LncRNA ANCR Suppresses the Progression of Hepatocellular Carcinoma Through the Inhibition of Wnt/β-Catenin Signaling Pathway.
Our study aimed to investigate the effect of anti-differentiation noncoding RNA (ANCR) on hepatocellular carcinoma (HCC) and its potential molecular mechanisms. The expression of ANCR was detected by qRT-RCR in both HCC tissues and HCC cells. Moreover, the relationship between ANCR expression and clinical parameters in HCC patients was investigated. The proliferation, cell clones, migration, invasion and apoptosis of MHCC97H and HCCLM3 cells were measured by MTT assay, colony formation assay, transwell assay and flow cytometry, respectively. The expressions of N-cadherin, vimentin, E-cadherin, cleaved caspase-3, Bax, Bcl-2, Wnt1, β-catenin and GSK-3β in MHCC97H and HCCLM3 cells were measured by Western blot. Our results showed that ANCR was lowly expressed in both HCC tissues and HCC cells. ANCR expression was closely associated with tumor size, tumor-node-metastasis (TNM) stages and vascular invasion in HCC. ANCR could dramatically inhibit cell proliferation, migration and invasion, as well as promote apoptosis in MHCC97H and HCCLM3 cells. ANCR could significantly increase the expression of cleaved caspase-3, Bax, E-cadherin and GSK-3β but reduce the expression of Bcl-2, N-cadherin, vimentin, Wnt1 and β-catenin in MHCC97H and HCCLM3 cells. In addition, Wnt/β-catenin pathway inhibitor (IWP-2) partially reversed the effects of silencing ANCR on the proliferation, migration, invasion and apoptosis of HCCLM3 cells. Our study demonstrated that ANCR can suppress cell proliferation, migration and invasion, as well as promote apoptosis of HCC cells via modulation of the Wnt/β-catenin signaling pathway.


Accuracy of postmortem radiography of excised air-inflated human lungs in assessment of pulmonary emphysema.
The accuracy of radiography of excised air-inflated lungs in assessing pulmonary emphysema at necropsy was evaluated in a series of 107 adults who had died in hospital by reading the radiographs and examining the pathological specimens independently. The radiographic and pathological assessments of the severity of emphysema correlated significantly (r = 0.87, p less than 0.0001). Mild emphysema was recognised radiographically in 88.7% and moderate in 94.9% of the lungs. One of 16 normal lungs (6.3%) was radiographically diagnosed as showing mild emphysema. Six out of 53 lungs (11.3%) with mild emphysema were radiographically assessed as normal. The correct radiographic recognition of the type of emphysema was possible in 86% of lungs with mild and 97.4% with moderate centrilobular emphysema and in 81.8% and 87.5% respectively of the lungs with mild and moderate paracicatricial emphysema, but in only 25.0% and 28.6% of the lungs with mild and moderate panlobular emphysema. Radiographical diagnosis of centrilobular and paracicatricial emphysema was verified pathologically in all lungs showing mild emphysema, but that of panlobular emphysema in only 66.7%. Radiography of excised air-inflated lungs is a rapid, convenient, and reliable method of recognising and assessing the severity of appreciable degrees of centrilobular and paracicatricial emphysema, but less reliable in recognising panlobular emphysema. After the procedure the specimen remains available for almost any other technique.


Complications associated with different insertion techniques for Hickman catheters.
A dependable central venous access is an essential prerequisite for the delivery of care to the cancer patients. This has become easier since the introduction of indwelling central venous catheters. However, pancytopenia, often encountered in haematological malignancies, does influence the morbidity associated with these catheters. In this study the effects of two different placement techniques of Hickman catheters were evaluated. A total of 177 Hickman catheters were inserted in patients suffering from haematological malignancies. In 112 patients the catheters were placed percutaneously into subclavian veins without prior tunnelling; in the other 65 patients these were introduced, after having been tunnelled, into cephalic/external jugular veins by a cut-down technique. The catheters remained in use in each patient for between 18 and 253 days. Excessive bleeding and haematoma formation occurred in a significantly higher proportion of patients from the cut-down group (61% and 41%, respectively) compared to patients from the percutaneous group (8% and 0%, respectively). These in turn had a profound impact on the incidence of infective complications. Catheter exit site infection, tunnel infection and septicaemia were observed in 26%, 18%, and 41%, respectively, of the patients from the cut-down group, while in patients from the percutaneous group, skin exit site infection was noted only in 7% and septicaemia in 19% of patients. It was concluded that the placement technique of these catheters exerts a significant influence on the immediate as well as delayed complications. The results indicate that the insertion technique requiring minimal dissection is more beneficial. It is therefore recommended that percutaneous insertion without tunnelling should be the technique of choice for catheter placement.


Mitochondrial DNA response to high altitude: a new perspective on high-altitude adaptation.
Mitochondria are the energy metabolism centers of the cell. More than 95% of cellular energy is produced by mitochondrial oxidative phosphorylation. Hypoxia affects a wide range of energy generation and consumption processes in animals. The most important mechanisms limiting ATP consumption increase the efficiency of ATP production and accommodate the reduced production of ATP by the body. All of these mechanisms relate to changes in mitochondrial function. Mitochondrial function can be affected by variations in mitochondrial DNA, including polymorphisms, content changes, and deletions. These variations play an important role in acclimatization or adaptation to hypoxia. In this paper, the association between mitochondrial genome sequences and high-altitude adaptation is reviewed.


How can we meet the health needs of child refugees, asylum seekers and undocumented migrants?
The numbers of people forcibly displaced from their homes because of conflict, persecution, natural disasters and famine is increasing globally, reaching 68.5 million at the end of 2017. Over half of the world's refugees are children. Child refugees, asylum seekers and undocumented migrants are exposed to multiple risk factors for poor physical and mental health throughout their migration experience. International treaties and national legislation recognise child migrants' 'right to health' and equitable access to healthcare, yet restrictive immigration policies, health system challenges and service provider barriers to care impede translation into practice. This review explores how the experiences of child refugees, asylum seekers and undocumented migrants in England impacts on their health and presents recommendations as to how their health needs can be met.


Variations in the force applied to flexion tests of the distal limb of horses.
A pressure-sensitive device was developed to measure the force applied to flexion tests of the distal limb of horses. The mean force applied by a group of experienced clinicians was 150 N which results in a moment on the flexed fetlock joint of about 28.5 Nm. The coefficient of variation of the force applied by one experienced clinician was only about 12 per cent, but the coefficient of variation between clinicians was considerably higher (20 per cent), irrespective of whether the clinicians were considered to be experienced or not. The mean force applied by a group of women examiners (114 N) was significantly lower than that applied by the group of male examiners. It is concluded that the flexion test used in the clinical examination of the locomotor system of the horse should be better standardised.


FixclipsTM - biological internal fixator for upper femoral osteotomies in cerebral palsy.
We describe the technique and results of 63 proximal femoral osteotomies in 39 cerebral palsy patients performed with the Fixclip (Corifix, Cirencester, UK) internal fixator system. Post-operative splintage was determined by soft tissue requirements and not to protect the femoral osteotomy. Three patients needed revision surgery for readjustment of the device and two patients had superficial infections. All osteotomies except one healed by 12-16 weeks. There were no mal-unions, or avascular necrosis. One patient had a non-union that united after revision surgery. The Fixclip system is modular and easily adjustable. The fixation, sitting just off the bone, is less disturbing to the periosteal blood supply and lateralises the fixation, like a wave plate, to load both the medial and lateral femoral cortices on weight-bearing. Compared to the other available fixation implants, Fixclips are biologically and mechanically very effective and well suited in cerebral palsy patients where rigid fixation with a plate can cause extensive loss of bone mass. (Hip International 2002; 12: 314-9).


Diffraction-based femtosecond pulse shaping with a two-dimensional spatial light modulator.
A new diffraction-based method is proposed and demonstrated for simultaneous shaping of both the phase and amplitude of femtosecond laser pulses by use of a phase-only two-dimensional spatial light modulator. The method suppresses certain types of temporal replica features ordinarily observed in femtosecond pulse shaping owing to imperfections in modulator devices and allows for multiplexed outputs suitable for use in various applications.


Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity.
Monocarboxylate transporter 4 (MCT4) is a pH-dependent bi-directional lactate transporter. Transport of lactate via MCT4 is increased by extracellular acidification. We investigated the critical histidine residue involved in pH regulation of MCT4 function. Transport of lactate via MCT4 was measured by using a Xenopus laevis oocyte expression system. MCT4-mediated lactate transport was inhibited by Zn2+ in a pH physiological condition but not in an acidic condition. The histidine modifier DEPC (diethyl pyrocarbonate) reduced MCT4 activity but did not completely inactivate MCT4. After treatment with DEPC, pH regulation of MCT4 function was completely knocked out. Inhibitory effects of DEPC were reversed by hydroxylamine and suppressed in the presence of excess lactate and Zn2+. Therefore, we performed an experiment in which the extracellular histidine residue was replaced with alanine. Consequently, the pH regulation of MCT4-H382A function was also knocked out. Our findings demonstrate that the histidine residue His382 in the extracellular loop of the transporter is essential for pH regulation of MCT4-mediated substrate transport activity.


Does operative fixation of an osteochondritis dissecans loose body result in healing and long-term maintenance of knee function?
Osteochondritis dissecans (OCD) can progress to loose body formation, resulting in a grade IV defect. The decision to fix versus excise the loose body is controversial. Published operative fixation outcomes are small case series with short follow-up. Operative fixation (ORIF) of the loose body into the grade IV defect will heal and approximate "normal" knee function at long-term follow-up. Case series; Level of evidence, 4. Twelve patients were identified who underwent ORIF of a knee OCD loose body into the grade IV osteochondral defects ranging in size from 2.0 to 8.0 cm(2) (mean, 3.5 cm(2)). After 12 weeks, hardware was removed, and healing was assessed. Long-term outcomes were assessed with a Knee injury and Osteoarthritis Outcome Score (KOOS) and a Marx activity score. Arthroscopy for screw removal revealed stable healing in 92% (11 of 12) of patients. No patients required subsequent surgery for a loose body. At an average of 9.2 years' follow-up (range, 3.8-15.8 years), 83% (10 of 12) of patients completed the KOOS. The KOOS subscale scores for pain (mean, 87.8; range, 67-100), other symptoms (mean, 81.8; range, 61-96), function in activities of daily living (mean, 93.1; range, 72-100), and sports and recreation function (mean, 74.0; range, 40-100) were not significantly lower than those of published age-matched controls. However the KOOS subscale score for knee-related quality of life (mean, 61.9; range, 31-88) was significantly lower (P = .003). Operative fixation of grade IV OCD loose bodies results in stable fixation. At an average 9 years after surgery, patients did not have symptoms of osteoarthritis pain and had normal function in activities of daily life. However, patients reported significantly lower knee-related quality of life. Operative fixation of OCD loose bodies is a better alternative to lesion excision.


