abundance pattern of the mantle. Combined with published data from mid-ocean ridge basalts, it is now clear that the convecting mantle has a maximum (20)Ne/(22)Ne isotopic composition, indistinguishable from that attributed to solar wind-implanted (SWI) neon in meteorites. This is distinct from the higher (20)Ne/(22)Ne isotopic value expected for solar nebula gases. The non-radiogenic xenon isotopic composition of the well gases shows that 20 per cent of the mantle Xe is 'solar-like' in origin, but cannot resolve the small isotopic difference between the trapped meteorite 'Q'-component and solar Xe. The mantle primordial (20)Ne/(132)Xe is approximately 1400 and is comparable with the upper end of that observed in meteorites. Previous work using the terrestrial (129)I - (129)Xe mass balance demands that almost 99 per cent of the Xe (and therefore other noble gases) has been lost from the accreting solids and that Pu-I closure age models have shown this to have occurred in the first ca 100Ma of the Earth's history. The highest concentrations of Q-Xe and solar wind-implanted (SWI)-Ne measured in meteorites allow for this loss and these high-abundance samples have a Ne/Xe ratio range compatible with the 'recycled-air-corrected' terrestrial mantle. These observations do not support models in which the terrestrial mantle acquired its volatiles from the primary capture of solar nebula gases and, in turn, strongly suggest that the primary terrestrial atmosphere, before isotopic fractionation, is most probably derived from degassed trapped volatiles in accreting material.By contrast, the non-radiogenic argon, krypton and 80 per cent of the xenon in the convecting mantle have the same isotopic composition and elemental abundance pattern as that found in seawater with a small sedimentary Kr and Xe admix. These mantle heavy noble gases are dominated by recycling of air dissolved in seawater back into the mantle. Numerical simulations suggest that plumes sampling the core-mantle boundary would be enriched in seawater-derived noble gases compared with the convecting mantle, and therefore have substantially lower (40)Ar/(36)Ar. This is compatible with observation. The subduction process is not a complete barrier to volatile return to the mantle.


Functionally similar vanadate-induced 8-azidoadenosine 5'-[alpha-(32)P]Diphosphate-trapped transition state intermediates of human P-glycoprotin are generated in the absence and presence of ATP hydrolysis.
P-glycoprotein (Pgp) is an ATP-dependent drug efflux pump whose overexpression confers multidrug resistance to cancer cells. Pgp exhibits a robust drug substrate-stimulable ATPase activity, and vanadate (Vi) blocks this activity effectively by trapping Pgp nucleotide in a non-covalent stable transition state conformation. In this study we compare Vi-induced [alpha-(32)P]8-azido-ADP trapping into Pgp in the presence of [alpha-(32)P]8-azido-ATP (with ATP hydrolysis) or [alpha-(32)P]8-azido-ADP (without ATP hydrolysis). Vi mimics P(i) to trap the nucleotide tenaciously in the Pgp.[alpha-(32)P]8-azido-ADP.Vi conformation in either condition. Thus, by using [alpha-(32)P]8-azido-ADP we show that the Vi-induced transition state of Pgp can be generated even in the absence of ATP hydrolysis. Furthermore, half-maximal trapping of nucleotide into Pgp in the presence of Vi occurs at similar concentrations of [alpha-(32)P]8-azido-ATP or [alpha-(32)P]8-azido-ADP. The trapped [alpha-(32)P]8-azido-ADP is almost equally distributed between the N- and the C-terminal ATP sites of Pgp in both conditions. Additionally, point mutations in the Walker B domain of either the N- (D555N) or C (D1200N)-terminal ATP sites that arrest ATP hydrolysis and Vi-induced trapping also show abrogation of [alpha-(32)P]8-azido-ADP trapping into Pgp in the absence of hydrolysis. These data suggest that both ATP sites are dependent on each other for function and that each site exhibits similar affinity for 8-azido-ATP (ATP) or 8-azido-ADP (ADP). Similarly, Pgp in the transition state conformation generated with either ADP or ATP exhibits drastically reduced affinity for the binding of analogues of drug substrate ([(125)I]iodoarylazidoprazosin) as well as nucleotide (2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate). Analyses of Arrhenius plots show that trapping of Pgp with [alpha-(32)P]8-azido-ADP (in the absence of hydrolysis) displays an approximately 2.5-fold higher energy of activation (152 kJ/mol) compared with that observed when the transition state intermediate is generated through hydrolysis of [alpha-(32)P]8-azido-ATP (62 kJ/mol). In aggregate, these results demonstrate that the Pgp.[alpha-(32)P]8-azido-ADP (or ADP).Vi transition state complexes generated either in the absence of or accompanying [alpha-(32)P]8-azido-ATP hydrolysis are functionally indistinguishable.


[Roaming through methodology. XXIV. Problems in generalizing from randomized intervention studies with selected patient populations].
The generalizability of intervention research is dependent of the degree of success in including patients who represent the disease category for which the intervention might be considered. To be relevant for medical practice, estimates of intervention effects need to be quantitatively generalizable. This requires specification of the characteristics of the intervention (e.g. dosage and timing) and of the disease outcome, and of socalled effect-modifying factors: disease severity, co-interventions and the characteristics of the patients which influence the magnitude of the intervention effect. Literature remains less clear about the necessity to specify these effect-modifying factors. If effect modification is seriously considered, the investigator must decide either to design the trial in such a way that the subgroup-specific effects may be estimated, or to restrict the study to one homogeneous stratum of patients. Despite many theoretical reasons and some empirical examples of substantial effect modification by characteristics of patients, systematic comparison of randomised (selected populations) and non-randomised studies (less selection) fail to show many differences. This suggests that differences between subgroups are not very frequent and that trial results, provided they are adequately specified, generally do have a high degree of generalizability.


Incidence and Diagnostic Challenges of Bowel Ischemia after Continuous-flow Left Ventricular Assist Device Therapy.
Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.


Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling.
The scarcity of malignant Hodgkin and Reed-Sternberg (HRS) cells hamper tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). Liquid biopsies, in contrast, show promise for molecular profiling of cHL due to relatively high circulating tumor DNA (ctDNA) levels1-4. Here, we show that the plasma representation of mutations exceeds the bulk tumor representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumors, we demonstrate HRS ctDNA shedding to be shaped by DNASE1L3, whose increased tumor microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R-mutations that are dependent on IL13 signaling and therapeutically targetable with IL4R blocking antibodies. Finally, using PhasED-Seq5 we demonstrate the clinical value of pre- and on-treatment ctDNA levels for longitudinally refining cHL risk prediction, and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL as well as capturing molecularly distinct subtypes with diagnostic, prognostic, and therapeutic potential.


Use of leftovers of monoclonal antibody products after partial extraction - A microbiological safety study.
In the absence of thorough microbiological, chemical and physical stability data, high amounts of pharmaceutical products, from which the seal has been broken, are to be discarded after preparation. We performed a generic microbiological validation study for several marketed monoclonal antibody products, in order to define conditions under which leftovers from partially extracted product can be used in order to minimize loss. From the daily practice of the Central Preparation Unit of the Netherlands Cancer Institute, used monoclonal antibody product vials were collected. To examine the integrity of the primary packaging, a VDT/S Vacuum Leak tester from Erweka was used. Vials were punctured with different types of spikes or a needle prior to experiments and examined for leakage afterward. In addition, microbiological monitoring was performed by broth simulation of the preparation method. All vials (631 vials, 18 different monoclonal antibody products) showed no leakage after puncturing with a 18 G needle. However, the use of a spike system resulted in leakage in 108 of the 435 tested vials. Results from the broth simulations confirmed a higher risk of contamination after puncturing with a spike as compared to needle-punctured vials (0.5% vs. 0.05%). When working under aseptic preparation conditions and making use of appropriate needle, the risk of contamination is acceptably low to justify storage and reuse of leftover monoclonal antibody product from a microbiological perspective. The spikes tested lead to an unacceptably high level of loss of integrity and subsequent risk of microbiological contamination if stored in a non-classified environment. We concluded that these results could be applied generically to all monoclonal antibody products with a primary packaging composed of a glass vial and rubber stopper.


