A mouse with humanized liver as an animal model for predicting drug effects and for studying hepatic viral infection: where to next?
The mouse is a common model used in evaluating drug metabolism and hepatitis infectivity. However, these models have limited value due to species difference in hepatic functions, leading to the creation of the chimeric mouse 12 years ago. These models were unique in that their hepatocytes had been replaced with human (hu) hepatocytes (dubbed the 'first-generation chimeric mouse'). Since then, the chimeric mouse has become a practical tool for this area of studies. However, some shortcomings have also been recognized. One major shortcoming is that the mouse cannot mimic hu-liver diseases due to immunodeficiency and also it is unable to provide sufficient amounts of blood for analysis compared to the rat. There are also issues around donor-to-donor variability of hu-hepatocytes such as variable engraftment efficiency. This review provides the current status of the first-generation chimeric mouse. Furthermore, the authors review studies intended to create a 'second-generation of the chimeric mouse' in which inflammation/immune-response cells as well as hepatocytes are humanized. A brief comment is also made on studies aiming at producing chimeric rats. Finally, the authors consider induced pluripotent stem cells (iPS cells) as new sources of hu-hepatocytes. The authors believe that the current rapid progress in the field of biotechnology should enable us to create a mouse model with a humanized liver that is made by iPS-derived hu-hepatocytes and hu-immune cells. This development will provide researchers with a model that will be able to effectively mimic human liver disease under experimental conditions.


Pityriasis lichenoides et varioliformis acuta: case report and review of the literature.
We report a case of a 63-year-old man hospitalized for a polymorphous generalized eruption consisting of maculopapules with peripheral scaling, vesicopustules, and ulceronecrotic and crusted lesions measuring 5-20 mm, localized on his trunk and extremities, particularly exuberant in the flexural area. Histopathology showed necrotic keratinocytes with exocytosis of red blood cells and lymphocytes and a dermal perivascular and periadnexal inflammatory infiltrate, composed of CD8+/CD4-/CD30- T cells, indicating the clinical diagnosis of pityriasis lichenoides et varioliformis acuta. He was treated with erythromycin and methylprednisolone reduced gradually over 5 months, with a slow but complete response; the patient was without lesions after 2 years of follow-up. The authors want to remind of this rare entity which may present difficulties in diagnosis and therapy.


[Renal denervation. Current developments].
METHODICAL INNOVATION: Renal denervation is a catheter-based, endovascular procedure for the treatment of drug-resistant hypertension. The aim of the therapy is to lower the blood pressure < 140/90 mmHg. Even after successful minimally invasive therapy patients usually continue to take three or more antihypertensive drugs. Currently there is no evidence that renal denervation is a good option for the treatment of well-controlled hypertension in order to dispense with antihypertensive drugs. In carefully selected patients the mean reduction in systolic and diastolic blood pressure after renal denervation is 25-30 mmHg and 10-15 mmHg, respectively. Procedure-related or device-related complications are rare. Ablation catheters from different manufactures differ greatly in handling properties; however, up to now there is no evidence for relevant differences in safety and efficacy between the devices available.


Increased risk of retinopathy of prematurity since increased O2 saturation targets: A multi-centre study.
Retinopathy of prematurity (ROP) is a leading cause of visual impairment in premature neonates. The BOOST II, SUPPORT and COT trials recommended increasing O2 saturation targets for pre-term neonates to reduce mortality; however, this is a risk factor for ROP. We aimed to determine whether these targets increased prevalence of ROP among pre-term neonates and higher risk groups. Retrospective cohort study conducted using data from the Australian and New Zealand Neonatal Network. 17 298 neonate cohort born 2012-2018 at <32 weeks' GA and/or <1500 g BW was analysed. Adjusted odds ratios (aORs) were calculated for post-2015 risk of: any ROP; ROP ≥ Stage 2; and treated ROP. Sub-analysis stratified at <28 GA, < 26 weeks' GA, <1500 g BW and <1000 g BW was performed. Risk of any ROP increased in the post-2015 group (aOR = 1.23, 95% confidence interval (CI) = 1.14-1.32), <28 weeks' GA (aOR = 1.31, 95% CI = 1.17-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.24, 95% CI = 1.14-1.34) and <1000 g (aOR = 1.34, 95% CI = 1.20-1.50). ROP ≥ Stage 2 increased at <28 weeks (aOR = 1.30, 95% CI = 1.16-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.18, 95% CI = 1.08-1.30), and <1000 g (aOR = 1.26, 95% CI = 1.13-1.42). O2 therapy guidelines since 2015 have resulted in decreased mortality but increased risk of ROP. Individualised NICU adjustments of ROP screening/follow-up methods are necessary to address the clinical burden.


Alterations in brain catecholamines during pregnancy.
During pregnancy mice are more susceptible to flurothyl-induced seizures than are non-pregnant controls. The potential role of brain catecholamines in mediating this behavior was examined in the present study. The concentration and turnover of norepinephrine (NE) and dopamine (DA) were measured in hippocampus, striatum, midbrain and cortex in control, pregnant and delivery-day mice. There were no significant changes from control in DA levels during pregnancy and parturition. The turnover of DA was not altered during pregnancy, except for a small increase in turnover rate in the hippocampus. The concentration of NE decreased during pregnancy, and rose at parturition. This effect was most striking in the hippocampus. The turnover of NE was markedly depressed during pregnancy, with the hippocampus again being most affected. These data imply a role for NE, but not DA in the mediation of increased seizure susceptibility during pregnancy.


In situ characterization of the agglutination of lectins via cross-linking of carbohydrates by time-resolved measurement of forward static light scattering.
We present real-time observations of a structurally variable process for cross-linking agglutination between multivalent lectins and glycoclusters using a small-angle forward static light scattering (F-SLS) technique. In this study, a cross-linking agglutination reaction was carried out using a tetravalent Neu5Acα2,6LacNAc-glycocluster and Sambucus sieboldiana agglutinin (SSA). The scattering intensity of time-resolved F-SLS increased with formation of the Neu5Acα2,6LacNAc-glycocluster-SSA cross-linked complex. Using this approach, fine sequential cross-linking agglutination between glycoclusters and lectins was observed in real-time. The rate of increase in the intensity of time-resolved F-SLS increased with the concentration of sialo-glycoclusters and SSA. Structural analysis based on the fractal dimension using time-resolved F-SLS patterns revealed that the density of the aggregates changed with progression of the cross-linking reaction until equilibrium was reached. This is the first report to evaluate the cross-linking agglutination reaction between glycoclusters and lectins and analysis of the subsequent structure of the obtained aggregates using time-resolved measurements of F-SLS.


Prevalence and prognostic impact of hsCRP elevation are age-dependent in women but not in men undergoing percutaneous coronary intervention.
High-sensitivity C-reactive protein (hsCRP) predicts outcomes after percutaneous coronary intervention (PCI). We studied the prevalence and prognostic impact of hsCRP elevation according to age in men and women undergoing PCI. We included patients undergoing PCI at our center from 2010 until 2017, excluding those with myocardial infarction (MI) on presentation, neoplastic disease and hsCRP >10 mg/L at baseline. Elevated hsCRP was defined as >3 mg/L. The outcome of interest was major adverse cardiac events (MACE) consisting of all-cause death, MI and target vessel revascularization. The association between hsCRP elevation and outcomes was assessed using adjusted Cox models. 10,432 men and 4,345 women were included. Elevation of hsCRP was present in 25.7% of men and 37.0% of women (p < .01). In men, prevalence of hsCRP elevation was stable across age strata (ptrend = .42). In women, hsCRP elevation was most prevalent in patients <50 years (44.6%) and decreased stepwise with increasing age (ptrend < .001). After stratifying the population into age quartiles (Q1: <59 years, Q2: 59-66 years, Q3: 67-74 years, Q4: ≥75 years), hsCRP elevation was associated with increased risk of MACE across all age groups in men (HR [95% CI] Q1: 1.49 [1.12-1.98]; Q2: 1.51 [1.21-2.06]; Q3: 1.76 [1.27-2.51]; Q4: 1.43[1.03-1.97]). In women, hsCRP elevation was associated with increased risk of MACE only among older patients (HR [95% CI] Q1: 1.08 [0.64-0.82]; Q2: 1.52 [0.93-2.46]; Q3: 1.65 [1.08-2.50]; Q4: 1.52 [1.02-1.28]). Among patients undergoing PCI, prevalence and prognostic value of hsCRP elevation were age-dependent exclusively in women.


Bias-Corrected Targeted Next-Generation Sequencing for Rapid, Multiplexed Detection of Actionable Alterations in Cell-Free DNA from Advanced Lung Cancer Patients.
Tumor genotyping is a powerful tool for guiding non-small cell lung cancer (NSCLC) care; however, comprehensive tumor genotyping can be logistically cumbersome. To facilitate genotyping, we developed a next-generation sequencing (NGS) assay using a desktop sequencer to detect actionable mutations and rearrangements in cell-free plasma DNA (cfDNA). An NGS panel was developed targeting 11 driver oncogenes found in NSCLC. Targeted NGS was performed using a novel methodology that maximizes on-target reads, and minimizes artifact, and was validated on DNA dilutions derived from cell lines. Plasma NGS was then blindly performed on 48 patients with advanced, progressive NSCLC and a known tumor genotype, and explored in two patients with incomplete tumor genotyping. NGS could identify mutations present in DNA dilutions at ≥ 0.4% allelic frequency with 100% sensitivity/specificity. Plasma NGS detected a broad range of driver and resistance mutations, including ALK, ROS1, and RET rearrangements, HER2 insertions, and MET amplification, with 100% specificity. Sensitivity was 77% across 62 known driver and resistance mutations from the 48 cases; in 29 cases with common EGFR and KRAS mutations, sensitivity was similar to droplet digital PCR. In two cases with incomplete tumor genotyping, plasma NGS rapidly identified a novel EGFR exon 19 deletion and a missed case of MET amplification. Blinded to tumor genotype, this plasma NGS approach detected a broad range of targetable genomic alterations in NSCLC with no false positives including complex mutations like rearrangements and unexpected resistance mutations such as EGFR C797S. Through use of widely available vacutainers and a desktop sequencing platform, this assay has the potential to be implemented broadly for patient care and translational research.


