The common sense model applied to hepatitis C: a qualitative analysis of the impact of disease comparison and witnessed death on hepatitis C illness perception.
Hepatitis C virus (HCV) accounts for 15,000 deaths in the United States yearly because people living with HCV are not identified in time to seek treatment, are ineligible for or refuse treatment, or face structural impediments to obtaining treatment such as lack of access to health care or lack of insurance. People who inject drugs (PWID) comprise a large proportion-estimates of up to 60-70%-of current and new HCV infected individuals and face many barriers to completing HCV treatment. We conducted 30 qualitative semi-structured interviews of current and former PWID seeking HCV treatment at an opioid-agonist treatment facility in New York City. We used thematic analysis, informed by grounded theory, to examine perceptions of HCV and decisions to initiate HCV treatment. We analyzed the themes that emerged via the common sense model (CSM) of illness perception theoretical framework. Using thematic analyses, two major themes emerged related to engagement in HCV treatment. First, participants independently compared HCV to HIV, and in so doing, emphasized the potential fatality of HCV and the need for treatment. Second, participants described witnessing others suffer or die from untreated HCV and expressed how these recollections impacted their desire to undergo treatment themselves. Together, these themes contributed to the way participants perceived HCV and informed their decisions to initiate treatment. Both themes reflect the CSM's "self-regulation" process, which posits that understanding the causes and consequences of an illness impacts one's ability to seek treatment to overcome this illness state. This paper offers insight into how clinicians can better understand and utilize HCV illness perceptions to evaluate willingness to engage in HCV treatment among PWID considering antiviral treatment modalities.


[Evaluation of methotrexate effect on the acute-phase response in rheumatoid arthritis after 12-week treatment].
DAS28 index calculated with regard for ESR, the number of swollen/painful joints and evaluation of the patient's condition by VAS is universally used to estimate activity of rheumatoid arthritis (RA). There is a variant of calculation using C-reactive protein (CRP) instead of ESR. Our experience indicates that ESR decreases more slowly than CRP during treatment and better reflects dynamics of patients' condition. From the practical standpoint it is important to estimate activity of RA because therapeutic modalities are chosen based on the DAS28 value. To study the influence of pharmaceutical form of methotrexate on the acute-phase response in rheumatoid arthritis. The study included 32 patients (24 women, 8 men) aged 19-76 (mean 47.5 +/- 28.5) yr with active RA (DAS28 > 3.2) 4-30 months (11.5 +/- 7.4, median 8) in duration. Diagnosis was made using AXR criteria (1987), none of the patients previously received methotrexate injections. Inclusion criteria: initially high ESR (Westegren, mm/hr) and/or CRP (mg/l measured by a highly sensitive method). All patients were given methotrexate subcutaneously for 12 weeks as monotherapy (initial dose 10 mg, maximum one 25 mg/week). The cumulative dose was 211.36 +/- 17.2 mg. Side effects did not require withdrawal of methotrexate. CRP level decreased faster than ERS: a 70% decrease of CRP by week 12 was recorded more frequently than that of ESR. Slow dynamics of the number of swollen joints compared with CRP may be due to the low cumulative dose of methotrexate. Duration of the disease had no effect on dynamics of acute phase characteristics. Methotrexate injections resulted in markedly delayed development of clinical signs of improvement compared with laboratory values. CFP levels fell down much faster than ESR, Remission or low activity of RA (estimated from DAS28) occurred only in 38% of the cases after 3 month monotherapy by methotrexate injections. It is concluded that efficacy of this drug should be estimated no sooner than 4 months after the onset of the treatment.


Natural selection with nuclear and cytoplasmic transmission. II. Tests with Drosophila from diverse populations.
Observations of intraspecific variation in organelle DNA have prompted a renewed interest in the evolutionary consequences of cytoplasmically transmitted factors. Attempts to quantify the significance of cytoplasmic effects are frequently limited by the difficulty in partitioning the cause of reciprocal cross differences among a series of possibilities. In the experiment reported here the nuclear genomes of a set of six lines of Drosophila melanogaster from diverse geographic locations were replaced in a series of cytoplasms. The segregation of the SM5 balancer chromosome was scored in a factorial design, and the data allowed a partitioning of variance such that cytoplasmic effects were distinguished from maternal effects and meiotic drive. An attempt was made to avoid the confounding problem of hybrid dysgenesis by performing the entire experiment (including chromosomal extractions) in a P cytotype. Results indicated a significant contribution of cytoplasm to the variance in SM5 segregation. Error variance showed an increasing trend as the experiment proceeded, and additional tests indicated that this was due to an accumulation of chromosomal mutations. These findings are interpreted in light of the population genetic theory that addresses the maintenance of cytoplasmic polymorphism.


Response of human spermatozoa to an internal calcium ATPase inhibitor, 2,5-di(tert-butyl) hydroquinone.
This study has investigated the effect of elevating intracellular calcium levels, using an internal calcium ATPase inhibitor, 2,5-di(tert-butyl) hydroquinone (TBQ), on human sperm function. Isolated sperm samples from five fertile donors were incubated in a capacitating media for up to 6 hr. After 0, 3, and 6 hr incubation, sperm were exposed to a range of TBQ concentrations; 100 microM, 10 microM, and 1 microM, for a fixed incubation period of 5 min. Controls were run for each experiment where sperm were incubated for 5 min in the absence of TBQ. Sperm capacitation and the acrosome reaction were monitored prior to and after exposure to TBQ, using the Chlortetracycline assay. In addition, sperm motility was assessed at each time point and after sperm had been exposed to TBQ. The treatment of sperm with TBQ caused a significant increase in the number of capacitated sperm with an optimum response being achieved in the presence of 100 microM TBQ. However, sperm motility was found not to be effected by the addition of TBQ. The results from the present study suggest that elevating intracellular calcium levels in human sperm by short exposure to a high concentration of TBQ can rapidly accelerate the capacitation process. Furthermore, the observation that TBQ did not elicit a change in sperm motility suggests that TBQ may be highly specific in its mode of action by acting within the head region of human sperm.


Allicin Overcomes Hypoxia Mediated Cisplatin Resistance in Lung Cancer Cells through ROS Mediated Cell Death Pathway and by Suppressing Hypoxia Inducible Factors.
The hypoxic microenvironment in NSCLC has been widely accepted as a contributor to both therapeutic resistance and tumor progression. In this study, we have explored Allicin, a key organosulfur compound present in garlic for its previously unreported effectiveness in the heterogeneous hypoxic tumor microenvironment of NSCLC. The effect of Allicin on the viability of NSCLC cells was determined by MTT assay. To determine the migration rate of treated cells compared to the control, scratch and transwell migration assays were performed. Flowcytometry was done to explore cell cycle distribution, apoptosis and ROS production in cells. Fluorescence microscopy was used to examine autophagy and DNA damage in cells. Dot blot was done to check genome wide methylation. RNA expression was detected by RT-PCR and protein expression by western blotting. Allicin significantly decreases cell viability, proliferation and migration of NSCLC cells in both normoxia and hypoxia. It elicits both apoptosis and autophagy pathway in A549 cells by ROS accumulation and facilitating S/G2-M phase arrest in both normoxia as well as hypoxia. We suggest that ROS/MAPK and ROS/JNK signaling pathway together govern the cytotoxic effect of allicin in NSCLC cells. Notably, allicin suppresses the expression of HIF-1α and HIF-2α in hypoxic cells, pointing towards a mechanism of its effectiveness in hypoxia. A long term passive demethylation was observed, with decreased mC and no change in TET expression, thereby ruling out active demethylation by allicin. Furthermore, allicin synergistically enhances growth inhibitory activity of low dose cisplatin to effectively overcome hypoxia induced cisplatin resistance in A549 cells. Altogether, our results elucidate a potential use of allicin in sensitizing hypoxic and chemoresistant NSCLC to cisplatin-based chemotherapy and provide new, affordable therapeutic strategy with reduced side effects.


High-resolution geospatial mapping of zero-dose and under-immunized children following Nigeria's 2021 multiple indicator cluster survey/national immunization coverage survey (MICS/NICS).
The "zero-dose" children are those without any routine vaccination or lacking the first dose of the diphtheria-tetanus-pertussis-containing vaccine. As per 2022 WHO/UNICEF estimates, globally, Nigeria has the highest number of zero-dose with over 2.3 million unvaccinated. We used data from the 2021 Nigeria Multiple Indicator Cluster Survey - National Immunisation Coverage Survey to identify zero-dose and under-immunized children. Geospatial modelling techniques were employed to determine the prevalence of zero-dose children and predict risk areas with under-immunized at a high resolution of 1x1 km. Both zero-dose and under-immunized children are more prevalent in socially deprived groups. Univariate and multivariate Bayesian analyses showed positive correlations between the prevalence of zero-dose and under-immunized children with factors like stunting, contraceptive prevalence, and literacy. The prevalence of zero-dose and under-immunized children varies significantly by region and ethnicity, with higher rates observed in the country's northern parts. Significant heterogeneity in the distribution of under-vaccinated children was observed. Nigeria needs to enhance its immunization system and coverage. Geospatial modelling can help deliver vaccines effectively to underserved communities. By adopting this approach, countries can ensure equitable vaccine access and contribute to global vaccination objectives.


Assessing the concordance of trauma registry data and hospital records.
This study examined the concordance of trauma registry and hospital records in Queensland in 1998. The design involved a retrospective review of records and documentation comparison. Demographic variables from the registry were matched to hospital data to obtain admission/diagnoses data. There were four main types of error identified which included: failure to identify relevant patients, inappropriate inclusion of patients, insufficient/inaccurate data in hospital records, and insufficient/inaccurate data in the trauma registry. Of the 87 cases with data quality issues, 63% were due to Queensland Trauma Registry (QTR) data errors, 5% were due to hospital data errors, and in 32% of cases the source of errors was undetermined. Of the potential 1759 trauma cases from 1998, 12 cases should have been included in the registry that were not, 71 cases should not have been included in the registry, and 4 cases were removed from the study due to insufficient or inaccurate hospital record data. Overall, a concordance rate of approximately 95% was found between the trauma registry records and the hospital records.