Biosurfactant production through Bacillus sp. MTCC 5877 and its multifarious applications in food industry.
In this study Bacillus sp. MTCC5877 was explored for the production of biosurfactant (BSs) and various carbon sources 1% (w/v), 0.5% (w/v) nitrogen sources were tested at different pH, and temperature. Yield was measured in terms of Emulsification index (EI), Oil Displacement Area (ODA) and Drop Collapse Area (DCA) and maximum emulsification activities of BSs were found (E24) 50%, 76% and 46%, respectively, and maximum ODA of 5.0, 6.2 and 4.7cm, were shown respectively. The BS was able to reduce the surface tension of water from 72 to 30mN/m and 72 to 32mN/m. Structural compositions of BS were confirmed by FTIR, GC-MS and NMR. Anti-adhesive property of BS was determined and found effective against biofilm formation. It could remove 73% Cd from vegetable which confirms its application in food industry.


[Microbiological investigation of diabetic foot infections].
The aim of the article was to determine the structure of infections agents in diabetic foot infections and their sensibility to antibiotics A total of 295 microbial isolates were obtained from 115 patients with confirmed diabetic foot infection, treated in 2005-2009 years. Of these aerobes were found in 92.88%, anaerobes - in 7.12%. Microbal associations, various aerbal bacteria were found in 58,49% of cases, associations of aerobes with anaerobes - in 17.92% of cases; from 21.70% of patients were isolated microbial monocultures. The most common gram positive infect in diabetic foot infection was S. aureus, gram negative - P. aeroginosa. Methicillinresistent S. aureus were - 57,52%. In 95.57% of cases S. aureus strains were sensitive to vancomicin. Strains of P.aeruginosa were highly resistant to all investigated antibiotics. Enterobactericeae shown high sensitivity to karbopenemes (95.96%). It is concluded, that success of antimicrobial therapy depends on correct choice of antibiotic, based on in time exposal of etiology of infection, determination of its sensitivity to antimicrobial remedy, considering of its pharmacocinetical features.


Nodal status and clinical outcomes in a large cohort of patients with triple-negative breast cancer.
To evaluate the clinical outcomes and relationship between tumor size, lymph node status, and prognosis in a large cohort of patients with confirmed triple receptor-negative breast cancer (TNBC). We reviewed 1,711 patients with TNBC diagnosed between 1980 and 2009. Patients were categorized by tumor size and nodal status. Kaplan-Meier product limit method was used to calculate overall survival (OS) and relapse-free survival (RFS). A Sidak adjustment was used for multiple group comparisons. Cox proportional hazards models were fit to determine the association of tumor size and nodal status with survival outcomes after adjustment for other patient and disease characteristics. Median age was 48 years (range, 21 to 87 years). At a median follow-up of 53 months (range, 0.7 to 317 months), there were 614 deaths and 747 recurrences. The 5-year OS was 80% for node-negative patients (N0), 65% for one to three positive lymph nodes (N1), 48% for four to nine positive lymph nodes (N2), and 44% for ≥ 10 positive lymph nodes (N3; P < .0001). The 5-year RFS rates were 67% for N0, 52% for N1, 36% for N2, and 33% for N3 (P < .0001). Pairwise comparison by nodal status showed that when comparing N0 with node-positive disease, there was a significant difference in OS and RFS (P < .001 all comparisons). However, when comparing N1 with N2 and N3 disease regardless of tumor size, there were no significant differences in OS or RFS. In patients with TNBC, once there is evidence of lymph node metastasis, the prognosis may not be affected by the number of positive lymph nodes.


MCSfM: Multi-Camera-Based Incremental Structure-From-Motion.
Fully perceiving the surrounding world is a vital capability for autonomous robots. To achieve this goal, a multi-camera system is usually equipped on the data collecting platform and the structure from motion (SfM) technology is used for scene reconstruction. However, although incremental SfM achieves high-precision modeling, it is inefficient and prone to scene drift in large-scale reconstruction tasks. In this paper, we propose a tailored incremental SfM framework for multi-camera systems, where the internal relative poses between cameras can not only be calibrated automatically but also serve as an additional constraint to improve the system robustness. Previous multi-camera based modeling work has mainly focused on stereo setups or multi-camera systems with known calibration information, but we allow arbitrary configurations and only require images as input. First, one camera is selected as the reference camera, and the other cameras in the multi-camera system are denoted as non-reference cameras. Based on the pose relationship between the reference and non-reference camera, the non-reference camera pose can be derived from the reference camera pose and internal relative poses. Then, a two-stage multi-camera based camera registration module is proposed, where the internal relative poses are computed first by local motion averaging, and then the rigid units are registered incrementally. Finally, a multi-camera based bundle adjustment is put forth to iteratively refine the reference camera and the internal relative poses. Experiments demonstrate that our system achieves higher accuracy and robustness on benchmark data compared to the state-of-the-art SfM and SLAM (simultaneous localization and mapping) methods.


Mini-mu bacteriophage with plasmid replicons for in vivo cloning and lac gene fusing.
New mini-Mu transposons with plasmid replicons were constructed with additional features for in vivo DNA cloning and lac gene fusing in Escherichia coli. These mini-Mu replicons can be used to clone DNA by growing them with a complementing Mu bacteriophage and by using the resulting lysate to transduce Mu-lysogenic cells. These mini-Mu phage have selectable genes for resistance to kanamycin, chloramphenicol, and spectinomycin-streptomycin, and replicons from the high-copy-number plasmids pMB1 and P15A and the low-copy, broad-host-range plasmid pSa. The most efficient of these elements can be used to clone genes 100 times more frequently than with the previously described mini-Mu replicon Mu dII4042, such that complete gene banks can be made with as little as 1 microliter of a lysate containing 10(6) helper phage. The 39-kilobase-pair Mu headful DNA packaging mechanism limits the size of the clones formed. The smallest of the mini-Mu elements is only 7.9 kilobase pairs long, allowing the cloning of DNA fragments of up to 31.1 kilobase pairs, and the largest of them is 21.7 kilobase pairs, requiring that clones carry insertions of less than 17.3 kilobase pairs. Elements have been constructed to form both transcriptional and translational types of lac gene fusions to promoters present in the cloned fragment. Two of these elements also contain the origin-of-transfer sequence oriT from the plasmid RK2, so that clones obtained with these mini-Mu bacteriophage can be efficiently mobilized by conjugation.


[Some factors influencing epilepsy course (according to an epidemiological survey)].
Epilepsy typology and some factors influencing polymorphism of epilepsy course are presented. The analysis of the results of entire clinical and epidemiological study conducted in patients with epilepsy from community settings of Jewish autonomy region was undertaken. Among 547 cases examined, the course type was determined in 502 patients. A contribution of constitutional and genetic factors was studied. Factors influencing, to a certain extent, the course type of epilepsy, i.e. sex, childhood speech disorders, psychomotor development delay, epileptic-like traits in premorbid adjustment, presence of postnatal complications, age at the disease onset, were detected. At the same time, such factors as antenatal and perinatal complications, presence of convulsing and nonconvulsing childhood paroxysmal states in epilepsy patient's anamnesis, positive family history of the disease, do not affect the disease course. The data obtained may be used for prognosis of early disease stages and during clinical examination of the patients.


Electrochemical Decoration of Carbon Nanotubes with Au Nanostructure for the Electroanalysis of Biomolecules.
An electrochemical route for the decoration of multiwalled carbon nanotubes (MWCNTs) with anisotropic Au nanostructures and the electroanalytical application of decorated MWCNTs are described. MWCNTs were electrochemically decorated with flowers and buds-like Au nanostructures in aqueous solution in the presence of KI. The flowers and buds-like nanostructures had an average size of 80 nm with a predominant Au(111) plane. The analytical application of the decorated MWCNTs in the electroanalysis of biologically important analytes, such as uric acid (UA), epinephrine (EN) and ascorbic acid (AA), was studied. The nanoparticles of flower-like morphology efficiently catalyze the oxidation of the bioanalytes at a less-positive potential. Simultaneous electroanalysis of AA, UA and EN have been achieved. Well separated individual voltammetric peaks were obtained in their coexistence. The decorated MWCNT modified electrode is very stable and highly sensitive towards UA and EN. It could detect micromolar levels of bioanalytes without any interference. The catalytic property of the nanostructures is superior to that of the conventional spherical nanoparticle. The morphology of the nanoparticle controls the electrocatalytic activity.