Influence of microwave vacuum drying on glass transition temperature, gelatinization temperature, physical and chemical qualities of lotus seeds.
This study investigated the effects of microwave power density on effective moisture diffusion coefficient (Deff), glass transition temperature (Tg), gelatinization temperature (TP), physical and chemical qualities of lotus seeds during microwave vacuum drying. Deff increased by 42% and 127% at 15W/g and 20W/g, respectively, when compared with 10W/g. TP was negatively correlated with the relaxation times of T21 and T22, while Tg was negatively correlated with the relative areas A22. The rates of change of color were observed to be divided roughly into two periods, consisting of a rapid change caused by enzymatic browning and a slow change caused by non-enzymatic browning. An equation is provided to illustrate the relationship of k1 and k2 of Peleg's model depending on power density during rehydration kinetics. The samples at 20W/g exhibited the higher content of amino acid (540.19mg/100gd.b.) while lower starch (17.53g/100gd.b.).


Causes of blind and partial sight certifications in England and Wales: April 2007-March 2008.
The last complete report on causes of blindness in England and Wales was for the data collected during April 1999-March 2000. This study updates these figures, with data collected during April 2007-March 2008. In England and Wales, registration for blindness and partial sight is initiated with certification by a consultant ophthalmologist with the consent of the patient. The main cause of visual impairment was ascertained where possible for all certificates completed during April 2007-March 2008 and a proportional comparison with 1999-2000 figures was made. We received 23,185 Certificates of Vision Impairment (CVIs), of which 9823 were for severe sight impairment (blindness) (SSI) and 12,607 were for sight impairment (partial sight) (SI). These totals were considerably lower than the numbers certified in the year ending 31 March 2000. In 16.6% of CVIs, there were multiple causes of visual impairment as compared with 3% of BD8s in 2000. Degeneration of the macula and posterior pole (mostly age-related macular degeneration (AMD)) contributed to vision impairment in 12,746 newly certified blind or partially sighted. AMD is still by far the leading cause of certified visual loss in England and Wales. Proportional comparisons are hampered by the increasing use of multiple pathology as a main cause of visual impairment, which is believed to have arisen owing to the change in certificate used for data collection. These figures are not estimates of the total numbers newly blind in the UK because not all those entitled to certification are offered and or accept it, but they do nevertheless document the number of people who are deemed to be sufficiently sight impaired to warrant support and have been both offered and accepted it. This is usually the case when no further ophthalmic intervention is thought likely to be of benefit in terms of restoring or improving vision.


Role of Adenoid-Nasopharyngeal Ratio in Assessing Adenoid Hypertrophy.
Most of the time, pediatrician is the first to see children with adenotonsillar hypertrophy (AH) and they mostly rely on clinical assessment with or without some investigation to refer these children to otorhinolaryngologist. Numerous methods have been described for evaluation of AH, but many of these methods are not possible to follow in busy pediatric outpatient unit either because of lack of cooperation from child or due to limited availability of test or due to cost constraints. This study has been conducted to determine the diagnostic accuracy of lateral neck X-ray (LNX) for assessing AH and to assess the correlation between adenoid size in LNX and clinical symptoms in a pediatric unit. Prospective study conducted in Department of ENT, Pathmavathy Medical Foundation, Kollam, Kerala, India from January 2015 to March 2016. 60 consecutive children of both genders, between the age group of 5 to 14 years, attending Department of Pediatrics with a provisional diagnosis of AH were included in the study. The symptom scores, radiographic ratio of adenoid to nasopharynx and endoscopic scorings were calculated. Lateral neck X-ray with calculation of adenoid-to-nasopharynx ratio is found to have significant correlation with patient reported symptoms and findings in nasal endoscopic examination (NE). LNX can be considered as a useful objective tool in evaluation of children with adenoid hypertrophy. Primary care physicians or pediatricians can confidently use lateral neck X-ray for making clinical decisions and can consider nasopharyngoscopy when clinical picture remains unclear or more evaluation is needed.


The complete chloroplast genomes of two Wisteria species, W. floribunda and W. sinensis (Fabaceae).
Wisteria floribunda and Wisteria sinensis are ornamental woody vines in the Fabaceae. The complete chloroplast genome sequences of the two species were generated by de novo assembly using whole genome next generation sequences. The chloroplast genomes of W. floribunda and W. sinensis were 130 960 bp and 130 561 bp long, respectively, and showed inverted repeat (IR)-lacking structures as those reported in IRLC in the Fabaceae. The chloroplast genomes of both species contained same number of protein-coding sequences (77), tRNA genes (30), and rRNA genes (4). The phylogenetic analysis with the reported chloroplast genomes confirmed close taxonomical relationship of W. floribunda and W. sinensis.


Understanding the impacts of intermittent electro field on the bioelectrochemical aniline degradation system: Performance, microbial community and functional enzyme.
On account of the lack of a sustainable electron donor source and the inhibitory effect of aniline on denitrogenation make it tough to achieve simultaneous removal of aniline and nitrogen. Herein, the strategy of adjusting electric field mode was applied to the electro-enhanced sequential batch reactors (E-SBRs: R1 (continuous ON), R2 (2 h-ON/2 h-OFF), R3 (12 h-ON/12 h-OFF), R4 (in the aerobic phase ON), R5 (in the anoxic phase ON)) to treat aniline wastewater. Aniline removal rate reached approximately 99% in the five systems. Decreasing electrical stimulation interval from 12 to 2 h significantly improved the electron utilization efficiency for aniline degradation and nitrogen metabolism. The total nitrogen removal was achieved from 70.31% to 75.63%. Meanwhile, the hydrogenotrophic denitrifiers of Hydrogenophaga, Thauera, and Rhodospirillales, enriched in reactors of minor electrical stimulation interval. Accordingly, the expression of functional enzyme related to electron transport was incremental with the proper electrical stimulation frequency.


Mechanistically Dissecting Autophagy: Insights from In Vitro Reconstitution.
Autophagy is a fundamental cellular mechanism responsible for bulk turnover of cytoplasmic components. It is broadly related to many cellular activities, physiological processes, and pathological conditions. Autophagy entails a spatiotemporal interaction between cytosolic factors and membranes that are remodeled to encapsulate autophagic cargo within an autophagosome. Although majority of the factors [autophagy-related gene (Atg) proteins] involved in autophagy have been identified by genetic studies, the mechanism accounting for how these factors act upon the membrane to remodel it and efficiently recruit cargo for degradation is unclear. In vitro reconstitution of several different aspects of autophagy has provided important insights into the understanding of the mechanistic details underlying autophagic membrane remodeling and cargo recruitment. Here, we highlight these efforts toward studying autophagy through in vitro approaches.


A systematic literature review on the economic impact of endemic disease in UK sheep and cattle using a One Health conceptualisation.
Endemic sheep and cattle diseases represent a constant strain and impact to animal health and welfare, the environment, public health, and the economy. Quantifying this impact helps to inform decisions on surveillance and control of livestock diseases. This systematic literature review had two objectives; to describe the economic impact of endemic sheep and cattle diseases in the United Kingdom using a broad conceptualisation of impact, and to investigate what variables (e.g. medication costs, loss of production) and methods are included in these calculations. The Prisma protocol for systematic literature reviews was followed. Searches were performed in Pubmed, Scopus and Web of Science using selected and trialled search terms. A total of 1129 papers were identified and screened for relevancy; 38 papers were selected for full review extracting and analysing data on disease, impact and methods. From this final selection of papers it was found that; 1) research in this area is mainly focused on the dairy sub-sector, 2) the most mentioned diseases were mastitis and lameness in dairy cattle; bovine viral diarrhoea in beef cattle; and ectoparasites in sheep with reported animal-level costs of £ 77-£ 548/cow/year, £ 26-£ 185/bovine animal/year and £ 40-£ 47/ewe/year, respectively, 3) numerous methods and variables were used to calculate or estimate the economic impact with most studies focussing on the direct producer impacts and less on the wider implications and affected stakeholders; and 4) it was common for studies to look at one disease in isolation rather than consider disease impact on the farm as a whole. It is recommended that future economic impact calculations on livestock disease include wider implications to estimate the true cost of disease. To generate the necessary data, a wider, more inclusive conceptualisation of impact will be needed to support the collection of data and facilitate communication between stakeholders. Systematic health data recording combined with assessment calculations and metrics that allow comparability within or across livestock sub-sectors will increase the informative value of these impact calculations.


On-the-ground health and safety experiences of non-union casino hotel workers: A focus-group study stratified by four occupational groups.
To understand the health- and safety-related experiences of specific occupations among non-union casino hotel employees to identify processes leading to worker health and safety risks. Using purposive, criterion sampling, 61 workers participated in 13 recorded focus groups (FGs). A semi-structured topic guide addressed work-related health and safety impacts, workplace hazards, and management responses, among others. FG transcripts were analyzed following grounded theory methodology. Demographic and occupational health information was collected via survey. Codes (97) were collapsed into seven themes: activities/exposures negatively affecting health/safety; barriers to health/safety; injury/pain occurrences; coping mechanisms; job vulnerability; management policies/enforcement; lack of management concern for employees. From these themes emerged the Dynamic Theoretical Framework of Employee Health and Safety Risk. "Management's lack of concern" creates a negative environment whereby employer-controlled factors jeopardize employees' health and safety. Interventions targeting management's lack of concern for employee health and safety could favorably change work-based risks.


Dilution of reporter gene with stuffer DNA does not alter the transfection efficiency of polyethylenimines.
Polyethylenimines (PEIs) are among the most efficient non-viral gene transfer agents developed so far. However, transfections with these polymers were shown to require a very high copy number of plasmid DNA per cell to achieve gene expression. Here, we investigate whether it is possible to reduce the amount of plasmid DNA while keeping a high transfection efficiency. Transfection experiments were performed under various conditions in order to study the interdependence between the amount of reporter DNA, the amine-to-phosphate ratio and the transfection efficiency. When suboptimal amounts of linear PEI 22 kDa/DNA complexes were used for transfection, a severe reduction in reporter gene expression was observed. On the other hand, for optimal amounts of PEI/DNA complexes more than half of the reporter gene can be replaced by carrier DNA or polyglutamic acid without substantially decreasing the transfection efficiency of the polymer both in cultured cells and after systemic administration in mice. When used under the same in vitro experimental conditions, the lipospermine DOGS, but not the monocationic lipid DOTAP, gave similar results. Taken together, our data suggest that the activity of compounds with endosome-buffering capacities, such as PEIs and lipospermines, requires a threshold amount of transfection agent. In addition, our results indicate that, in many gene transfer situations, it will be possible to lower the dose of active plasmid thus reducing costs and the risk of immune stimulation triggered by bacterial DNA.