Sub-10 nm colloidal lithography for circuit-integrated spin-photo-electronic devices.
Patterning of materials at sub-10 nm dimensions is at the forefront of nanotechnology and employs techniques of various complexity, efficiency, areal scale, and cost. Colloid-based patterning is known to be capable of producing individual sub-10 nm objects. However, ordered, large-area nano-arrays, fully integrated into photonic or electronic devices have remained a challenging task. In this work, we extend the practice of colloidal lithography to producing large-area sub-10 nm point-contact arrays and demonstrate their circuit integration into spin-photo-electronic devices. The reported nanofabrication method should have broad application areas in nanotechnology as it allows ballistic-injection devices, even for metallic materials with relatively short characteristic relaxation lengths.


Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death.
The actin-modulating protein Wiskott-Aldrich syndrome protein verprolin homologous-1 (WAVE1) and a novel CNS-specific protein, pancortin, are highly enriched in adult cerebral cortex, but their functions are unknown. Here we show that WAVE1 and pancortin-2 interact in a novel cell death cascade in adult, but not embryonic, cerebral cortical neurons. Focal ischemic stroke induces the formation of a protein complex that includes pancortin-2, WAVE1, and the anti-apoptotic protein Bcl-xL. The three-protein complex is associated with mitochondria resulting in increased association of Bax with mitochondria, cytochrome c release, and neuronal apoptosis. In pancortin null mice generated using a Cre-loxP system, ischemia-induced WAVE1-Bcl-xL interaction is diminished, and cortical neurons in these mice are protected against ischemic injury. Thus, pancortin-2 is a mediator of ischemia-induced apoptosis of neurons in the adult cerebral cortex and functions in a novel mitochondrial/actin-associated protein complex that sequesters Bcl-xL.


Investigating the Link between Lynch Syndrome and Breast Cancer.
Lynch syndrome is an inherited genetic disorder associated with a predisposition to early-onset colorectal and endometrial cancers, but breast cancer risk in these patients is debated. The aim of this study is to evaluate breast cancer rates in a cohort of Lynch syndrome patients, as well as to identify women who may be eligible for additional breast cancer specific genetic testing or enhanced breast surveillance (contrast-enhanced magnetic resonance imaging (MRI) screening). Using a hereditary colorectal cancer registry at a single academic institution for identification of patients with Lynch syndrome, a retrospective chart review was performed of 188 women with DNA mismatch repair (MMR) mutations. The Tyrer-Cuzick model was used to estimate breast cancer risk in patients without breast cancer. The prevalence of breast cancer differed based on mutation type (p=0.0043), as 27% of women with a PMS2 mutation were diagnosed with breast cancer, compared to 3%, 4%, and 9% in MLH1, MSH2, and MSH6 patients. The average age at diagnosis for women with a PMS2 mutation was 46.7 years. Additionally, 7.5% of unaffected women had an estimated lifetime risk of breast cancer greater than 20%. 46/188 (24.4%) of patients were eligible for breast specific genetic testing. Our analysis suggests that Lynch syndrome patients with PMS2 mutations may be at higher risk of developing breast cancer. Additionally, the personal and family history of cancer suggests crossover in eligibility for breast specific genetic testing in a significant number of patients (16.5-24.4%). Also, many women are eligible for enhanced breast surveillance (7.5%) which would otherwise not be offered.


Cell fouling resistance of polymer brushes grafted from ti substrates by surface-initiated polymerization: effect of ethylene glycol side chain length.
This paper presents a comparative study on the antifouling properties of poly(ethylene glycol) (PEG)-based polymer coatings prepared by surface-initiated polymerization (SIP). Three types of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMEMA) polymer thin films of approximate 100 nm thickness were grafted from a catechol initiator that was immobilized on a Ti substrate. OEGMEMA monomers containing side chains of 4, 9, and 23 EG units were used in surface-initiated atom transfer radical polymerization (SI-ATRP) to form POEGMEMA-4, -9, and -23 polymer brushes. The chemical composition, thickness, and wettability of the polymer brushes were characterized by X-ray photoelectron spectroscopy (XPS), ellipsometry, and static water contact angle measurements, respectively. The dependence of antifouling performance on EG side chain length was systemically tested and compared by 3T3 fibroblast cell adhesion assays. Results from 4-h cell culture experiments revealed the complete absence of cell attachment on all the grafted Ti substrates. Excellent cell fouling resistance continued with little dependence on EG side chain length up to three weeks, after which long-term antifouling performance depended on the EG chain length as the grafted samples reached confluent cell coverage in 7, 10, and 11 weeks for POEGMEMA-4, -9, and -23, respectively.


Orientia tsutsugamushi stimulates an original gene expression program in monocytes: relationship with gene expression in patients with scrub typhus.
Orientia tsutsugamushi is the causal agent of scrub typhus, a public health problem in the Asia-Pacific region and a life-threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushi altered the expression of more than 4,500 genes, as demonstrated by microarray analysis. The expression of type I interferon, interferon-stimulated genes and genes associated with the M1 polarization of macrophages was significantly upregulated. O. tsutsugamushi also induced the expression of apoptosis-related genes and promoted cell death in a small percentage of monocytes. Live organisms were indispensable to the type I interferon response and apoptosis and enhanced the expression of M1-associated cytokines. These data were related to the transcriptional changes detected in mononuclear cells isolated from patients with scrub typhus. Here, the microarray analyses revealed the upregulation of 613 genes, which included interferon-related genes, and some features of M1 polarization were observed in these patients, similar to what was observed in O. tsutsugamushi-stimulated monocytes in vitro. This is the first report demonstrating that monocytes are clearly polarized in vitro and ex vivo following exposure to O. tsutsugamushi. These results would improve our understanding of the pathogenesis of scrub typhus, during which interferon-mediated activation of monocytes and their subsequent polarization into an M1 phenotype appear critical. This study may give us a clue of new tools for the diagnosis of patients with scrub typhus.


Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells.
In humans both UV-A and UV-B can cause gene mutations and suppress immunity, which leads to skin cancer, including melanoma. Inhibition of reactive oxygen species (ROS) and reactive nitrogen species (RNS) appears particularly promising as ROS and RNS production by both UV-A and UV-B contributes to inflammation, immunosuppression, gene mutation and carcinogenesis. We evaluated the effect of two lichen compounds, sphaerophorin (depside) and pannarin (depsidone) on pBR322 DNA cleavage induced by hydroxyl radicals (()OH), and by nitric oxide (NO), and their superoxide anion (O(2)(-)) scavenging capacity. In addition, we investigated the growth inhibitory activity of these compounds against human melanoma cells (M14 cell line). Sphaerophorin and pannarin showed a protective effect on plasmid DNA and exhibited a superoxide dismutase like effect. The data obtained in cell culture show that these lichen metabolites inhibit the growth of melanoma cells, inducing an apoptotic cell death, demonstrated by the fragmentation of genomic DNA (COMET and TUNEL Assays) and by a significant increase of caspase-3 activity, and correlated, at least in part, to the increase of ROS generation, These results confirm the promising biological properties of sphaerophorin and pannarin and encourage further investigations on their molecular mechanisms.


Improving pig health through genomics: a view from the industry.
Health is one of the most important contributors to animal welfare, productivity and profitability in pig production today. For the past 30 years, pig breeders have focused on genetic improvement of lean growth, feed efficiency, meat quality and reproduction. However, in recent years, selection objectives have been broadened to include livability, robustness and disease resistance. A DNA marker for selection of resistance to F18+ E. coli has been available for several years. This marker decreases mortality and improves growth on farms experiencing post-weaning scours and/or oedema disease. However, for most diseases affecting intensive production systems such as porcine reproductive and respiratory syndrome (PRRS), porcine circovirus type 2-associated diseases (PCVAD), Haemophilus parasuis, and swine influenza virus, resistance is a complex and polygenic trait. Selection for improved resistance to these diseases will be incremental and require use of multiple markers in complex breeding schemes. Novel technologies such as pig gene microarrays, single nucleotide polymorphism (SNP) panels and advanced bioinformatics are being used to identify new health candidate genes for these economically important diseases. Lagging behind, however, is availability of large DNAdatasets from pedigreed populations with accurately measured health phenotypes that are needed to identify associations between SNPs and health traits. Increased focus on datasets with health traits will be the key to finding useable discoveries with new genomics technologies. Currently, the industry uses dozens of SNP markers to increase the accuracy of selection for complex breeding objectives, including disease resistance. As the pig genome is sequenced and barriers to genotyping thousand of markers are eliminated, genomic selection for health traits will receive increasing attention from commercial breeders.


Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type.
ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features, and to compare results to solid ACC. Genome wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, four with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), and five solid ACC. In addition, Ki67 index and p53 immunopositivity was assessed. ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.


Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): 18-month experience with telemedicine screening.
To report the 18-month experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative. Retrospective analysis of the SUNDROP archival data between 1 December 2005 and 30 May 2007, evaluating this new diagnostic technology for ROP screening. All 97 consecutively enrolled infants in the SUNDROP network. All patients were screened using the RetCam II, and evaluated by the SUNDROP reading center at Stanford University. Nurses were trained to obtain five images in each eye. All patients were screened by an ophthalmologist trained in diagnosing ROP within 1 week of discharge from the hospital. Outcomes included referral-warranted disease, need for treatment, and anatomic outcomes. Referral-warranted disease was defined as any Early Treatment Retinopathy of Prematurity Disease Type 2 or greater, threshold disease, any plus disease, and any stage 4 or higher disease. In the initial 18-month period, the SUNDROP telemedicine screening initiative has not missed any referral-warranted disease for ROP. A total of 97 infants (194 eyes) were enrolled, resulting in 443 unique examinations and 4,929 unique images. The mean birth weight of the infants was 1,186.9 grams, with a mean gestational age at birth of 28.9 weeks. Seven infants were identified with referral-warranted disease; six patients underwent laser photocoagulation and completely regressed. The one remaining patient regressed spontaneously, and did not require intervention. Calculated sensitivity and specificity was 100% and 98.9% respectively. No patient progressed to retinal detachment or other adverse outcome. Inadequate exposure, artifact, poor visualization of the periphery, and lack of a complete standardized image set in some patients were identified as areas requiring further assessment. The SUNDROP telemedicine screening initiative for ROP has proven to have a high degree of sensitivity and specificity for identification of referral-warranted disease. Training was easily implemented. All cases of referral-warranted disease were captured. There were no adverse outcomes.


