Interstitial deletion of chromosome 13 involving the region 13q14.
A patient with an interstitial deletion 13q14 is described who has decreased erythrocyte esterase D activity and who has not developed a retinoblastoma.


Osmotic stress-induced lignin synthesis is regulated at multiple levels in alfalfa (Medicago sativa L.).
Alfalfa is an important forage crop. Yield and quality are frequently threatened by extreme environments such as drought and salt stress. As a component of the cell wall, lignin plays an important role in the abiotic stress response, the mechanisms of which have not been well clarified. In this study, we combined physiological, transcriptional, and metabolic analyses to reveal the changes in lignin content in alfalfa under mannitol-induced osmotic stress. Osmotic stress enhanced lignin accumulation by increasing G and S units, which was associated with increases in enzyme activities and decreases in 8 intermediate metabolites. Upon combined analysis of the transcriptome and metabolome, we identified five key structural genes and several coexpressed transcription factors, such as MYB and WRKY, which may play a core role in regulating lignin content and composition under osmotic stress. In addition, lignin synthesis was positively regulated by ABA but negatively regulated by ethylene under osmotic stress. These results provide new insight into the regulatory mechanism of lignin synthesis under abiotic stress.


Primary vulvar squamous cell carcinomas with high T cell infiltration and active immune signaling are potential candidates for neoadjuvant PD-1/PD-L1 immunotherapy.
A profound insight into the immune landscape of vulvar squamous cell carcinoma (VSCC) is lacking. Here, an in-depth interrogation of T cell infiltration, local immune contexture, signaling pathways and checkpoint molecule expression was performed in early-stage and late-stage VSCC. The type, location, and infiltration pattern of T cells were studied in 109 patients with primary VSCC FIGO stage I-III. RNA expression of genes involved in immune oncology and oncogenic signaling pathways was analyzed in 40 VSCC, matched for prognostic clinicopathological variables, analyzed for HPV and p53 status, and selected based on T cell infiltration. High intraepithelial infiltration with CD4 or CD8 T cells was associated with longer overall and recurrence-free survival and formed an independent prognostic factor, outperforming molecular subtype and stage of the disease. Strong T cell infiltrated VSCC displayed a coordinated immune response reflected by a positive association between T cells and different lymphocyte and myeloid cell subsets. The expression of genes involved in the migration of T cells and myeloid cells, T cell activation and costimulation, interferon (IFN)-γ signaling, cytotoxicity and apoptosis was higher than in low infiltrated tumors. An active immune signaling profile was observed in all inflamed, part of the altered-excluded and not in altered-immunosuppressed or deserted VSCC. While several checkpoint molecules were overexpressed, only PD-L1 expression displayed discriminatory ability and clinical usefulness. High PD-L1 expression was detected in all inflamed and ~60% of the altered-excluded VSCC. An active immune signaling profile is present in 35% of primary FIGO I-III VSCCs, suggesting potential responsiveness to neoadjuvant PD-1/PD-L1 immunotherapy.


Cell-mediated cytotoxicity to rabbit liver-specific lipoprotein in chronic active hepatitis.
Cell-mediated cytotoxicity to 51Cr-labelled avian red blood cells coated by rabbit liver-specific lipoprotein was evaluated in 27 patients with untreated chronic active hepatitis (11 were HBsAg-positive). A significantly increased cytotoxicity was recorded in 10 of the 11 patients with HBsAg-positive chronic active hepatitis and in 13 of the 16 HBsAg-negative patients. The addition of rabbit LSP to the test system reduced to normal the cytotoxicity index in all the positive cases. Moreover, in order to evaluate the organ-specificity of cytotoxicity to rabbit LSP-coated cells, we added to the test system a macromolecular kidney protein fraction which was unable to block the cytoxicity in any of the positive cases. In 12 selected cases, which had previously shown an increased cytotoxicity to rabbit LSP-coated red blood cells, the incubation of their lymphocytes at 37 degrees C for 30 min in a plastic Petri dish resulted in the abolition of cytotoxicity. Our findings seem to indicate that cell-mediated cytotoxicity to LSP can also be detected with an antigen, not prepared from human liver. This is a further evidence that patients with chronic active hepatitis develop an immunological reactivity to not species-specific antigenic determinants in LSP.


Regeneration and Agrobacterium-mediated transformation of hop (Humulus lupulus L.).
An efficient procedure for direct organogenesis and regeneration of hop (Humulus lupulus L.) was established. For the first time Agrobacterium-mediated genetic transformation of hop (cv. "Tettnanger") was achieved. Shoot internodes from in vitro cultures were identified as the most suitable type of explant for regeneration. Using this type of explant, a shoot-inducing medium was developed that supported direct organogenesis of approximately 50% of the explants. Plantlets were successfully rooted and transferred to the greenhouse. Overall, in less than 6 months hop cultures propagated in vitro were regenerated to plants in the greenhouse. Agrobacterium-mediated genetic transformation was performed with the reporter gene GUS (beta-glucuronidase). The presence and function of transgenes in plants growing in the greenhouse was verified by PCR (polymerase chain reaction) and enzyme assay for GUS activity, respectively. We have obtained 21 transgenic plants from 1,440 explants initially transformed, yielding an overall transformation efficiency of 1.5%.