LncRNA MIR497HG inhibits colorectal cancer progression by the miR-3918/ACTG2 axis.
The roles of long non-coding RNAs (lncRNAs) have been discussed and analysed in previous studies. The messenger RNAs (mRNAs) are frequently reported to be regulated by lncRNAsin colorectal cancer (CRC).Here,we elucidated the role of themRNAactin gamma 2 (ACTG2) in CRC progression using SW837 and LOVO cells. Gene expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) and subcellular localization was assessed using subcellular fractionation assay. Cell counting kit-8 (CCK-8), colony formation, and Transwell assayswere performed to detectCRCcell phenotypes.RNApulldown, luciferase reporter, andRNAimmunoprecipitation (RIP) assays were conducted to reveal the interactionsamongmicroRNA-3918 (miR-3918), lncRNAmir-497-195 cluster host gene (MIR497HG) and ACTG2. The ACTG2 level was downregulated in CRC cells and samples. ACTG2 overexpression suppressed CRC cell proliferation, migration, and invasion. Additionally, miR-3918 inhibition increased the level of ACTG2 and the interaction between miR-3918 and ACTG2 was verified. MIR497HG was markedly downregulated in CRC cells and samples. Overexpression of MIR497HG decreased miR-3918 expression while increased ACTG2 expression. Further, the inhibitory effects exerted by MIR497HG overexpression on malignant phenotypes of CRC cells were reversed by ACTG2 knockdown.MIR497HGexerts inhibitory effects on CRC progression by the miR-3918/ACTG2 axis.Our study conducted a systematic analysis of the biological roles of ACTG2, miR-3918 and MIR497HG, and the relationship among them in CRC progression. ACTG2 and MIR497HG were found to be tumour suppressors in CRC cell growth. More importantly, a novel ceRNA network, with MIR497HG as a ceRNA to regulate the miR-3918/ACTG2 axis, was found to play a key role in CRC cell proliferation, migration and invasion.


Tacrolimus-induced apoptotic signal transduction pathway.
Tacrolimus (FK506) has been widely used as an immunosuppressant. We examined the effects of FK506 on expression of apoptotic signal transduction pathway proteins of Jurkat human T lymphocytes. We investigated the effects of FK506 on apoptosis, cell viability, caspase family protein activity, Western blotts of Bcl-2, Bak, Fas, Fas-L, CDK4, and cyclin D1, as well as reactive oxygen species (ROS) generation and mitochondrial membrane potential transition. Cells were cultured in the presence or absence of FK506. Flow cytometric analysis was performed after staining with propidium iodide. Viability of Jurkat cells was decreased by the addition of FK506 in dose- and time- dependent manner. FK506-induced cytotoxicity was characterized by G0/G1 phase cell cycle arrest. FK506-induced cell death was confirmed by apoptosis characterized by nuclear fragmentation and caspase-3 protease activation. FK506 induced no change in catalytic activity of caspase-6, -8, and -9 proteases. No change in expression of Bcl-2 protein was noted but we confirmed increased expression of Bak protein. No changes of expressions of Fas and Fas-L were seen. Increased expressions of CDK4 and cyclin D1 were identified. In addition, pharmacological scavenging study of ROS, including H2O2, revealed that cytotoxicity was achieved by generation of ROS, which might modulate Bak protein expression and mitochondrial dysfunction. In conclusion, FK506-induced cell death was apoptotic, characterized by nuclear fragmentation and caspase-3 activation. FK506 induced G0/G1 phase cell cycle arrest via expression of CDK4 and cyclin D1. Apoptosis was also achieved by generation of H2O2, which modulated Bak protein expression and mitochondrial dysfunction.


Exposure to high thermal conditions for a long time induces apoptosis and decreases total RNA concentration in peripheral blood mononuclear cells among Indian Zebu-Jersey crossbreds.
Global warming has grave consequences on livestock production systems and profound negative effects on animal production. This study aimed to carry out an in vitro thermal stress stimulation (TSS) of bovine peripheral blood mononuclear cells (PBMCs) using different thermal assault conditions (TACs), including normal to extreme temperatures and varying durations of thermal exposure (DTE) to understand how PBMCs of Indian Zebu-Jersey crossbreds respond to various levels and durations of heat shock. Ten milliliters of blood were collected from 70 Indian Zebu-Jersey crossbreds under aseptic conditions and were sampled for isolating PBMCs. Peripheral blood mononuclear cells were divided into seven groups, each comprising 10 PBMC samples isolated from 10 different animals. Aliquots of 500 μL of PBMCs were stressed by exposure to different TACs (37, 40, and 45°C) for DTEs of 3 or 6 h. Subsequently, the cells were harvested. The control unstressed samples (500 μL aliquots of PBMCs) were exposed to no TAC (0°C) and zero DTE (0 h). Total RNA from all the treatment groups of PBMCs were isolated and quantitated. We found a very strong association between TACs and RNA levels. In addition, PBMCs viability was negatively affected by heat shock. This led to an exponential reduction in PBMC count as TACs toughened. Only 3.59 × 105 ± 0.34 cells/mL were viable after exposure to 45°C for a 6 h DTE. This cell viability was lower than that measured in controls subjected to no stress and zero time DTE (2.56 × 107 ± 0.22 cells/mL). We also observed a reduction in the concentration of RNA isolated from thermally stressed PBMCs. In vitro TSS of PBMCs provided biological information on the response of cellular systems to heat shock after exposure to TACs. This will help to mitigate and manage the effects of thermal stress in bovine species. The association between the reduction in PBMC count after in vitro TSS and the expression of heat shock protein 70 gene will be investigated in the future to further understand how Indian Zebu-Jersey crossbreds respond to in vitro thermal conditions. This will be used to determine the in vivo response of Indian Jersey crossbreds to different environmental thermal conditions and will further enable the in vivo understanding of thermotolerance potentials of bovine species for better adaptation, survival, and production performance.


Progression to musculoskeletal deformity in childhood dystonia.
Dystonia is a movement disorder characterized by involuntary muscle contractions, resulting in abnormalities of posture and movement. Children with dystonia are at risk of developing fixed musculoskeletal deformities (FMDs). FMDs cause pain, limit function and participation and interfere with care. We aimed to explore factors relating to the development of FMD in a large cohort of children with dystonia. The case notes of all children referred to our Complex Motor Disorder service between July 2005 and December 2011 were reviewed. Data from 279 children (median age 9 years 10 months, Standard Deviation 4 years 2 months) with motor disorders including a prominent dystonic element were analyzed. Parametric accelerated failure time regression was used to identify the factors related to development of contractures. FMDs were present at referral in more than half (n = 163, 58%) of cases. Three quarters (n = 120, 74%) of children with FMD had deformities around the hip, and 42% had spinal deformity (n = 68). Compared to pure primary dystonia, FMD onset was earlier with a diagnosis of secondary or heredodegenerative dystonia, and a mixed spastic-dystonic phenotype (all p < 0.001). FMD onset was also earlier with increasing Gross Motor Function Classification System (GMFCS) level (p < 0.001). The effect of aetiological classification was lost when controlling for GMFCS level and motor phenotype. Children with secondary or heredodegenerative dystonia are at greater risk of progression to FMD compared to primary dystonia, likely due to more severe dystonia within these groups. Children with additional spasticity are at particular risk, requiring close monitoring.


Bacteroides species from the oral cavity and oral-associated diseases of cats.
One hundred and sixty-seven strains of Bacteroides were isolated from 71 subcutaneous fight-wound abscesses of cats, 21 cases of feline pyothorax, normal gingival margins from 10 cats and 6 cases of feline gingivitis. Bacteroides species constituted (as a proportion of all anaerobic isolates examined) 44.5% from subcutaneous abscesses, 33.7% from pyothoraxes, 37.5% from normal gingiva and 27.7% from diseased gingiva. Bacteroides tectum comprised 43.7% or 73 of 167 strains, followed by the black- or brown-pigmented asaccharolytic feline species of B. gingivalis, B. salivosus and Group B, comprising 32.3% or 54 of 167 strains. B. heparinolyticus (some 10% or 17 of 167 strains) was the next most common species described. The remainder consisted of two strains of B. fragilis and 21 unspeciated strains. Bacteroides tectum was frequently isolated from subcutaneous abscesses (43.7%) and pyothoraxes (46.6%), and it constituted some 33% of anaerobic isolated from normal gingiva. Bacteroides heparinolyticus was more commonly encountered in purulent lesions (abscesses and pyothoraxes) than in the oral cavity.


CD38 expression levels in chronic lymphocytic leukemia B cells are associated with activation marker expression and differential responses to interferon stimulation.
CD38, a surface protein whose expression increases upon normal B-cell activation, is a marker of disease aggression in B-cell chronic lymphocytic leukemia (B-CLL). Higher percentages of CD38-expressing CLL B cells may be found in lymphoid compartments compared to peripheral blood. Therefore, it is possible that although CLL B cells are resting, CD38 may be a marker of recent cell activation prior to entry into the periphery. To address this hypothesis, we examined the association of CD38 expression with other activation antigens identified in gene expression profiling experiments and include CD18, CD49d, CD20, and subunit 5 of the anaphase-promoting complex/cyclosome. We found that all these markers were more highly expressed in leukemic B cells from CD38-positive CLL patients. Lastly, because interferon is known to modulate CD38 expression, we used IFN-alpha to test the ability of CLL B cells to increase CD38 expression in vitro. Interestingly, IFN stimulation only modulated CD38 expression in CLL B cells that already expressed CD38. Taken together, these data suggest that CD38 is a marker of a more recently activated CLL B cell. This in turn may explain the biological and clinical differences between CD38-positive type B-CLL and CD38-negative type B-CLL.


Distribution Patterns of Subgroups of Inhibitory Neurons Divided by Calbindin 1.
The inhibitory neurons in the brain play an essential role in neural network firing patterns by releasing γ-aminobutyric acid (GABA) as the neurotransmitter. In the mouse brain, based on the protein molecular markers, inhibitory neurons are usually to be divided into three non-overlapping groups: parvalbumin (PV), neuropeptide somatostatin (SST), and vasoactive intestinal peptide (VIP)-expressing neurons. Each neuronal group exhibited unique properties in molecule, electrophysiology, circuitry, and function. Calbindin 1 (Calb1), a ubiquitous calcium-binding protein, often acts as a "divider" in excitatory neuronal classification. Based on Calb1 expression, the excitatory neurons from the same brain region can be classified into two subgroups with distinct properties. Besides excitatory neurons, Calb1 also expresses in part of inhibitory neurons. But, to date, little research focused on the intersectional relationship between inhibitory neuronal subtypes and Calb1. In this study, we genetically targeted Calb1-expression (Calb1+) and Calb1-lacking (Calb1-) subgroups of PV and SST neurons throughout the mouse brain by flexibly crossing transgenic mice relying on multi-recombinant systems, and the distribution patterns and electrophysiological properties of each subgroup were further demonstrated. Thus, this study provided novel insights and strategies into inhibitory neuronal classification.