Preservation of photic blink reflex in Leber's hereditary optic neuropathy.
To examine whether the early response of photic blink reflex (PBR) is spared in patients with Leber's hereditary optic neuropathy (LHON). Twenty-six patients with bilateral optic neuropathy (visual acuity < or = 0.1) and central scotomata were divided into LHON group with one of three mitochondrial DNA mutations at nucleotide position of 3460, 11778, or 14484 and non-LHON group without them. Latencies of the PBR early response and those of the electrically evoked blink reflex (EBR) response were compared among the 26 patients and 20 healthy volunteers. In controls, average latency of the PBR response was 50.3 +/- 2.4 msec and was in accordance with previous reports. Ten of eleven patients with LHON had normal PBR responses, whereas 12 of 15 controls without LHON had abnormal responses (P = 0.0005). Latencies of EBR responses were normal in all but one patient with LHON. The afferent fibers of the PBR early response, as well as those of the light reaction, are reported to terminate presumably in the pretectum. Together with the reported evidence of the preserved light reaction in patients with LHON, we presume that W retinal ganglion cells may project common afferent fibers of these two neuronal pathways and may be preferentially spared in patients with LHON.


Interferon lambda receptor-1 isoforms differentially influence gene expression and HBV replication in stem cell-derived hepatocytes.
In the tolerogenic liver, inadequate or ineffective interferon signaling fails to clear chronic HBV infection. Lambda IFNs (IFNL) bind the interferon lambda receptor-1 (IFNLR1) which dimerizes with IL10RB to induce transcription of antiviral interferon-stimulated genes (ISG). IFNLR1 is expressed on hepatocytes, but low expression may limit the strength and antiviral efficacy of IFNL signaling. Three IFNLR1 transcriptional variants are detected in hepatocytes whose role in regulation of IFNL signaling is unclear: a full-length and signaling-capable form (isoform 1), a form that lacks a portion of the intracellular JAK1 binding domain (isoform 2), and a secreted form (isoform 3), the latter two predicted to be signaling defective. We hypothesized that altering expression of IFNLR1 isoforms would differentially impact the hepatocellular response to IFNLs and HBV replication. Induced pluripotent stem-cell derived hepatocytes (iHeps) engineered to contain FLAG-tagged, doxycycline-inducible IFNLR1 isoform constructs were HBV-infected then treated with IFNL3 followed by assessment of gene expression, HBV replication, and cellular viability. Minimal overexpression of IFNLR1 isoform 1 markedly augmented ISG expression, induced de novo proinflammatory gene expression, and enhanced inhibition of HBV replication after IFNL treatment without adversely affecting cell viability. In contrast, overexpression of IFNLR1 isoform 2 or 3 partially augmented IFNL-induced ISG expression but did not support proinflammatory gene expression and minimally impacted HBV replication. IFNLR1 isoforms differentially influence IFNL-induced gene expression and HBV replication in hepatocytes. Regulated IFNLR1 expression in vivo could limit the capacity of this pathway to counteract HBV replication.


Clinical Profile and Outcome of Myasthenic Crisis In Central Taiwan.
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies to acetylcholine receptors of the skeletal muscle. Myasthenic crisis (MC) is a complication observed during both early and late stage MG cases. In this study, we examined current treatments and three years outcomes in patients with MG and MC. We also investigated the impact of thymectomy and systemic lupus erythematosus (SLE) in patients with MG and MC. In this retrospective study, we reviewed the medical records of all patients admitted to one teaching hospital between January 2006 and December 2014 and identified those for whom discharge diagnosis included the International Classification of Diseases, ninth revision (ICD-9) codes corresponding to MG (358.X, all extensions and all positions). We identified 29 patients and 49 hospitalizations. Among these patients, the cause for initial hospitalization was MG in 16 cases and MC in 13 cases. Six out of the 16 MG patients were readmitted within 3 years; with 2 of the cases due to MC. Eight of the initial 13 MC patients were readmitted within 3 years, and 6 of the cases due to MC. Among these 15 MC patients, 14 were admitted to the intensive care unit (ICU), and 8 were intubation and put on mechanical ventilators. The median ICU stay was 7 days (3-45). Both MG patients who were also diagnosed with SLE experienced MC. One patient died during the first-time hospitalization, and one patient died during re-hospitalization within 2 years. Plasma exchange (PE) is the main treatment modality of MC, and most patients in our cohort had a good response. Infection is the most common trigger of MC and a significant cause of death. Despite significant morbidity and mortality in patients with MC, a favorable long-term outcome is possible with intensive treatment. Key Words: myathenia gravis, myasthenic crisis, systemic lupus erythematosus, outcome.


Myoclonus-dystonia syndrome due to tyrosine hydroxylase deficiency.
To present a new family with tyrosine hydroxylase deficiency (THD) that presented with a new phenotype of predominant, levodopa-responsive myoclonus with dystonia due to compound heterozygosity of one previously reported mutation in the promoter region and a novel nonsynonymous mutation in the other allele, thus expanding the clinical and genetic spectrum of this disorder. We performed detailed clinical examination of the family and electrophysiology to characterize the myoclonus. We performed analysis of the TH gene and in silico prediction of the possible effect of nonsynonymous substitutions on protein structure. Electrophysiology suggested that the myoclonus was of subcortical origin. Genetic analysis of the TH gene revealed compound heterozygosity of a point mutation in the promoter region (c.1-71 C>T) and a novel nonsynonymous substitution in exon 12 (c.1282G>A, p.Gly428Arg). The latter is a novel variant, predicted to have a deleterious effect on the TH protein function and is the first pathogenic TH mutation in patients of African ancestry. We presented a THD family with predominant myoclonus-dystonia and a new genotype. It is important to consider THD in the differential diagnosis of myoclonus-dystonia, because early treatment with levodopa is crucial for these patients.


[Monitoring and adjustment of immunosuppression after heart transplantation].
Heart transplantation remains the best therapeutic option for the treatment of end-stage heart failure. However, good survival rates can be obtained only if patients are closely monitored, particularly for their immunosuppressive regimens. Currently, a triple-drug regimen usually based on calcineurin-inhibitors (cyclosporin A or tacrolimus), anti-proliferative agents and steroids is used in most recipients. New agents such as the mTOR inhibitors, a more recently developed class of immunosuppressive drugs, can also be used in some patients. The aim of this article is to review currently used immunosuppressive regimens after heart transplantation, and to propose some individualized options depending on specific patient characteristics and recent pharmacological developments in the field.


Increased expression and local accumulation of the prion protein, Alzheimer Aβ peptides, superoxide dismutase 1, and nitric oxide synthases 1 & 2 in muscle in a rabbit model of diabetes.
Muscle disease associated with different etiologies has been shown to produce localized accumulations of amyloid and oxidative stress-related proteins that are more commonly associated with neurodegeneration in the brain. In this study we examined changes in muscle tissue in a classic model of diabetes and hyperglycemia in rabbits to determine if similar dysregulation of Alzheimer Aβ peptides, the prion protein (PrP), and superoxide dismutase 1 (SOD1), as well as nitric oxide synthases is produced in muscle in diabetic animals. This wild-type rabbit model includes systemic physiological expression of human-like Alzheimer precursor proteins and Aβ peptides that are considered key in Alzheimer protein studies. Diabetes was produced in rabbits by injection of the toxic glucose analogue alloxan, which selectively enters pancreatic beta cells and irreversibly decreases insulin production, similar to streptozotocin. Quadriceps muscle from rabbits 16 wks after onset of diabetes and hyperglycemia were analyzed with biochemical and in situ methods. Immunoblots of whole muscle protein samples demonstrated increased PrP, SOD1, as well as neuronal and inducible Nitric oxide synthases (NOS1 and NOS2) in diabetic muscle. In contrast, we detected little change in Alzheimer Aβ precursor protein expression, or BACE1 and Presenilin 1 levels. However, Aβ peptides measured by ELISA increased several fold in diabetic muscle, suggesting a key role for Aβ cleavage in muscle similar to Alzheimer neurodegeneration in this diabetes model. Histological changes in diabetic muscle included localized accumulations of PrP, Aβ, NOS1 and 2, and SOD1, and evidence of increased central nuclei and cell infiltration. The present study provides evidence that several classic amyloid and oxidative stress-related disease proteins coordinately increase in overall expression and form localized accumulations in diabetic muscle. The present study highlights the capacity of this wild-type animal model to produce an array of hallmark pathological features that have also been described in other muscle diseases.