[Link between cerebral blood flow and brain metabolism: validity and limits].
A century ago, Roy and Sherrington suggested that there was a direct relationship between cerebral metabolism and brain blood flow. While this concept is now generally accepted, it is still the subject of considerable debate. There is undoubtedly a link between local metabolism and local blood flow, but the mechanisms involved remain unknown. Several factors, such as H+, K+, CO2, lactate, and recently adenosine, have been suggested as chemical modulators adapting the blood flow in the tissue to local metabolic demand. The demonstration of a functional innervation of the pial and intracerebral blood vessels has led to the hypothesis of autonomic and central nervous regulation of cerebral blood flow (CBF). Most neurotransmitters and neuromodulators, appear to be implicated in this regulatory mechanism. The endothelial cells also play a part in vasomotor effects, as they can produce relaxing (EDRF) and constricting (EDCF) factors in response to a variety of stimuli. Thus it is now no longer possible to consider metabolism as the only factor regulating cerebral blood flow; nervous, endothelial, myogenic and humoral factors must also be included.


Mitral Annulus Calcification and Cardiac Conduction Disturbances: A DANCAVAS Sub-study.
Due to its location very close to the bundle of His, mitral annulus calcification (MAC) might be associated with the development of atrioventricular (AV) conduction disturbances. This study assessed the association between MAC and AV conduction disturbances identified by cardiac implantable electronic device (CIED) use and electrocardiographic parameters. The association between MAC and traditional cardiovascular risk factors was also assessed. This cross-sectional study analyzed 14,771 participants, predominantly men aged 60-75 years, from the population-based Danish Cardiovascular Screening trial. Traditional cardiovascular risk factors were obtained. Using cardiac non-contrast computed tomography imaging, MAC scores were measured using the Agatston method and divided into absent versus present and score categories. CIED implantation data were obtained from the Danish Pacemaker and Implantable Cardioverter Defibrillator Register. A 12-lead electrocardiogram was available for 2,107 participants. Associations between MAC scores and AV conduction disturbances were assessed using multivariate regression analyses. MAC was present in 22.4% of the study subjects. Participants with pacemakers for an AV conduction disturbance had significantly higher MAC scores (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.01-1.23) than participants without a CIED, whereas participants with a CIED for other reasons did not. Prolonged QRS-interval was significantly associated with the presence of MAC (OR, 1.45; 95% CI, 1.04-2.04), whereas prolonged PQ-interval was not. Female sex and most traditional cardiovascular risk factors were significantly associated with high MAC scores. MAC was associated with AV conduction disturbances, which could improve our understanding of the development of AV conduction disturbances.


Response to Cabazitaxel Beyond 20 Cycles in A Patient with Penile Metastasis of Prostate Cancer: A Case Report.
Penile metastases are extremely rare events and generally occurs at a late stage of primary disease. They mostlyoriginate from prostate and bladder in the genitourinary tract. Penile metastases have a dismal prognosis and verylow survival rates. We report a case of penile metastasis in 70-year-old geriatric male patient with prostatic adenocarcinomawho was treated with cabazitaxel chemotherapy beyond 20 cycles with a good response and acceptableminimal toxicity.


Basal and thyroliberin-stimulated prolactin synthesis in single-cell cultures and in populations of rat pituitary cells.
1. Newly synthesized prolactin was obtained from cultures of rat pituitary tumour cells (GH4C1 cells) after incubation with [35S]methionine. 2. Radioactive synthesized and secreted prolactin was quantified by an immunoprecipitation method by using disc-gel electrophoresis of the dissolved immunoprecipitate in the presence of sodium dodecyl sulphate. By using a microanalytical modification, hormone synthesis and secretion could also be studied in single-cell cultures. This technique was combined with a cytoimmunofluorescence method in which rhodamine-conjugated antibodies were used for studying intracellular prolactin. 3. The presence of radioactive synthesized and secreted prolactin was demonstrated in nine out of 13 single-cell cultures. Cell cultures containing 10 cells or more and clonal populations originating from one cell always secreted radioactive prolactin. 4. Thyroliberin treatment (2 muM) for 24h increased the extracellular accumulation of radioactive prolactin in five out of seven single-cell cultures and always in populations of cells. 5. The number of cells showing prolactin specific fluorescence increased from 20 to 50% and the intensity of this fluorescence became greater after thyroliberin treatment. 6. Studies of [35S]prolactin secretion from single cells and immunochemical detection of intracellular prolactin showed that some cells in an unsynchronized population did not secret radioactive prolactin or show prolactin specific fluorescence. 7. The quantitative effect of thyroliberin as studied in single-cell cultures suggested that the main if not the only effect was to increase prolactin synthesis in cells already producing hormone.


[Acute type A aortic dissection with Birt-Hogg-Dubé syndrome; report of a case].
We describe a 76-year-old woman with cardiac tamponade who was admitted to our hospital. She underwent ascending and partial arch aortic replacement to treat acute type A aortic dissection. However, postoperative respiratory failure developed and a chest X-ray revealed right lung pneumothorax. The lung was finally expanded after difficulties with prolonged tube drainage. Chest computed tomography(CT) showed multiple cystic changes in the bilateral lungs. Her sister and her daughter also had a history of spontaneous pneumothorax. We finally diagnosed Birt-Hogg-Dube syndrome after deoxyribonucleic asid(DNA)sequencing of folliculin( FLCN) gene.


[The spectrum of pathogens in 187 cases of pulmonary fungal disease diagnosed by histopathology-a retrospective analysis].
Objective: To investigate the spectrum of pathogens causing lung fungal disease diagnosed by histopathology through histochemical special staining, compared to the fungal culture results, and to further evaluate the diagnostic value of histochemical special staining in pulmonary fungal disease. Methods: We performed a retrospective analysis of 187 cases of pulmonary fungal disease diagnosed by histopathology in Peking Union Medical College Hospital from 2001 to 2015 (including 92 cases with pulmonary resection or open lung biopsy, 33 with percutaneous lung biopsy and 62 ones with fiberoptic bronchoscopic lung biopsy). All cases were treated with hexamine silver, PAS, mucus carmine and acid-fast staining in addition to conventional HE staining. The clinical records and the fungal culture results were reviewed. Results: There were 103 male and 84 female patients, aged from 12 to 70 years [average (48±14) years]. There were 85 cases(45.5%) of pulmonary aspergillosis(including 60 cases of invasive infection and 25 cases of aspergilloma), 51 cases(27.3%) of pulmonary cryptococosis, 6 cases (3.2%)of pulmonary mucormycosis, 3 cases(1.6%) of pulmonary histoplasmosis, 3 cases (1.6%)of pulmonary candidiasis, and 2 cases (1.1%) of pneumocystosis, while in the remaining 37 cases (19.8%) the pathogens could not be clearly classified by microscopy due to limited tissue or degeneration. Among the 88 patients with pulmonary fungal disease diagnosed by histopathology from 2011 to 2015, 35 ones (39.9%) were detected by fungal culture (including lung biopsy, intraoperative swab, blood, bronchoalveolar lavage fluid and sputum, etc.). The diagnostic results of 18 cases were completely consistent between histopathological examination and fungal culture (18/35, 51.4%), while 13 cases (13/35, 37.1%) were diagnosed by histopathology but no fungi were cultured, and in 3 cases (3/35,8.6%) the culture was positive for fungi which could not be classified clearly by histopathology. In another case the pathogen was found to be Cryptococcus histopathologically but the lavage culture grew"candida", but the patient's blood cryptococcal antigen was positive. Conclusions: Among patients with histopathological diagnosis of pulmonary fungal disease, pulmonary aspergillosis was the most common, followed by pulmonary cryptococcosis, pulmonary mucormycosis, pulmonary histoplasmosis, pulmonary candidiasis and pneumocystosis. A small number of cases could not be classified by histopathology through histochemical special staining. There was a high consistency in discovering fungal pathogens between pathological histochemical special staining and culture method, but 37% pulmonary fungal disease diagnosed by histopathology were culture negative. In practice, the role of histochemical special staining in diagnosing pulmonary fungal disease should be paid more attention.


Spontaneous Reduction of Fractured Thoracolumbar Spine With Complete Dislocation: Case Report With Literature Review.
Fractures and dislocations with complete lateral displacement of the spine at the lumbar and thoracic levels are some of the most severe types of thoracolumbar trauma. They are usually caused by high-energy trauma and accompanied by extreme, life-threatening injuries and neurological deficits that vary in severity, which may delay operative intervention. It is often difficult to reduce such a complex fracture-dislocation because of the force that the muscles exert on the bone and the injured part of the spinal cord. No absolute guidelines for reduction, fixation, decompression, and fusion of this type of injury have been established. We report a rare case of spontaneous reduction of the fractured thoracolumbar spine with complete dislocation and discuss the management of such severe injuries through review of the existing literature.