Analysis of the estimation of bleeding using several proposed haematometric equations.
Among various methods for estimating blood loss, the gravimetric method is the most accurate; however, its use in routine practice is complicated. Although several equations have been proposed for this purpose, there is no consensus on the most suitable. A cross-sectional study was conducted in seven secondary and tertiary hospitals between March and July 2018 including all patients undergoing total hip arthroplasty or hip prosthesis replacement under general or regional anaesthesia. We compared blood loss estimates obtained using the gravimetric method (weighing gauzes and pads and measuring volumes of blood collected by suction during surgery) and using three different equations, two of which considered intravenous fluids (CRYS 3.5 and 1.5) and a third which did not (the traditional equation). Additionally, intraclass correlation coefficients (ICCs) and Bland-Altman plots were used. The mean blood loss estimated using the gravimetric method was 513.7 ± 421.7 mL, while estimates calculated using the CRYS 3.5, CRYS 1.5 and traditional equations were 737.2 ± 627.4, 420.8 ± 636.2 and 603.4 ± 386.3 mL, respectively. Comparing these results, we found low levels of agreement (based on ICCs), except when using the traditional equation (ICC: 0.517). The limits of agreement comparing external blood loss with the estimates from the equations ranged from - 1655.6 to 1459.2 in the case of the CRYS 1.5 equation to - 839.6 to 1008.4 in the case of the traditional equation. For use in clinical practice, haematological index-based equations, regardless of whether they consider fluids administered, do not show sufficiently strong correlations with gravimetric estimates of intraoperative blood loss.


The isolation and characterization of the 25-hydroxyvitamin D-binding protein from chick serum.
The binding protein for 15-hydroxyvitamin D3 (25-OH-D3) was isolated from chick serum. The molecular weight was 60,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, without the existence of sub-units. Its sedimentation coefficient was 4.3 S. The isoelectric points of the major and minor components were 6.1 and 5.9, respectively. Addition of 25-hydroxyvitamin D3 causes an anodal shift in the isoelectric point of the two forms of the binding protein. Heating at 60 degrees C slowly destroys the binding protein but the addition of vitamin D metabolites increases its thermostability. The binding protein has probably a single binding site for all vitamin D metabolites and its association constant for 25-OH-D3 at 4 degrees C and pH 7.4 is 10(9) M-1. The same affinity is found for 24,25-dihydroxyvitamin D3 but 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 have a 3- and 10-fold lower affinity, respectively. The amino acid composition is very similar to that of the human and rat binding protein. The concentration of chick 25-hydroxyvitamin D3-binding protein was higher in egg-laying hens (10 microM) than in immature hens (4 microM) or immature or adult roosters (4 microM). Chick plasma contains virtually only a 4 S form of the 25-hydroxyvitamin D3-binding protein but partially hemolyzed chick serum also contains a 6 S form. Addition of pure actin to chick plasma or serum converts all 4 S form to the 6 S form. The serum 25-hydroxyvitamin D3-binding protein is thus heterogenous since it exists in two 4 S forms (with different pI) and a 6 S form (complexed with actin). No evidence was found for the existence of a separate vitamin D3-binding protein.


Effect of organic/inorganic nanoparticles on performance of polyurethane nanocomposites for potential wound dressing applications.
This study focuses on the evaluation and modification of polyurethane (PU) membranes containing organic and inorganic nanoparticles for potential use as a wound dressing. For the purpose of PU nanocomposite preparation, chitosan (CS) was converted into nanoparticles by the ionic-gelation method to improve its blending capability with the PU matrix. These CS nanoparticles (nano-CS) were obtained as a hydrophilic organic filler with different contents and were utilized along with inorganic titanium dioxide (TiO2) nanoparticles in the nanocomposite membrane preparation. The membranes were prepared using phase inversion technique and their microstructure was controlled by manipulating the solvent non-solvent exchange rate. Obtained results demonstrate that addition of polymer solvent to nonsolvent induced a microstructure alteration from finger-like to sponge-like, which is more suitable for fluid uptake and consequently more useful for wound dressing applications. Similar results were obtained by introduction of nanoparticles to membranes. Due to the polar nature of nanoparticles and their effects on PU structure, prepared membranes showed 71.5% improve in swelling when compared to neat PU. Moreover, the reinforcement effect of nanoparticles caused an 18.94% increase in ultimate tensile strength in comparison with bare PU film, while elongation at break was not affected considerably. In addition, prepared PU nanocomposite films showed suitable antibacterial activity of 69% against Staphylococcus aureus and did not show any toxicity to human fibroblast cells. Based on these results, simultaneous use of TiO2 and chitosan nanoparticles can improve both physical and antibacterial properties of PU as an ideal wound dressing.


Rare-earth-platinum alloy nanoparticles in mesoporous zeolite for catalysis.
Platinum is a much used catalyst that, in petrochemical processes, is often alloyed with other metals to improve catalytic activity, selectivity and longevity1-5. Such catalysts are usually prepared in the form of metallic nanoparticles supported on porous solids, and their production involves reducing metal precursor compounds under a H2 flow at high temperatures6. The method works well when using easily reducible late transition metals, but Pt alloy formation with rare-earth elements through the H2 reduction route is almost impossible owing to the low chemical potential of rare-earth element oxides6. Here we use as support a mesoporous zeolite that has pore walls with surface framework defects (called 'silanol nests') and show that the zeolite enables alloy formation between Pt and rare-earth elements. We find that the silanol nests enable the rare-earth elements to exist as single atomic species with a substantially higher chemical potential compared with that of the bulk oxide, making it possible for them to diffuse onto Pt. High-resolution transmission electron microscopy and hydrogen chemisorption measurements indicate that the resultant bimetallic nanoparticles supported on the mesoporous zeolite are intermetallic compounds, which we find to be stable, highly active and selective catalysts for the propane dehydrogenation reaction. When used with late transition metals, the same preparation strategy produces Pt alloy catalysts that incorporate an unusually large amount of the second metal and, in the case of the PtCo alloy, show high catalytic activity and selectivity in the preferential oxidation of carbon monoxide in H2.


A facile synthesis, antibacterial, and antitubercular studies of some piperidin-4-one and tetrahydropyridine derivatives.
The raise in clinical significance of multidrug-resistant bacterial pathogens has directed us to synthesize 2,6-diarylpiperidin-4-one and Delta(3)-tetrahydropyridin-4-ol based benzimidazole and O-arylsulfonyl derivatives. X-ray crystal structure of tetrahydropyridinol (23) confirmed a change in conformation and orientation of substituents upon amide formation. Antibacterial activities evaluated against a wide number of bacterial pathogens (both sensitive and multidrug-resistant) revealed that 19, 27 against Staphylococcus aureus, 27 against Enterococcus faecalis, and 19, 21, 23, and 27 against Enterococcus faecium are significantly good at lowest MIC(90) (16 microg/mL). Inhibitory power noticed by 23 against Vancomycin-Linezolid-resistant E. faecalis and 27 against Vancomycin-resistant E. faecium are onefold better than the standard Linezolid and Trovafloxacin drugs, respectively. Moreover, antitubercular activity for the selected compounds against Mycobacterium tuberculosis H37Rv revealed that compounds 23, 24, and 27 expressed onefold improved potency compared to the standard Rifampicin drug.


An Algorithm for the Analysis of the 3D Spatial Organization of the Genome.
We present an algorithm, and its MATLAB implementation, based on mathematical methods to detect and localize 3D multicolor DNA FISH spots in fluorescence cell image z-stacks. This algorithm provides a method to measure the relative positioning of spots in the nucleus and inter-spot distances with the aim to enrich our understanding of the 3D spatial organization of the genome within the cell nucleus.


ICER report on Alzheimer's disease: implications from a patient perspective.
DISCLOSURES: No funding was received for the writing of this commentary. The author has nothing to disclose.


Laparoscopic partial nephrectomy versus laparoscopic cryoablation for the small renal tumor.
We sought to compare perioperative and short-term outcomes of laparoscopic partial nephrectomy versus laparoscopic cryoablation in patients with peripheral small renal tumors. Prospectively accrued data of patients with a small renal tumor (< or = 3 cm) undergoing laparoscopic partial nephrectomy (group 1, n = 153) or laparoscopic cryoablation (group 2, n = 78) were compared retrospectively. Patients undergoing laparoscopic partial nephrectomy were younger (mean age, 60.6 vs 65.6 years; P = 0.005), healthier (American Society of Anesthesiologists class 3/4 present in 46% vs 75%; P = 0.001), had a lower baseline serum creatinine (90.1 vs 106.0 micromol/L [1.02 vs 1.2 mg/dL]; P = 0.01), a larger tumor size (2.3 vs 2.1 cm; P = 0.02), and fewer cases of solitary kidneys (5% vs 23%; P = 0.000). Laparoscopic partial nephrectomy was associated with greater blood loss (211 vs 101 mL; P = 0.000) and a higher incidence of delayed complications after hospital discharge (16.3% vs 2.2%; P = 0.01) compared with cryoablation. Both groups were comparable with regard to operative time (P = 0.77), intraoperative complications (P = 0.1), postoperative complications (P = 0.55), hospital stay (P = 0.13), convalescence (P = 0.96), and postoperative serum creatinine (112.2 vs 123.7 micromol/L [1.27 vs 1.4 mg/dL]; P = 0.31). Local recurrence was detected over a mean follow-up time of 5.8 months in group 1 (0.6%) and 24.6 months in group 2 (3%). Although the technical simplicity, decreased blood loss, and somewhat lower complication rate are attractive features of renal cryotherapy, this must be balanced against the current lack of long-term follow-up data that are needed to confirm the oncologic adequacy of this developmental procedure. Laparoscopic partial nephrectomy, albeit a technically advanced procedure, duplicates established open principles and has therefore evolved to become our current minimally invasive nephron-sparing procedure of choice in the majority of patients with a small renal tumor.


Pupil cycle time in optic neuritis.
A thin slit-lamp beam illuminating the pupil margin produced clearly visible pupil oscillations. These oscillations were timed with a stopwatch, thus producing a measurement of the "pupil cycle time". The pupil cycle time was remarkably stable in various testing situations and repeatable within +/- 3% over extended periods of time. When the iris muscles were normally innervated and responsive, the pupil cycle time was dependent on the speed of conduction and the number and strength of optic nerve impulses. Pupil cycle time can be measured in most persons with active or inactive optic neuritis. In the few patients whose light reflex is so poor that the pupil cycle time cannot be measured, the inability to induce cycling can itself be taken as a definite abnormality of the light reflex arc. Only 5% of normal persons 12 to 50 years of age are expected to have a pupil cycle time in either eye longer than 954 msec, or a difference in pupil cycle time between the two eyes longer than 70 msec. Pupil cycle time was significantly longer in patients with optic neuritis, with a P-value less than .001. The pupil cycle time is similar to visual evoked response latency time in that it can detect and quantitate subclinical defects in optic nerve conduction time. Pupil cycle time is objective and quantitative for each eye individually. It is a fast, simple, and reliable clinic test of optic nerve function.