[Repeated ultrasound-guided transrectal prostate biopsy in patients with negative histologic test].
The screening programs for prostate cancer will affect a number increasing of patients over 50 years with consequence rising the bioptic demand. Nevertheless the istopathologic results are negatives for carcinoma in the most part of patients. It's evident that a part of carcinomas are lost at biopsy. Two hundred four patients where submitted at second bioptic session after a maximum of 12 months. Our results show a percent probability of positive findings in 12%. In 75% cancer diagnosed in that second session had clinically significance. Prostate specific antigen (PSA) value, in our study, is the most positive predictive parameter for prostate cancer at second biopsy. Patients with PSA > 10 ng/ml have a risk 7 times greater of having a prostatic cancer respect to patients with PSA < 10 ng/ml. PSA density, PSA velocity and the presence of ipoecoic areas previously biopsied, aren't risk factors for detection of prostate cancer at second bioptic session.


Factors associated with signs of temporomandibular pain: an 11-year-follow-up study on Finnish adults.
Background: Pain in the temporomandibular region is a main complaint causing disability and distress among temporomandibular disorders sufferers.Objectives: The aim of the study was, over an 11-year follow-up on Finnish adult population, to investigate the prevalence of clinically assessed pain-related temporomandibular disorder (TMD) signs, i.e. temporomandibular joint (TMJ) and masticatory muscles (MM) pain on palpation, and their association with sociodemographic background and denture status.Methods: The data were based on the nationally representative Finnish Health 2000 and Health 2011 Surveys (BRIF8901). The sample comprised 1210 adults who underwent clinical oral examinations including TMD signs assessment. Statistical evaluations included chi-square tests and logistic regressions.Results: The prevalence of palpatory MM pain decreased from 9.5% at baseline to 4.6% in the follow-up. Cross-sectionally, presence of palpatory MM pain significantly associated with gender (p < .001, p = .002) and educational level (p < .001, p = .001) in both years, and with age (p = .006) and denture status (p = .022) at baseline. The prevalence of palpatory TMJ pain increased from 2.1% at baseline to 3.5% in the follow-up. Presence of palpatory TMJ pain significantly associated with gender in both years (p = .012, p = .032). Female gender, lower education and palpatory MM pain at baseline predicted palpatory MM pain in the follow-up.Conclusion: Palpatory MM pain is relatively prevalent in adults, yet with a favourable prognosis. Women and people with low education are more susceptible groups. Previous experience of palpatory MM pain increases the risk of exhibiting it later in life.


Feeding preterm infants after hospital discharge: effect of dietary manipulation on nutrient intake and growth.
The objective of this study was to compare formula intake, the time of weaning, and growth in preterm infants (< or = 1750-g birth weight, < or = 34-wk gestation) fed a standard term or preterm infant formula after initial hospital discharge. Infants were randomized at hospital discharge to be fed a preterm infant formula from discharge to 6 mo corrected age (group A), a term formula from discharge to 6 mo (group B), or the preterm formula (discharge to term) and the term formula (term to 6 mo (group C). Infants were seen biweekly (discharge to term) and monthly (term to 6 mo), when intake was measured and anthropometry and blood sampling were performed. The results were analyzed using ANOVA. Although nutrient intake was similar, at 6 mo girls were lighter (6829 versus 7280 g) and shorter (64.4 versus 66.0 cm) than boys (p < 0.05). Patient characteristics were similar between the treatment groups. Although the volume of intake differed (B > C > A; p < 0.001), energy intake was similar in the groups. Because of differences in formula composition, protein, calcium, and phosphorus intakes differed (B < C < A; p < 0.001). Lower protein intakes were related to lower blood urea nitrogen levels (B < C < A; p < 0.001). At 6 mo, infant boys in B and C were lighter (6933, 6660 < 7949 g), shorter (65.3, 64.9 < 67.1 cm), and had a smaller head circumference (43.7, 43.7 < 44.8 cm; p < 0.05) than infants in group A. Preterm infants were found to increase their volume of intake to compensate for differences in energy density between formulas. After hospital discharge, infant boys fed a preterm formula grew faster than infant girls fed a preterm formula or infant boys fed a term formula.


Systems Pharmacology: A Unified Framework for Prediction of Drug-Target Interactions.
Drug discovery is one important issue in medicine and pharmacology area. Traditional methods using target-based approach are usually time-consuming and ineffective. Recently, the problems are approached in a system-level view and therefore it is called systems pharmacology. This research field deals with the problems in drug discovery by integrating various kinds of biomedical and pharmacological data and using advanced computational methods. Ultimately, the problems are more effectively solved. One of the most important problem in systems pharmacology is prediction of drug-target interactions. In this review, we are going to summarize various computational methods for this problem. More importantly, we formed a unified framework for the problem. In addition, to study human health and disease in a more systematically and effectively, we also presented an integrated scheme for a wider problem of prediction of disease-gene-drug associations. By presenting the unified framework and the integrated scheme, underlying computational methods for problems in systems pharmacology can be understood and complex relationships among diseases, genes and drugs can be identified effectively.


Hawthorn Herbal Preparation from Crataegus oxyacantha Attenuates In Vivo Carbon Tetrachloride -Induced Hepatic Fibrosis via Modulating Oxidative Stress and Inflammation.
Hawthorn (HAW) is a herbal preparation extracted from Crataegus oxyacantha. HAW has cardioprotective, antioxidants, anti-inflammatory, and anti-hypotensive effects. HAW's effect on hepatic fibrosis remains, however, unknown. This study evaluated the impact of HAW on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats and elucidated its mechanisms. HAW reduced liver index and the serum liver enzyme markers and reduced liver damage, and fibrosis as confirmed by histopathological scoring of hematoxylin-eosin staining. Collagen deposition was reduced in HAW group compared to CCl4 group as confirmed by Masson staining, hydroxyproline content, and both mRNA and protein levels of alpha-smooth muscle actin, collagen 1 and 3. HAW also down regulated the gene expressions of inflammatory markers including interleukin-IL-1β, tumor necrosis factor-α, transforming growth factor-β 1, nuclear factor kappa-B, and cyclooxygenase-2 and decreased the myeloperoxidase activity. The effects of HAW was also associated with decreased levels of hepatic oxidative stress markers (malondialdehyde and P.Carbonyl) and with increased activity of superoxide dismutase. Those effects are possibly mediated by blocking the pro-oxidant machinery and down regulating the inflammatory and profibrotic responses. Finally, chlorogenic acid, epicatechin, rutin, vitexin quercetin, and iso quercetin were identified as the major species of polyphenols of the HAW herbal preparation used here. Therefore, HAW's potent protecting effects against liver fibrosis predicts a significant beneficial application.


Coronary vasoconstriction during myocardial ischemia induced by rises in metabolic demand in patients with coronary artery disease.
In patients with coronary artery disease, a maximal vasodilation of the coronary microcirculation is generally assumed to occur during myocardial ischemia induced by rises in metabolic demand. However, vasoconstriction has been documented during severe prolonged ischemia in animals. The aim of this study was to investigate coronary vasomotor tone during pacing-induced ischemia in humans. The study included 11 patients with exercise-induced ischemia and single-vessel disease of the left anterior descending artery and 7 control subjects with normal coronary arteries. Blood flow velocity was monitored with a Doppler catheter in the left anterior descending artery. Coronary resistance index was calculated as the ratio between mean arterial pressure and flow velocity. Measurements were obtained at baseline, after intracoronary adenosine (2 mg), and during maximal atrial pacing in the absence and presence of adenosine. After adenosine administration at rest, coronary resistance decreased more in control subjects than in patients (25 +/- 7% of baseline versus 61 +/- 19%; P < .01). Coronary resistance decreased in all control subjects (P < .01) both at maximal pacing (60 +/- 17% of baseline) and after administration of adenosine during tachycardia (31 +/- 13% of baseline). By contrast, all 10 ischemic patients displayed increased coronary resistance at maximal heart rate (221 +/- 131% of baseline; P < .01 versus baseline, P < .01 versus control subjects). At this stage, adenosine decreased coronary resistance to 44 +/- 20% of values observed before injection. Additionally, it reduced ST-segment depression in 5 of 8 patients. In patients with coronary artery disease, transient myocardial ischemia induced by increased metabolic demand is not associated with maximal vasodilation. Rather, an inappropriate severe microvascular vasoconstriction is present that can be abolished by intracoronary adenosine.


Evaluation of the MB/BacT mycobacterium detection system for susceptibility testing of Mycobacterium tuberculosis.
The MB/BacT mycobacterium detection system was evaluated for its performance in the susceptibility testing of Mycobacterium tuberculosis. Eighty-three M. tuberculosis isolates were processed. Results for all isoniazid-, rifampin- and streptomycin-susceptible, isoniazid-resistant, and rifampin-resistant M. tuberculosis isolates with the MB/BacT system agreed 100% with those obtained by the agar proportion method. The agreements between the two methods for streptomycin- and ethambutol-resistant isolates were 96.4 and 90.4%, respectively. The susceptibility test results were obtained in 7 days, on average. These data demonstrate that the MB/BacT system is an accurate, nonradiometric method for rapid susceptibility testing of M. tuberculosis.