Effects of in vitro versus in vivo red cell labeling on image quality in gastrointestinal bleeding studies.
Both in vivo and in vitro red cell labeling methods are available for performing gastrointestinal bleeding studies. While in vitro labeling has been shown to result in higher binding efficiency, no comparison of clinical image quality has been reported between those techniques. This study compares in vivo and in vitro methods using both subjective and objective measurements of image quality. A consecutive series of gastrointestinal bleeding studies performed on 23 patients using in vivo labeling was compared to a series of 23 studies using in vitro labeling. Images at 30 min postinjection were randomized and analyzed by two observers. Subjective evaluation of image quality, as well as renal activity, was based on a comparison of femoral vein and inferior vena cava activity to adjacent background using numerical scores with a scale of 0-3. Image quality using the subjective scores was further classified as acceptable and poor. Target-to-background measurements of femoral vein to adjacent soft tissue in the thigh and inferior vena cava to adjacent abdominal background also were made. In vitro label subjective image quality was acceptable in 87% and 91% of cases for vascular and renal activity, respectively, but only 35% and 52% for in vivo labeling. In vitro label target-to-background ratios were significantly better than in vivo label for the femoral vein and inferior vena cava, as well as for the subjective assessment of vascular image quality, but not for renal activity. In vitro red cell labeling improves clinical image quality as compared with in vivo labeling. Both subjective and objective measurements of image quality are useful for comparing the results of labeling methods.


Impact of sternal notch-to-nipple distance and resection weight asymmetry on complication rates and patient reported outcomes in reduction mammaplasty.
While there are numerous predictive models for estimating resection weight, their accuracy may not be strong. Through institutional data of patients who received reduction mammaplasty, this study demonstrates that preoperative sternal notch-to-nipple distance is not an optimal predictive factor for differences in final resection weight, complication rates, and patient reported outcomes. Our results showed that there is a weak correlation between preoperative sternal notch to nipple asymmetry and final resection weight asymmetry. Additionally, significant breast asymmetry is not tied to an increase in complication rates or poorer patient reported outcomes. There is an indication to reconsider the use of such absolute measures for determining who may benefit from reduction mammaplasty.


Outcomes of interventions for recurrent disease after endoluminal intervention for superficial femoral artery disease.
Aggressive endoluminal therapy for superficial femoral artery (SFA) occlusive disease is commonplace, but the outcomes of current management of recurrent disease have not been well defined. This study examined the outcomes of endoluminal and open interventions for recurrent SFA disease. A database of patients undergoing endovascular treatment of the SFA between 1986 and 2008 was retrospectively queried, and those with recurrent disease were selected. Outcomes were determined by Kaplan-Meier survival analyses, and the Cox proportional hazard model was used for time-dependent variables. Symptomatic SFA disease resulted in endovascular treatment in 735 limbs in 631 patients (64% male; average age, 67 years). The restenosis rate was 16% +/- 3% at 5 years. Restenosis developed in 222 patients, of whom 58 remained asymptomatic and 164 underwent repeat intervention comprising percutaneous transluminal angioplasty (PTA) in 59% and bypass in 41%. Bypass was used for critical ischemia (rest pain/tissue loss: 52% repeat PTA vs 75% bypass) and in more extensive recurrent disease (TransAtlantic Inter-Society Consensus [TASC] II C/D lesions: 42% repeat PTA vs 67% bypass). Primary and repeat PTA had mean +/- standard error of the mean equivalent cumulative patency (73% +/- 9% vs 73% +/- 3% at 5 years) and duration of symptom relief (66% +/- 3% vs 63% +/- 6%). Bypass had significantly superior outcomes for patency (93% +/- 8%) and symptom relief (81% +/- 8%), but morbidity was 28% vs 16% for PTA. Critical ischemia, TASC-II lesion (C/D), and one-vessel tibial runoff were significant predictors of failure in the repeat PTA group. Reintervention is required in a minority of patients selected for SFA angioplasty. Bypass for recurrent disease is used more commonly for extensive disease and is associated with superior long-term outcomes but higher mortality. Bypass rather than repeat PTA may be the better strategy for progressive, complex recurrent disease.


Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function.
SB 203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4- pyridyl)imidazole], a selective cytokine suppressive binding protein/p38 kinase inhibitor, was evaluated in several models of cytokine inhibition and inflammatory disease. It was demonstrated clearly to be a potent inhibitor of inflammatory cytokine production in vivo in both mice and rats with IC50 values of 15 to 25 mg/kg. SB 203580 possessed therapeutic activity in collagen-induced arthritis in DBA/LACJ mice with a dose of 50 mg/kg resulting in significant inhibition of paw inflammation and serum amyloid protein levels. Antiarthritic activity was also observed in adjuvant-induced arthritis in the Lewis rat when SB 203580 was administered p.o. at 30 and 60 mg/kg. Evidence for disease-modifying activity in this model was indicated by an improvement in bone mineral density and by histological evaluation. Additional evidence for beneficial effects on bone resorption was provided in the fetal rat long bone assay in which SB 203580 inhibited 45Ca release with an IC50 of 0.6 microM. In keeping with the inhibitory effects on lipopolysaccharide-induced tumor necrosis factor-alpha in mice, SB 203580 was found to reduce mortality in a murine model of endotoxin-induced shock. In immune function studies in mice treated with SB 203580 (60 mg/kg/day for 2 weeks), there was some suppression of an antibody response to ovalbumin, whereas cellular immune functions measured ex vivo were unaffected. This novel profile of activity strongly suggests that cytokine inhibitors could provide significant benefit in the therapy of chronic inflammatory disease.


Porous silicene as a hydrogen purification membrane.
We investigated theoretically the hydrogen permeability and selectivity of a porous silicene membrane via first-principles calculations. The subnanometer pores of the silicene membrane are designed as divacancy defects with octagonal and pentagonal rings (585-divacancy). The porous silicene exhibits high selectivity comparable with graphene-based membranes for hydrogen over various gas molecules (N2, CO, CO2, CH4, and H2O). The divacancy defects in silicene are chemically inert to the considered gas molecules. Our results suggest that the porous silicene membrane is expected to find great potential in gas separation and filtering applications.


Regulation of cel genes of C. cellulolyticum: identification of GlyR2, a transcriptional regulator regulating cel5D gene expression.
Transcription and expression regulation of some individual cel genes (cel5A, cel5I, cel5D and cel44O) of Clostridium cellulolyticum were investigated. Unlike the cip-cel operon, these genes are transcribed as monocistronic units of transcription, except cel5D. The location of the transcription initiation sites was determined using RT-PCR and the mRNA 5'-end extremities were detected using primer extension experiments. Similarly to the cip-cel operon, cel5A and cel5I expressions are regulated by a carbon catabolite repression mechanism, whereas cel44O and cel5D expressions do not seem to be submitted to this regulation. The role of the putative transcriptional regulator GlyR2 in the regulation of cel5D expression was investigated. The recombinant protein GlyR2 was produced and was shown to bind in vitro to the cel5D and glyR2 promoter regions, suggesting that besides regulating its own expression, GlyR2 may regulate cel5D expression. To test this hypothesis in vivo, an insertional glyR2 mutant was generated and the effect of this disruption on cel5D expression was evaluated. Levels of cel5D mRNAs in the mutant were 16 fold lower than that of the wild-type strain suggesting that GlyR2 acts as an activator of cel5D expression.


Oxidative stress response in an anaerobe, Bacteroides fragilis: a role for catalase in protection against hydrogen peroxide.
Survival of Bacteroides fragilis in the presence of oxygen was dependent on the ability of bacteria to synthesize new proteins, as determined by the inhibition of protein synthesis after oxygen exposure. The B. fragilis protein profile was significantly altered after either a shift from anaerobic to aerobic conditions with or without paraquat or the addition of exogenous hydrogen peroxide. As determined by autoradiography after two-dimensional gel electrophoresis, approximately 28 newly synthesized proteins were detected in response to oxidative conditions. These proteins were found to have a broad range of pI values (from 5.1 to 7.2) and molecular weights (from 12,000 to 79,000). The hydrogen peroxide- and paraquat-inducible responses were similar but not identical to that induced by oxygen as seen by two-dimensional gel protein profile. Eleven of the oxidative response proteins were closely related, with pI values and molecular weights from 5.1 to 5.8 and from 17,000 to 23,000, respectively. As a first step to understanding the resistance to oxygen, a catalase-deficient mutant was constructed by allelic gene exchange. The katB mutant was found to be more sensitive to the lethal effects of hydrogen peroxide than was the parent strain when the ferrous iron chelator bipyridyl was added to culture media. This suggests that the presence of ferrous iron in anaerobic culture media exacerbates the toxicity of hydrogen peroxide and that the presence of a functional catalase is important for survival in the presence of hydrogen peroxide. Further, the treatment of cultures with a sublethal concentration of hydrogen peroxide was necessary to induce resistance to higher concentrations of hydrogen peroxide in the parent strain, suggesting that this was an inducible response. This was confirmed when the bacterial culture, treated with chloramphenicol before the cells were exposed to a sublethal concentration of peroxide, completely lost viability. In contrast, cell viability was greatly preserved when protein synthesis inhibition occurred after peroxide induction. Complementation of catalase activity in the mutant restored the ability of the mutant strain to survive in the presence of hydrogen peroxide, showing that the catalase (KatB) may play a role in oxidative stress resistance in aerotolerant anaerobic bacteria.


Validation and characterization of the computerized laryngeal analyzer (CLA) technique.
The aim of this study was to investigate the response characteristics of the Computerized Laryngeal Analyzer (CLA) and the validity of the noninvasive CLA method to detect swallowing-induced laryngeal elevation correctly. Two healthy adults and two experimental models were used in the study. The CLA technique identified all swallowing events but was unable to discriminate between swallowing and other movements of the tongue or the neck. The computer program produced a derivated response to a square wave signal. Stepwise bending increments of the sensor displayed a linear amplitude response. The degree of laryngeal elevation could not be estimated with the CLA technique, and it was not possible to draw any reliable conclusions from the recordings as to whether the larynx was moving upward or downward.


Gene clusters governing the production of hemolysin and mannose-resistant hemagglutination are closely linked in Escherichia coli serotype O4 and O6 isolates from urinary tract infections.
The genes encoding alpha-hemolysin and mannose-resistant hemagglutination were shown to be closely linked in cloned DNA from two Escherichia coli urinary tract isolates of serotypes O4 (J96) and O6 (C1212). DNA hybridization experiments demonstrated that the hly and mrh gene clusters of other E. coli O6 serotypes were also linked. Colony hybridizations showed that most normal fecal E. coli do not contain hly and mrh DNA but much of the intervening DNA between these two gene clusters is common among all E. coli. We have further demonstrated that there is a small (about 1 kilobase) region of homology located on both sides of the hly sequence and present elsewhere in the C1212 strain. We suggest that linkage of hly and mrh occurred through a transposition event, and we discuss the potential significance of this linkage in the acquisition of virulence determinants by these bacteria.


HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration.
The capsid (CA) lattice of the HIV-1 core plays a key role during infection. From the moment the core is released into the cytoplasm, it interacts with a range of cellular factors that, ultimately, direct the pre-integration complex to the integration site. For integration to occur, the CA lattice must disassemble. Early uncoating or a failure to do so has detrimental effects on virus infectivity, indicating that an optimal stability of the viral core is crucial for infection. Here, we introduced cysteine residues into HIV-1 CA in order to induce disulphide bond formation and engineer hyper-stable mutants that are slower or unable to uncoat, and then followed their replication. From a panel of mutants, we identified three with increased capsid stability in cells and found that, whilst the M68C/E212C mutant had a 5-fold reduction in reverse transcription, two mutants, A14C/E45C and E180C, were able to reverse transcribe to approximately WT levels in cycling cells. Moreover, these mutants only had a 5-fold reduction in 2-LTR circle production, suggesting that not only could reverse transcription complete in hyper-stable cores, but that the nascent viral cDNA could enter the nuclear compartment. Furthermore, we observed A14C/E45C mutant capsid in nuclear and chromatin-associated fractions implying that the hyper-stable cores themselves entered the nucleus. Immunofluorescence studies revealed that although the A14C/E45C mutant capsid reached the nuclear pore with the same kinetics as wild type capsid, it was then retained at the pore in association with Nup153. Crucially, infection with the hyper-stable mutants did not promote CPSF6 re-localisation to nuclear speckles, despite the mutant capsids being competent for CPSF6 binding. These observations suggest that hyper-stable cores are not able to uncoat, or remodel, enough to pass through or dissociate from the nuclear pore and integrate successfully. This, is turn, highlights the importance of capsid lattice flexibility for nuclear entry. In conclusion, we hypothesise that during a productive infection, a capsid remodelling step takes place at the nuclear pore that releases the core complex from Nup153, and relays it to CPSF6, which then localises it to chromatin ready for integration.


[NAG vibrio sensitivity to antibiotics].
Sensitivity of 575 NAG-vibrio strains isolated from various substrates in 1978-1980 to 14 antibiotics was studied and compared with the results of an analogous study performed in 1968 by Z. V. Ermolyeva et al. It was shown that sensitivity of NAG-vibrio to chloramphenicol, ampicillin, cephaloridine and streptomycin decreased. However, NAG-vibrio remain to be sensitive to tetracycline, chloramphenicol and gentamicin. Resistance of the majority of the strains to ampicillin, carbenicillin, cephaloridine and polymyxin M was noted.


Management of injuries to the anterior cruciate ligament: results of a survey of orthopaedic surgeons in Canada.
To identify the approaches to management of anterior cruciate ligament (ACL) injury by Canadian orthopedic surgeons. A questionnaire was mailed to 234 physicians randomly chosen from the Canadian Orthopaedic Association directory to obtain the following information: 1) how orthopaedic surgeons diagnose acute hemarthroses; 2) how patients in any of three common ACL injury scenarios would be managed; 3) what variations exist in surgical technique; and 4) how patient variables such as age, gender, and alignment influence the decision-making process. The return rate was 72%, and 56% of respondents were from academic centers. Patients such as those described in the protocol are routinely managed by 80% of the respondents. The diagnosis of acute hemarthrosis is predominantly made by means of clinical examination and radiographs. Magnetic resonance imaging (MRI) is used occasionally by 43% and routinely by 6% of those who responded; arthroscopy is used routinely by 24%. For the competitive athlete with a complete ACL tear, 64% would recommend reconstruction and 33% would recommend bracing and rehabilitation. For reconstruction, 59% would use bone-patellar tendon-bone (B-PT-B) autograft and 32% would use hamstring tendon autograft; 40% would incorporate the ACL stump during reconstruction. Of the respondents, 77% would advocate ACL reconstruction for competitive athletes with chronic ACL injury. Of these, 63% would use B-PT-B autograft and 27% would use hamstring tendons. If bracing and rehabilitation failed, 98% would recommend ACL reconstruction. In ACL reconstruction, synthetic augmentation would be used by 12% in chronic cases and by 16% in acute cases. In making the decision to perform ACL reconstruction, 53% consider limb alignment to be important and 67% consider moderate patellofemoral pain to be important. Seventy-one percent are influenced by patellofemoral pain when choosing a surgical technique, with a trend toward semitendinosis autograft rather than B-PT-B autograft reconstruction. For the 8-year-old child with an acute ACL injury, 63% of the respondents would recommend rehabilitation and bracing. For the 14-year-old, 45% would recommend rehabilitation and bracing and 37% would recommend ACL reconstruction after physeal closure. The results of the survey indicate that, with respect to some of the issues, there is a wide variation in management of acute and chronic ACL injuries among Canadian orthopedic surgeons. Future research and randomized, controlled clinical trials should be directed toward these areas.


Molecular analysis of bacterial diversity in kerosene-based drilling fluid from the deep ice borehole at Vostok, East Antarctica.
Decontamination of ice cores is a critical issue in phylogenetic studies of glacial ice and subglacial lakes. At the Vostok drill site, a total of 3650 m of ice core have now been obtained from the East Antarctic ice sheet. The ice core surface is coated with a hard-to-remove film of impure drilling fluid comprising a mixture of aliphatic and aromatic hydrocarbons and foranes. In the present study we used 16S rRNA gene sequencing to analyze the bacterial content of the Vostok drilling fluid sampled from four depths in the borehole. Six phylotypes were identified in three of four samples studied. The two dominant phylotypes recovered from the deepest (3400 and 3600 m) and comparatively warm (-10 degrees C and -6 degrees C, respectively) borehole horizons were from within the genus Sphingomonas, a well-known degrader of polyaromatic hydrocarbons. The remaining phylotypes encountered in all samples proved to be human- or soil-associated bacteria and were presumed to be drilling fluid contaminants of rare occurrence. The results obtained indicate the persistence of bacteria in extremely cold, hydrocarbon-rich environments. They show the potential for contamination of ice and subglacial water samples during lake exploration, and the need to develop a microbiological database of drilling fluid findings.


Predictors of chronic kidney disease and utility of risk prediction scores in HIV-positive individuals.
The current study aimed to validate existing risk prediction scores and identify predictors of chronic kidney disease (CKD) in the setting of HIV. A retrospective cohort study of HIV-positive individuals (n = 748) with baseline estimated glomerular filtration rate (eGFR) more than 60 ml/min was conducted at the Alfred Hospital, Melbourne, Australia. Multivariable regression analysis was performed to determine factors associated with development of CKD, defined as two consecutive measurements of eGFR less than 60 ml/min. The performance of CKD risk scores proposed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group and Scherzer and colleagues were estimated by the area under the receiver operator curve (AUROC). CKD developed in 37 individuals (5.0%), at a median of 4.7 (interquartile range 2.2, 6.2) years. Older age [odds ratio (OR) 3.03, 95% confidence interval (CI): 1.20, 7.65, P = 0.02] and lower baseline eGFR (OR 10.39, 95% CI: 4.73, 22.83, P < 0.001) were associated with the development of CKD. Neither current, nor cumulative tenofovir disoproxil fumarate (TDF) use was associated with progression to CKD [current TDF hazard ratio (HR) 1.05, 95% CI: 0.54, 2.07, P = 0.88; cumulative TDF HR 1.03, 95% CI: 0.86, 1.24, P = 0.75]. The short D:A:D and Scherzer scores were well calibrated, with the short D:A:D score demonstrating superior discrimination (short D:A:D AUROC 0.85, Scherzer AUROC 0.78, P = 0.02). Older individuals and those with a lower baseline eGFR are at higher risk for CKD. Risk prediction tools may be useful in identifying those at greatest risk, who may benefit from aggressive management of risk factors.


Intraocular dendritic cells characterize HLA-B27-associated acute anterior uveitis.
Uveitis describes a heterogeneous group of inflammatory eye diseases characterized by infiltration of leukocytes into the uveal tissues. Uveitis associated with the HLA haplotype B27 (HLA-B27) is a common subtype of uveitis and a prototypical ocular immune-mediated disease. Local immune mechanisms driving human uveitis are poorly characterized mainly due to the limited available biomaterial and subsequent technical limitations. Here, we provide the first high-resolution characterization of intraocular leukocytes in HLA-B27-positive (n = 4) and -negative (n = 2) anterior uveitis and an infectious endophthalmitis control (n = 1) by combining single-cell RNA-sequencing with flow cytometry and protein analysis. Ocular cell infiltrates consisted primarily of lymphocytes in both subtypes of uveitis and of myeloid cells in infectious endophthalmitis. HLA-B27-positive uveitis exclusively featured a plasmacytoid and classical dendritic cell (cDC) infiltrate. Moreover, cDCs were central in predicted local cell-cell communication. This suggests a unique pattern of ocular leukocyte infiltration in HLA-B27-positive uveitis with relevance to DCs.