Employment choices in conditions of physician oversupply: a study of graduates of San Francisco internal medicine programs, 1979-1984.
The authors surveyed 297 internists who completed residency or fellowship training at six San Francisco institutions from 1979 through 1984 to assess how the recent expanded supply of physicians has affected their intensity of practice and their decisions about location of practice. The vast majority of internists (93%) settled in metropolitan areas, with 56% remaining in the San Francisco Bay Area, despite that region's already high concentration of physicians. Mean annual income, in 1984 dollars, was slightly more than figures from national surveys of physicians of similar age ($72,560 vs. $71,900), but reported mean work week was shorter (54.8 hours vs. 60.5). Although subspecialists earned significantly more than generalists, this was because they worked more hours. Those who graduated later were significantly less likely to be in private practice in 1985, mainly because they initially selected salaried institutional work more often than earlier graduates (p less than 0.001). Women worked 85% of the men's work week and subspecialized significantly less often (p less than 0.05). These findings suggest that internists trained in already "over-doctored" areas will continue to settle there or in similar communities.


Gene markers of normal villous maturation and their expression in placentas with maturational pathology.
The placenta demonstrates a recognized sequence of histomorphologic maturation throughout pregnancy, and in some cases, shows abnormally advanced (AVM) or delayed (DVM) villous maturation. While AVM and DVM have important clinical implications, it is unknown whether they truly represent a state of accelerated/delayed normal maturation or a state of pathological maldevelopment. The purpose of our study is, therefore, to address this challenge via a genome-wide search for expression markers of normal villous maturation (NM) and the assessment of these genes in cases of maturational pathology. A total of 142 placentas, previously evaluated by gene expression microarray, were reviewed histologically and classified as NM, AVM, or DVM. Expression data from healthy NM placentas underwent Pearson correlations with gestational age (GA) and network/pathway analysis to identify candidate gene markers. Candidates were then validated in an independent microarray dataset and used to calculate "molecular GAs" of placentas with maturational pathology. Analysis of NM placentas yielded 17 candidate markers of normal villous maturation, of which 11 were independently validated. Genes with expression increasing across gestation were associated with transcription and metabolism, while those demonstrating decreasing expression were involved in cell cycle and division. Molecular GA was 5.3 weeks older than true GA among AVM placentas (p < 0.001), and 1.1 weeks younger among DVM placentas (p = 0.149). We have found evidence of advanced molecular GA in AVM placentas, while molecular alterations in DVM placentas were merely suggestive of delayed maturation. In the future, these findings will need to be validated with additional techniques such as in situ hybridization or immunohistochemistry.


Secondary immune deficiencies associated with biological therapeutics.
Biological therapeutics have been utilized in the past several years for the treatment of various autoimmune, cardiovascular, and neoplastic conditions. As these agents target both pathologic and physiologic components of inflammatory and immune systems, the scientific community has been challenged to identify potential secondary immune deficiencies associated with their use. This article will focus on biological agents used for the treatment of rheumatoid arthritis, including tumor necrosis factor-a inhibitors, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4 Ig), rituximab, and interleukin-1 receptor agonist (IL-1Ra). Both clinical and in vitro studies have been done to explore the potential immunomodulatory and immunosuppressive effects of these agents.


Enhanced multisensory integration in older adults.
Information from the different senses is seamlessly integrated by the brain in order to modify our behaviors and enrich our perceptions. It is only through the appropriate binding and integration of information from the different senses that a meaningful and accurate perceptual gestalt can be generated. Although a great deal is known about how such cross-modal interactions influence behavior and perception in the adult, there is little knowledge as to the impact of aging on these multisensory processes. In the current study, we examined the speed of discrimination responses of aged and young individuals to the presentation of visual, auditory or combined visual-auditory stimuli. Although the presentation of multisensory stimuli speeded response times in both groups, the performance gain was significantly greater in the aged. Most strikingly, multisensory stimuli restored response times in the aged to those seen in young subjects to the faster of the two unisensory stimuli (i.e., visual). The current results suggest that despite the decline in sensory processing that accompanies aging, the use of multiple sensory channels may represent an effective compensatory strategy to overcome these unisensory deficits.


Dynamic transitions from smooth to rough to twinning in dislocation motion.
The motion of dislocations in response to stress dictates the mechanical behaviour of materials. However, it is not yet possible to directly observe dislocation motion experimentally at the atomic level. Here, we present the first observations of the long-hypothesized kink-pair mechanism in action using atomistic simulations of dislocation motion in iron. In a striking deviation from the classical picture, dislocation motion at high strain rates becomes rough, resulting in spontaneous self-pinning and production of large quantities of debris. Then, at still higher strain rates, the dislocation stops abruptly and emits a twin plate that immediately takes over as the dominant mode of plastic deformation. These observations challenge the applicability of the Peierls threshold concept to the three-dimensional motion of screw dislocations at high strain rates, and suggest a new interpretation of plastic strength and microstructure of shocked metals.


Restriction fine specificity of long-term, hapten-specific cytotoxic T cell clones: analysis with H-2Kbm-mutant mice and H-2Kb-specific monoclonal antibodies.
The cell-mediated cytotoxic response against autologous cells modified with the sulfhydryl reagent I-AED [N-iodo-acetyl-N-(5-sulfonic-1-naphthyl) ethylene diamine] has been described by Levy, R. B., Shearer, G. M., Richardson, J. C. and Henkart, P. A., [J. Immunol. 1981. 127: 523.]. We have established two H-2Db- and eight H-2Kb-restricted, AED-specific long-term cytotoxic T lymphocyte (CTL) clones of C57BL/10 origin. The growth of these clones has been dependent upon presence of both antigen and interleukin 2. Cytotoxicity and proliferation analysis of AED-specific Kb-restricted CTL clones with target and stimulator cells from Kbm-mutant mice demonstrated two categories of clones (A and B) based on different reactivity patterns against hapten-modified Kbm-mutant cells. AED-modified target cells of bm5, bm6 and bm9 origin were lysed by type A clones but not by type B clones, in contrast to AED-modified bm3, bm8 and bm11 target cells which were lysed by type B but not by type A clones. None of the clones lysed AED-modified bm1 target cells, but all of them lysed AED-modified bm4 and bm10 target cells. The restriction fine specificities for both cytolytic and proliferative activities of the analyzed clones were identical. A panel of monoclonal antibodies (mAb) directed against the Kb molecule was used to inhibit lysis of AED-modified target cells by CTL clones. mAb which recognize a cluster of allodeterminants located in the second external domain (C1 domain) of the Kb molecule [Hämmerling, G. J., Rüsch, E., Tada, N., Kimura, S. and Hämmerling, U., Proc. Natl. Acad. Sci. USA 1982. 79: 4737] only inhibited type B clones, whereas inhibition of both type of clones was observed with mAb specific for allodeterminants clustered in the N-terminal region of Kb. These findings suggest that different regions on the Kb molecule serve as self determinants for H-2-restricted cytotoxicity. We also demonstrate that allodeterminants recognized by mAb and self determinants involved in H-2 restriction need not be identical. Our data also support the notion that covalent AED modification of H-2 molecules is not necessary to generate the self plus X antigen for CTL recognition.


Sentinel node biopsy in squamous cell cancer of the oral cavity and oral pharynx: a diagnostic meta-analysis.
The sentinel node biopsy concept has been gaining support in the head and neck cancer literature during only the last few years, and several pilot studies have been published. This procedure aims to avoid unnecessary treatment to the clinically negative neck by identifying the patients with occult neck disease. We performed a systematic review and a diagnostic meta-analysis of all published literature regarding sentinel node biopsies in head and neck cancer until December 2003 using established guidelines. Using the pooled sensitivity rates obtained from the meta-analysis and treatment outcomes from published literature, we created a decision analysis model to identify the treatment arm with better payoffs. A total of 301 patients with oral cavity primary tumors and 46 patients with oropharyngeal primary tumors from 19 articles were included for the meta-analysis. The pooled sensitivity result using the random effects model was 0.926 (95% confidence interval, 0.852-0.964). The cumulative payoff for the sentinel node biopsy arm was lower than that for the elective node dissection arm by about 1%. The payoffs were assigned for the recurrence and mortality rates only and did not take into account the morbidity caused by the procedures. The sentinel node biopsy procedure has shown high sensitivity rates in pilot studies for oral and oropharyngeal squamous cell cancer across the globe and is reliable and reproducible. This study provides a firm evidence base for forthcoming trials on the role of sentinel node biopsy in head and neck cancer.


Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche architecture.
Limbal epithelial stem cells are responsible for the maintenance of the human corneal epithelium and these cells reside in a specialised stem cell niche. They are located at the base of limbal crypts, in a physically protected microenvironment in close proximity to a variety of neighbouring niche cells. Design and recreation of elements of various stem cell niches have allowed researchers to simplify aspects of these complex microenvironments for further study in vitro. We have developed a method to rapidly and reproducibly create bioengineered limbal crypts (BLCs) in a collagen construct using a simple one-step method. Liquid is removed from collagen hydrogels using hydrophilic porous absorbers (HPAs) that have custom moulded micro-ridges on the base. The resulting topography on the surface of the thin collagen constructs resembles the dimensions of the stromal crypts of the human limbus. Human limbal epithelial cells seeded onto the surface of the constructs populate these BLCs and form numerous layers with a high proportion of the cells lining the crypts expressing putative stem cell marker, p63α. The HPAs are produced using a moulding process that is flexible and can be adapted depending on the requirements of the end user. Creation of defined topographical features using this process could be applicable to numerous tissue-engineering applications where varied 3-dimensional niche architectures are required.