A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis.
Genes controlling muscle size and survival play important roles in muscle wasting diseases. In Drosophila melanogaster metamorphosis, larval abdominal muscles undergo two developmental fates. While a doomed population is eliminated by cell death, another persistent group is remodelled and survives into adulthood. To identify and characterize genes involved in the development of remodelled muscles, we devised a workflow consisting of in vivo imaging, targeted gene perturbation and quantitative image analysis. We show that inhibition of TOR signalling and activation of autophagy promote developmental muscle atrophy in early, while TOR and yorkie activation are required for muscle growth in late pupation. We discovered changes in the localization of myonuclei during remodelling that involve anti-polar migration leading to central clustering followed by polar migration resulting in localization along the midline. We demonstrate that the Cathepsin L orthologue Cp1 is required for myonuclear clustering in mid, while autophagy contributes to central positioning of nuclei in late metamorphosis. In conclusion, studying muscle remodelling in metamorphosis can provide new insights into the cell biology of muscle wasting.


Stimulation of mitogen-activated protein kinase activity by different secretory stimuli in rat basophilic leukemia cells.
Ag-induced cross-linking of IgE bound to its high affinity receptor (Fc epsilon RI) at the surface of basophils or mast cells triggers a number of biochemical events culminating in the release of several inflammatory mediators. In rat basophilic leukemia (RBL-2H3) cells expressing the G protein-coupled m1 muscarinic receptor, Ag/IgE-induced cross-linking of Fc epsilon RI, calcium ionophore A23187, and carbachol through M1 receptors stimulated tyrosine phosphorylation of several proteins, including two of 42 and 44 kDa. Proteins of identical molecular masses were recognized by anti-MAP-kinase antibodies, and these immunoreactive proteins exhibited in part a slightly increased molecular mass on SDS polyacrylamide gels after incubation of cells with secretory stimuli. All stimuli led to the activation of MAP kinase, which co-purified on Mono Q chromatography with 42- and 44-kDa proteins, which were tyrosine phosphorylated in response to secretory stimuli and reacted with anti-(MAP kinase) antibodies. Finally, 42- and 44-kDa proteins immunoprecipitated by anti-MAP-kinase antibodies and anti-phosphotyrosine antibodies were recognized by anti-phosphotyrosine and anti-MAP-kinase antibodies, respectively. Primarily threonine and tyrosine residues were found to be phosphorylated in 42- and 44-kDa proteins immunoprecipitated from [32P]phosphate-labeled cells that had been treated with secretory stimuli. The dose dependence of secretagogue-induced MAP kinase activation correlated with that of increases in serotonin release from activated cells, and the maximum of MAP kinase activation coincided with the maximum rate of secretion. Down-regulation or inhibition of protein kinase C as well as incubation of cells with the tyrosine kinase inhibitor genistein markedly inhibited MAP kinase activation in parallel with serotonin release. Taken together, these findings demonstrate that 42- and 44-kDa MAP kinases are activated in response to secretory stimuli and provide some evidence for a functional link between MAP kinase activation and signaling events leading to mediator release in RBL cells.


A family with mental retardation, variable macrocephaly and macro-orchidism, and linkage to Xq12-q21.
A family with X linked inheritance of mental retardation (XLMR) is presented. There are 10 mentally retarded males and two affected females in two generations. There are four obligatory carriers, one of whom is described as "slow". Most affected males show macrocephaly and macro-orchidism, which are typical signs of the fragile X syndrome, but have been tested cytogenetically and by analysis of the FMR1 gene and do not have this syndrome. However, some normal males in the family also exhibit macro-orchidism and macrocephaly. Linkage analysis using markers derived from the X chromosome indicates that the causative gene in this family is located in the proximal long arm of the X chromosome, in the interval Xp11-q21. Maximum lod scores of 2.96 with no recombination were found at three loci in Xq13-q21: DXS1111, DXS566, and DXS986. Recombination was observed with DXS1002 (Xq21.31) and DXS991 (Xp11.2), loci separated by about 30 Mb. Although isolation of the gene in this family will be difficult because of the size of the region involved, the localisation should be helpful in investigating other similar families with XLMR, macrocephaly, and macro-orchidism not attributable to FMR1.


A link between chronic asthma and chronic infection.
Asthma is a prevalent disease with marked effects on quality of life and economic societal burden. However, the cause of asthma and its pathophysiology are not completely defined. Recently, the possibility that chronic infection may play a role has been suggested. We sought to define the association between Mycoplasma and Chlamydia species and chronic asthma. We performed a comparison study of asthmatic patients and normal control subjects. Fifty-five patients with chronic stable asthma were compared with 11 normal control subjects by using PCR, culture, and serology for Mycoplasma species, Chlamydia species, and viruses from the nasopharynx, lung, and blood. Bronchoalveolar lavage cell count and differential, as well as tissue morphometry, were also evaluated. Computer-generated scoring for the degree of chronic sinusitis in asthmatic patients was additionally evaluated. Thirty-one of 55 asthmatic patients had positive PCR results for Mycoplasma (n = 25) or Chlamydia species (n = 6), which were mainly found on lung biopsy specimens or in lavage fluid. Only 1 of 11 normal control subjects had positive PCR results for Mycoplasma species. The distinguishing phenotype between asthmatic patients with positive and negative PCR results was the significantly greater number of tissue mast cells in the group with positive results. A significant number of patients with chronic stable asthma demonstrate the presence of Mycoplasma species, Chlamydia species, or both in their airways, with the distinguishing feature of increased mast cell number. These findings need further delineation but may help us to understand the pathophysiology of asthma and new treatment options.


Toxicity of medical glove materials: a pilot study.
Cytotoxicity of 14 glove materials representing 4 natural rubber latex, 6 synthetic rubber and 4 synthetic polymeric materials was evaluated using dimethylthiazol diphenyltetrazolium (MTT), agar overlay and filter diffusion tests. Cell responses after contact with extracts of glove materials and contact with glove materials were assessed. One synthetic rubber glove (nitrile rubber) and 2 synthetic polymeric gloves (polyvinyl chloride) were non-toxic in all 3 tests, while 5 synthetic rubbers exhibited varying degrees of cytotoxicity, depending on the test. A severe cytotoxic response to both extracts of natural rubber latex materials and contact with natural rubber latex was verified in the 3 tests, indicating a need for consideration when selecting gloves, or other products, used in close skin contact.


Photoreceptor cell death by apoptosis in dogs with sudden acquired retinal degeneration syndrome.
To examine the role of apoptosis in retinal photoreceptor degeneration in dogs with sudden acquired retinal degeneration syndrome (SARDS). Retinas from 3 dogs with SARDS and from 2 clinically normal adult dogs. Apoptosis was identified by in situ end-labeling and observation of characteristic morphologic changes by light microscopy. The degree of photoreceptor degeneration varied with duration of vision loss in SARDS-affected eyes. The retina of all 3 SARDS-affected eyes had numerous (34, 61, and 70) apoptotic nuclei per section that were overwhelmingly located in the outer nuclear layer. Apoptotic nuclei were not detected, or were rare in similarly sized retinal sections from normal dogs. Inflammation was not an important feature of SARDS. Apoptosis appears to be at least 1 mechanism of photoreceptor cell death in dogs with SARDS. Because apoptosis appears to be a final common pathway in many retinal degeneration syndromes, future treatment strategies that control apoptosis in other diseases may be applicable to dogs with SARDS. Halting this pathway may allow some photoreceptors to survive and, perhaps, preserve vision.


Designing and regulating health insurance exchanges: lessons from Massachusetts.
The Massachusetts health care reform provides preliminary evidence on the function of health insurance exchanges and individual insurance markets. This paper describes the type of products consumers choose and the dynamics of consumer choice. Evidence shows that choice architecture, including product standardization and the use of heuristics (rules of thumb), affects choice. In addition, while consumers often choose less generous plans in the exchange than in traditional employer-sponsored insurance, there is considerable heterogeneity in consumer demand, as well as some evidence of adverse selection. We examine the role of imperfect competition between insurers, and document the impact of pricing and product regulation on the level and distribution of premiums. Given our extensive choice data, we synthesize the evidence of the Massachusetts exchange to inform the design and regulation on other exchanges.


[Cutaneous metastases of rectal cancer].
Colorectal carcinoma is a tumour that very infrequently gives rise to cutaneous metastases and when it does so, it is rarely via the haematogenous route. We present the case of a 55-year old male diagnosed with an adenocarcinoma of the rectum (lower third), clinical stage T3N2M0. Initially treated with neoadjuvant radiochemotherapy, he was operated on eight weeks later, with an extended abdominoperineal amputation. The anatomopathological result was mucinous adenocarcinoma of the rectum, clinical stage ypT3bN1. Following a postoperative period without complications, the patient received chemotherapeutic treatment with capecitabine. Eighteen months later the patient reported the progressive appearance of subcutaneous nodules in different localizations. In the computerized tomography test multiple images were objectivized suggesting metastasis at the hepatic and pulmonary levels, as well as subcutaneous lesions. The biopsy-excision of one of the subcutaneous nodules corroborated the suspicion of metastasis of the adenocarcinoma of the rectum. Chemotherapy treatment was considered for the patient, which was not administered due to the rapid deterioration of the patient leading to his death.