Low rank updated LS-SVM classifiers for fast variable selection.
Least squares support vector machine (LS-SVM) classifiers are a class of kernel methods whose solution follows from a set of linear equations. In this work we present low rank modifications to the LS-SVM classifiers that are useful for fast and efficient variable selection. The inclusion or removal of a candidate variable can be represented as a low rank modification to the kernel matrix (linear kernel) of the LS-SVM classifier. In this way, the LS-SVM solution can be updated rather than being recomputed, which improves the efficiency of the overall variable selection process. Relevant variables are selected according to a closed form of the leave-one-out (LOO) error estimator, which is obtained as a by-product of the low rank modifications. The proposed approach is applied to several benchmark data sets as well as two microarray data sets. When compared to other related algorithms used for variable selection, simulations applying our approach clearly show a lower computational complexity together with good stability on the generalization error.


Survival analysis for all-cause revision following primary total hip arthroplasty with a medial collared, triple-tapered primary hip stem versus other implants in real-world settings.
Patients that undergo total hip replacement (THA) are at risk of revision surgery. This study evaluated the cumulative incidence of revision following a medial collared, triple tapered (MCTT) primary hip stem versus other implants in real-world settings using electronic medical records. This was a retrospective cohort study that used the Mercy Healthcare Systems - Orthopedics Database (MHSOD) to identify ACTIS total hip system, a MCTT primary hip stem for THA, and any other primary THA between 2016 and 2020. A Kaplan-Meier analysis was conducted to evaluate the risk of revision over time between the MCTT hip stem and other implants. In order to control for the confounding, a multivariable Cox model was developed to evaluate the risk of revision between the two groups. There were 1213 patients treated with MCTT hip stem and 6916 patients treated with other implants. The Kaplan-Meier analysis showed statistically significant difference (p value = .006) in cumulative incidences for all-cause revisions between the MCTT hip stem and other implants. The cumulative incidence at 3 years was 1.08% (0.43-2.72%) for the MCTT hip stem, while it was 2.63% (2.19-3.16%) for other implants. After adjusting for patient demographics, clinical characteristics, prescribed medications, and surgeon characteristics, the multivariable Cox proportional hazard model showed the MCTT hip stem was statistically significantly associated with 57% lower risk of revisions compared with other implants (HR, 0.43; 95% CI, 0.19-0.97; p-value = .042). This real-world study found that the incidence of revision after treatment with MCTT primary hip stem was significantly lower than for other implants.


[Antibiotic sensitivity of bacteria in the genus Proteus in relation to the source of isolation and specific classification].
One hundred and ninety-one Proteus strains isolated from patients with various pathological processes were studied with respect to their sensitivity to 14 antibiotics. It was shown that their resistance depended on the isolation source and microbial species. Amikacin proved to be the most active agent. It was efficient against all the Proteus species, irrespective of the isolation source. Among the drugs efficient against P. mirabilis and P. vulgaris there were gentamicin, tobramycin and sisomicin sulphates.


Rhabdomyolysis caused by hot air sauna burn.
Sauna-related burns are rare, even in Finland where sauna bathing is a popular leisure pastime. Burns induced by hot air are even more rare and constitute a very small subgroup of all sauna burns. Hot air burns are characterised by a combination of full thickness skin damage with deep tissue destruction. We report here on six consecutive patients suffering from hot air sauna burns with rhabdomyolysis. All six patients were middle-aged, the majority of them men. Acute excessive consumption of alcohol exacerbated by a hot environment resulted in dehydration and loss of consciousness. Immobility and prolonged exposure to hot, dry air resulted in third degree regional burns with 5-32% TBSA. Rhabdomyolysis was evident on admission. The laboratory values of plasma creatine kinase (P-CK), plasma myoglobin (PM), blood pH, and serum potassium (S-K) during the first five days were evaluated. Aggressive fluid management and correction of acidosis and myoglobinuria were started on admission. Surgical management consisted of early, aggressive excision at fascial level, in some patients involving sacrifice of the upper layers of muscle. Even so, mortality in this small series was 50%. The best indicator of poor prognosis was a highly elevated CK value on the second post-injury day.


From NAFLD to NASH to cirrhosis-new insights into disease mechanisms.
NAFLD has evolved as a serious public health problem in the USA and around the world. In fact, NASH-the most serious form of NAFLD-is predicted to become the leading cause of liver transplantation in the USA by the year 2020. The pathogenesis of NAFLD and NASH, in particular the mechanisms responsible for liver injury and fibrosis, is the result of a complex interplay between host and environmental factors, and is at the centre of intense investigation. In this Review, we focus on recently uncovered aspects of the genetic, biochemical, immunological and molecular events that are responsible for the development and progression of this highly prevalent and potentially serious disease. These studies bring new insight into this complex disorder and have led to the development of novel therapeutic and diagnostic strategies that might enable a personalized approach in the management of this disease.