Hydroxyproline stimulates inflammation and reprograms macrophage signaling in a rat kidney stone model.
Meals rich in oxalate are associated with calcium oxalate (CaOx) kidney stone disease. Hydroxy-L-proline (HLP) is an oxalate precursor found in milk and collagen-containing foods. HLP has been shown to induce CaOx crystal formation in rodents. The purpose of this study was to evaluate the effect of HLP induced oxalate levels on inflammation and renal leukocytes during crystal formation. Male Sprague-Dawley rats (6-8 weeks old) were fed a control diet containing no oxalate for 3 days before being randomized to continue the control diet or 5% HLP for up to 28 days. Blood, 24 h urine, and kidneys were collected on Days 0, 7, 14, or 28. Urinary oxalate levels, crystal deposition, and renal macrophage markers were evaluated using ion chromatography-mass spectrometry, immunohistochemistry, and qRT-PCR. Renal leukocytes were assessed using flow cytometry and RNA-sequencing. HLP feeding increased urinary oxalate levels and renal crystal formation in animals within 7 days. HLP also increased renal macrophage populations on Days 14 and 28. Transcriptome analysis revealed that renal macrophages from animals fed HLP for 7 days were involved in inflammatory response and disease, stress response to LPS, oxidative stress, and immune cell trafficking. Renal macrophages isolated on Day 14 were involved in cell-mediated immunological pathways, ion homeostasis, and inflammatory response. Collectively, these findings suggest that HLP-mediated oxalate levels induce markers of inflammation, leukocyte populations, and reprograms signaling pathways in macrophages in a time-dependent manner. Additional studies investigating the significance of oxalate on renal macrophages could aid in our understanding of kidney stone formation.


Free fatty acid metabolism in "stunned" myocardium.
To assess whether myocardial lipid metabolism is altered in the "stunned" myocardium we have studied the metabolism of (1-14C)-palmitate during reperfusion in a modified rat heart preparation. Hearts were perfused retrogradely at a physiological flow rate (2 ml/min) in a non-recirculating system with erythrocyte-enhanced Krebs-Henseleit buffer containing albumin 0.4 mM, glucose 11 mM, palmitate 0.4 mM and trace amounts of (1-14C)-palmitate. Left ventricular pressure was measured by a latex balloon in the left ventricular cavity. Control hearts were perfused at constant flow for 120 min. To achieve reversible ischaemic damage, myocardial perfusion was reduced by 95% for 40 min, followed by reperfusion at the control flow rate for 60 min (reperfusion group). For comparison, irreversible damage was produced by calcium free perfusion (calcium paradox group). In the reperfusion group, the developed pressure was severely depressed 5 min after reperfusion to 23% of the value in the control group (p less than 0.05) but recovered to 84% (NS) at 60 min. In the calcium paradox group, mechanical activity ceased completely without recovery. Myocardial uptake of (1-14C)-palmitate in the reperfusion group was similar to the control experiments for the entire reperfusion period, whereas a marked depression was observed in the calcium paradox group. 14CO2 production was severely depressed at the onset of reperfusion in both the reperfusion and calcium paradox group to 42% (p less than 0.05) and 29% (p less than 0.05) respectively. In contrast to the calcium paradox group, 14CO2 production in the reperfusion group recovered progressively to 70% (NS) of the control value during the 60 min of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of interaction between noise and toluene on auditory function in the rat.
Rats were exposed to toluene (1000 ppm, 16 h/d, 5 d/w, 2 w), or noise (100 dB Leq, 10 h/d, 7 d/w, 4 w) or toluene followed by noise. Auditory function was tested by brainstem audiometry using a 1/3 octave filtered sine wave stimulus at the frequencies 1.6, 3.15, 6.3, 12.5 and 20.0 kHz. A high-frequency auditory impairment was observed after exposure to toluene alone and noise alone. A slight recovery was recorded 1 and 6 months after the toluene exposure. Toluene followed by noise resulted in a higher threshold at all frequencies. A slight recovery was recorded 6 months post-exposure. The threshold shift exceeded the summated loss caused by toluene alone and by noise alone, particularly at 3.15 and 6.3 kHz. The latencies varied only slightly. The results indicate that the major cause of the auditory impairment was cochlear damage and that only minor injury was caused to the auditory pathways.


Monitoring sarcopenia with wearable devices: a systematic review protocol.
Sarcopenia is a highly prevalent muscle dysfunction among older adults and is associated with adverse events. The periodic monitoring enables an early screening of patients at risk and control of the progression of muscle impairment. Wearable devices have been used as clinical support for sarcopenia detection. Therefore, this review aims to identify how wearable devices have been used to screen sarcopenia. Searches will be conducted from August 2023 on PubMed, CINHAL, Embase, Web of Science and SciELO databases. We will include cross-sectional and/or baseline data from prospective studies reporting the use of wearable devices to investigate sarcopenia. Studies that discuss only the development of algorithms or applications for the assessment of sarcopenia or unavailable full texts will be excluded. The main reviewer will conduct the initial search and exclusion of duplicates, while two independent reviewers will select studies, extract data and assess the methodological quality using the Appraisal tool for Cross-sectional Studies. No previous ethical approval is required for this review. The findings of this review will be submitted to a scientific journal and disclosed at international scientific conferences. CRD42022356040.


Physical interaction between STAT3 and AP1 in cervical carcinogenesis: Implications in HPV transcription control.
The constitutive activation and aberrant expression of Signal Transducer and Activator of Transcription 3 (STAT3) plays a key role in initiation and progression of cervical cancer (CaCx). How STAT3 influences HPV transcription is poorly defined. In the present study, we probed direct and indirect interactions of STAT3 with HPV16/18 LCR. In silico assessment of cis-elements present on LCR revealed the presence of potential STAT3 binding motifs. However, experimental validation by ChIP-PCR could not confirm any specific STAT3 binding on HPV16 LCR. Protein-protein interaction (PPI) network analysis of STAT3 with other host transcription factors that bind LCR, highlighted the physical association of STAT3 with c-FOS and c-JUN. This was further confirmed in vitro by co-immunoprecipitation, where STAT3 co-immunoprecipitated with c-FOS and c-JUN in CaCx cells. The result was supported by immunocytochemical analysis and colocalization of STAT3 with c-FOS and c-JUN. Positive signals in proximity ligation assay validated physical interaction and colocalization of STAT3 with AP1. Colocalization of STAT3 with c-FOS and c-JUN increased upon IL-6 treatment and decreased post-Stattic treatment. Alteration of STAT3 expression affected the subcellular localization of c-FOS and c-JUN, along with the expression of viral oncoproteins (E6 and E7) in CaCx cells. High expression of c-JUN in tumor tissues correlated with poor prognosis in both HPV16 and HPV18 CaCx cohort whereas high expression of STAT3 correlated with poor prognosis in HPV18 CaCx lesions only. Overall, the data suggest an indirect interaction of STAT3 with HPV LCR via c-FOS and c-JUN and potentiate transcription of viral oncoproteins.


Time Out from Sex or Romance: Sexually Experienced Adolescents' Decisions to Purposefully Avoid Sexual Activity or Romantic Relationships.
Researchers have given significant attention to abstinence among adolescents, but far less is known about purposeful avoidance of sexual activity (and relationship involvement). Typically, it is assumed that, once adolescents have initiated sexual activity, they will thereafter engage in sexual activity if given the opportunity. However, it is unclear whether that is true as some research indicates that many adolescents engage in sexual activity intermittently. Sexually experienced adolescents may purposefully avoid engaging in sexual activity for a period of time and, if so, this has implications for understanding their sexual decision-making. We used a mixed methods approach to investigate sexually experienced adolescents' decisions to purposefully avoid further sexual activity and/or romantic relationships with a focus on how common these decisions are and factors influencing them. Participants were 411 (56 % female) adolescents (16-21 years old) who completed an on-line survey that assessed reasons for each type of avoidance, religiosity, sexual esteem, sexual distress, sexual coercion, and dysfunctional sexual beliefs. Overall, 27 % of participants had engaged in sexual avoidance and 47 % had engaged in romantic avoidance. Significantly more female than male adolescents reported sexual and romantic avoidance. Adolescents' reasons for sexual avoidance included: lack of sexual pleasure or enjoyment, relationship reasons, negative emotions, values, fear of negative outcomes, negative physical experience, and other priorities. Reasons for romantic avoidance included: effects of previous relationship, not interested in commitment, wrong time, other priorities, negative emotions, no one was good enough, and sexual concerns. Logistical regressions were used to assess associations between age, religiosity, sexual esteem, sexual distress, experience of sexual coercion, and dysfunctional sexual beliefs and having engaged in romantic and/or sexual avoidance. The female adolescents who had avoided sexual activity were more likely to have experienced sexual coercion. The male adolescents who had avoided sexual activity were more religious and likely to have experienced sexual coercion. The male adolescents who had avoided romantic relationships were more sexually distressed and likely to have experienced sexual coercion. No associations were found for romantic avoidance among female adolescents. These results reflect considerable agency in the decision-making of adolescents in intimate contexts. They are discussed in terms of their challenge to current discourses about rampant adolescent sexuality as well as their implications for education and prevention interventions that incorporate personal choice and decision-making into their protocols.


Galpha12 and galpha13 are phosphorylated during platelet activation.
The ubiquitously expressed G-proteins G12 and G13 whose function is currently not clear have been shown to be activated in platelet membranes through receptors that stimulate platelet aggregation. We used intact human platelets to determine whether alpha subunits of both G-proteins can be phosphorylated under physiological conditions. Activation of human platelets by thrombin and the thromboxane A2 receptor agonist U46619 lead to phosphorylation of Galpha12 and Galpha13. Phosphorylation occurred rapidly after addition of thrombin and was not mediated by glycoprotein IIb/IIIa (integrin alphaIIbbeta3) activation. Phosphorylation of Galpha12 and Galpha13 could be mimicked by phorbol 12-myristate 13-acetate, and thrombin-induced phosphorylation was inhibited by the protein kinase C inhibitor calphostin C indicating an involvement of protein kinase C in Galpha12/13 phosphorylation induced by thrombin in human platelets. The phosphorylation of both G protein alpha subunits was reconstituted in COS-7 cells cotransfected with Galpha12 or Galpha13 and different protein kinase C isoforms. Among the protein knase C isoforms tested, protein kinase C beta, delta, and epsilon were most effective in promoting phosphorylation of Galpha12 and Galpha13 in a phorbol 12-myristate 13-acetate-dependent manner. These data demonstrate that Galpha12 and Galpha13 are phosphorylated under in vivo conditions and that this phosphorylation involves protein kinase C.


Preparation of chitosan/sodium alginate/nano cellulose composite for the efficient removal of cadmium (II) cations from wastewater and soil systems.
In this study, chitosan/sodium alginate/nano cellulose (CSA-N) nanocomposite hydrogels were prepared using a completely green route and used as sorbents to adsorb Cd2+ ions from water and soil systems of an environmental aspect. The sorbents were characterized by FTIR, SEM, and XRD. The influences of initial Cd2+ concentration, the presence of nano cellulose, type of the polluted environment, and ionic strength on adsorption and desorption isotherms were investigated. The maximum adsorption capacity of cadmium onto CSA was significantly increased from 2264.9 to 4380.97 μmol/g when the system was changed from soil to water, respectively. While, the maximum adsorption capacity of cadmium onto CSA-N was almost the same in the soil and wastewater systems, i.e., 3419.5 and 3230.3 µmol/g, respectively. The results indicated that Langmuir and Freundlich models provided the best fit for the experimental adsorption data for CSA and CSA-N, respectively. By comparing the amounts of Δq, the difference between adsorption and desorption amounts, the CSA was not economically feasible sorbent at high initial concentrations of Cd2+ in the wastewater system, while, CSA-N was demonstrated to be a more efficient adsorbent than CSA for cadmium removal from both the soil and wastewater systems.