Characteristics of Changes in Intrathecal Baclofen Dosage over Time due to Causative Disease.
Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.


Lead monoxide α-PbO: electronic properties and point defect formation.
The electronic properties of polycrystalline lead oxide consisting of a network of single-crystalline α-PbO platelets and the formation of native point defects in the α-PbO crystal lattice are studied using first-principles calculations. The results suggest that the polycrystalline nature of α-PbO causes the formation of lattice defects (i.e., oxygen and lead vacancies) in such a high concentration that defect related conductivity becomes the dominant mechanism of charge transport. The neutral O vacancy forms a defect state at 1.03 eV above the valence band which can act as a deep trap for electrons, while the Pb vacancy forms a shallow trap for holes located just 0.1 eV above the valence band. The ionization of O vacancies can account for the experimentally found dark current decay in ITO/PbO/Au structures.


[Surgical treatment of stomach cancer: analysis of our personal experience].
The "curative" treatment of gastric carcinoma includes the complete removal of the tumour and of the nodes involved without any macroscopic residual of disease (RO). Out of 326 patients with gastric cancer observed, a series of 114 consecutive patients underwent surgical resection (total gastrectomy or subtotal distal gastrectomy) with D2 or D3 lymphadenectomy. Overall operative mortality was 5.3%. Since 1988 no postoperative death occurred. Overall morbidity was 15.8%, specific morbidity 10.5%, reduced after 1988 to 6.6%. No significant differences in operative mortality and need of blood transfusions were recorded between D2 and D3 lymphadenectomy. Overall 5-year survival was 32%. Univariate and multivariate analysis showed that only T and N stages are significant prognostic factors, whereas tumour location, total or subtotal gastrectomy in antral cancers, extent of lymphadenectomy (D2 vs D3) and histology were not significantly related to survival. Since most studies have clearly shown that T and N stages are the most important prognostic factors in gastric cancer, the present aim should be to plan the extent of surgical resection according to the T and N stages characteristics of the neoplasm.


The epitranscriptome of high-grade gliomas: a promising therapeutic target with implications from the tumor microenvironment to endogenous retroviruses.
Glioblastoma (GBM) comprises 45.6% of all primary malignant brain cancers and is one of the most common and aggressive intracranial tumors in adults. Intratumoral heterogeneity with a wide range of proteomic, genetic, and epigenetic dysregulation contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. To date, numerous clinical trials have been developed to target the proteome and epigenome of high-grade gliomas with promising results. However, studying RNA modifications, or RNA epitranscriptomics, is a new frontier within neuro-oncology. RNA epitranscriptomics was discovered in the 1970s, but in the last decade, the extent of modification of mRNA and various non-coding RNAs has emerged and been implicated in transposable element activation and many other oncogenic processes within the tumor microenvironment. This review provides background information and discusses the therapeutic potential of agents modulating epitranscriptomics in high-grade gliomas. A particular emphasis will be placed on how combination therapies that include immune agents targeting hERV-mediated viral mimicry could improve the treatment of GBM.


Excitation energy transfer and trapping in higher plant Photosystem II complexes with different antenna sizes.
We performed picosecond fluorescence measurements on well-defined Photosystem II (PSII) supercomplexes from Arabidopsis with largely varying antenna sizes. The average excited-state lifetime ranged from 109 ps for PSII core to 158 ps for the largest C(2)S(2)M(2) complex in 0.01% α-DM. Excitation energy transfer and trapping were investigated by coarse-grained modeling of the fluorescence kinetics. The results reveal a large drop in free energy upon charge separation (>700 cm(-1)) and a slow relaxation of the radical pair to an irreversible state (∼150 ps). Somewhat unexpectedly, we had to reduce the energy-transfer and charge-separation rates in complexes with decreasing size to obtain optimal fits. This strongly suggests that the antenna system is important for plant PSII integrity and functionality, which is supported by biochemical results. Furthermore, we used the coarse-grained model to investigate several aspects of PSII functioning. The excitation trapping time appears to be independent of the presence/absence of most of the individual contacts between light-harvesting complexes in PSII supercomplexes, demonstrating the robustness of the light-harvesting process. We conclude that the efficiency of the nonphotochemical quenching process is hardly dependent on the exact location of a quencher within the supercomplexes.


A comparison of the combination of atropine and glycopyrrolate with atropine alone for the reversal of muscle relaxant.
Muscle relaxant is commonly used in general anesthesia to facilitate surgery. When finishing the operation, anesthesiologists reverse the muscle relaxant with anticholinesterase, neostigmine, combined with anticholinergic for prevention of unwanted side effects from neostigmine. The only existed anticholinergic in Thailand is atropine, which has a more rapid onset than neostigmine resulting in initial tachycardia. Lately, we have glycopyrrolate that cause less increase in initial heart rate. Therefore, we would like to study the effect of heart rate of the combination between atropine and glycopyrrolate to counteract the effect of neostigmine. Evaluate the different increase in heart rate after the reversal of muscle relaxant with neostigmine combined with atropine or glycopyrrolate plus atropine. The study was a randomized controlled trial study. Fifty-one, ASA I or II patients undergoing elective gynecological surgery under general anesthesia technique were enrolled in the present study. They were randomly assigned by computer-generated random sequence into two groups, control group and intervention group. Control group received neostigmine 2.5 mg and atropine 1.2 mg, intervention group received neostigmine 2.5 mg, glycopyrrolate 0.2 mg and atropine 0.6 mg for reversal of neuromuscular block after finishing the operation. Both groups received the same anesthetic agents including muscle relaxant. Heart rate was recorded before drugs administration and at 1, 3, 5, and 7 minutes after injection. We also recorded heart rate in the PA CU at 0, 15, 30, 45, and 60 minutes. Secondary outcome was incidence of arrhythmia during the observation in PACU. There was no difference in age and baseline heart rate between the two groups. There was no different increase in heart rate after administration of reversal agent between control group and intervention group at any time (p-value = 0.496). No incidence of significant arrhythmia in both groups. There is no significant different increase in heart rate in 0.2 mg glycopyrrolate plus 0.6 mg atropine group compared to 1.2 mg atropine alone for antagonizing muscarinic effects of 2.5 mg neostigmine. Therefore, atropine 0.6 mg and glycopyrrolate 0.2 mg is an alternative to antagonize muscarinic effects of neostigmine.


Understanding Youth Antisocial Behavior Using Neuroscience through a Developmental Psychopathology Lens: Review, Integration, and Directions for Research.
Youth antisocial behavior (AB) is an important public health concern impacting perpetrators, victims, and society. Functional neuroimaging is becoming a more common and useful modality for understanding neural correlates of youth AB. Although there has been a recent increase in neuroimaging studies of youth AB and corresponding theoretical articles on the neurobiology of AB, there has been little work critically examining the strengths and weaknesses of individual studies and using this knowledge to inform the design of future studies. Additionally, research on neuroimaging and youth AB has not been integrated within the broader framework of developmental psychopathology. Thus, this paper provides an in-depth review of the youth AB functional neuroimaging literature with the following goals: 1. to evaluate how this literature has informed our understanding of youth AB, 2. to evaluate current neuroimaging studies of youth AB from a developmental psychopathology perspective with a focus on integrating research from neuroscience and developmental psychopathology, as well as placing this research in the context of other related areas (e.g., psychopathy, molecular genetics), and 3. to examine strengths and weaknesses of neuroimaging and behavioral studies of youth AB to suggest how future studies can develop a more informed and integrated understanding of youth AB.


Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards.
Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals' patience to wait for a delayed reward.


Unified optimization criterion for energy converters.
We propose a unified optimization criterion for energy converters. It represents the best compromise between energy benefits and losses for a specific job and neither an explicit evaluation of entropies nor the consideration of environmental parameters are required. For all considered systems the criterion predicts a performance regime laying between those of maximum efficiency and maximum useful energy. Such regime has been invoked as optimum not only in macroscopic heat engines but also in some molecular motors.