Differential effects of haloperidol and clozapine on ionotropic glutamate receptors in rats.
Despite multiple lines of investigation the effect of neuroleptics on glutamate-mediated neurotransmission remains controversial. To study the effects of typical and atypical neuroleptics on selected parameters of glutamate-mediated neurotransmission, male Sprague-Dawley rats were randomly assigned to a 21-day oral treatment course with vehicle, haloperidol (HDL), or clozapine (CLZ). Coronal slices of rat brain were then incubated with tritiated ligands to measure NMDA, AMPA, and kainate receptor, and glutamate reuptake site density. Regions of interest included the frontal cortex, anterior cingulate cortex, dorsal striatum, ventral striatum, and the nucleus accumbens. CLZ increased the density of AMPA receptors significantly in the frontal and anterior cingulate cortices compared with normal controls. In the dorsal and ventral striatum, and nucleus accumbens as a whole, CLZ-treated rats had a higher AMPA receptor density compared with both the HDL- and vehicle-treated controls. Additionally, within the nucleus accumbens, CLZ-treated rats had a higher density of AMPA receptors compared with the HDL group in the core, and at trend level in the shell. There was a group by region interaction for NMDA receptor density, primarily reflecting the tendency of HDL treated rats to have high receptor densities in the frontal and anterior cingulate cortices. Kainate receptors and glutamate reuptake site densities did not differ significantly across groups. These results suggest a critical role for glutamate in the mediation of atypical antipsychotic drug action in anatomically-specific regions, and further encourage the investigation of glutamate neurotransmitter systems in schizophrenia.


[Alexithymia in personal characteristics of patients with coronary heart diseases].
Psychological status was assessed in 120 patients with coronary heart disease (CHD) according to MMPI, Toronto alexithymic scale. Alexithymia was diagnosed in 49.1% of the examinees. They were characterized by difficulties in definition of their feelings, absence of dreams and fantasies, introversion, inclination to depressive response to stress, hypochondria eventuating in senesthopathy. The above psychological and pathopsychological traits in CHD patients require psychotherapeutic and chemotherapeutic correction in order to enhance efficacy of the treatment.


Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial.
Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.


Unused natural variation can lift yield barriers in plant breeding.
Natural biodiversity is an underexploited sustainable resource that can enrich the genetic basis of cultivated plants with novel alleles that improve productivity and adaptation. We evaluated the progress in breeding for increased tomato (Solanum lycopersicum) yield using genotypes carrying a pyramid of three independent yield-promoting genomic regions introduced from the drought-tolerant green-fruited wild species Solanum pennellii. Yield of hybrids parented by the pyramided genotypes was more than 50% higher than that of a control market leader variety under both wet and dry field conditions that received 10% of the irrigation water. This demonstration of the breaking of agricultural yield barriers provides the rationale for implementing similar strategies for other agricultural organisms that are important for global food security.


Investigation of the infertile couple: a one-stop outpatient endoscopy-based approach.
Transvaginal hydrolaparoscopy (THL) is a new culdoscopic technique for exploration of the pelvic cavity that takes advantage of micro-endoscopic technology and uses aquaflotation for inspection of the tubo-ovarian structures. In infertility patients, THL is systematically combined with mini-hysteroscopy, chromopertubation, fimbrioscopy and, when indicated, salpingoscopy. Mini-hysteroscopy in combination with the chromopertubation test allows accurate assessment of the uterine cavity and tubal patency. The transvaginal access combined with the aquaflotation during THL facilitates detailed inspection of the tubo-ovarian structures and detection of subtle pelvic disease. This combined transvaginal endoscopic approach allows complete evaluation of the reproductive tract. THL is better tolerated than hysterosalpingography, less invasive than standard laparoscopy, and can be used safely as a first line investigation of the female partner in a one-stop infertility clinic.


[Echo- and electrocardiographic signs of different forms of hypertrophic cardiomyopathy].
Twenty-six patients with idiopathic and secondary hypertrophic cardiomyopathies were examined. The diagnostic value of echo- and electrocardiographic signs of hypertrophic cardiomyopathy is discussed, the more important among those being the thickness and shape of the interventricular septum, anterosystolic movement of the anterior cusp of the mitral valve, electrocardiographic evidence of left-ventricular hypertrophy and left-atrial changes, abnormal Q waves.


Factor XIII-A subunit Val34Leu polymorphism is associated with the risk of thrombosis in patients with antiphospholipid antibodies and high fibrinogen levels.
Recent reports have described the factor XIII A subunit (FXIII-A) Val34Leu polymorphism as a protective factor against venous and arterial thrombosis. The aim of this study was to investigate the association between the FXIII-A Val34Leu polymorphism, its interaction with fibrinogen concentration, and thrombosis in patients with antiphospholipid antibodies (aPL). We included 172 consecutive patients with aPL: 88 with primary antiphospholipid syndrome (APS), 38 with APS associated with systemic lupus erythematosus (APS-SLE), 32 with SLE and aPL but without APS (SLE-aPL), and 14 asymptomatic individuals with aPL (A-aPL). The FXIII-A Val34Leu polymorphism was assessed by polymerase chain reaction techniques. We found no significant differences in FXIII-A Leu34 allele frequencies between primary APS (allele frequency 0.22), APS-SLE (0.23), SLE-aPL (0.22) and A-aPL (0.32) patients, or between patients with (0.21) and without thrombosis (0.26). FXIII-A Leu34 allele frequencies were significantly lower in patients with thrombosis and those in the upper fibrinogen tertile (>3.40 g/l) (allele frequency 0.07) compared with patients without thrombosis in the upper fibrinogen tertile (0.29) and patients with (0.29) and without (0.25) thrombosis in the mid- and lower fibrinogen tertiles. The FXIII-A Leu34 allele had a protective effect against thrombosis in patients in the upper fibrinogen tertile (odds ratio [OR] = 0.20, 95% confidence interval [CI] 0.07-0.60) but not in those in the other tertiles (OR = 1.20, 95% CI 0.67-2.16). The FXIII-A Leu34 allele seems to have a protective effect on the development of thrombosis in patients with aPL, but only in those with high plasma fibrinogen values.


[Effect of soy isoflavones on the incidence of 7, 12-dimethylbenz (alpha) anthracene-induced breast tumors in rats].
To study the effect of soy isoflavones (SI) at various doses on the incidence of breast tumors induced by 7, 12-dimethyl-benz(a) anthracene (DMBA) in ovariectomized and normal rats. 96 SD female rats were randomly divided into ovariectomized group and normal group. Rats in the former group were ovariectomized, then those in each group were randomly placed into six subgroups: blank control, positive control, estrogen control, SI of high dose (100 mg/kg SI), moderate dose (50 mg/kg SI) and low dose(10 mg/kg SI) group according to the body weight. All rats received a single oral dose of 5 mg DMBA, except for the blank control and were palpated weekly to monitor the tumor development. Body weight and diet intake were also recorded weekly. Rats were executed 24 weeks after DMBA administration, the incidence of breast tumors in each group was computed and the activities of superoxide dismutase (SOD) and contents of malondialdehyde (MDA) in rats' plasma were examined. Compared with the positive group, incidence of breast tumors in ovariectomized rats at high, moderate and low dose SI group was not statistically different (P>0.05), and the activities of SOD in those groups were statistically lower(P<0.01); however, incidence of breast tumors in normal rats at high and moderate dose SI group was statistically different from the positive group (P<0.01), and the activities of SOD in those groups were statistically higher(P<0.01). SI of 50 mg/kg and 100 mg/kg could decrease the incidence of breast tumors in normal rats, which may be related to the higher activities of SOD induced by SI; however, SI could not decrease the incidence of breast tumors and inhibit the activities of SOD in ovariectomized rats. The effects of SI on the incidence of breast tumors and antioxidant activities may be influenced by different basal levels of estrogen in ovariectomized and normal rats.


Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil.
Type I and II inosine monophosphate dehydrogenases (IMPDH) are the targets of mycophenolic acid (MPA), a widely used immunosuppressant. The aims of this study were: to check the presence of controversial polymorphisms in the IMPDH II gene; to look for new ones; and to investigate potential associations between the most frequent SNPs in both IMPDH genes and clinical outcome in renal transplant recipients. The DNA and clinical data of 456 patients from two clinical trials were collected. We sequenced the IMPDH II gene in 80 patients and we genotyped the 456 patients' DNA for the IMPDH II rs4974081, rs11706052, 787C>T and the IMPDH I rs2278293 and rs2278294 SNPs, all of which were earlier reported to be potentially involved in MPA treatment related outcome. We investigated the associations of biopsy proven acute rejection (BPAR), leucopenia, cytomegalovirus infections and other infections with these IMPDH polymorphisms, as well as with demographic, biological and treatment data using multivariate analysis. Many IMPDH II variant alleles referenced in Genbank were not detected and no new polymorphisms were identified. In the whole group of 456 patients, the IMPDH I rs2278294 SNP was associated with a lower risk of BPAR and a higher risk of leucopenia over the first year post-transplantation. No other IMPDH I or IMPDH II polymorphism was significantly associated with any clinical outcome. Interestingly, calcineurin inhibitor and MPA exposures below the therapeutic range increased the risk of BPAR. Cytomegalovirus infection was the factor most closely linked with leucopenia, whereas tacrolimus was associated with fewer infections than cyclosporine. IMPDH II genotyping may not improve MPA treatment outcome over the first year post-transplantation, in contrast to MPA and calcineurine inhibitor therapeutic drug monitoring and IMPDH I genotyping.


Are Malaysian Diabetic Patients Ready to Use The New Generation of Health Care Service Delivery? A Telehealth Interest Assessment.
The idea of launching an internet-based self-management program for patients with diabetes led us to do a cross-sectional study to find out about the willingness, interest, equipment, and level of usage of computer and internet in a medium- to low-social class area and to find the feasibility of using e-telemonitoring systems for these patients. A total of 180 patients with type 2 diabetes participated in this study and fulfilled the self-administered questionnaire in Diabetes Clinic of Primary Medical Center of University Kebangsaan Malaysia Medical Centre; the response rate was 84%. We used the universal sampling method and assessed three groups of factors including sociodemographic, information and communication technology (ICT), willingness and interest, and disease factors. Our results showed that 56% of the patients with diabetes were interested to use such programs; majority of the patients were Malay, and patients in the age group of 51-60 years formed the largest group. Majority of these patients studied up to secondary level of education. Age, education, income, and money spent for checkup were significantly associated with the interest of patients with diabetes to the internet-based programs. ICT-related factors such as computer ownership, computer knowledge, access to the internet, frequency of using the internet and reasons of internet usage had a positive effect on patients' interest. Our results show that among low to intermediate social class of Malaysian patients with type 2 diabetes, more than 50% of them can and wanted to use the internet-based self-management programs. Furthermore, we also show that patients equipped with more ICT-related factors had more interest toward these programs. Therefore, we propose making ICT more affordable and integrating it into the health care system at primary care level and then extending it nationwide.