[Possibility of obtaining the anaform of E. coli enterotoxin].
The nontoxic (on the model of raw edema in white mice) anaform of E. coli enterotoxin was obtained under the action of heat and formalin. In the process of detoxication the charge of the enterotoxin molecules was changed. The toxoid thus obtained preserved the antigenic activity of the initial preparation and, when used for the immunization of rabbits, stimulated the production of active antitoxic sera.


Patient-Reported Outcomes in an Observational Cohort of HIV-1-Infected Adults on Darunavir/Cobicistat-Based Regimens: Beyond Viral Suppression.
This prospective, multicenter, non-interventional cohort study enrolling human immunodeficiency virus (HIV)-1-infected, virally suppressed adult outpatients in Italy aimed to describe results obtained from patient-reported outcome questionnaires regarding treatment satisfaction and symptom perceptions in HIV-1-positive patients who switched to cobicistat-boosted darunavir antiretroviral regimens, coming from ritonavir-boosted protease inhibitors. Patients entered this study between June 2016 and February 2017, once their treating physician had considered them eligible for cobicistat-boosted darunavir-based treatment as per clinical practice. Patients' satisfaction regarding regimen and current symptom burdens were assessed using two previously validated, patient-reported outcome questionnaires: HIV Treatment Satisfaction Questionnaire (HIV-TSQ) and HIV Symptoms Distress Module (HIV-SDM). These questionnaires were administered at prespecified time-points: enrollment (Visit 1), 4-8 weeks later (Visit 2), and 48 ± 6 weeks after study enrollment (Visit 4). Data of patient-reported outcome total scores for both questionnaires are presented as median with 25th-75th percentiles. Questionnaires scores were analyzed overall and stratified by gender when applicable. A p value of less than 0.05 was considered statistically significant. A sensitivity analysis was conducted to evaluate the role of lost to follow-up, using the "last observation carried forward" method. A total of 348 patients were enrolled in this study; 296 patients (208 male and 88 female) provided both evaluable HIV-TSQ and HIV-SDM at enrollment and at 4-8 weeks, while 250 patients (174 male and 76 female) provided questionnaire data at enrollment and at 48 ± 6 weeks. The total scores of HIV-TSQ showed improvements in patient satisfaction in the overall population both at Visit 2 and Visit 4 (p < 0.001, sign test) and also when stratified by gender throughout the study period. In addition, the overall burden of symptoms, as shown by the HIV-SDM scores, decreased. Switching to a cobicistat-boosted darunavir-based therapy led to overall increased patient satisfaction and reduced symptom burden when compared with previous regimens. The use of patient-reported outcomes in clinical daily practice could provide a useful tool towards achieving guideline goals to achieve "fourth 90", having 90% of virally suppressed patients with a good health-related quality of life.


Regulation of Wnt signaling by Sox proteins: XSox17 alpha/beta and XSox3 physically interact with beta-catenin.
Using a functional screen in Xenopus embryos, we identified a novel function for the HMG box protein XSox17 beta. Ectopic expression of XSox17 beta ventralizes embryos by inhibiting the Wnt pathway downstream of beta-catenin but upstream of the Wnt-responsive gene Siamois. XSox17 beta also represses transactivation of a TCF/LEF-dependent reporter construct by Wnt and beta-catenin. In animal cap experiments, it both activates transcription of endodermal genes and represses beta-catenin-stimulated expression of dorsal genes. The inhibition activity of XSox17 beta maps to a region C-terminal to the HMG box; this region of XSox17 beta physically interacts with the Armadillo repeats of beta-catenin. Two additional Sox proteins, XSox17 alpha and XSox3, likewise bind to beta-catenin and inhibit its TCF-mediated signaling activity. These results reveal an unexpected mechanism by which Sox proteins can modulate Wnt signaling pathways.


Timing of antisynchronous calling: A case study in a harbor seal pup (Phoca vitulina).
Alternative mathematical models predict differences in how animals adjust the timing of their calls. Differences can be measured as the effect of the timing of a conspecific call on the rate and period of calling of a focal animal, and the lag between the two. Here, I test these alternative hypotheses by tapping into harbor seals' (Phoca vitulina) mechanisms for spontaneous timing. Both socioecology and vocal behavior of harbor seals make them an interesting model species to study call rhythm and timing. Here, a wild-born seal pup was tested in controlled laboratory conditions. Based on previous recordings of her vocalizations and those of others, I designed playback experiments adapted to that specific animal. The call onsets of the animal were measured as a function of tempo, rhythmic regularity, and spectral properties of the playbacks. The pup adapted the timing of her calls in response to conspecifics' calls. Rather than responding at a fixed time delay, the pup adjusted her calls' onset to occur at a fraction of the playback tempo, showing a relative-phase antisynchrony. Experimental results were confirmed via computational modeling. This case study lends preliminary support to a classic mathematical model of animal behavior-Hamilton's selfish herd-in the acoustic domain. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assessing the invariance of a culturally competent multi-lingual unmet needs survey for immigrant and Australian-born cancer patients: a Rasch analysis.
The purpose of this study was to assess the invariance of a culturally competent multi-lingual unmet needs survey. A cross-sectional study was conducted among immigrants of Arabic-, Chinese- and Greek-speaking backgrounds, and Anglo-Australian-born controls, recruited through Cancer Registries (n = 591) and oncology clinics (n = 900). The survey included four subscales, with newly developed items addressing unmet need in culturally competent health information and patient support (CCHIPS), and items adapted from existing questionnaires addressing physical and daily living (PDL), sexuality (SEX) and survivorship (SURV) unmet need. The survey was translated into Arabic, Chinese and Greek. Rasch analysis was carried out on the four domains. Whilst many items were mistargeted to less prevalent areas of unmet need, causing substantial floor effects in person estimates, reliability indices were acceptable. The CCHIPS domain showed differential item functioning (DIF) for cultural background and language, and the PDL domain showed DIF for treatment phase and gender. The results for SEX and SURV domains were limited by floor effects and missing responses. All domains showed adequate fit to the model after DIF was resolved and a small number of items were deleted. The study highlights the intricacies in designing a culturally competent survey that can be applied to culturally and linguistically diverse groups across different treatment contexts. Overall, the results demonstrate that this survey is somewhat invariant with respect to these factors. Future refinements are suggested to enhance the survey's cultural competence and general validity.


Visual recovery after transsphenoidal removal of pituitary adenomas.
We reviewed the records of 100 consecutive patients with histologically verified pituitary adenomas who underwent transsphenoidal decompression of the optic nerves and chiasm. The patients' ages ranged from 18 to 80 years, with a median of 52 years. Preoperatively, all patients had objective signs of visual acuity or field defects. Postoperatively, visual acuity was normal or improved in 79% of the eyes and the visual fields were normal or improved in 74%. The visual outcome (for both acuity and fields) was better in younger patients and those with a shorter duration of symptoms. Patients with lesser degrees of preoperative visual acuity compromise had better postoperative visual acuity outcome. However, the severity of preoperative visual field defects did not seem to predict postoperative field outcome, and even patients with severe preoperative field defects often had striking postoperative improvement. Patients who had undergone prior operation were less likely to have either visual acuity or visual field improvement after reoperation. Postoperative deterioration in visual acuity was noted in only 5 patients (6 eyes). Complications were few. There were 4 instances of cerebrospinal fluid rhinorrhea, but only 2 patients needed operative repair. There was no instance of permanent diabetes insipidus, although 17 patients developed transient diabetes insipidus. In most cases, visual improvement was sustained. The average duration of follow-up was 26 months. Three patients required a subsequent operation to correct visual loss in the immediate postoperative period, but only 1 patient has undergone late operation for recurrence of tumor. There was no operative mortality.


Maximum-entropy calculation of the electron density at 4 A resolution of Pf1 filamentous bacteriophage.
A 4 A electron-density map of Pf1 filamentous bacterial virus has been calculated from x-ray fiber diffraction data by using the maximum-entropy method. This method produces a map that is free of features due to noise in the data and enables incomplete isomorphous-derivative phase information to be supplemented by information about the nature of the solution. The map shows gently curved (banana-shaped) rods of density about 70 A long, oriented roughly parallel to the virion axis but slewing by about 1/6th turn while running from a radius of 28 A to one of 13 A. Within these rods, there is a helical periodicity with a pitch of 5 to 6 A. We interpret these rods to be the helical subunits of the virion. The position of strongly diffracted intensity on the x-ray fiber pattern shows that the basic helix of the virion is right handed and that neighboring nearly parallel protein helices cross one another in an unusual negative sense.


Recent progress on methods for estimating and updating large phylogenies.
With the increased availability of sequence data and even of fully sequenced and assembled genomes, phylogeny estimation of very large trees (even of hundreds of thousands of sequences) is now a goal for some biologists. Yet, the construction of these phylogenies is a complex pipeline presenting analytical and computational challenges, especially when the number of sequences is very large. In the past few years, new methods have been developed that aim to enable highly accurate phylogeny estimations on these large datasets, including divide-and-conquer techniques for multiple sequence alignment and/or tree estimation, methods that can estimate species trees from multi-locus datasets while addressing heterogeneity due to biological processes (e.g. incomplete lineage sorting and gene duplication and loss), and methods to add sequences into large gene trees or species trees. Here we present some of these recent advances and discuss opportunities for future improvements. This article is part of a discussion meeting issue 'Genomic population structures of microbial pathogens'.


Hip arthroplasty after extracapsular hip fracture: a matched pair cohort analysis.
Eighteen patients with a prior intertrochanteric or basicervical hip fracture had a total or bipolar hip arthroplasty. The clinical and radiographic results of these patients were compared to a control group of patients (matched for age, gender, associated diagnoses, and length of follow-up) who had a primary total hip arthroplasty. There was a significant increase in intraoperative blood loss, operative time, and number of units of blood transfused in the fracture group compared to the primary arthroplasty group. The mean preoperative Harris hip scores were not significantly different between the two groups, but the postoperative scores were significantly lower for the fracture group (p < .001). There was no notable difference in the rates of radiographic loosening or heterotopic ossification between the two groups. The results of this study suggest that patients should be counseled preoperatively that the functional outcome of hip arthroplasty after internal fixation of extracapsular hip fractures is decreased compared to control patients with a primary total hip arthroplasty.