Double-pointed 30-gauge needle for keratocentesis.
A new, efficient instrument for performing keratocentesis for aqueous humour aspiration and anterior chamber microinfusion is described. It consists of a double-pointed 30-gauge needle, a liquid container (a nonflexible vinyl tube plugged at one end with a rubber stopper) and a aspiration-infusion syringe connected to the container and needle by a flexible vinyl tube. The instrument's advantages are a safer technique, complete collection of the aqueous humour and better handling of the sample.


Comparison of Two Lighting Assessment Methods when Reading with Low Vision.
Lighting assessments are an important component of low-vision rehabilitation but are rarely studied systematically. Our study indicates that preferred lighting levels support improvements in reading ease and enjoyment, independently of the evaluation technique. To determine preferred illumination level and color temperature, the LuxIQ is quicker to administer and covers broad options of settings. The purpose of this study was to determine if preferred lighting, as assessed by the LuxIQ versus a standard lighting assessment, leads to better reading outcomes in individuals with low vision. Preferred lighting was assessed at home with visually impaired persons (mean age, 75.3 years), using the LuxIQ (n = 18) or a standard technique based on trying out light bulbs of various intensity and color temperature (n = 16). Maximum reading speed and reading acuity were measured before the lighting intervention and then under the preferred lighting conditions. A 1-month telephone follow-up evaluated the (1) compliance with the lighting recommendations and, for those who modified their lighting, (2) their level of satisfaction with the length of reading time and eye strain felt during reading. Compared with usual lighting conditions, most participants preferred a cooler temperature at a higher illuminance level. Neither lighting assessment type appeared to lead to substantially improved objectively measurable reading outcomes. At the 1-month follow-up, 56% of the participants had modified their lighting, having a significant effect on satisfaction (P < .01), independent of assessment method. Of 18 respondents, 16 (87.5%) mentioned that reading was more enjoyable or easier with the lighting modifications. Both lighting assessment methods lead to comparable results, but the LuxIQ is easier and faster to use. More research is needed to determine whether the LuxIQ is suitable to be incorporated into clinical practice.


Patients' perspectives of a pharmacist-provided clinical pharmacogenomics service.
Aim: To assess the perspectives and experiences of patients who participated in a pharmacist-provided clinical pharmacogenomics (PGx) service. Methods: We conducted individual semistructured interviews with 16 patients who received a pharmacist-provided PGx service. Qualitative data were analyzed to identify pertinent themes. Results: The major themes identified were: heterogeneity of patient PGx experiences and preferences, pharmacists as appropriate providers of PGx services, considerations regarding the use of PGx results in routine healthcare and perceived applications of PGx testing. Theme-derived considerations included the need to establish appropriate pre-genotyping expectations, individualize patient education, facilitate collaboration with patients' providers and sustainably update patients' PGx information over time. Conclusion: Patient-specific perspectives such as these are important to consider when providing clinical PGx services, with intention of optimizing patient experiences.


[Facioscapuloperoneal muscular dystrophy: correlation between a phenotype and genotype].
Thirty four symptomatic and 17 presymptomatic (PS) patients from 21 autosomal dominant facioscapuloperoneal muscular dystrophy (FSPMD) families were found by the probe p13E-11 and enzymes EcoRI/BlnI to have DNA fragments size (DFS) between 13-35 kb (double digestion) and in other 8 PS patients - 37-39 kb, in one PS woman - 45 kb caused by deletion related to the disease and linked with chromosome 4q35. In all the families which had the same or different DFS ranging between 13-35 kb we observed similar clinical variability of phenotypes (the static muscle pattern), the severity of the disease (SD) and daily-life work disability (LD) in the families and between the families. We found no significant correlation between DFS and the phenotype, DFS and the age at onset of the disease, DFS and SD, DFS and LD. Thus, it is confirmed that the probe p13E-11 can be used for detecting DFS between 13-35 kb (or 37 kb) (double digestion) for FSPMD which are assigned with chromosome 4q35. However, in patients with typical FSHD the 4q35-linked EcoRI fragment detected by p13E-11 is usually shorter than 38 kb. Therefore, we believe that the detected DFS cannot be the criterion for establishing genetic heterogeneity of FSHD. It is possible that FSPD and FSHD are allelic diseases.


Thulium fiber laser: The new kid on the block.
Laser technology in urology is currently used for both stone lithotripsy and prostate enucleation. Thulium fiber laser (TFL) is a novel laser, with initial studies showing potential benefits over other lasers both in terms of its effectiveness and safety profile. In the first part of this review, a descriptive analysis of the theoretical concepts behind TFL was performed. This part focused on the physics and laser parameters as applied to the clinical practice. These were interpreted in the context of other lasers, namely, the Holmium:YAG laser to highlight the theoretical advantages as well as potential pitfalls offered by the TFL. In the second part of the review, a narrative synthesis of in-vitro studies regarding TFL and its modifications is performed assessing stone-related parameters, namely, ablation rate, operative time retropulsion, and safety. TFL achieved high ablation rates in most studies and performed better than Holmium:YAG laser across a range of different settings and ablation modes when the two lasers were compared. Moreover, its ability to use low pulse energy ensures minimal stone retropulsion with the retropulsion threshold estimated to be 2-4 times higher than that of Holmium:YAG laser. From a safety viewpoint, TFL poses no additional risks than other lasers, although it does potentially lead to slightly higher temperatures in the surrounding tissues during lithotripsy. The unique properties of TFL have made it an attractive alternative to conventional laser techniques currently used in urology. Clinical studies are required before its application can become more widespread.


The effect of select systemic medications on outcomes in diabetics with central retinal vein occlusion.
Diabetes mellitus is a risk factor for central retinal vein occlusion (CRVO); however, it is unclear whether certain commonly used medications among diabetics or glycemic control impact visual outcomes in diabetic eyes with CRVO. To evaluate the effect of select systemic medications and glycemic control on presenting features, treatment burden, and outcomes in patients with diabetes who develop a central retinal vein occlusion (CRVO). Retrospective longitudinal cohort study at a single tertiary academic referral center from 2009-2017 investigating eyes of patients being treated for diabetes mellitus at CRVO onset. Eyes with a prior history of anti-vascular endothelial growth factor (anti-VEGF) therapy or laser treatment within the year prior to CRVO onset were excluded. Main outcomes and measures were visual acuity (VA), central subfield thickness (CST), cystoid macular edema (CME), and number of intravitreal injections and laser treatment throughout follow-up. We identified 138 eyes of 138 participants who were diabetic at CRVO onset. Of these, 49% had an ischemic CRVO. Median follow-up time was 25.5 months. Fifty-five eyes (40%) had a HbA1c within 6 months of CRVO presentation. HbA1c was positively correlated with both presenting CST (p = 0.04) and presence of CME (p < 0.01). In all 138 eyes, mean presenting VA was 20/246, and mean final VA was 20/364. Better-presenting VA was significantly associated with aspirin 325 mg use (p = 0.04). Lower CST at presentation was significantly associated with metformin use (p = 0.02). Sitagliptin use at CRVO onset was associated with a lower prevalence of CME at final follow-up (p < 0.01). Lower final CST was significantly associated with glipizide use at CRVO onset (p = 0.01). There were no significant associations between systemic medications or HbA1c and treatment burden or final VA (p > 0.05). Although aspirin 325 mg, metformin, sitagliptin, and glipizide were associated with better-presenting VA, lower-presenting CST, lower prevalence of macular edema at final visit, and lower final CST, respectively, none of these systemic agents or glycemic control were associated with decreased treatment burden or improved visual outcomes in diabetics with CRVO.


The ultrastructure of isolated glial (Müller) cells from the turtle retina.
Sarthy and Lam (1978) described a method for isolation of glial (Müller) cells from turtle retina which involves papain treatment, mechanical dissociation of the retinae, and subsequent separation of the dispersed cells by velocity sedimentation at unit gravity. In order to establish the cytologic integrity and the extent of contamination, we have carried out ultrastructural studies on the isolated cells using scanning and transmission electron microscopy. During the course of these studies we have also examined the effect of papain on the morphology of the retina. Scanning electron microscopic studies show that the isolated cells have a free surface with limited extraneous material attached. The basal portion of the cell is organized as end bulbs with a convoluted surface while the apical region is specialized with long microvilli. Transmission electron microscopy shows that the isolated cells have intact plasma membranes with very few interruptions. The cytoplasm is dense and contains the normal complement of smooth endoplasmic reticulum, microtubules, and filaments. The extent of contamination as estimated from serial sections of a single cell is about 10-15% of the total cell volume. These studies indicate that Müller cells isolated by this technique should be useful for metabolic studies and for characterizing the Müller cell surface.