Radiation therapy of synchronous bilateral breast carcinoma (SBBC) using multiple techniques.
The purpose of this study was to establish intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans for synchronous bilateral breast cancer (SBBC) and to compare those plans with the previous treatment plans using 3D conformal radiation therapy (3DCRT). The differences among the treatments were also statistically compared regarding dosimetry distribution and treatment efficiency. The research was conducted with 10 SBBC patients. The study established IMRT (12 fields with a single isocenter) and VMAT (2 partial arcs with a single isocenter) treatment plans for SBBC patients and then compared those plans with 3DCRT (8 fields with multiple isocenters). The plans were evaluated based on a dose-volume histogram analysis. For planning target volumes (PTVs), the mean doses and the values of V95%, V105%, conformity index, and homogeneity index were reported. For the organs at risk, the analysis included the mean dose, maximum dose, and VXGy, depending on the organs (lungs, heart, and liver). To objectively evaluate the efficiency of the treatment plans, each plan's beam times, treatment times (including set-up time), and monitor units were compared. Tukey test and one-way analysis of variance were used to compare the PTV and organs at risk values of the 3 techniques. Additionally, the independent-samples t-test was used to compare the 2 techniques (IMRT and VMAT) based on the values of Rt. PTV and Lt. PTV (p < 0.05). For PTV dose distribution, IMRT showed increases of approximately 1.2% in Dmean and of approximately 5.7% in V95% dose distribution compared with 3DCRT. In comparison to VMAT, 3DCRT showed about 3.0% higher dose distribution in Dmean and V95%. IMRT was the best in terms of conformity index and homogeneity index (p < 0.05), whereas 3DCRT and VMAT did not significantly differ from each other. In terms of dose distribution on lungs, heart, and liver, the percentage of volume at high doses such as V30Gy and V40Gy was approximately 70% lower for IMRT and approximately 40% lower for VMAT than for 3DCRT. For distribution volumes of low doses such as V5% and V10%, that for 3DCRT was approximately 60% smaller than for IMRT and approximately 70% smaller than for VMAT. Comparison between IMRT and VMAT showed that the IMRT was superior in all distribution factors. VMAT showed better treatment efficiency than 3DCRT or IMRT. Among the SBBC radiotherapy treatment plans, IMRT was superior to 3DCRT and VMAT in terms of PTV dose distribution, whereas VMAT showed the most outstanding treatment efficiency.


Development and validation of a dietary screener for carbohydrate intake in endurance athletes.
Studies have shown that the majority of endurance athletes do not achieve the minimal recommended carbohydrate (CHO) intake of 6 g/kg of body weight (BW), with potentially negative impacts on recovery and performance. The purpose of this study was to develop and validate a rapid and easy to use dietary screener to identify athletes who do and do not achieve a CHO intake > 6 g/kg BW in the context of endurance sports. The dietary screener was developed using multiple logistic regression modeling of data from a sample of 1571 non-athlete adults (826 women and 745 men, mean age 44.75 ± 14.2 years) among whom dietary intake was assessed using a validated web-based food frequency questionnaire (web-FFQ). Three models were developed based on whole food intake using the 5, 10 and 15 most significant variables predicting CHO intake. The three models were then validated in a target population of non-elite endurance athletes having taken part in multisport events (n = 175, 64 women and 111 men, mean age 37.1 ± 11.3 years) and compared using sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) and c-statistics. The 15-variables model provided significantly better accuracy in predicting CHO intake adequacy in non-elite endurance athletes (c-statistic = 0.94) compared with the 10- and 5-variables model (c-statistic = 0.90 and 0.71 respectively). The 15-variables model predicts CHO intake adequacy in the target population of endurance athlete with a sensitivity of 89.5%, a specificity of 87.3% and PPV and NPV of 77.3 and 94.5%, respectively. We have successfully developed a short and valid dietary screener that identifies endurance athletes at risk of not achieving a CHO intake > 6 g/kg BW. Use of this rapid screener may help alleviate the highly prevalent issue of suboptimal CHO consumption in the endurance sports realm.


Navigating a research partnership between academia and industry to assess the impact of personalized genetic testing.
To describe the process of structuring a partnership between academic researchers and two personalized genetic testing companies that would manage conflicts of interest while allowing researchers to study the impact of this nascent industry. We developed a transparent process of ongoing communication about the interests of all research partners to address challenges in establishing study goals, survey development, data collection, analysis, and manuscript preparation. Using the existing literature on conflicts of interest and our experience, we created a checklist for academic and industry researchers seeking to structure research partnerships. Our checklist includes questions about the risk to research participants, sponsorship of the study, control of data analysis, freedom to publish results, the impact of the research on industry customers, openness to input from all partners, sharing results before publication, and publication of industry-specific data. Transparency is critical to building trust between partners. Involving all partners in the research development enhanced the quality of our research and provided an opportunity to manage conflicts early in the research process. Navigating relationships between academia and industry is complex and requires strategies that are transparent and responsive to the concerns of all. Employing a checklist of questions prior to beginning a research partnership may help to manage conflicts of interest.