Russell-Silver syndrome and hypopituitarism. Patient report and literature review.
Russell-Silver syndrome (RSS) is a sporadic form of prenatal onset dwarfism with typical facial features, variable asymmetry, and linear growth 3 to 4 SDs below the mean. Endocrinologic studies are usually normal; however, six cases of RSS with growth hormone deficiency have been reported, three of which had additional pituitary abnormalities. We describe another case, a 7-year-old girl with RSS and deficiencies of growth hormone, corticotropin, and thyroid-stimulating hormone. Replacement therapy including growth hormone resulted in an improved growth velocity, though twice the usual dose of growth hormone was required and short stature persisted. Since growth hormone secretion is usually normal in RSS, the existence of individuals with RSS phenotype and hypopituitarism including growth hormone deficiency suggests etiologic heterogeneity. We recommend that those individuals with RSS phenotype and a continuous significant decline in height velocity be investigated for pituitary abnormalities. Unusually high replacement doses of growth hormone may be required to overcome deficiency.


Shoulder impingement syndrome in relation to shoulder intensive work.
To analyse the risk of shoulder impingement syndrome relative to shoulder intensive work. A cross sectional study of a historical cohort of 1591 workers employed between 1986 and 1993 at a slaughterhouse or a chemical factory. Workers not doing tasks in slaughtering or meat processing constituted the reference group. Intensity of shoulder work in meat processing tasks was assessed by video based observations. Information on shoulder disorders was collected by questionnaire and by physical examinations. Impingement syndrome was diagnosed when shoulder symptoms had been present for at least 3 months during the past year and there were signs of subacromial impingement in the corresponding shoulder at physical examination. Shoulder function was assessed at the same occasion with the Constant scoring technique. Prevalence of shoulder impingement syndrome was analysed according to job title and cumulative exposure. Prevalence ratio for shoulder impingement syndrome was 5.27 (95% confidence interval (95% CI), 2.09 to 12.26) among currently working and 7.90 (95% CI, 2.94 to 21.18) among former slaughterhouse workers. Transformed model based prevalence ratios according to years in slaughterhouse work showed an overall association between cumulative exposure and risk for shoulder impingement syndrome. This study supports the hypothesis that shoulder intensive work is a risk factor for impingement syndrome of the shoulder. Despite the historical cohort design healthy worker selection may have influenced the exposure-response relation found.


PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone.
Midzone microtubules of mammalian cells play an essential role in the induction of cell cleavage, serving as a platform for a number of proteins that play a part in cytokinesis. We demonstrate that PRC1, a mitotic spindle-associated Cdk substrate that is essential to cell cleavage, is a microtubule binding and bundling protein both in vivo and in vitro. Overexpression of PRC1 extensively bundles interphase microtubules, but does not affect early mitotic spindle organization. PRC1 contains two Cdk phosphorylation motifs, and phosphorylation is possibly important to mitotic suppression of bundling, as a Cdk phosphorylation-null mutant causes extensive bundling of the prometaphase spindle. Complete suppression of PRC1 by siRNA causes failure of microtubule interdigitation between half spindles and the absence of a spindle midzone. Truncation mutants demonstrate that the NH2-terminal region of PRC1, rich in alpha-helical sequence, is important for localization to the cleavage furrow and to the center of the midbody, whereas the central region, with the highest sequence homology between species, is required for microtubule binding and bundling activity. We conclude that PRC1 is a microtubule-associated protein required to maintain the spindle midzone, and that distinct functions are associated with modular elements of the primary sequence.


Structure and function of the N-terminal nucleolin binding domain of nuclear valosin-containing protein-like 2 (NVL2) harboring a nucleolar localization signal.
The N-terminal regions of AAA-ATPases (ATPase associated with various cellular activities) often contain a domain that defines the distinct functions of the enzymes, such as substrate specificity and subcellular localization. As described herein, we have determined the solution structure of an N-terminal unique domain isolated from nuclear valosin-containing protein (VCP)-like protein 2 (NVL2(UD)). NVL2(UD) contains three α helices with an organization resembling that of a winged helix motif, whereas a pair of β-strands is missing. The structure is unique and distinct from those of other known type II AAA-ATPases, such as VCP. Consequently, we identified nucleolin from a HeLa cell extract as a binding partner of this domain. Nucleolin contains a long (∼300 amino acids) intrinsically unstructured region, followed by the four tandem RNA recognition motifs and the C-terminal glycine/arginine-rich domain. Binding analyses revealed that NVL2(UD) potentially binds to any of the combinations of two successive RNA binding domains in the presence of RNA. Furthermore, NVL2(UD) has a characteristic loop, in which the key basic residues RRKR are exposed to the solvent at the edge of the molecule. The mutation study showed that these residues are necessary and sufficient for nucleolin-RNA complex binding as well as nucleolar localization. Based on the observations presented above, we propose that NVL2 serves as an unfoldase for the nucleolin-RNA complex. As inferred from its RNA dependence and its ATPase activity, NVL2 might facilitate the dissociation and recycling of nucleolin, thereby promoting efficient ribosome biogenesis.


Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study.
Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973-2011), and Linköping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106-1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.


Anatomical investigations on root, stem, and leaf of Gentiana olivieri Griseb.
Gentiana olivieri Griseb. (Afat) (Gentianaceae), which has many bioactive compounds is used as antidiabetic, hepatoprotective, digestive aid, antidepressant, and antianemic in traditional medicine. Root, stem, and leaf sections of G. olivieri were taken free hand or by sliding microtome and examined on light microscope. Anatomical characters of the species were observed to be similar to the usual features of Gentianaceae anatomy. Intraxylary phloem, which was primarily the distinguishing feature between Gentianoideae and Menyanthoideae sub-families was observed in G. olivieri roots.


Relationship between primary open angle glaucoma and blood pressure.
Background: Glaucoma is commonly defined as high intra ocular pressure (≥21 mmHg) with optic neuropathy characterised by progressive loss of retinal ganglion cells which is associated with characteristic structural damage to the optic nerve and visual field loss. There are several studies investigating relation between primary open angle glaucoma (POAG) and both systemic hypertension and especially night hypotension. Our aim was to compare 24-h ambulatory blood pressure variability of patients with glaucoma followed-up in the eye outpatient clinic with that of patients free of glaucoma.Methods: A total of 75 patients were included in the study, 35 in the patient group and 40 in the control group. Both groups were compared for daytime, night-time, and whole day mean systolic and diastolic blood pressure (BP) readings in the ambulatory blood pressure testing.Results: Mean daytime systolic BP of the glaucoma patients was 119.5 ± 11.6 mmHg, and 128.3 ± 15.5 mmHg for control group (p = 0.008). The night-time systolic blood pressure, whole day systolic BP, and mean diastolic BP were significantly lower in patients with glaucoma (p = 0.001, p = 0.001, p = 0.028, respectively). In multiple regression analysis, we identified daytime systolic BP, night-time systolic BP, and whole day systolic BP were independent risk factors for developing glaucoma.Conclusion: If the progression of the disease is noticeable in patients with glaucoma at follow-up, night-time hypotension should be ruled out with ambulatory blood pressure and if this is observed medical treatments used by the patients should be reviewed and necessary measures should be taken.


Nonunions of fractures of the proximal and distal thirds of the shaft of the femur.
Subtrochanteric and supracondylar fractures of the femur are challenging, and specific anatomic and mechanical problems make fixation precarious. With careful selection of devices and techniques, nonunions may be avoided. Nonunion treatment requires strong immobilization and osteogenesis stimulation with bone grafts. Non-invasive and semi-invasive salvage systems are not as effective as invasive procedures. The first goal of salvage is union. Joint function and muscle strength are secondary goals to be achieved later.


Multivariate syndromic surveillance for cattle diseases: Epidemic simulation and algorithm performance evaluation.
Multivariate Syndromic Surveillance (SyS) systems that simultaneously assess and combine information from different data sources are especially useful for strengthening surveillance systems for early detection of infectious disease epidemics. Despite the strong motivation for implementing multivariate SyS and there being numerous methods reported, the number of operational multivariate SyS systems in veterinary medicine is still very small. One possible reason is that assessing the performance of such surveillance systems remains challenging because field epidemic data are often unavailable. The objective of this study is to demonstrate a practical multivariate event detection method (directionally sensitive multivariate control charts) that can be easily applied in livestock disease SyS, using syndrome time series data from the Swiss cattle population as an example. We present a standardized method for simulating multivariate epidemics of different diseases using four diseases as examples: Bovine Virus Diarrhea (BVD), Infectious Bovine Rhinotracheitis (IBR), Bluetongue virus (BTV) and Schmallenberg virus (SV). Two directional multivariate control chart algorithms, Multivariate Exponentially Weighted Moving Average (MEWMA) and Multivariate Cumulative Sum (MCUSUM) were compared. The two algorithms were evaluated using 12 syndrome time series extracted from two Swiss national databases. The two algorithms were able to detect all simulated epidemics around 4.5 months after the start of the epidemic, with a specificity of 95%. However, the results varied depending on the algorithm and the disease. The MEWMA algorithm always detected epidemics earlier than the MCUSUM, and epidemics of IBR and SV were detected earlier than epidemics of BVD and BTV. Our results show that the two directional multivariate control charts are promising methods for combining information from multiple time series for early detection of subtle changes in time series from a population without producing an unreasonable amount of false alarms. The approach that we used for simulating multivariate epidemics is relatively easy to implement and could be used in other situations where real epidemic data are unavailable. We believe that our study results can support the implementation and assessment of multivariate SyS systems in animal health.


Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity.
Frontostriatal circuitry is implicated in the cognitive distortions associated with gambling behaviour. 'Near-miss' events, where unsuccessful outcomes are proximal to a jackpot win, recruit overlapping neural circuitry with actual monetary wins. Personal control over a gamble (e.g., via choice) is also known to increase confidence in one's chances of winning (the 'illusion of control'). Using psychophysiological interaction (PPI) analyses, we examined changes in functional connectivity as regular gamblers and non-gambling participants played a slot-machine game that delivered wins, near-misses and full-misses, and manipulated personal control. We focussed on connectivity with striatal seed regions, and associations with gambling severity, using voxel-wise regression. For the interaction term of near-misses (versus full-misses) by personal choice (participant-chosen versus computer-chosen), ventral striatal connectivity with the insula, bilaterally, was positively correlated with gambling severity. In addition, some effects for the contrast of wins compared to all non-wins were observed at an uncorrected (p < .001) threshold: there was an overall increase in connectivity between the striatal seeds and left orbitofrontal cortex and posterior insula, and a negative correlation for gambling severity with the connectivity between the right ventral striatal seed and left anterior cingulate cortex. These findings corroborate the 'non-categorical' nature of reward processing in gambling: near-misses and full-misses are objectively identical outcomes that are processed differentially. Ventral striatal connectivity with the insula correlated positively with gambling severity in the illusion of control contrast, which could be a risk factor for the cognitive distortions and loss-chasing that are characteristic of problem gambling.


[The effect of thyroliberin on the change in structure of various of lipid bilayer regions in biological membranes in vivo].
Thyroliberin (TRH) influence on microviscosity and thermoinduced structural transitions of biological membranes has been studied using spin probes and ESR technique. It was shown that TRH in three investigated concentrations (10(-6), 10(-10) and 10(-16) mol/l) in vivo resulted in increasing of the lipid microviscosity in the hydrophobic areas (20 A): the time of rotary correlation of 16-doxyl-stearic acid elevated by 17-50%. There were no statistically significant effects in the regions localized more close to the surface (8 A): the order parameter of 5-doxyl-stearic acid was not changed. The picture of thermoinduced structural transitions in described in this article. Under the action of TRH in vivo both the shift of structural transitions and the changes in their number have been observed. The results obtained indicated that the mechanism of the TRH effect has a non-receptor component.


Transition from wind pollination to insect pollination in sedges: experimental evidence and functional traits.
Transitions from wind pollination to insect pollination were pivotal to the radiation of land plants, yet only a handful are known and the trait shifts required are poorly understood. We tested the hypothesis that a transition to insect pollination took place in the ancestrally wind-pollinated sedges (Cyperaceae) and that floral traits modified during this transition have functional significance. We paired putatively insect-pollinated Cyperus obtusiflorus and Cyperus sphaerocephalus with related, co-flowering, co-occurring wind-pollinated species, and compared pairs in terms of pollination mode and functional roles of floral traits. Experimentally excluding insects reduced seed set by 56-89% in putatively insect-pollinated species but not in intermingled wind-pollinated species. The pollen of putatively insect-pollinated species was less motile in a wind tunnel than that of wind-pollinated species. Bees, beetles and flies preferred inflorescences, and color-matched white or yellow models, of putatively insect-pollinated species over inflorescences, or color-matched brown models, of wind-pollinated species. Floral scents of putatively insect-pollinated species were chemically consistent with those of other insect-pollinated plants, and attracted pollinators; wind-pollinated species were unscented. These results show that a transition from wind pollination to insect pollination occurred in sedges and shed new light on the function of traits involved in this important transition.


The interplay between genotype, metabolic state and cofactor treatment governs phenylalanine hydroxylase function and drug response.
The discovery of a pharmacological treatment for phenylketonuria (PKU) raised new questions about function and dysfunction of phenylalanine hydroxylase (PAH), the enzyme deficient in this disease. To investigate the interdependence of the genotype, the metabolic state (phenylalanine substrate) and treatment (BH(4) cofactor) in the context of enzyme function in vitro and in vivo, we (i) used a fluorescence-based method for fast enzyme kinetic analyses at an expanded range of phenylalanine and BH(4) concentrations, (ii) depicted PAH function as activity landscapes, (iii) retraced the analyses in eukaryotic cells, and (iv) translated this into the human system by analyzing the outcome of oral BH(4) loading tests. PAH activity landscapes uncovered the optimal working range of recombinant wild-type PAH and provided new insights into PAH kinetics. They demonstrated how mutations might alter enzyme function in the space of varying substrate and cofactor concentrations. Experiments in eukaryotic cells revealed that the availability of the active PAH enzyme depends on the phenylalanine-to-BH(4) ratio. Finally, evaluation of data from BH(4) loading tests indicated that the patient's genotype influences the impact of the metabolic state on drug response. The results allowed for visualization and a better understanding of PAH function in the physiological and pathological state as well as in the therapeutic context of cofactor treatment. Moreover, our data underscore the need for more personalized procedures to safely identify and treat patients with BH(4)-responsive PAH deficiency.


Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures.
Fractures and subsequent morbidity determine the impact of established postmenopausal osteoporosis. Health-related quality of life (HRQOL) has become an important outcome criterion in the assessment and follow-up of osteoporotic patients. As part of the baseline measurements of the Multiple Outcomes of Raloxifene Evaluation (MORE) study, HRQOL was assessed in 751 osteoporotic (bone mineral density [BMD] T score > or = -2.5) women from Europe with or without vertebral fractures (VFX). This was done using the quality of life questionnaire of the European Foundation for Osteoporosis (QUALEFFO), Nottingham Health Profile (NHP) and the EQ-5D (former EuroQol). QUALEFFO contains questions in five domains: pain, physical function, social function, general health perception, and mental function. Each domain score and QUALEFFO total scores are expressed on a 100-point scale, with 0 corresponding to the best HRQOL. In comparison with patients without VFX, those with VFX were older (66.2 +/- 5.9 years vs. 68.8 +/- 6.3 years; p < 0.001), had higher prevalence of nonvertebral fractures (25% vs. 36%; p = 0.002), and higher QUALEFFO scores (worse HRQOL; total score, 26 +/- 14 vs. 36 +/- 17; p < 0.001). QUALEFFO scores increased progressively with increasing number of VFX, especially lumbar fractures (p < 0.001). Patients with a single VFX already had a significant increase in QUALEFFO scores (p < 0.05). Similar, though weaker, associations were seen for NHP and EQ-5D scores. This study confirms decreased HRQOL for patients with prevalent VFX. In osteoporotic patients, QUALEFFO scores change in relation to the number of VFX. QUALEFFO is suitable for clinical studies in patients with postmenopausal osteoporosis.


Invited Commentary: Beyond Individuals-Area Poverty and Health, or the Search for an Impactful Epidemiology.
In this commentary, I reflect on the paper "Poverty and Health: Prospective Evidence From the Alameda County Study" by Haan et al. (Am J Epidemiol. 1987;125(6):989-998), which together with supporting work ushered in a surge of epidemiologic interest in the impact of social contexts on health. I discuss why the paper was influential and how the premise of this type of work influenced theories and methods in epidemiology. The paper is placed in the broader context of the nature of evidence in epidemiology and the ultimate purpose of epidemiologic inquiry.


In vivo optical imaging of folate receptor-β in head and neck squamous cell carcinoma.
Folate receptor (FR) expression, although known to be elevated in many types of cancer and inflammatory cells, has not been well characterized in head and neck squamous cell carcinoma (HNSCC). We hypothesized that tumor infiltrating inflammatory cells expressing FR-β could allow fluorescent visualization of HNSCC tumors using folate conjugated dyes even when FR expression in cancer cells is low. Retrospective review of clinical pathologic specimens and in vivo animal study. A tissue microarray with tumor and tumor-free tissue from 22 patients with HNSCC was stained with antibodies to FR-α and FR-β. We characterized FR-β(+) cells by examining CD45, CD68, CD206, and transforming growth factor (TGF)-β expression. To investigate fluorescent imaging, mice with orthotopic tumor xenografts were imaged in vivo after intravenous injections of folate conjugated fluorescein isothiocyanate (folate-FITC) and were histologically evaluated ex vivo. All tumor samples demonstrated significant FR-β staining and negligible FR-α staining. FR-β(+) cells found in tumors coexpressed CD68 and had increased expression of CD206 and TGF-β characteristic of tumor-associated macrophages. In the xenograft models, tumors showed strong in vivo fluorescence after folate-FITC injection in contrast to surrounding normal tissues. Histologic examination of the xenograft tissue similarly showed folate-FITC uptake in areas of inflammatory cellular infiltrate. Although HNSCC tumor cells do not express FR, HNSCC tumors contain a significant population of FR-β-expressing macrophages. Folate conjugated fluorescent dye is able to specifically target and label tumor xenografts to permit macroscopic fluorescence imaging due to FR-β expression on the infiltrating inflammatory cells.


L-ficolin is a pattern recognition molecule specific for acetyl groups.
L-ficolin and H-ficolin are molecules of the innate immune system. Upon recognition of a suitable target they activate the complement system. The ligand recognition structure of ficolins is contained within a fibrinogen-like domain. We examined the selectivity of the ficolins through inhibiting the binding to bacteria or to beads coupled with N-acetylglucosamine. The binding of L-ficolin to Streptococcus pneumoniae 11F and the beads was inhibited by N-acetylated sugars and not by non-acetylated sugars. However, it was also inhibited by other acetylated compounds. Based on this selectivity L-ficolin is not easily defined as a lectin. The binding of H-ficolin to Aerococcus viridans was not inhibited by any of the sugars or other compounds examined. Based on the selectivity of L-ficolin we developed a new purification procedure involving affinity chromatography on N-acetylcysteine-derivatized Sepharose. The column was loaded in the presence of EDTA and high salt, and L-ficolin was eluted by decreasing the salt concentration. Further purification was achieved by ion exchange chromatography.


What Do Medical Students Actually Want from Learning Communities? A Comprehensive Needs Assessment.
This article was migrated. The article was marked as recommended. Purpose: The demanding nature of medical education has been well-described. Learning Communities (LCs) have been formed in a number of medical schools to address unmet needs such as wellness, social support, and academic/career counseling. However, there is limited information regarding the student perspective in shaping LC goals and activities. This study examined that perspective using a needs assessment survey. Methods: A formal needs assessment survey was completed by 510 medical students. The survey included 16 Likert-scale items and one open response item. Topics focused on student well-being, career planning, meaningful professional relationships, and academic success. Results: As expected, residency success and academic performance were the domains ranked as most important. Of note, the domain of wellness was ranked as less important overall. Results also varied by medical school year and gender. Conclusion: Formal assessment of student needs can serve as a guide to the development of LC programming, hopefully increasing student engagement.