Urinothorax-an underdiagnosed cause of acute dyspnea: report of a bilateral and of an ipsilateral urinothorax case.
Urinothorax (UT) is a rare and often undiagnosed condition, defined as the presence of urine in the pleural cavity due to the retroperitoneal leakage of urine accumulation, known as urinoma, into the pleural space. UT usually is a transudative pleural effusion that presents in patients with obstructive uropathy and it may occur following surgical procedures in the ureter or kidney such as ESWL, PCNL, and URS. Its diagnosis requires a high degree of clinical suspicion since the respiratory symptoms tend to be absent or mild and the urological signs tend to dominate. However, UT may rarely present with severe and acute dyspnea as well. The objectives of this study are to describe two new cases of this rare entity, a bilateral case and an ipsilateral case focusing on the side that occurs according to the affected renal insult, and to alert the physicians to include UT in their differential diagnosis of pleural effusions especially in patients with recent urinary tract disorders.


Evaluation of pedagogical impact of Business English textbooks on teaching critical thinking skills.
One goal of undergraduate courses in Business English is teaching critical thinking, but this goal has been hindered by disagreement over how to teach those skills. Many textbooks pay insufficient attention to critical thinking skills. It remains unclear how effective existing textbooks are in helping teachers teach these skills. In this article, we report on a study which uses the Knowledge Process framework to qualitatively and quantitatively evaluate five textbooks in the Market Leader series. The presence of four knowledge processes in the textbooks is examined to see how effective the distribution of those processes is in teaching critical thinking skills. Although four knowledge processes are found in the textbooks, there is an imbalance among sub-processes, which leads to lack of scaffolding for teaching critical thinking skills. It is thus recommended that textbook developers and teachers design a sequence of scaffolded tasks to help teach critical thinking skills.


Effect of hormonal contraceptives during breastfeeding on infant's milk ingestion and growth.
To measure infants' breast milk intake and infant growth when their mothers initiated either combined oral contraceptive (COC), levonorgestrel-releasing intrauterine system, or etonogestrel-releasing implant, or copper intrauterine device (IUD) as a reference group. Prospective trial. University-based hospital. On postpartum day 42, 40 women initiated a contraceptive method according to their choice. Deuterium (D2O; 0.5 g/kg mother's weight) was ingested by mothers on postpartum days 42, 52, and 63 as a marker of total body fluid. Infants' milk intake from 42 to 63 postpartum days was assessed by measurement of D2O levels in infants' saliva and infant growth by measuring their body weight, height, and tibia length. Women recorded all infant feed and changes of diapers wet with urine. Breastfeeding continuation was assessed at 6 months postpartum. Infant mean milk intake, mean growth increase, mean number of breastfeeding episodes, daily wet diaper changes, and mean duration of exclusively breastfeeding (~5 months) were similar in the four groups. Use of a COC, the two progestin-only contraceptives, or copper IUD did not affect the amount of infant milk intake and growth up to 9 weeks of age. The incidence of full breastfeeding and breastfeeding continuation was similar with contraceptive hormonal use and no use. NCT01388582.


Do clerkship schemes effectively improve pharmacy students' understanding of and attitudes regarding pharmaceutical care?--a pre-post study in China Pharmaceutical University.
Clerkship is potentially an effective measure of improving the pharmacy students' understanding of and attitudes toward pharmaceutical care. This research aimed to validate whether clerkship schemes in China effectively improve pharmacy students' understanding of and attitudes toward PC, and discuss on how to improve the clerkship schemes for better quality. A pre-post and self-administrated questionnaire survey among three continuous years of students was conducted to measure Chinese fifth-year clinical pharmacy students' differences in understanding of pharmaceutical care and attitudes toward pharmaceutical care before and after their clerkship schemes. Statistical analysis was conducted on the retrieved data. 602 respondents completed the post-part survey (drop rate = 1.8%). Correct rates of all statements regarding students' understanding of pharmaceutical care were generally increased, but the rates of respondents holding correct understanding of the primary goal of pharmaceutical care (71.9 to 85.0%), the necessity of drug information support in pharmaceutical care (77.1 to 87.5%) and the patients' role and duty when receiving pharmaceutical care (66.1 to 70.6%) were unsatisfactory before the clerkship and the improvement was not significant. Most statements regarding students' attitudes toward pharmaceutical care were improved in general. However, rates of respondents holding negative attitudes toward students performing pharmaceutical care during their clerkship (3.7 to 7.5%) and choosing pharmaceutical care provider as their career after clerkship schemes (10.8 to 14.8%) had increased after the clerkship schemes. Clerkship generally improves clinical pharmacy students' understanding of and attitudes toward pharmaceutical care, yet adjustments are also required in some contents of the clerkship for further improvements in its outcomes.


Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Nivolumab plus Cabozantinib Joins Immune Checkpoint Inhibition Combination Therapies for Treatment-naïve Metastatic Clear-Cell Renal Cell Carcinoma.
Longer follow-up and new trial data from phase 3 randomised controlled trials investigating immune checkpoint blockade (PD-1 or its ligand PD-L1) in advanced clear-cell renal cell carcinoma (RCC) have recently become available. The CheckMate 9ER trial demonstrated an improved progression-free survival (PFS) and overall survival (OS) benefit for the combination of cabozantinib plus nivolumab. A Keynote-426 update demonstrated an ongoing OS benefit for pembrolizumab plus axitinib in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups, while an update of CheckMate 214 confirmed the long-term benefit of ipilimumab plus nivolumab in IMDC intermediate and poor risk patients. The RCC Guidelines Panel continues to recommend these tyrosine kinase inhibitors + immunotherapy (IO) combination across IMDC risk groups in advanced first-line RCC and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate and poor risk. PATIENT SUMMARY: New data from trials of immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit with the combination of cabozantinib plus nivolumab and pembrolizumab plus axitinib and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.


Performance evaluation of an aqueous-organic phase separator for post-column reactions in high-performance liquid chromatography, and its application to the enhanced detection of some basic drugs of abuse.
A phase separator is described that is suitable for post-column HPLC applications. It operates with commonly used HPLC eluents and immiscible organic solvents as long as the two phases remain immiscible. It is compatible with gradient elution systems. Separation efficiency is routinely better than 0.8, which ensures that analyte peak heights are about 95% of the maximum height under these conditions. An application for the detection of pethidine, cocaine, methadone, piritramide and dipipanone at 0.8-1.8 ng on-column loadings is described.


Is personalized medicine finally arriving?
It's no gold rush, but dozens of players are emerging in personalized medicine, with biotechs, big and small, leading the way. Some big pharma companies and even payers remain skeptical, but economics aside, the real winners will be patients.


Chemical pollution, respiratory allergy and asthma: a perspective.
The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop in June 2005 to address the speculation that exposure to specific chemicals, and/or chemical pollutants in general, may play an important role in the increased prevalence of allergy and asthma in 'westernized' societies. This paper summarises one perspective arrived at during this workshop. It was acknowledged that certain chemicals and certain types of pollution might trigger or exacerbate asthmatic reactions in sensitised subjects. However, overall levels of pollution appear not to have had a major impact upon the prevalence of atopic allergy. Epidemiological studies suggest that pollution may in some circumstances protect from acquisition of sensitisation. Increasing exposure to household chemicals may enhance pre-existing allergies, but evidence for their causation of allergy is lacking. Other risk factors considered included societal dietary changes and exposure to endotoxins. Future research needs were identified which included epidemiological studies employing exposure and biomonitoring data, studies on domestic exposure to chemicals and their association with the incidence of allergy and asthma, and prospective birth cohort studies employing well-defined aspects of lifestyle, diet, chemical and endotoxin exposure as factors that may drive susceptibility to allergy and asthma.


The structure of human complement component C7 and the C5b-7 complex.
The molecular architecture of human complement component C7 was elucidated at several structural levels. The complete primary structure of C7 was derived from the cDNA sequence of clones isolated from a human liver library. C7 is a mosaic protein that consists of 821 amino acids. The amino-terminal two-thirds of C7 has 23-30% homology with complement components C8 and C9. In addition, the carboxyl-terminal third contains four cysteine-rich segments that have overlapping internal homology. The protein is a single polypeptide chain with 28 disulfide bonds and is glycosylated at two sites. Virtually all the cysteines are found in small units of 35-77 amino acids that exhibit homology with those of various proteins including the low density lipoprotein receptor, epidermal growth factor precursor, thrombospondin, and blood coagulation factors IX and X. The secondary structural analysis, estimated by circular dichroism, suggested a high content of beta-sheet (38%) and beta-turns (24%). The tertiary structure, visualized by transmission electron microscopy, indicated a flexible elongated molecule with dimensions of 151 X 59 X 43 A. The quaternary structure of the C5b-7 complex bound to lipid vesicles was observed to be in the form of monomers or dimers. The monomer C5b-7 consists of a leaflet and a long flexible stalk, and the dimer has two leaflets linked through a supercoiled stalk. Membrane binding is mediated by the stalk part of the complexes. Using a radioiodinated photoreactive cross-linking reagent bound to the polar head group of phosphatidylethanolamine, the stalk part of the C5b-7 complex could be labeled preferentially, and it was found to consist mainly of C6 and C7. Thus, C7 plays a major role in bringing about the hydrophilic-amphiphilic transition during the formation of the membrane attack complex, and it serves as a membrane anchor for the C5b-7 complex.


Myocardial assessment using tissue doppler imaging in preterm very low-birth weight infants before and after red blood cell transfusion.
To investigate myocardial velocities in anemic very low-birth weight (VLBW) preterm infants, pre and post red blood cells transfusion using tissue Doppler imaging echocardiography. Forty-eight VLBW preterm infants34 weeks and>2 weeks old were prospectively divided: Transfused symptomatic infants (Hematocrit (Hct)<0.30 (n=32)) and non transfused asymptomatic controls (control 1, Hct >0.30 (n=9) and control 2, Hct <0.30 (n=7)). Echocardiography was performed before and 3-5 days after transfusion in the transfused, and the controls were studied at similar intervals. Non parametric tests were used for statistical analysis. Left ventricular (LV) systolic velocity increased (transfused (4.6±0.70 vs 6.0±0.65, P<0.01)) as did LV diastolic velocities (P<0.01) without significant difference over time in each control. The percentage change in LV velocity following transfusion correlated negatively (ρ=0.36) with pre transfusion Hct. There is a significant increase in myocardial performance following transfusion, which is related to the severity of the anemia.