[Histogenesis and development of membranous basal cell adenoma of the salivary gland].
To investigate the histogenesis and development of membranous basal cell adenoma in the salivary glands. A histological and immunohistochemical study was carried out on 12 cases of membranous basal cell adenoma in the salivary glands. In 4 cases, multiple focal proliferations of striated ducts in the surrounding salivary gland were conspicuous, which allowed tracing the development of the tumors from their origin. The earliest changes were characterized by hyperplasia of the basal cells of striated ducts. Continuous ductal proliferation lead to the formation of microadenomas. Proliferation of basal cells of the striated ducts apparently participate in, and play a main role in the histogenesis of some membranous basal cell adenomas of the salivary glands.


Alcohol use by urban bicyclists is associated with more severe injury, greater hospital resource use, and higher mortality.
Alcohol use is a risk factor for severe injury in pedestrians struck by motor vehicles. Our objective was to investigate alcohol use by bicyclists and its effects on riding behaviors, medical management, injury severity, and mortality within a congested urban setting. A hospital-based, observational study of injured bicyclists presenting to a Level I regional trauma center in New York City was conducted. Data were collected prospectively from 2012 to 2014 by interviewing all bicyclists presenting within 24 h of injury and supplemented with medical record review. Variables included demographic characteristics, scene-related data, Glasgow Coma Scale (GCS), computed tomography (CT) scans, and clinical outcomes. Alcohol use at the time of injury was determined by history or blood alcohol level (BAL) >0.01 g/dL. Of 689 bicyclists, 585 (84.9%) were male with a mean age of 35.2. One hundred four (15.1%) bicyclists had consumed alcohol prior to injury. Alcohol use was inversely associated with helmet use (16.5% [9.9-25.1] vs. 43.2% [39.1-47.3]). Alcohol-consuming bicyclists were more likely to fall from their bicycles (42.0% [32.2-52.3] vs. 24.2% [20.8-27.9]) and less likely to be injured by collision with a motor vehicle (52.0% [41.7-62.1] vs. 67.5% [63.5-71.3]). 80% of alcohol-consuming bicyclists underwent CT imaging at presentation compared with 51.5% of non-users. Mortality was higher among injured bicyclists who had used alcohol (2.9% [0.6-8.2] vs. 0.0% [0.0-0.6]). Adjusted multivariable analysis revealed that alcohol use was independently associated with more severe injury (Adjusted Odds Ratio 2.27, p = 0.001, 95% Confidence Interval 1.40-3.68). Within a dense urban environment, alcohol use by bicyclists was associated with more severe injury, greater hospital resource use, and higher mortality. As bicycling continues to increase in popularity internationally, it is important to heighten awareness about the risks and consequences of bicycling while under the influence of alcohol.


Analysis of polycyclic aromatic hydrocarbons adsorbed on particles of atmospheric interest using pressurised fluid extraction.
Pressurised fluid extraction (PFE) was used for the measurement of 13 polycyclic aromatic hydrocarbons (PAHs) adsorbed on different types of particles: two model particles (PAH-coated silica, PAH-coated graphite) and two natural atmospheric particles (urban dust and diesel exhaust, from NIST reference materials). Samples were analysed by gas chromatography coupled to mass spectrometry. Extraction efficiency was evaluated with internal standard recovery yields and was shown to depend on the nature of the particle, on the structure of the analytes and on the PAH concentration. Extraction conditions (toluene, 130 degrees C, 130 bar, 2 x 8-min static cycles) were optimised to extract PAHs when strongly interacting with solid matrices and were validated by the analysis of two PAH-certified materials.


Orbital exenteration reconstruction using a superficial temporalis muscle flap: The "Carpaccio flap", an innovative approach.
Malignant orbital diseases may lead surgeons to practice an orbital exenteration associated with chemotherapy and/or radiotherapy to ensure curative treatment. That radical procedure makes physicians consider reconstructive filling in order to allow prothesis wearing and reduce esthetic and social after-effects. We first describe the clinical case of a 6-year-old patient who presented an orbital rhabdomyosarcoma and underwent an orbital exenteration with immediate reconstruction by a superficial temporal pedicled on the middle temporalis muscle flap. Through that case-report, we propose an original temporal flap to repair ipsilateral midface defects which may reduce donor site side effects and allow furthers corrections. In pediatrics cases, our Carpaccio flap was an available regional tool to rehabilitate an irradiated orbital socket with an appropriate bulking and vascularization effect after subtotal exenteration. Furthermore, we prescribe that flap as a posterior orbital filling, when eyelid and conjunctiva are spared, to prepare orbital prosthesis implementation. A mild sunken temporal fossa appears with our procedure but by preserving the deep layer of the temporalis muscle, autologous reconstruction such as lipofilling are permitted in post-radiotherapy condition to enhance esthetic sequelae.