Role of complement during experimental Candida infection in mice.
The role of complement during experimental Candida albicans infection was investigated in mice. It was found that complement-positive CF-1 mice, infected with the test organism, survived significantly longer than complement-deficient mice of the same strain. This implies the participation of the relatively late acting complement component in host defense mechanisms directed against this systemic mycotic infection.


Effect of dietary methylmercury and seleno-methionine on Sacramento splittail larvae.
The effects of methylmercury (MeHg) and selenium (Se) contamination on food webs in the San Francisco Estuary have received considerable attention during the past decade. However, knowledge of their effects on native fishes of California is lacking. This study investigated the interactive effects of dietary MeHg and seleno-methionine (SeMet) on Sacramento splittail (Pogonichthys macrolepidotus) larvae. Twelve diets containing increasing levels of SeMet (0.64, 8.2 and 35.0 microg Se g(-1) diet) and MeHg (0.01, 0.13, 4.7 and 11.7 microg Hg g(-1) diet) were fed to 21-day post-hatch larvae for 4 weeks in 2-L beakers at 25 degrees C. Fish were fed twice a day at a feeding rate of 40, 30, 25 and 20% of body weight during the 1st, 2nd, 3rd and 4th week, respectively. At the end of week 4, no significant difference (P>0.05) was observed among treatments for mortality, body length or weight, and condition factor. Bioaccumulation of Hg and Se responded positively and significantly (P<0.05) to their dietary concentrations. The molar ratio of Se/Hg in diets was linearly correlated to the ratio of Se/Hg in fish. Dietary Se inhibited Hg accumulation, which was negatively correlated to the dietary Se/Hg ratio. Histopathological examination revealed severe gill anomaly and liver glycogen depletion in fish fed the 11.7 microg Hg g(-1) diet. Liver glycogen depletion and kidney tubular dilation were found in larvae fed the 11.7 microg Hg and 11.7 microg Hg+35 microg Se g(-1) diets. In conclusion, dietary Hg enhanced Se accumulation but dietary Se inhibited Hg accumulation in splittail. Dietary Se showed a protective effect in fish fed the high MeHg diet. This protection was related to the dietary Se/Hg ratio, which is a more reliable criterion for evaluating the interactive effect between Se and Hg in splittail.


Amino-acid sequence data of beta-tubulin from Physarum polycephalum myxamoebae.
Starting with 7.7 mg of a beta-tubulin isolated from myxamoebae of the slime mould Physarum polycephalum, 90% of the sequence has been determined by the Edman degradation of peptides generated by cyanogen bromide, trypsin and Staphylococcus aureus protease. Differences to other beta-tubulins are mainly conservative and spread evenly throughout the chain except for a high concentration at the C-terminus. The Physarum beta-tubulin shows most homology to Chlamydomonas beta-tubulin (90.5%) and least homology to yeast beta-tubulin (S. cerevisiae, 73.4%). Two tryptic peptides were isolated in approximately equal quantities which were identical except in one position (S/ALTVPELTQRMFDA) showing that at least two beta-tubulins are present in myxamoebae. However, since this was the only heterogeneity found, these beta-tubulins are probably very similar.


Substrate Distortion and the Catalytic Reaction Mechanism of 5-Carboxyvanillate Decarboxylase.
5-Carboxyvanillate decarboxylase (LigW) catalyzes the conversion of 5-carboxyvanillate to vanillate in the biochemical pathway for the degradation of lignin. This enzyme was shown to require Mn(2+) for catalytic activity and the kinetic constants for the decarboxylation of 5-carboxyvanillate by the enzymes from Sphingomonas paucimobilis SYK-6 (kcat = 2.2 s(-1) and kcat/Km = 4.0 × 10(4) M(-1) s(-1)) and Novosphingobium aromaticivorans (kcat = 27 s(-1) and kcat/Km = 1.1 × 10(5) M(-1) s(-1)) were determined. The three-dimensional structures of both enzymes were determined in the presence and absence of ligands bound in the active site. The structure of LigW from N. aromaticivorans, bound with the substrate analogue, 5-nitrovanillate (Kd = 5.0 nM), was determined to a resolution of 1.07 Å. The structure of this complex shows a remarkable enzyme-induced distortion of the nitro-substituent out of the plane of the phenyl ring by approximately 23°. A chemical reaction mechanism for the decarboxylation of 5-carboxyvanillate by LigW was proposed on the basis of the high resolution X-ray structures determined in the presence ligands bound in the active site, mutation of active site residues, and the magnitude of the product isotope effect determined in a mixture of H2O and D2O. In the proposed reaction mechanism the enzyme facilitates the transfer of a proton to C5 of the substrate prior to the decarboxylation step.


Cytology of suture granulomas in post-hysterectomy vaginal smears.
In histologic sections, foreign body giant cells are often associated with a granulomatous reaction to embedded suture material. However, this finding is unusual in exfoliative cytology samples. We describe the cytologic findings associated with suture granulomas in nine vaginal smears obtained from four women, ages 53 to 72. The patients had undergone hysterectomy for endometrial adenocarcinoma (three patients) and cervical carcinoma in situ (one patient). Smears taken 6 to 34 mo after surgery showed a moderate to severe acute inflammatory reaction, foreign body giant cells, and polarizable suture material. A vaginal cuff biopsy from one patient confirmed the diagnosis. Although multinucleated giant cells in postmenopausal vaginal smears are usually a non-specific finding, phagocytosed refractile material observed post hysterectomy may reflect a chronic tissue reaction to suture material. The presence of an acute inflammatory reaction, foreign body type giant cells, and the appropriate past surgical history, should prompt the pathologist to rapidly screen the slide under polarized light to evaluate the possibility of suture granulomas.


Regulation of insulin secretion from beta-cell lines derived from transgenic mice insulinomas resembles that of normal beta-cells.
Insulin secretory physiology has been characterized in tumor cell lines derived by primary culture of insulinomas that developed in transgenic mice expressing the large T-antigen of SV40 in pancreatic islet beta-cells. Cells in one of these lines, beta TC-3, contain large amounts of insulin (3100 +/- 294 ng/100 micrograms cellular protein). Constitutive release of insulin over 2 h in static incubation was low at 31.9 ng/100 micrograms protein and was increased 2-fold by glucose (16.7 mM) and 8-fold by depolarizing concentrations of potassium (45 mM). Isobutylmethylxanthine (IBMX; 0.5 mM) and forskolin (5 and 50 microM), which elevated cellular levels of cAMP, were ineffective as secretagogues, but dramatically potentiated glucose and potassium effects on insulin release (6.5- and 4-fold, respectively). A variety of other known insulin secretagogues stimulated insulin release in a manner analogous to their effects in normal islets. The sulfonylurea glipizide (1 microM) and the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (1 microM) stimulated insulin release 3.4- and 13.7-fold, respectively. The cholinergic agonist carbachol (2 microM) was ineffective alone, but potentiated glucose-induced insulin release 2.8-fold. Comparable stimulation of insulin release by glucose (16.7 mM) and glucose (16.7 mM) plus IBMX (0.5 mM) was noted with several other beta TC lines, which were derived independently from separate transgenic mice. Glucose- and glucose- plus IBMX (0.5 mM)-induced insulin release occurred progressively from 0.15-16.7 mM, indicating that insulin release from beta TC-3 cells occurred at much lower levels than that from normal islets. However, as in the normal islet, the glucose concentration dependency for insulin release was highly correlated (r = 0.93) with the glucose concentration dependency for glucose utilization (measured by 3H2O formation from [5-3H]glucose). This suggests that glucose induces insulin release from beta TC-3 cells by a mechanism similar to that in the normal islet. The high insulin content, the multifold stimulation of insulin release by a variety of secretagogues, their convenient propagation in culture, and the renewable source of these cell lines make the beta TC cells a convenient model for studies of beta-cell function.


Strategy for optimizing LC-MS data processing in metabolomics: a design of experiments approach.
A strategy for optimizing LC-MS metabolomics data processing is proposed. We applied this strategy on the XCMS open source package written in R on both human and plant biology data. The strategy is a sequential design of experiments (DoE) based on a dilution series from a pooled sample and a measure of correlation between diluted concentrations and integrated peak areas. The reliability index metric, used to define peak quality, simultaneously favors reliable peaks and disfavors unreliable peaks using a weighted ratio between peaks with high and low response linearity. DoE optimization resulted in the case studies in more than 57% improvement in the reliability index compared to the use of the default settings. The proposed strategy can be applied to any other data processing software involving parameters to be tuned, e.g., MZmine 2. It can also be fully automated and used as a module in a complete metabolomics data processing pipeline.


Levodopa response in dementia with lewy bodies: a 1-year follow-up study.
To evaluate levodopa responsiveness in patients with probable dementia with Lewy bodies (DLB) compared to early Parkinson's disease (PD) patients. Twenty four cases with DLB and 21 with PD underwent a baseline assessment with UPDRS (sub-item II and III) and an acute levodopa challenge test. Positive response to acute levodopa test was defined as an improvement of at least 15% in the tapping test, and at least 25% in the walking test and rigidity or tremor score. Subsequently, all patients were treated continuously with levodopa and evaluated after 6 and 12 months by means of UPDRS II/III. Positive response to the acute levodopa test was observed in 55% of DLB patients (acute DLB responders), and in 90% of PD patients (acute PD responders). Acute DLB responders showed increased latency, and reduction of both duration and amplitude of response to acute levodopa in comparison with acute PD responders. At the 6-month follow-up visit, acute DLB responders showed a greater motor benefit compared with acute DLB non-responders. This improvement was similar to that observed in PD patients. However, at 1-year follow-up acute DLB responders showed a faster worsening of UPDRS III scores compared with acute PD responders, implying a reduction of levodopa efficacy. Positive response to acute levodopa test can occur in DLB patients and may be predictive of long-term benefit of chronic levodopa therapy, although the motor improvement is less impressive than in PD patients.