Issues of environmental compliance in developing countries.
Environmental laws define the scarcity of environmental resources as they affect the factor endowment of a country and therefore its position in the international division of labour. There is now also a general agreement that applying the "polluter pays" principle should solve environmental problems. As the burden of abatement increases, as measured by the ratio of abatement expenditure to sales, there is definitely an incentive for firms to either invest in cleaner technology or more efficient abatement technology. There is also evidence that taxes and charges, designed to internalise externalities, can actually affect trade. It is interesting to know if the developing countries face particular market access problems in the face of stringent environmental standards and regulations. While it is true that stringent measures impose market access restrictions and cause limitations on competitiveness, this is much more widely felt by the developing countries because of lack of infrastructure and monitoring facilities, limited technology choices, inadequate access to environment-friendly raw materials, lack of complete information, presence of small-scale exporters and emergence of environmental standards in sectors of export interest to developing countries. The small and medium enterprises often divert sales either to the domestic market or to external markets where environmental requirements are less stringent, in order to save on their costs. In developing countries, 80% of the tanning industry is comprised of small and medium enterprises (SMEs) processing raw to semi-finished leather, usually less than 2 tons per day. In Europe and other developed countries the SMEs in the leather sector have vanished due to strict environmental legislation and this will likely occur in developing countries also. The environmental legislation has not always been practical, either because the laws are too ambitious or unrealistic in certain parameters, or because they have lacked effective instrumentation and institutional support. Some environmental regulations have not succeeded as they do not match the technical requirements and economic reality of the country or region, or because they do not take the institutional capabilities of the society that has to implement them into consideration. For the survival and sustenance of the SMEs in the leather industry, it may be a viable alternative to carry out the tanning process in a decentralized fashion such that the raw to semi-finished process is carried out in the large scale sector while the semi-finished to finished process could either be reserved or open to competition as per the countries' requirements. But the issue of concern is whether it is fair that the raw to semi-finished tanning process, containing 70% of the pollution discharge should be undertaken by developing countries alone, especially if it is at the cost of their survival! However, the game analysed in the paper reveals that tanning units in developing countries would prefer to comply with the regulations and stay in the industry, the alternatives being to collude or to compete!


Bioengineered Braided Micro-Nano (Multiscale) Fibrous Scaffolds for Tendon Reconstruction.
A braided multiscale fibrous scaffold consisting of aligned PCL micro/collagen-bFGFnano fibers was fabricated (mPCL-nCol-bFGF) to mimic native tendon tissue architecture which was further coated with alginate to aid in prevention of peritendinous adhesion. The bFGF release kinetics showed a sustained release of growth factors for a period of 20 days. Further, in vitro cell viability, attachment, and proliferation were performed using rabbit tenocytes under static and dynamic conditions. mPCL-nCol-bFGF showed a higher cell proliferation and enhanced expression of tenogenic markers compared to mPCL-nCol (braided scaffold without bFGF). When subjected to dynamic stimulation in a bioreactor, mPCL-nCol-bFGF-DS (braided scaffold with bFGF after dynamic stimulation) showed enhanced cellular proliferation and tenogenic marker expression, compared to mPCL-nCol-bFGF. The in vivo studies of the cell seeded scaffold after dynamic stimulation in Achilles tendon defect model showed tendon tissue regeneration with aligned collagen morphology within 12 weeks of implantation.


Age Differences in Emotion Regulation and Facial Muscle Reactivity to Emotional Films.
Age-related declines in many cognitive abilities are common in healthy aging. However, the ability to effectively regulate emotions is preserved, and possibly even enhanced, in late adulthood. This capacity has been examined most commonly in relation to low-intensity emotional stimuli that typically involve static pictures. Evidence is suggesting that older adults may become overwhelmed when exposed to emotional cues of heightened intensity. In the current study, we assessed whether older adults retain the ability to regulate emotions successfully when exposed to more emotionally evocative (e.g., dynamic) stimuli. Young and older adults were instructed to regulate, using expressive suppression, their outward behavioral expression of emotions while viewing dynamic stimuli involving amusing and sad films. Facial reactivity, as indexed using electromyography, self-rated emotional experience, and memory for the stimuli were assessed. The results showed that, relative to young adults, older adults were unable to suppress zygomaticus (cheek) activity to amusing films or corrugator (brow) reactivity to sad films, which is likely due to their relatively reduced facial muscle reactivity. Expressive suppression did not affect young or older adults' subjective feelings or memory for the stimuli. Our findings suggest that there are age differences in facial muscle reactivity to amusing and sad cues of heightened intensity. These findings suggest that older adults' ability to effectively regulate emotions may be limited, at least with expressive suppression, in the context of high-intensity emotional cues. Further research is needed to investigate possible exceptions the preservation of emotion regulation in older adults.


Circulating arginine metabolites in Alzheimer's disease and vascular dementia: A systematic review and meta-analysis.
Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is analytically challenging, alternative, stable circulatory biomarkers of NO synthesis may be useful to unravel new pathophysiological mechanisms and treatment targets in dementia. We conducted a systematic review and meta-analysis of the circulating concentrations of arginine metabolites linked to NO synthesis, arginine, citrulline, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine, and ornithine, in Alzheimer's disease and vascular dementia. We searched for relevant studies in PubMed, Scopus, and Web of Science from inception to the 31st of May 2023. The JBI checklist and GRADE were used to assess the risk of bias and the certainty of evidence, respectively. In 14 selected studies, there were no significant between-group differences in arginine and ornithine concentrations. By contrast, compared to controls, patients with dementia had significantly higher ADMA (standard mean difference, SMD=0.62, 95% CI 0.06-1.19, p = 0.029), SDMA (SMD=0.70, 95% CI 0.34-1.35, p<0.001), and citrulline concentrations (SMD=0.50, 95% CI 0.08-0.91, p = 0.018). In subgroup analysis, the effect size was significantly associated with treatment with cholinesterase inhibitors and/or antipsychotics for ADMA, and underlying disorder (Alzheimer's disease), study continent, and analytical method for citrulline. Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).


Palliative Care in New York State Nursing Homes: A Descriptive Study.
To describe the current landscape of palliative care (PC) in nursing homes (NHs) in New York State (NYS). A statewide survey was completed by 149 respondents who named 61 different NHs as their workplace. Questions were related to presence, type, and composition of PC programs; perceptions of PC; barriers to implementing PC; and qualifying medical conditions. Hospice is less available than palliative or comfort care programs, with three-fourths of NYS NH responded providing a PC program. In general, medical directors and physicians were more similar in perspective about the role/impact of PC compared to nursing and others. There was general agreement about the positive impact and role of PC in the NH. Funding and staffing were recognized as barriers to implementing PC. There is growing penetration of PC programs in NH facilities in NYS, with good perception of the appropriate utilization of PC programs. Financial reimbursement and staffing are barriers to providing PC in the NH and need to be addressed by the health-care system.


Interprofessional communication between oncologic specialists and general practitioners on end-of-life issues needs improvement.
Timely end-of-life (EOL) discussions between patients and physicians are considered essential for high-quality EOL care, but research shows that these discussions frequently do not occur or occur late. In oncology, one barrier for timely EOL discussions is poor collaboration between oncologic specialists and GPs. To explore interprofessional communication and coordination between oncologic specialists and GPs on EOL discussions. We conducted in-depth interviews with 16 GPs and 14 oncologic specialists. Interviews were recorded, transcribed verbatim and analysed using qualitative content analysis. EOL discussions were primarily considered the role of the GP, but oncologists' perceptions of their own roles in discussing EOL issues varied. Interprofessional coordination on who discusses what and when was mostly absent. Interprofessional communication of EOL issues usually proceeded using the patient as intermediary. This functioned well but only if three essential conditions were met: the specialist being realistic to patients about limits of treatment, informing the GP adequately and the GP being proactive in initiating EOL issues in time. However, when these conditions were absent, timely EOL discussions did not seem to occur. EOL discussions are rarely a subject of direct interprofessional communication and mainly proceed through the patient as intermediary. For implementation of EOL discussions into regular care, earlier interprofessional communication and coordination is needed, particularly if barriers for such discussions occur.