Ribosomal position and contacts of mRNA in eukaryotic translation initiation complexes.
The position of mRNA on 40S ribosomal subunits in eukaryotic initiation complexes was determined by UV crosslinking using mRNAs containing uniquely positioned 4-thiouridines. Crosslinking of mRNA positions (+)11 to ribosomal protein (rp) rpS2(S5p) and rpS3(S3p), and (+)9-(+)11 and (+)8-(+)9 to h18 and h34 of 18S rRNA, respectively, indicated that mRNA enters the mRNA-binding channel through the same layers of rRNA and proteins as in prokaryotes. Upstream of the P-site, the proximity of positions (-)3/(-)4 to rpS5(S7p) and h23b, (-)6/(-)7 to rpS14(S11p), and (-)8-(-)11 to the 3'-terminus of 18S rRNA (mRNA/rRNA elements forming the bacterial Shine-Dalgarno duplex) also resembles elements of the bacterial mRNA path. In addition to these striking parallels, differences between mRNA paths included the proximity in eukaryotic initiation complexes of positions (+)7/(+)8 to the central region of h28, (+)4/(+)5 to rpS15(S19p), and (-)6 and (-)7/(-)10 to eukaryote-specific rpS26 and rpS28, respectively. Moreover, we previously determined that eukaryotic initiation factor2alpha (eIF2alpha) contacts position (-)3, and now report that eIF3 interacts with positions (-)8-(-)17, forming an extension of the mRNA-binding channel that likely contributes to unique aspects of eukaryotic initiation.


Study on the application of parent-of-origin specific DNA methylation markers to forensic genetics.
In paternity test, especially in motherless cases, the allele inherited from father (obligatory gene, OG) often cannot be determined. The paternity exclusion probability (PE) of a genetic marker is reduced considerably. Therefore, it is necessary to develop a new technique, by which the parental origin of alleles can be determined without genealogical analysis. In this paper, we explored the possibility of using parent-of-origin specific DNA methylation markers to determine the parental origin of alleles, choosing the imprinted single nucleotide polymorphism (SNP) locus rs220028 (A/G) as a model system. We typed the SNP by mutagenically separated PCR (MS-PCR). The frequencies of alleles were A = 0.5085, G = 0.4915; the unbiased heterozygosity was 0.5020. In order to discriminate between the maternal allele and paternal allele, post-digestion MS-PCR, a novel PCR based methylation analysis and SNP typing technique was developed and performed on 18 heterozygous children, and the methylated maternal allele was detected specifically. As a pilot study on the use of epigenetic markers in forensic genetics, our results demonstrated the feasibility of using parent-of-origin specific DNA methylation markers to determine the parental origin of alleles.


[Thoracic radiography is indicated in the examination of acute abdomen! The cause of abdominal symptoms may be found in the thorax].
Plain x-rays of the abdomen remain an integral feature of the diagnostic work-up in cases of acute abdomen. Chest x-rays, often recommended in the USA, are standard routine at only one third of Swedish radiology units. The article outlines the advantages of including chest x-ray in the abdominal examination: it facilitates the detection of pneumoperitoneum, it yields (pre-operative) cardiopulmonary information, and it may show abdominal pain to be of extra-abdominal aetiology. Regarding the latter point, a study of 555 cases showed the chest x-ray to yield valuable information in 14 cases.


Mapping the World Health Organization Disability Assessment Schedule (WHODAS 2.0) onto SF-6D Using Swedish General Population Data.
Mapping algorithms can be used for estimating quality-adjusted life years (QALYs) when studies apply non-preference-based instruments. In this study, we estimate a regression-based algorithm for mapping between the World Health Organization Disability Assessment Schedule (WHODAS 2.0) and the preference-based instrument SF-6D to obtain preference estimates usable in health economic evaluations. This was done separately for the working and non-working populations, as WHODAS 2.0 discriminates between these groups when estimating scores. Using a dataset including 2258 participants from the general Swedish population, we estimated the statistical relationship between SF-6D and WHODAS 2.0. We applied three regression methods, i.e., ordinary least squares (OLS), generalized linear models (GLM), and Tobit, in mapping onto SF-6D from WHODAS 2.0 at the overall-score and domain levels. Root mean squared error (RMSE) and mean absolute error (MAE) were used for validation of the models; R2 was used to assess model fit. The best-performing models for both the working and non-working populations were GLM models with RMSE ranging from 0.084 to 0.088, MAE ranging from 0.068 to 0.071, and R2 ranging from 0.503 to 0.608. When mapping from the WHODAS 2.0 overall score, the preferred model also included sex for both the working and non-working populations. When mapping from the WHODAS 2.0 domain level, the preferred model for the working population included the domains mobility, household activities, work/study activities, and sex. For the non-working population, the domain-level model included the domains mobility, household activities, participation, and education. It is possible to apply the derived mapping algorithms for health economic evaluations in studies using WHODAS 2.0. As conceptual overlap is incomplete, we recommend using the domain-based algorithms over the overall score. Different algorithms must be applied depending on whether the population is working or non-working, due to the characteristics of WHODAS 2.0.


Effects of temperature on the adults and progeny of the predaceous mite Lasioseius japonicus (Acari: Blattisociidae) fed on the cereal mite Tyrophagus putrescentiae (Acari: Acaridae).
The predatory mite Lasioseius japonicus Ehara is a newly recorded species in China that has been shown to have great potential as a biological control agent. The species is a soil-dwelling mite that is known to prey on various pests including economically important mites, fungus gnats and other terricolous arthropods. Considering that temperature is one of the most important factors affecting the population dynamics of arthropods, the development, survival and reproduction of L. japonicus were evaluated under indoor conditions at seven temperatures: 19, 22, 25, 28, 31, 34 and 37 °C, at 75% relative humidity and L0:D24 h photoperiod. The mites were fed on the cereal mite Tyrophagus putrescentiae (Schrank) and the data were analyzed using the two-sex life table. The results demonstrated that L. japonicus could complete their development and reproduce at temperatures between 19 and 34 °C, but were unsuccessful at 37 °C. Increasing temperature shortened the development time of the pre-adult stage and the average generation time (T). The life table parameters indicated that at temperatures from 22 to 31 °C the development rate and reproduction of L. japonicus were highest: at 22, 25, 28 and 31 °C the net reproduction rate (R0) was 55.5, 61.6, 61.2 and 59.0, respectively, and the average fecundity rate (F) was 81.7, 88.0, 102.0 and 86.8, respectively. The maximum values of intrinsic population growth rate (r) (0.341) and finite rate of increase (λ) (1.407) occurred at 31 °C.


Clinical and Multimodal Imaging Findings and Risk Factors for Ocular Involvement in a Presumed Waterborne Toxoplasmosis Outbreak, Brazil1.
In 2015, an outbreak of presumed waterborne toxoplasmosis occurred in Gouveia, Brazil. We conducted a 3-year prospective study on a cohort of 52 patients from this outbreak, collected clinical and multimodal imaging findings, and determined risk factors for ocular involvement. At baseline examination, 12 (23%) patients had retinochoroiditis; 4 patients had bilateral and 2 had macular lesions. Multimodal imaging revealed 2 distinct retinochoroiditis patterns: necrotizing focal retinochoroiditis and punctate retinochoroiditis. Older age, worse visual acuity, self-reported recent reduction of visual acuity, and presence of floaters were associated with retinochoroiditis. Among patients, persons >40 years of age had 5 times the risk for ocular involvement. Five patients had recurrences during follow-up, a rate of 22% per person-year. Recurrences were associated with binocular involvement. Two patients had late ocular involvement that occurred >34 months after initial diagnosis. Patients with acquired toxoplasmosis should have long-term ophthalmic follow-up, regardless of initial ocular involvement.


Dieulafoy disease of the bronchus involving bilateral arteries: A case report and literature review.
Dieulafoy disease of the bronchus is a rare vascular deformity. To the best of our knowledge, reports of these involving both lung vascular are hitherto absent. A 67-year-old male was admitted to our department due to agnogenic hemoptysis. Bronchoscopy was performed and some smooth, pulsatile nodular lesions were found in the middle and lower lobes, Computed tomography angiography of the bronchial artery confirmed a left bronchial artery arising from the aortic arch at T4 level, and both bronchial arteries were dilated and tortuous. Bronchial artery embolization was performed successfully. The patient was discharged with no hemoptysis. In addition, patient is under follow-up until today without any further incidents. This case reminds us that Dieulafoy disease of the bronchus could be a potential etiology for unexplained hemoptysis. The clinician should be aware of this disease when bronchoscopy revealed multiple some smooth, pulsatile nodular lesions, thereafter, bronchoscope biopsy should be avoided, as it could lead to fatal hemoptysis.


Synergistic Antiproliferative Effects of Combined γ -Tocotrienol and PPAR γ Antagonist Treatment Are Mediated through PPAR γ -Independent Mechanisms in Breast Cancer Cells.
Previous findings showed that the anticancer effects of combined γ -tocotrienol and peroxisome proliferator activated receptor γ (PPAR γ ) antagonist treatment caused a large reduction in PPAR γ expression. However, other studies suggest that the antiproliferative effects of γ -tocotrienol and/or PPAR γ antagonists are mediated, at least in part, through PPAR γ -independent mechanism(s). Studies were conducted to characterize the role of PPAR γ in mediating the effects of combined treatment of γ -tocotrienol with PPAR γ agonists or antagonists on the growth of PPAR γ negative +SA mammary cells and PPAR γ -positive and PPAR γ -silenced MCF-7 and MDA-MB-231 breast cancer cells. Combined treatment of γ -tocotrienol with PPAR γ antagonist decreased, while combined treatment of γ -tocotrienol with PPAR γ agonist increased, growth of all cancer cells. However, treatment with high doses of 15d-PGJ2, an endogenous natural ligand for PPAR γ , had no effect on cancer cell growth. Western blot and qRT-PCR studies showed that the growth inhibitory effects of combined γ -tocotrienol and PPAR γ antagonist treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and prostaglandin D2 (PGD2) synthesis. In conclusion, the anticancer effects of combined γ -tocotrienol and PPAR γ antagonists treatment in PPAR γ negative/silenced breast cancer cells are mediated through PPAR γ -independent mechanisms that are associated with a downregulation in COX-2, PGDS, and PGD2 synthesis.