Prenatal presentation of cervical congenital neuroblastoma.
To describe a cervical neuroblastoma revealed in the prenatal period. We were recently confronted with a case of fetal solid neck mass suggestive of teratoma, which proved postnatally to be a neuroblastoma. Combining this case with a review of recent literature, we have evaluated the diagnostic tools required for increased precision in the prenatal diagnosis and perinatal management of fetal solid neck masses. Detailed ultrasound and MRI of fetal neck and liver, in conjunction with amniocentesis for measurement of homovanillic acid levels, should enable fetal medical practitioners to consider the diagnosis of fetal cervical neuroblastoma. Fetal cervical neuroblastoma is an extremely rare condition that has not been previously reported, but should be considered in the presentation of fetal solid neck masses.


Photoaffinity labeling and partial purification of the beta cell sulfonylurea receptor using a novel, biologically active glyburide analog.
An iodinated analog of the sulfonylurea, glyburide, has been synthesized which can be labeled to high specific activity and used to photolabel the sulfonylurea receptor. 5-Iodo-2-hydroxy-"glyburide", has an iodo group replacing the chlorine at position 5 and a methoxy residue replacing the hydroxy group at position 2 on the benzamido ring. This analog retains biologic activity stimulating insulin secretion from a hamster beta cell line (HIT cells) at the same ED50 (0.4 nM) as glyburide. Scatchard analysis demonstrated high and low affinity binding sites on HIT cell membranes (Kd values of 0.36 nM and 277 nM and Bmax values of 1.6 and 100 pmol/mg of membrane protein, respectively). Competitive binding assays with unlabeled glyburide or 5-iodo-2-hydroxyglyburide yield Ki values of 0.5 and 1.0 nM, respectively. The analog can be covalently linked by ultraviolet irradiation to a membrane protein of Mr = 140,000. The photolabeling is completely blocked by unlabeled glyburide or the analog. Two other species of Mr = 65,000 and 43,000 are also photolabeled; these may be the low affinity sites. After photolabeling, the receptor has been purified partially by chromatographic procedures and is suitable for obtaining peptide sequence. The 140,000 molecular weight protein is identified as the sulfonylurea receptor since its binding constant, 0.36 nM, is closely correlated with its ability to stimulate insulin secretion (ED50 congruent to 0.4 nM).


Customised birthweight models: do they increase identification of at-risk infants?
The study aims to describe the cohort of women and babies who are classified as small-for-gestational age (SGA) at term by both an Australian customised birthweight model (CBM) and a commonly used population-based standard, and to investigate and compare the utility of these models in identifying babies at risk of experiencing adverse outcomes Routinely collected data on 54 890 singleton-term births at the Mater Mothers' Hospitals, Brisbane, with birthweight less than 4000 g between January 1997 and December 2008, was extracted. Each birth was classified as SGA (<10th centile) or not SGA by either and/or both methods: population-based standards (SGApop ) and CBM (SGAcust ). Babies classified as SGApop , SGAcust or SGAboth were compared with those not classified as SGA by both methods using relative risk and 95% confidence interval, and those only classified as SGAcust were compared with those only classified as SGApop . Maternal demographics, maternal risk factors for fetal growth restriction, pregnancy and labour complications and adverse neonatal outcomes are reported. A total of 4768 (8.7%) births were classified as SGApop , while 6479 (11.8%) were SGAcust of whom 4138 (63.9%) were also classified as SGApop . Maternal risk factors such as smoking and hypertension were statistically higher for the SGAcust group when compared with SGApop . For the majority of adverse neonatal outcomes, a trend was noted to increased identification using the CBM. The CBM provides a modest improvement when compared to a population-based standard to identity term infants at birth who are at risk of adverse neonatal outcomes.


Autoradiographic determination of regional cerebral blood flow in the immature rat.
Seven-day-old rats (15 g body weight) were injected subcutaneously with iodo-[14C] antipyrine (5 microCi). After a variable period, each pup was decapitated and arterial blood collected for scintillation counting. Brains were immediately removed and either prepared for isotopic counting or frozen for autoradiography. The brain:blood partition coefficient was determined [0.944 +/- 0.006 ml/g (mean +/- SEM)]. Both cerebral blood flow (CBF) and regional CBF (RCBF) were calculated according to a formula derived from the Fick equation. CBF equaled 66 +/- 4 ml/100 g/min (mean +/- SEM), a value midway between reported 1-day-old rat CBF and adult rat CBF. Autoradiographs were of sufficient quality to permit microdensitimetric readings of a minimum of 11 structures. RCBF ranged from 20 ml/100 g/min in subcortical white matter to 71 ml/100 g/min in the brain stem. Immature rat RCBF, as a proportion of adult rat RCBF, was greatest in brain stem. Previously thought not feasible, this technique provides a reliable and relatively simple means of measuring both CBF and RCBF in the very small laboratory animal.