Comparative oncology: ErbB-1 and ErbB-2 homologues in canine cancer are susceptible to cetuximab and trastuzumab targeting.
To facilitate comparative oncology trials we compared the biological and molecular homologies of canine (dog; Canis lupus familiaris) and human tumor-associated antigens ErbB-1 and -2. Further, we investigated whether they could serve as targets for anti-ErbB-1 (cetuximab) and anti-ErbB-2 antibodies (trastuzumab), which are highly relevant in human clinical oncology. Immunohistochemistry of canine mammary cancer showed ErbB-1 overexpression in 3/10 patients and ErbB-2 in 4/10. We report 91% amino acid homology for ErbB-1 and 92% for ErbB-2 between canine and human molecules. Modeling of canine on human ErbB-1 revealed that the cetuximab epitope only differs by 4 amino acids: Lys443 is replaced by Arg, Ser468 by Asn, Gly471 by Asp, and Asn473 by Lys in canines. The trastuzumab binding site is identical in human and canine ErbB-2 apart from a single amino acid change (Pro557 to Ser). Binding of cetuximab and trastuzumab to canine mammary carcinoma cells CF33, CF41, Sh1b and P114 was confirmed by flow cytometry. Both antibodies significantly inhibited canine tumor cell proliferation partly due to growth arrest in G(0)/G(1) phase. We explain the lower efficiency on the tested canine than on human SKBR3 and A431 cells, by a 2-log lower expression level of the canine ErbB-1 and -2 molecules. Our results indicate significant homology of human and canine Erb-1 and -2 tumor associated antigens. The fact that the canine homologues express the cetuximab and trastuzumab epitopes may facilitate antibody-based immunotherapy in dogs. Importantly, the striking similarities of ErbB-1 and -2 molecules open up avenues towards comparative strategies for targeted drug development.


The role and influence of 'champions' in a community-based lifestyle risk modification programme.
This article describes the training and implementation of the Waist Disposal Challenge in service clubs in Western Australia in 2009-2010. Ninety-three Champions from 52 clubs were trained to deliver educational presentations to 1100 peers and facilitate a BMI competition among 764 peers. Champions reported significant improvements in their knowledge and confidence to motivate their peers to make changes to their diet and physical activity with 82% of participants completing the BMI competition and on average 58% experiencing and sustaining a BMI reduction for 12 months. It is evident that the Champions had influenced the uptake and success of the intervention.


Fever in the returned traveler.
With the rising popularity of international travel to exotic locations, family physicians are encountering more febrile patients who recently have visited tropical countries. In the majority of cases, the fever is caused by a common illness such as tracheobronchitis, pneumonia, or urinary tract infection. However, fever in returned travelers always should raise suspicion for a severe or potentially life-threatening tropical infection. In addition to the usual medical history, physicians should obtain a careful travel history, a description of accommodations, information about pretravel immunizations or chemoprophylaxis during travel, a sexual history, and a list of exposures and risk factors. The extent and type of lymphadenopathy are important diagnostic clues. Altered mental status with fever is an alarm symptom and requires urgent evaluation and treatment. Malaria must be considered in patients who traveled even briefly within an endemic area. Enteric fever is treated with fluoroquinolones, dengue fever with supportive measures only, leptospirosis with penicillin or doxycycline, and rickettsial infections with doxycycline.


The effects of sampling on delimiting species from multi-locus sequence data.
As a fundamental unit in biology, species are used in a wide variety of studies, and their delimitation impacts every subfield of the life sciences. Thus, it is of utmost importance that species are delimited in an accurate and biologically meaningful way. However, due to morphologically similar, cryptic species, and processes such as incomplete lineage sorting, this is far from a trivial task. Here, we examine the accuracy and sensitivity to sampling strategy of three recently developed methods that aim to delimit species from multi-locus DNA sequence data without a priori assignments of samples to putative species. Specifically, we simulate data at two species tree depths and a variety of sampling strategies ranging from five alleles per species and five loci to 20 alleles per species and 100 loci to test (1) Structurama, (2) Gaussian clustering, and (3) nonparametric delimitation. We find that Structurama accurately delimits even relatively recently diverged (greater than 1.5 N generations) species when sampling 10 or more loci. We also find that Gaussian clustering delimits more deeply divergent species (greater than 2.5 N generations) relatively well, but is not sufficiently sensitive to delimit more recently diverged species. Finally, we find that nonparametric delimitation performs well with 25 or more loci if gene trees are known without error, but performs poorly with estimated gene genealogies, frequently over-splitting species and mis-assigning samples. We thus suggest that Structurama represents a powerful tool for use in species delimitation. It should be noted, however, that intraspecific population structure may be delimited using this or any of the methods tested herein. We argue that other methods, such as other species delimitation methods requiring a priori putative species assignments (e.g. SpeDeSTEM, Bayesian species delimitation), and other types of data (e.g. morphological, ecological, behavioral) be incorporated in conjunction with these methods in studies attempting to delimit species.


Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy.
Obesity, an ongoing significant public health problem, is a part of complex disease characterized as metabolic syndrome. Medaka and zebrafish are useful aquatic experimental animals widely used in the field of toxicology and environmental health sciences and as a human disease models. In medaka, simple feeding of a high fat diet (HFD) can induce body weight gain, excessive accumulation of visceral adipose tissue, hyperglycemia, hyperlipidemia, and steatohepatitis, which mimics human metabolic syndrome. In the present study, to explore the possibility that the adult medaka fed with HFD (HFD-medaka) can be used as an animal model for human metabolic syndrome-associated glomerular disease, including obesity-related glomerulopathy (ORG), we analyzed structural alterations and protein expression in the mesonephric kidney of HFD-medaka. We found that the histopathology was consistent with glomerulomegaly accompanied by the dilation of glomerular capillaries and proliferative expansion of the mesangium, a condition partially comparable to human ORG. Moreover, expressions of several kinds of kidney disease-related proteins (such as MYH9, SM22α) were significantly elevated. Thus, the HFD-medaka has a high potential as an animal model useful for exploring the mechanism underling human ORG.


Malakoplakia of the adrenal gland.
The clinical and pathological features of a case of malakoplakia of the adrenal gland occurring in a woman with Escherichia coli infection are described. This lesion mimicked a neoplasm, the true diagnosis only being revealed by histological examination. The light and electron microscopic features are described and it is suggested that malakoplakia is due to an abnormal macrophage response to E coli infection.


Description of the EuroTARGET cohort: A European collaborative project on TArgeted therapy in renal cell cancer-GEnetic- and tumor-related biomarkers for response and toxicity.
For patients with metastatic renal cell cancer (mRCC), treatment choice is mainly based on clinical parameters. With many treatments available and the limited response to treatment and associated toxicities, there is much interest in identifying better biomarkers for personalized treatment. EuroTARGET aims to identify and characterize host- and tumor-related biomarkers for prediction of response to tyrosine kinase inhibitor therapy in mRCC. Here, we describe the EuroTARGET mRCC patient cohort. EuroTARGET is a European collaborative project designed as an observational study for which patients with mRCC were recruited prospectively in 62 centers. In addition, 462 patients with mRCC from previous studies were included. Detailed clinical information (baseline and follow-up) from all patients was entered in web-based case record forms. Blood was collected for germline DNA and pharmacokinetic/pharmacodynamic analyses and, where available, fresh-frozen tumor material was collected to perform tumor DNA, RNA, kinome, and methylome analyses. In total, 1,210 patients with mRCC were included. Of these, 920 received a tyrosine kinase inhibitor as first-line targeted treatment (sunitinib [N = 713, 78%], sorafenib [N = 41, 4%], or pazopanib [N = 166, 18%]) and had at least 6 months of outcome assessment (median follow-up 15.3 months [interquartile range: 8.5-30.2 months]). Germline DNA samples were available from 824 of these patients, fresh-frozen tumor material from 142 patients, fresh-frozen normal kidney tissue from 95 patients, and tissue microarrays created from formalin-fixed paraffin-embedded tumor material from 247 patients. Of the 920 patients, germline DNA variant chip data were successfully generated for 811 patients (Illumina HumanOmniExpress BeadChip). For 80 patients, next-generation exome sequencing of germline and tumor DNA was performed, tumor RNA sequencing was performed for 124 patients, kinome activity measured and processed for 121 patients (PamChip), and methylome data (Illumina Infinium HumanMethylation450 BeadChip) were created for 116 RCC tissues (and 23 normal kidney tissues). For 73 out of the 920 patients, all platform data types were generated. In addition, 40 patients were included in a pharmacokinetic/pharmacodynamic phase IV substudy. Analysis of EuroTARGET cohort data will contribute to personalization of therapy for patients with mRCC. The extensive clinical data and multiplatform EuroTARGET data will be freely available.