Acute severe asthma: differences in therapies and outcomes among pediatric intensive care units.
To determine differences in therapies and outcomes among pediatric intensive care units for patients with acute severe asthma. Retrospective cohort study. Eleven pediatric intensive care units participating in the Pediatric Intensive Care Evaluations. Patients were 1528 children with a primary diagnosis of asthma. None. We studied severity of illness, length of stay, and use of invasive interventions. The patients at the centers had similar median physiologic measures of illness and Pediatric Risk of Mortality III scores. The patients received a wide range of invasive interventions depending on institution, including mechanical ventilation (3% to 47%), arterial catheter placement (4% to 46%), central venous catheter (2% to 51%), and determination of a blood gas (24% to 70%). At institutions where mechanical ventilation was used more commonly (>20%, high use), intensive care and hospital stays were longer for asthmatic patients regardless of mechanical ventilation requirement compared with centers with lower use of mechanical ventilation. The status of "high-use center" was an independent predictor for intensive care stay (p = .005) and hospital length of stay (p = .017) as well as duration of mechanical ventilation (p = .014) after adjustment for age, degree of hypercarbia, maximal respiratory rate, use of an arterial catheter, and Pediatric Risk of Mortality III scores among ventilated children. We found that use of invasive interventions including mechanical ventilation and vascular monitoring varied greatly by institution. Centers with higher use of mechanical ventilation had longer median intensive care stay and hospital stays. Pediatric asthma management for acute severe asthma may be improved by clear elucidation of the institutional practices where fewer invasive interventions were used to achieve better outcomes.


The evolution of monomeric and oligomeric betagamma-type crystallins. Facts and hypotheses.
The case of homologous monomeric gamma-type and oligomeric beta-type crystallins has been described and analyzed in evolutionary terms. Data and hypotheses from molecular genetics and structural investigations converge and suggest a novel three-phase model for the evolutionary history of crystallin-type proteins. In the divergent cascades of monomeric and oligomeric crystallins, a pivotal role was played by alterations in the gene segments encoding the C-terminal extensions and the intermotif or interdomain linker peptides. These were genomic hot spots where evolution experimented to produce the modern variety of betagamma-crystallin-type quaternary structures.


Neck circumference as a simple tool for identifying the metabolic syndrome and insulin resistance: results from the Brazilian Metabolic Syndrome Study.
To investigate the relationship of the neck circumference (NC) with the metabolic syndrome (MetS) and insulin resistance (IR) in a large Brazilian population-based sample, within a wide range of adiposity and glucose tolerance, and to establish cut-off values of the NC for MetS and IR. The NC correlates with cardiovascular risk factors, IR and components of MetS. Upper-body subcutaneous (sc) fat, as estimated by the NC, is associated with cardiovascular risk factors as much as abdominal fat, which is usually estimated by the waist circumference (WC). There are few epidemiological population-based studies on the clinical significance of the NC to MetS and IR. This is a cross-sectional study. About 1053 Brazilian adults (18-60 years). Patients with BMI 18.5-40.0 kg/m(2), with normal glucose tolerance or type 2 diabetes (T2DM), were submitted to anthropometric measurements including waist circumference (WC), NC and BMI. Abdominal visceral fat (VF) was assessed by ultrasound. Insulin sensitivity (IS) was assessed by euglycaemic-hyperinsulinaemic clamp (10% of total sample) and HOMA-IR. Spearman correlations were used to evaluate the association between NC and IR and MetS risk factors. Receiver operating characteristic (ROC) curves were used for gender-specific cut-off values for the prediction of IR and MetS. Binary logistic regression analysis was used to assess the chance of developing IR or MetS according to the enlargement of NC and WC. The sample consisted of 28.6% men, with a mean age of 39.4 (12 years). T2DM diagnosis was present in 306 individuals, of whom 34% were men. NC correlated with WC and BMI in both men and women (P < 0.001). In both genders, NC showed a positive correlation with triglycerides, fasting glucose, fasting insulin and HOMA-IR, and NC had a negative association with high-density lipoprotein (HDL). NC and IS showed a moderate negative correlation. A significant correlation was demonstrated between VF and NC. In the ROC curves, NC presented the largest AUC for IR in women (P < 0.001), while NC presented a large AUC for MetS in both genders. Neck circumference measurements are an alternative and innovative approach for determining body fat distribution. The NC is positively associated with MetS risk factors, IR and VF, with established cut-off values for the prediction of MetS and IR.


Limitations in the interpretation of intravenous carotid digital subtraction angiography.
To evaluate the limitations of intravenous carotid digital subtraction angiography (DSA) in the diagnosis of carotid disease, studies of 130 patients were reviewed. Factors that resulted in a nondiagnostic study included: (1) misregistration larynx artifact overlying the carotid bifurcation; (2) external carotid or vertebral artery overlying the internal carotid artery; and (3) poor arterial contrast density secondary to poor cardiac function. As a result of these limitations, the ideal of adequate demonstration of both carotid bifurcations in two opposite oblique projections or an oblique and anteroposterior projection was achieved in only 34 patients (26%). Of 126 carotid bifurcations that were seen adequately in two or more different projections, 19 (15%) showed an abnormality in one projection but appeared normal in another. These abnormalities would not have been detected had the vessel been visualized only in the spuriously normal-appearing projection. These and other limitations of intravenous DSA, such as contrast load and morbidity, are discussed.


Isolation and characterization of chicken bile matrix metalloproteinase.
Avian bile is rich in matrix metalloproteinases (MMP), the enzymes that cleave extracellular matrix proteins such as collagens and proteoglycans. Changes in bile MMP expression have been correlated with hepatic and gall bladder pathologies, but the significance of their expression in normal, healthy bile is not understood. We hypothesized that the MMP in bile may aid the digestion of native collagens that are resistant to conventional gastric proteases. Hence, the objective of this study was to characterize the bile MMP and check its regulation in association with dietary factors. We used substrate zymography, azocoll protease assay, and gelatin affinity chromatography to identify and purify the MMP from chicken bile. Using zymography and SDS PAGE, 5 bands at 70, 64, 58, 50, and 42 kDa were detected. The bands corresponding to 64, 50, and 42 kDa were identified as MMP2 using trypsin in-gel digestion and matrix-assisted laser desorption time-of-flight mass spectrometry and peptide mass fingerprinting. Chickens fed diets containing gelatin supplements showed higher levels of MMP expression in the bile by both azocoll assay and zymography. We conclude that the bile MMP may be associated with the digestion of collagens and other extracellular matrix proteins in avian diets.


Caspase-mediated cleavage of C53/LZAP protein causes abnormal microtubule bundling and rupture of the nuclear envelope.
Apoptotic nucleus undergoes distinct morphological and biochemical changes including nuclear shrinkage, chromatin condensation and DNA fragmentation, which are attributed to caspase-mediated cleavage of several nuclear substrates such as lamins. As most of active caspases reside in the cytoplasm, disruption of the nuclear-cytoplasmic barrier is essential for caspases to reach their nuclear targets. The prevailing proposed mechanism is that the increase in the permeability of nuclear pores induced by caspases allows the caspases and other apoptotic factors to diffuse into the nucleus, thereby resulting in the nuclear destruction. Here, we report a novel observation that physical rupture of the nuclear envelope (NE) occurs in the early stage of apoptosis. We found that the NE rupture was caused by caspase-mediated cleavage of C53/LZAP, a protein that has been implicated in various signaling pathways, including NF-κB signaling and DNA damage response, as well as tumorigenesis and metastasis. We also demonstrated that C53/LZAP bound indirectly to the microtubule (MT), and expression of the C53/LZAP cleavage product caused abnormal MT bundling and NE rupture. Taken together, our findings suggest a novel role of C53/LZAP in the regulation of MT dynamics and NE structure during apoptotic cell death. Our study may provide an additional mechanism for disruption of the nuclear-cytoplasmic barrier during apoptosis.


Pretargeting with bispecific fusion proteins facilitates delivery of nanoparticles to tumor cells with distinct surface antigens.
Tumor heterogeneity, which describes the genetically and phenotypically distinct subpopulations of tumor cells present within the same tumor or patient, presents a major challenge to targeted delivery of diagnostic and/or therapeutic agents. An ideal targeting strategy should deliver a given nanocarrier to the full diversity of cancer cells, which is difficult to achieve with conventional ligand-conjugated nanoparticles. We evaluated pretargeting (i.e., multistep targeting) as a strategy to facilitate nanoparticle delivery to multiple target cells by measuring the uptake of biotinylated nanoparticles by lymphoma cells with distinct surface antigens pretreated with different bispecific streptavidin-scFv fusion proteins. Fusion proteins targeting CD20 or tumor-associated glycoprotein 72 (TAG-72) mediated the specific in vitro uptake of 100nm biotin-functionalized nanoparticles by Raji and Jurkat lymphoma cells (CD20-positive and TAG-72-positive cells, respectively). Greater uptake was observed for pretargeted nanoparticles with increasing amounts of surface biotin, with 6- to 18-fold higher uptake vs. non-biotinylated nanoparticle and fusion protein controls. Fully biotin-modified particles remained resistant to cultured macrophage cell uptake, although they were still quickly cleared from systemic circulation in vivo (t1/2<1h). For single Raji tumor-bearing mice, pretargeting with CD20-specific FP significantly increased nanoparticle tumor targeting. In mice bearing both Raji and Jurkat tumors, pretargeting with both fusion proteins markedly increased nanoparticle targeting to both tumor types, compared to animals dosed with nanoparticles alone. These in vitro and in vivo observations support further evaluations of pretargeting fusion protein cocktails as a strategy to enhance nanoparticle delivery to a diverse array of molecularly distinct target cells.