Brain abscesses in children--a cooperative study of 83 cases.
This study reviews our experience in 83 cases of brain abscesses in children diagnosed at seven teaching hospitals during the 10-year period from June 1978 to July 1987. The average age of the patients was 7 years, with 12% of them less than 1 year old. The male-to-female ratio was 1.7:1. Of the brain abscesses, 90.4% were detected by CT brain scan. A total of 50.6% patients had congenital heart disease, and 20.4% patients had sepsis and/or meningitis. Only 6% cases had ear, nose, and throat infection. Sixty-eight (81.9%) patients received a combination of antibiotics and surgical treatment. The cerebral abscesses were totally excised in 26 cases, aspirated and partially excised in 6, and aspirated in 32. Sixty patients had pus cultures from the cerebral abscesses. Organisms were isolated in 29 (49.2%) of them. Streptococcus was by far the most common organism. The overall outcome was: 49 (59%) alive; 16 (19.3%) dead; 18 (21.7%) lost to follow-up. Among the 16 mortalities, the causes of death were due to failure to treat the diseases causing the brain abscesses. We had a better outcome in patients whose cerebral abscesses were totally excised or whose abscesses were aspirated, and in patients who were older than 1 year of age.


Reliability of visual performance measurement under optical degradation.
Small groups of experienced subjects wore three types of bifocal contact lens which were shown to reduce visual performance at distance and near conditions. Monitor-based contrast sensitivity, Pelli-Robson contrast threshold, and high- and low-contrast visual acuity were each measured on two separate occasions. For each bifocal contact lens type the test-retest difference did not increase significantly with reduction in visual performance. Despite this the reliability of the visual performance measures was shown to be reduced compared to previous reports with normal well-corrected subjects and the test-retest repeatability coefficients (95% confidence limits) increased as the average visual performance declined. The poor reliability is of interest to the practitioner fitting bifocal contact lenses, and confirms previous suggestions that reliability may be related to visual degradation (e.g. ocular disease). In addition Pelli-Robson contrast thresholds were shown to be correlated with the spatial frequency represented by the presumed fundamental frequency of the component letters.


Hand washing practice among public primary school children and associated factors in Harar town, eastern Ethiopia: An institution-based cross-sectional study.
Hand washing with soap and water reduces the risk of diarrheal episode by 28-48% and acute respiratory infection by 20-50%. However, there is limited evidence on hand washing practices among students in Eastern Ethiopia, particularly in Harari town. Therefore, this study aimed to determine hand washing practice among primary school students and associated factors in Harar town, Eastern Ethiopia. An institution-based cross-sectional study was applied among 670 students in Harar town from June 1 to 30, 2021. A multi-stage sampling was employed; 6 out of 20 schools were selected through simple random sampling, while eligible children from each school was selected by probability proportional to size sampling method. Data were collected using a pre-tested questionnaire with a face-to-face interview technique and via observation. The data were analyzed using SPSS software version 23. Binary and mult-variable analysis were used to determine the association between factors and outcome variable. Finally, a p-value of < 0.05 was considered to declare a statistically significant association. A total of 670 participants were included in the study, of which 248 (37.0%) had washed their hands [95% CI: 33.3-40.06]. Being in grade 8 Adjusted Odd Ratio[AOR = 4.9; 95% Confidence Interval (CI): 2.28-10.52], living in an urban area [AOR = 3.49; 95% CI: 1.29-9.40], having role models (parents [AOR = 4.41; 95% CI: 1.79-10.86], teachers [AOR = 3.69; 95% CI: 1.39-8.81], and health professionals [AOR = 3.17, 95% CI: 1.17-8.63]), availability of hand washing facility [AOR = 3.62; 95% CI: 1.57-8.34], access to soap and water [AOR = 2.89; 95% CI: 1.39-5.98] and being membership of water sanitation and hygiene (WASH) club [AOR = 2.39; 95% CI: 1.41-4.03] were found to be significantly associated with hand washing practice. The current study found that nearly a third of students practiced proper hand washing. Hand washing practice was influenced by students' grade level, residence, referents (role models for hand washing), presence of a hand washing facility, access to water and soap, and membership of WASH club. Therefore, the finding revealed that there is a need to improve hand-washing practices in schools by concerned agencies.


Ag nanoparticle decorated MnO2 flakes as flexible SERS substrates for rhodamine 6G detection.
Smart design of advanced substrates for surface-enhanced Raman scattering (SERS) activity is challenging but vital. Herein, we synthesized a new kind of AgNPs/MnO2@Al flexible substrate as a SERS substrate for the detection of the analyte rhodamine 6G (R6G). The fabrication of porous MnO2 nanoflakes on Al foil was conducted via a facile hydrothermal strategy. Owing to the large active surface area of the MnO2 nanoflakes, the Ag nanoparticles were immobilized and displayed superior SERS performance with a low detection concentration of 1 × 10-6 M for R6G. In addition, the SERS performance was found to be strongly related to the morphology of the MnO2@Al substrate material. Our smart design may provide a new method of construction for other advanced SERS substrates for the detection of R6G.