TiN-alloy coatings for temperature control of space vessels.
The problem of combining the temperature control of a space vehicle with the mechanical and chemical stability of the surface is addressed. With the absorption of solar radiation and the emission of thermal radiation considered the static and dominant factors that determine the equilibrium temperature of a spherical object, a simple model is formulated. Realistic variations of the two material-dependent parameters, solar absorptance alpha and hemispherical emittance epsilon, permit a large change in the equilibrium temperature, from less than -50 to more than +150 degrees C. It is pointed out that for a generalized gray surface, i.e., one made from a material whose reflectance-emittance has the same value within the visible and the thermal wavelength regions, the equilibrium temperature is approximately 5 degrees C, independent of the numerical value of the reflectance. With the requirement for electrical conductivity also taken into account, TiN alloys are identified as candidate materials. Measurements and calculations of some of them indicate that this group may contain a material that fulfills all the requirements. The experimental reflectance spectrum is used in estimating the equilibrium temperature for different TiN alloys; one Ti-Al-N-alloy with a gradient content of Al is found to have the lowest equilibrium temperature, 66 degrees C.


Amorphous calcium phosphate-containing orthodontic cement for band fixation: an in vitro study.
To evaluate the shear bond strength (SBS) and fracture mode of amorphous calcium phosphate (ACP)-containing and conventional glass-ionomer cement (GIC) for band fixation. Sixty extracted human third molars were embedded in acrylic resin blocks, leaving the buccal surface of the crowns parallel to the base of the molds. The teeth were randomly divided into two groups containing 30 teeth each. GIC (group 1, Ketac-Cem) or ACP-containing orthodontic cement (group 2, Aegis-Ortho) was applied onto microetched strip band material (4.0 × 3.8 mm), which was then attached to the tooth surfaces. With a universal testing machine, each cemented band strip was shear mode loaded until failure. Thereafter, all teeth and band strips were examined under 10× magnification. The remaining cement was assessed with a modified Adhesive Remnant Index (ARI). The SBS data were analyzed using the t test and the fracture modes by the chi-square test. There was no significant difference between the bond strength of group 1 (GIC, mean: 28.9 ± 15.2 MPa) and group 2 (ACP-containing cement, mean: 26.3 ± 11.8 MPa). The fracture modes differed significantly between the two groups (P<.01). Both groups had a similar level of SBS. The fracture sites of the ACP-containing cement were predominantly in the enamel-cement interface.


Self-Care Index and Post-Acute Care Discharge Score to Predict Discharge Destination of Adult Medical Inpatients: Protocol for a Multicenter Validation Study.
Delays in patient discharge can not only lead to deterioration, especially among geriatric patients, but also incorporate unnecessary resources at the hospital level. Many of these delays and their negative impact may be preventable by early focused screening to identify patients at risk for transfer to a post-acute care facility. Early interprofessional discharge planning is crucial in order to fit the appropriate individual discharge destination. While prediction of discharge to a post-acute care facility using post-acute care discharge score, the self-care index, and a combination of both has been shown in a single-center pilot study, an external validation is still missing. This paper outlines the study protocol and methodology currently being used to replicate the previous pilot findings and determine whether the post-acute care discharge score, the self-care index, or the combination of both can reliably identify patients requiring transfer to post-acute care facilities. This study will use prospective data involving all phases of the quasi-experimental study "In-HospiTOOL" conducted at 7 Swiss hospitals in urban and rural areas. During an 18-month period, consecutive adult medical patients admitted to the hospitals through the emergency department will be included. We aim to include 6000 patients based on sample size calculation. These data will enable a prospective external validation of the prediction instruments. We expect to gain more insight into the predictive capability of the above-mentioned prediction instruments. This approach will allow us to get important information about the generalizability of the three different models. The study was approved by the institutional review board on November 21, 2016, and funded in May 2020. Expected results are planned to be published in spring 2021. This study will provide evidence on prognostic properties, comparative performance, reliability of scoring, and suitability of the instruments for the screening purpose in order to be able to recommend application in clinical practice. DERR1-10.2196/21447.


Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison with culture and Xpert® MTB/RIF.
Enhanced tuberculosis (TB) case finding using detection rats in Tanzania. To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients. A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert. Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone. Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.


Efficacy Assessment of the High-Frequency High-Intensity Focused Ultrasound as a New Treatment for Actinic Keratosis.
Actinic keratosis (AK) is the most common precancerous cutaneous lesion, with risk of progression to cutaneous squamous cell carcinoma. In the current study, we evaluated the efficacy of 20-MHz high-intensity focused ultrasound (HIFU), as a new treatment modality for AK. Patients with AK lesions (grades I-III) treated with HIFU were included in the study. The clinical assessment was performed 3 months after therapy. Twenty-one patients (14 men, 7 women) with 108 AK lesions (grades I-III) were included in the current study. Ages ranged from 62 to 85 years (mean 72.6 years). Clinically complete resolution of the actinic damage in the treated area was detected in 72.2% of lesions. Furthermore, 28 lesions (26%) showed a reduction of the AK grade, or partial response, after the therapy. Most of the patients experienced annoying but short pain during the procedure. However, late adverse effects of the therapy, such as hypopigmentation, hyperpigmentation and erythema were reported only in a small portion of the lesions. 20-MHz HIFU could be an effective and safe alternative treatment for AK.


Mathematics summer schools for acoustics research training.
Mathematical methods are important for research in many aspects of acoustics. Most researchers in acoustics in the United Kingdom do not have access to master level courses to broaden their postgraduate study, so they advance their fundamental mathematical methodologies taught at undergraduate level through independent learning. They develop their mathematical skills as appropriate rather than being made aware of the potential of advanced mathematical tools at the onset of their research career. Attempts to improve this situation were made through summer schools held in 2003 and 2005 at Southampton University and in 2007 at Salford University. The background to these Summer Schools, their content and structure, recruitment figures and student feedback are reported together with conclusions about their performance and role particularly in respect of PhD completion.


Radiosynoviorthesis in haemophilic joint disease.
The effects of radiosynoviorthesis on chronic haemophilic arthropathic joints were studied in six patients with severe haemophilia by a follow up study which spanned two and a half years. On clinical grounds the treatment was successful because pain and bleeding frequency diminished, although radiographic examination showed further deterioration of the treated joint. Chromosome damage was not detected. We conclude that radiosynoviorthesis is apparently changing the bleeding pattern of articular tissues without arresting the destruction and deformation of joints.


Accuracy and calibration of commercial oligonucleotide and custom cDNA microarrays.
We compared the accuracy of microarray measurements obtained with oligonucleotide arrays (GeneChip, Affymetrix) with a laboratory-developed cDNA array by assaying test RNA samples from an experiment using a paradigm known to regulate many genes measured on both arrays. We selected 47 genes represented on both arrays, including both known regulated and unregulated transcripts, and established reference relative expression measurements for these genes in the test RNA samples using quantitative reverse transcriptase real-time PCR (QRTPCR) assays. The validity of the reproducible (average coefficient of variation = 11.8%) QRTPCR measurements were established through application of a new mathematical model. The performance of both array platforms in identifying regulated and non-regulated genes was identical. With either platform, 16 of 17 definitely regulated genes were correctly identified, and no definitely unregulated transcript was falsely identified as regulated. Accuracy of the fold-change measurements obtained with each platform was assessed by determining measurement bias. Both platforms consistently underestimate the relative changes in mRNA expression between experimental and control samples. The bias observed with cDNA arrays was predictable for fold-changes <250-fold by QRTPCR and could be corrected by the calibration function F(c) = F(a(cDNA))(q), where F(a(cDNA)) is the microarray-determined fold-change comparing experimental with control samples, q is the correction factor and F(c) is the calibrated value. The bias observed with the commercial oligonucleotide arrays was less predictable and calibration was unfeasible. Following calibration, fold-change measurements generated by custom cDNA arrays were more accurate than those obtained by commercial oligonucleotide arrays. Our study demonstrates systematic bias of microarray measurements and identifies a calibration function that improves the accuracy of cDNA array data.


Molecular and cellular pathology of hepatocellular carcinoma.
Mutations of the p53 gene are common in hepatocellular carcinoma (HCC) and have been found in 13-33% of HCC in Asia and 23% of HCC in Hong Kong. In addition, p53 overexpression has been found to be associated with poorer cellular differentiation and larger tumour size and may be a late event in hepatocarcinogenesis. The p53 gene is important in controlling cell cycle, apoptosis and DNA repair. The cyclin-dependent kinase inhibitor p21WAF1/CIP1 , which is downstream of p53, is regulated by both p53-dependent and p53-independent pathways. We found that HCC with p53 mutations had lower levels of p21 expression than those without p53 mutations. Moreover, p21 protein expression of the tumours was significantly higher in the tumours than in the corresponding non-tumorous livers. When the tumours were stratified into two groups, those with higher expression were found to have a significantly lower incidence of multiple tumour nodules and lower incidence of tumour microsatellite formation. p21 Expression was, however, not associated with p53 expression. Higher p21 expression is associated with solitary tumour nodules and fewer tumour microsatellites, but may not be enough to suppress tumour progression. Insulin-like growth factor II (IGF-II) gene has complex regulation of transcription resulting in multiple mRNA being produced and different mRNA occur in the adult and foetus. Using northern blot analysis, repression of normal adult promoter and re-expression of foetal promoters of IGF-II are common events in HCC, with repression of the normal adult promoter in 93% of the HCC transcripts and re-expression of the foetal transcripts (6 and 5 kb, respectively) in 40% of tumours. In addition, IGF-II expression was significantly more frequent in older patients. This may suggest that spontaneous expression of IGF-II late in life may promote the growth of tumours which have already arisen through other mechanisms, but foetal re-expression, itself, may not be enough to contribute to tumour progression.