Automatic Diagnosis of Alzheimer's Disease and Mild Cognitive Impairment Based on CNN + SVM Networks with End-to-End Training.
Alzheimer's disease (AD) is an irreversible neurodegenerative disease, and, at present, once it has been diagnosed, there is no effective curative treatment. Accurate and early diagnosis of Alzheimer's disease is crucial for improving the condition of patients since effective preventive measures can be taken in advance to delay the onset time of the disease. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET : PET) is an effective biomarker of the symptom of AD and has been used as medical imaging data for diagnosing AD. Mild cognitive impairment (MCI) is regarded as an early symptom of AD, and it has been shown that MCI also has a certain biomedical correlation with PET. In this paper, we explore how to use 3D PET images to realize the effective recognition of MCI and thus achieve the early prediction of AD. This problem is then taken as the classification of three categories of PET images, including MCI, AD, and NC (normal controls). In order to get better classification performance, a novel network model is proposed in the paper based on 3D convolution neural networks (CNN) and support vector machines (SVM) by utilizing both the excellent abilities of CNN in feature extraction and SVM in classification. In order to make full use of the optimal property of SVM in solving binary classification problems, the three-category classification problem is divided into three binary classifications, and each binary classification is being realized with a CNN + SVM network. Then, the outputs of the three CNN + SVM networks are fused into a final three-category classification result. An end-to-end learning algorithm is developed to train the CNN + SVM networks, and a decision fusion algorithm is exploited to realize the fusion of the outputs of three CNN + SVM networks. Experimental results obtained in the work with comparative analyses confirm the effectiveness of the proposed method.


[Activation of protein biosynthesis in outgrowing spores of Bacillus subtilis].
The programme of protein synthesis as an indicator for the control of gene expression was examined during outgrowth of Bacillus subtilis spores. At various stages of outgrowth cells of Bacillus subtilis were labelled with 35S-L-methionine. Extracted proteins were separated on two-dimensional gels according to O'Farrell (1975). Three groups of proteins were synthesized during outgrowth: 1. During all stages of outgrowth a great number of "vegetative genes" is expressed. The programme of protein synthesis of the outgrowing cell is very similar to that of a vegetative cell. 2. Only a few proteins--probably the products of outgrowth-genes--are synthesized especially in outgrowing spores and turned off at different stages of outgrowth. 3. The synthesis of a minor group of vegetative proteins is triggered during different stages of outgrowth. In contrast to earlier assumptions (comp. Torriani and Levinthal 1967, Hansen et al. 1970, Galizzi et al. 1976) we suggest that only a small portion of the genome is activated during outgrowth as a dependent sequence. These results are discussed on the basis of earlier concepts about the regulation of outgrowth as a developmentally regulated gene expression programme.


Investigation of iterative image reconstruction in low-dose breast CT.
There is interest in developing computed tomography (CT) dedicated to breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence has been found that suggests that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image total-variation minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with a focus on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics.


Isolation and characterization of variant benzo[a]pyrene-resistant T47D human breast-cancer cells.
T47D human breast cancer cells were grown in 1 microM benzo[a]pyrene (BaP) for 3.5 months, and 2 BaP-resistant (BaPr) variant cell lines (CS and C10) were isolated. Decreased aryl hydrocarbon (Ah)-responsiveness in the CS and C1O BaPr cells was characterized by lower (80 to 900/o) induction of CYP1A1-dependent activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), lower levels of the nuclear Ah receptor complex and significantly decreased Ah receptor mRNA levels. Nuclear estrogen receptor (ER) binding and ER mRNA levels were similar in wild-type and mutant cell lines, whereas epidermal growth factor receptor mRNA levels were significantly decreased in the variant BaPr T47D cells. 17beta-Estradiol induced proliferation of both wild-type and BaPr T47D cells, and TCDD inhibited this response but did not down-regulate nuclear ER levels. The unique characteristics of the BaPr T47D variant cells will be used to further elucidate the mechanism of interaction between the ER and Ah receptor signalling pathways.


A rare case of centronuclear myopathy with DNM2 mutation: genotype-phenotype correlation.
Centronuclear myopathy (CNM) is a group of rare genetic muscle disorders characterized by muscle fibers with centrally located nuclei. The most common forms of CNM have been attributed to X-linked recessive mutations in the MTM1 gene; autosomal-dominant mutations in the DNM2 gene-encoding dynamin-2, the BIN1 gene; and autosomal-recessive mutations in BIN1, RYR1, and TTN genes. Dominant CNM due to DNM2 mutations usually follows a mild clinical course with the onset in adolescence. Currently, around 35 mutations of the DNM2 gene have been identified in CNM; however, the underlying molecular mechanism of DNM2 mutation in the pathology of CNM remains elusive, and the standard clinical characteristics have not yet been defined. Here, we describe the case of a 17-year-old female who presented with proximal muscle weakness along with congenital anomalous pulmonary venous connection (which has not been described in previous cases of CNM), scoliosis, and lung disease without a significant family history. Her creatine kinase level was normal. Histology, special stains, and electron microscope findings on her skeletal muscle biopsy showed CNM with the characteristic features of a DNM2 mutation, which was later confirmed by next-generation sequencing. This case expands the known clinical and pathological findings of CNM with DNM2 gene mutation.


Prevalence estimates of genital Chlamydia trachomatis infection in Belgium: results from two cross-sectional studies.
Chlamydia trachomatis (chlamydia) is the most diagnosed sexually transmitted infection in Belgium. Screening programs focus on young women, due to the implications of chronic asymptomatic infections for reproductive health. Thereby, the frequency of infections in men and older adults is underestimated. This study aimed to estimate the point-prevalence of chlamydia in the broader Belgian population, to inform evidence-based prevention and control strategies. We conducted two cross-sectional prevalence studies of chlamydia infection in the population of Belgium aged 16-59 years, 2018-2020. In the CT1 study 12,000 representative individuals were randomly selected from the national register and invited by letter to collect a urine sample at home. The CT2 study used urine samples collected through the Belgian Health Examination Survey. Molecular detection of chlamydia DNA was performed using Xpert® or Abbott Real-Time CT/NG assays. Weighted estimated prevalence and 95% confidence interval (CI) was calculated per gender and age groups of 16/18-29, 30-44 and 45-59 years, relative to the general Belgian population. Data collected on sociodemographic variables and sexual behavior were used to identify potential risk factors for chlamydia infection through calculation of the odds ratio (OR). The population-wide weighted estimated prevalence was 1.54% (95% CI 0.78-3) in CT1 and 1.76% (95% CI 0.63-4) in CT2. We observed no statistically significant difference between men and women or age groups. Civil relationship status (OR = 14.1 (95% CI 1.78-112), p < 0.01), sexual intercourse with a casual partner (OR = 6.31 (95% CI 1.66-24.1), p < 0.01) and > 3 sexual partners in the last 12 months (OR = 4.53 (95% CI 1.10-18.6), p = 0.02) were associated with higher relative risk for chlamydia infection. Nationwide prevalence studies are relevant to assess the distribution of chlamydia and inform public health actions. The overall low prevalence and heterogeneous distribution of chlamydia in the general Belgian population needs to be considered for future strategies and potential harm of testing and treating asymptomatic individuals need to be taken into account. Effective case management should include appropriate treatment of symptomatic patients and partner notification, and prevention strategies should encourage behaviors such as condom use.


Aspirin at any dose above 30 mg offers only modest protection after cerebral ischaemia.
There is continuing debate about the relative efficacy of low (< 100 mg per day), medium (300 to 325 mg per day), and high (> 900 mg per day) doses of aspirin in patients after a transient ischaemic attack or non-disabling stroke. The purpose of this study was to resolve the issue. Thus a minimeta-analysis was performed on data from 10 randomised trials of aspirin only v control treatment in 6171 patients after a transient ischaemic attack or nondisabling stroke. The data on the trials were listed in an appendix of the report on the second cycle of the Antiplatelet Trialists' Collaboration. There was virtually no difference in relative risk reduction for low, medium, and high doses of aspirin (13%, 9%, and 14% respectively). This equivalence corresponds with the results of the UK-TIA trial in a direct comparison of 300 and 1200 mg. The Dutch TIA trial showed no difference in efficacy of 30 and 283 mg. It is concluded that aspirin at any dose above 30 mg daily prevents 13% (95% confidence interval 4-21) of vascular events and that there is a need for more efficacious drugs.


The rice StMADS11-like genes OsMADS22 and OsMADS47 cause floral reversions in Arabidopsis without complementing the svp and agl24 mutants.
During floral induction and flower development plants undergo delicate phase changes which are under tight molecular control. MADS-box transcription factors have been shown to play pivotal roles during these transition phases. SHORT VEGETATIVE PHASE (SVP) and AGAMOUS LIKE 24 (AGL24) are important regulators both during the transition to flowering and during flower development. During vegetative growth they exert opposite roles on floral transition, acting as repressor and promoter of flowering, respectively. Later during flower development they act redundantly as negative regulators of AG expression. In rice, the orthologues of SVP and AGL24 are OsMADS22, OsMADS47, and OsMADS55 and these three genes are involved in the negative regulation of brassinosteroid responses. In order to understand whether these rice genes have maintained the ability to function as regulators of flowering time in Arabidopsis, complementation tests were performed by expressing OsMADS22 and OsMADS47 in the svp and agl24 mutants. The results show that the rice genes are not able to complement the flowering-time phenotype of the Arabidopsis mutants, indicating that they are biologically inactive in Arabidopsis. Nevertheless, they cause floral reversions, which mimic the SVP and AGL24 floral overexpressor phenotypes. Yeast two-hybrid analysis suggests that these floral phenotypes are probably the consequence of protein interactions between OsMADS22 and OsMADS47 and other MADS-box proteins which interfere with the formation of complexes required for normal flower development.