Deficiency of glucose-6-phosphate dehydrogenase found in a case of hepatic fructose-1,6-diphosphatase deficiency.
The first case of fructose-1,6-diphosphatase (FDPase) deficiency in Japan showed a decreased activity of glucose-6-phosphate dehydrogenase (G6PD) in the liver, white, and red blood cells. In the enzymatic study of G6PD which was partially purified from red cells, the following characteristics were observed in the enzyme of the patient. 1) The G6PD activity of the patient was reduced to 17% of normal, but no evidence of a hemolytic episode was found in his past and family history. 2) In the investigation of G6PD of the patient, no abnormalities were observed in its enzymatic parameters such as electrophoretic mobility, Km for G6P and NADP, Ki for NADPH, the utilization of 2-deoxy G6P and deamino NADP, heat-stability, and pH curves. 3) The dissociation constants of red blood cell G6PD for NADP and NADPH, which were obtained from the investigations on the reactivation of cold-inactivated G6PD at 37 degrees C, were about 3 times higher in the patient as compared to the values of the normal controls. Based on these findings, it might be concluded that the G6PD deficiency found in the red blood cells of this case of a FDPase deficiency is a unique variant, which could not be characterized by using only the method recommended by a World Health Organization (WHO) scientific group. Considering that the abnormality observed in the G6PD of this patient was a decrease in the affinity of the enzyme for its coenzymes, the dissociation constants for the coenzymes in reactivation process might be another important kinetic parameter in characterizing the G6PD deficiency.


Neospora caninum and Hammondia heydorni are separate species/organisms.
Neospora caninum and Hammondia heydorni are two coccidian parasites with morphologically similar oocysts in canine feces. It was recently proposed that they are one species. In this paper, we review the biology and morphology of these parasites and present evidence that N. caninum and H. heydorni are separate species.


Bright long-lived luminescence of silicon nanocrystals sensitized by two-photon absorbing antenna.
Silicon nanocrystals of the average diameter of 5 nm, functionalized with 4,7-di(2-thienyl)-2,1,3-benzothiadiazole chromophores (TBT) and dodecyl chains, exhibit near-infrared emission upon one-photon (1P) excitation at 515 nm and two-photon (2P) excitation at 960 nm. By using TBT chromophores as an antenna we were able to enhance both 1P and 2P absorption cross-sections of the silicon nanocrystals to more efficiently excite their long-lived luminescence. These results chart a path to two-photon-excitable imaging probes with long-lived oxygen-independent luminescence - a rare combination of properties that should allow for a substantial increase in imaging contrast.


Motor system plasticity after unilateral injury in the developing brain.
In maturity, motor skills depend on the corticospinal tract (CST) and brainstem pathways that together synapse on interneurons and motoneurons in the spinal cord. Descending signals to spinal neurons that mediate voluntary control can be distinguished from peripheral sensory signals, primarily for feedback control. These motor system circuits depend initially on developmental genetic mechanisms to establish their connections and neural activity- and use-dependent synaptic refinement during the early postnatal period to enable motor skills to develop. In this review we consider four key activity-dependent developmental mechanisms that provide insights into how the motor systems establish the proper connections for skilled movement control and how the same mechanisms also inform the mechanisms of motor impairments and developmental plasticity after corticospinal system injury: (1) synaptic competition between the CSTs from each hemisphere; (2) interactions between the CST and spinal cord neurons; (3) synaptic competition between the CST and proprioceptive sensory fibres; and (4) interactions between the developing corticospinal motor system and the rubrospinal tract. Our findings suggest that the corticospinal motor system effectively 'oversees' development of its subcortical targets through synaptic competition and trophic-like interactions and this has important implications for motor impairments after perinatal cortical stroke. Neural activity-dependent processes inform the brain and spinal cord response to injury. The corticospinal motor system may 'oversee' development of its downstream subcortical targets through activity, trophic-like interactions, and synaptic competition.


[Modified histological methods using a nuclear dye gallocyanine].
It is suggested that a nuclear stain; gallocyanine, be used simultaneously with the three main histological staining methods: hematoxylin-eosin, Van-Gieson's, and Nissl' stainings. This modification is technically simple, gives preparations of a high quality, and is time- and labour-saving.


Biochemical characteristics of dissociatively isolated aortic proteoglycans and their binding capacity to hyaluronic acid.
Proteoglycans were extracted from pigeon aortas with 4.0 M guanidine hydrochloride containing protease inhibitors to characterize the proteoglycan (PG) types, to examine and define their association with hyaluronic acid, and to compare pigeon aortic PG with human aortic PG isolated and characterized under similar conditions. Following chromatography of guanidine hydrochloride extracts on Sepharose CL-4B under dissociative conditions, two populations of PG were isolated. PG I, eluting at the column void volume, contained predominantly (83.2%) chondroitin sulfate whereas PG II, eluting at a Kav of 0.40, contained predominantly dermatan sulfate (54.7%). Following centrifugation, 76 and 63% of PG I and PG II, respectively, were located in the bottom two-fifths (p greater than 1.43 g/ml) of a CsCl gradient. Only PG I, predominantly chondroitin sulfate, was effective in associating with hyaluronic acid to form high molecular weight aggregates. The specific association was illustrated by removing endogenous arterial hyaluronic acid remaining in the preparation and demonstrating increasing formation of aggregate with increasing addition of human umbilical cord high molecular weight hyaluronic acid. The results of the study illustrate that artery PG of the pigeon are similar in distribution to those described for the human aorta and contain at least three types of PG, a chondroitin sulfate PG, a dermatan sulfate PG, and a polydisperse heparan sulfate PG. The chondroitin sulfate PG but not the dermatan sulfate PG are capable of forming high molecular weight aggregates with hyaluronic acid.