Association of shared decision making with inpatient satisfaction: a cross-sectional study.
We assessed inpatient perceived shared decision making (SDM) and tested the association of SDM with inpatient satisfaction in public tertiary hospitals in Shanghai, China. A cross-sectional survey of 2585 inpatients in 47 public tertiary hospitals in Shanghai in July and August 2018 was conducted. We assessed overall SDM and 4 aspects of SDM and tested the factors influencing SDM and the association of SDM with patient satisfaction (patient satisfaction with physician services, medical expenses, outcomes and overall inpatient care), by adopting linear or two-level regression models. The positive response rate (PRR) and high positive response rate (HPRR) to overall SDM among the inpatients of public tertiary hospitals in Shanghai were relatively high (95.30% and 87.86%, respectively), while the HPRR to "My physician informed me of different treatment alternatives" was relatively low (80.09%). In addition, the inpatients who underwent surgery during admission had higher HPRRs and adjusted HPRRs to overall SDM than those who did not undergo surgery. The study showed that the adjusted high satisfaction rates (HSRs) with physician services, medical expenses, outcomes and overall inpatient care among the inpatients with high level of overall SDM were higher (96.50%, 68.44%, 89.50% and 92.60%) than those among the inpatients without a high level of overall SDM (71.77%, 35.19%, 57.30% and 67.49%). The greatest differences in the adjusted HSRs between the inpatients with and without a high level of SDM were found in inpatient satisfaction with medical expenses and informed consent in SDM. Moreover, 46.22% of the variances in the HSRs with overall inpatient care across the hospitals were attributed to the hospital type (general hospitals vs. specialty hospitals). Inpatient PRRs and HPRRs to SDM in public tertiary hospitals in Shanghai are relatively high overall but lower to information regarding alternatives. SDM can be affected by the SDM preference of both the patients and physicians and medical condition. Patient satisfaction can be improved through better SDM and should be committed at the hospital level.


Living donor liver transplantation with alternative porto-left gastric vein anastomosis in patients with post-Kasai extrahepatic portal vein obstruction.
EPVO is a common cause of prehepatic portal hypertension in pediatric patients and sometimes results in cavernous transformation of the PV. We herein present the cases of two patients who underwent LDLT for EPVO with post-Kasai biliary atresia. PV reconstruction was performed with a porto-left gastric vein anastomosis. The patient who underwent PV reconstruction using an interposition vein graft is doing well without surgical complications, whereas PV anastomotic stenosis was detected three months after LDLT in the patient who did not receive an interposition vein graft. The availability of vein grafts is limited in the LDLT setting. In such cases, performing PV reconstruction with varicose veins using interposition vein grafts is a feasible and valuable alternative option for obtaining a sufficient portal blood flow. Our experiences suggest that using interposition vein grafts may be appropriate for preventing the anastomotic stenosis caused by the fragility of varicose veins.


NK cell receptors of the orangutan (Pongo pygmaeus): a pivotal species for tracking the coevolution of killer cell Ig-like receptors with MHC-C.
CD94, NKG2, Ly49, and killer cell Ig-like receptor (KIR) expressed by orangutan peripheral blood cells were examined by cloning and sequencing cDNA from a panel of individuals. Orthologs of human CD94, NKG2A, D, and F were defined. NKG2C and E are represented by one gene, Popy-NKG2CE, that is equidistant from the two human genes. Several Popy-CD94, NKG2A, and NKG2CE alleles were defined. Popy-Ly49L is expressed in cultured NK cells and has a sequence consistent with it encoding a functional receptor. Orangutan KIR corresponding to the three KIR lineages expressed in humans and chimpanzees were defined. Popy-KIR2DL4 of lineage I is the only ortholog of a human or chimpanzee KIR, but in all individuals examined, the transcripts of this gene produced premature termination, either in the D2 domain or at the beginning of the cytoplasmic domain. Ten Popy-KIR3DL and one Popy-KIR3DS of lineage II are all closely related, but represent the products of at least two genes. The two Popy-KIR2DL and four Popy-KIR2DS of lineage III also represent two genes, both being more related to KIR2DS4 than to other human and chimpanzee KIR of lineage III. The Popy-KIR2D include ones predicted to be specific for the C1 epitope of MHC-C, but none specific for C2. This correlates with the observation that all orangutan MHC-C allotypes examined have the C1 motif.


Cutaneous reactions induced by oxcarbazepine in Southern Han Chinese: incidence, features, risk factors and relation to HLA-B alleles.
Oxcarbazepine (OXC) is a promising alternative for patients who cannot tolerate carbamazepine. Recently, however, it has been reported that OXC-induced cutaneous adverse drug reactions (cADRs) are prevalent and may lead to drug discontinuation. Additionally, these reactions are thought to be associated with HLA-B*1502. This study aims to investigate the incidence, features and risk factors of OXC-cADRs, and to explore their relation to HLA-B alleles in Southern Han Chinese. A prospective study was performed to investigate the incidence, features and risk factors of OXC-cADRs, in which 252 new users were recruited. To examine the association between OXC-cADRs and HLA-B alleles, 14 maculopapular eruption (MPE) cases, including 9 additional cases beyond this prospective observation, were genotyped by PCR-SSP and sequencing. Thirty-five OXC-tolerant patients served as controls. Five patients (2.0%) developed an OXC-cADR, and all were mild MPE. History of other AED allergy (p=0.005, OR=121.23) and non-AED allergy (p=0.006, OR=59.92) were significant risk factors for OXC-cADRs in multivariate logistic regression analysis. Only one patient with OXC-MPE was positive for HLA-B*1502; and the frequency of HLA-B*1502 in OXC-MPE did not differ significantly from that in OXC-tolerant controls. Four HLA-B*1302 alleles were detected in OXC-MPE cases, which was significantly different from that in general population of southern Han Chinese (p=0.001, OR=7.83). The incidence of OXC-induced cADRs was low, and no severe reactions occurred. Patients with a history of allergy are more susceptible to OXC-cADRs. No significant association between HLA-B*1502 and OXC-MPE was found. The associations between OXC-MPE and HLA alleles warrant further studies.


Clinical outcomes meta-analysis: measuring subendocardial perfusion and efficacy of transmyocardial laser revascularization with nuclear imaging.
Randomized and nonrandomized clinical trials have tried to assess whether or not TMR patients experience an increase in myocardial perfusion. However there have been inconsistencies reported in the literature due to the use of different nuclear imaging modalities to test this metric. The primary purpose of this meta-analysis was to determine whether SPECT, MUGA and PET scans demonstrate changes in myocardial perfusion between lased and non-lased subjects and whether laser type affects myocardial perfusion. The secondary purpose was to examine the overall effect of laser therapy on clinical outcomes including survival, hospital re-admission and angina reduction. Sixteen studies were included in the primary endpoint analysis after excluding all other non-imaging TMR papers. Standardized mean difference was used as the effect size for all quantitative outcomes and log odds ratio was used as the effect size for all binary outcomes. Statistically significant improvements in myocardial perfusion were observed between control and treatment groups in myocardial perfusion at 6-month follow up using PET imaging with a porcine model. However non-significant differences were observed in patients at 3 and 12 months using SPECT, PET or MUGA scans. Both CO2 and Ho:YAG laser systems demonstrated an increase in myocardial perfusion however this effect was not statistically significant. In addition both laser types displayed statistically significant decreases in patient angina at 3, 6 and 12 months but non-significant increases in survival rates and decreases in hospital re-admissions. In order to properly assess myocardial perfusion in TMR subjects, subendocardial perfusion needs to be analyzed via nuclear imaging. PET scans can provide this level of sensitivity and should be utilized in future studies to monitor and detect perfusion changes in lased and non-lased subjects.


High-resolution mapping of quantitative trait loci by selective recombinant genotyping.
Selective recombinant genotyping (SRG) is a three-stage procedure for high-resolution mapping of a QTL that has previously been mapped to a known confidence interval (target C.I.). In stage 1, a large mapping population is accessed and phenotyped, and a proportion, P, of the high and low tails is selected. In stage 2, the selected individuals are genotyped for a pair of markers flanking the target C.I., and a group of R individuals carrying recombinant chromosomes in the target interval are identified. In stage 3, the recombinant individuals are genotyped for a set of M markers spanning the target C.I. Extensive simulations showed that: (1) Standard error of QTL location (SEQTL) decreased when QTL effect (d) or population size (N) increased, but was constant for given "power factor" (PF = d(2)N); (2) increasing the proportion selected in the tails beyond 0.25 had only a negligible effect on SEQTL; and (3) marker spacing in the target interval had a remarkably powerful effect on SEQTL, yielding a reduction of up to 10-fold in going from highest (24 cM) to lowest (0.29 cM) spacing at given population size and QTL effect. At the densest marker spacing, SEQTL of 1.0-0.06 cM were obtained at PF = 500-16,000. Two new genotyping procedures, the half-section algorithm and the golden section/half-section algorithm, allow the equivalent of complete haplotyping of the target C.I. in the recombinant individuals to be achieved with many fewer data points than would be required by complete individual genotyping.


A New Method for Diaphragmatic Maximum Relaxation Rate Ultrasonographic Measurement in the Assessment of Patients With Diaphragmatic Dysfunction.
Measurements of ultrasound diaphragmatic motion, amplitude, force, and velocity of contraction may provide important and essential information about diaphragmatic fatigue, weakness, or paralysis. In this paper, we propose and evaluate a semi-automated analysis system for measuring the diaphragmatic motion and estimating the maximum relaxation rate (MRR_SAUS) from ultrasound M-mode images of the diaphragmatic muscle. The system was evaluated on 27 M-mode ultrasound images of the diaphragmatic muscle [20 with no resistance (NRES) and 7 with resistance (RES)]. We computed semi-automated ultrasound MRR measurements on all NRES/RES images, using the proposed system (MRR_SAUS = 3.94 ± 0.91/4.98 ± 1.98 [1/s]), and compared them with the manual measurements made by a clinical expert (MRR_MUS = 2.36 ± 1.19/5.8 ± 2.1 [1/s],) and those made by a reference manual method (MRR_MB = 3.93 ± 0.89/3.73 ± 0.52 [1/sec], performed manually with the Biopac system. MRR_SAUS and MRR_MB measurements were not statistically significantly different for NRES and RES subjects but were significantly different with the MRR-MUS measurements made by the clinical expert. It is anticipated that the proposed system might be used in the future in the clinical practice in the assessment and follow up of patients with diaphragmatic weakness or paralysis. It may thus potentially help to understand post-operative pulmonary dysfunction or weaning failure from mechanical ventilation. Further validation and additional experimentation in a larger sample of images and different patient groups is required for further validating the proposed system.