Biocompatibility, degradability, bioactivity and osteogenesis of mesoporous/macroporous scaffolds of mesoporous diopside/poly(L-lactide) composite.
Bioactive mesoporous diopside (m-DP) and poly(L-lactide) (PLLA) composite scaffolds with mesoporous/macroporous structure were prepared by the solution-casting and particulate-leaching method. The results demonstrated that the degradability and bioactivity of the mesoporous/macroporous scaffolds were significantly improved by incorporating m-DP into PLLA, and that the improvement was m-DP content-dependent. In addition, the scaffolds containing m-DP showed the ability to neutralize acidic degradation products and prevent the pH from dropping in the solution during the soaking period. Moreover, the scaffolds containing m-DP enhanced attachment, proliferation and alkaline phosphatase activity of MC3T3-E1 cells, which were also m-DP content-dependent. Furthermore, the histological and immunohistochemical analysis results showed that the scaffolds with m-DP significantly promoted new bone formation and improved the materials degraded in vivo, indicating good biocompatibility. The results suggested that the mesoporous/macroporous scaffolds of the m-DP/PLLA composite with osteogenesis had a potential for bone regeneration.


Effects of the angiogenesis inhibitor angiostatin on the growth of CC531 colon carcinoma cells in vitro and in a laparoscopic animal model of peritoneal carcinomatosis.
As angiogenesis is one of the key steps in tumor growth, invasion, and metastasis, antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. We investigated the cytotoxic, anti-adhesive, and anti-invasive effects of angiostatin in vitro and on intraperitoneal tumor growth in a laparoscopic rat model of peritoneal carcinomatosis using CC531 colon adenocarcinoma cells. The in vitro adhesion and cytotoxicity assays were performed with microtiter plates, and the invasion assay with Transwell dual chambers. Normal saline was used as control. In in vivo experiments, CC531 adenocarcinoma cells were intraperitoneally given to Wistar Albino Glaxo rats after the establishment of a pneumoperitoneum. The animals received angiostatin in different doses intraperitoneally, and in some, angiostatin was additionally administered subcutaneously. Saline was used as control. After 21 days, the animals were euthanized to determine the intra-abdominal tumor weight. In in vitro experiments, there was no effect of angiostatin on the viability of tumor cells in the cytotoxicity assay, but there was a significant inhibition of tumor cell adhesion and invasion (p<0.05 and p<0.01) in all angiostatin concentrations. In in vivo experiments, an intraperitoneal application of 20 microg angiostatin, but not 10 microg, significantly (p<0.005) decreased the intraperitoneal tumor weight compared with controls. This effect was most pronounced after the combined intraperitoneal and subcutaneous applications. Angiostatin given intraperitoneally at a dose of 20 microg alone or in combination with subcutaneous application significantly diminishes intraperitoneal tumor growth in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic surgery for colorectal cancer.


The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis.
To assess the diagnostic performance of serum CA-125 measurement in the detection of endometriosis. Meta-analysis. Twenty-three studies comparing serum CA-125 levels and laparoscopically confirmed endometriosis. Serum CA-125 measurement and laparoscopy. Sensitivity and specificity of serum CA-125 measurement in the diagnosis of endometriosis with laparoscopy as the reference standard. The estimated summary receiver operating characteristic curves showed that the performance of serum CA-125 measurement in the diagnosis of endometriosis grade I/IV is limited, whereas its performance in the diagnosis of endometriosis grade III/IV is better. Despite its limited diagnostic performance, we believe that the routine use of serum CA-125 measurement in patients with infertility might be justified. In contrast to laparoscopy, serum CA-125 measurement is an inexpensive test that is not a burden for the patient. It could identify a subgroup of patients who are more likely to benefit from early laparoscopy. Studies reporting on the mutual dependence between serum CA-125 measurement and data from the history and physical examination are needed.


The diaphragm and lubricant gel for prevention of cervical sexually transmitted infections: results of a randomized controlled trial.
We evaluated the effectiveness of the Ortho All-Flex Diaphragm, lubricant gel (Replens) and condoms compared to condoms alone on the incidence of chlamydial and gonococcal infections in an open-label randomized controlled trial among women at risk of HIV/STI infections. We randomized 5045 sexually-active women at three sites in Southern Africa. Participants who tested positive for curable STIs were treated prior to enrollment as per local guidelines. Women were followed quarterly and tested for Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (GC) infection by nucleic-acid amplification testing (Roche Amplicor) using first-catch urine specimens. STIs detected at follow-up visits were treated. We compared the incidence of first infection after randomization between study arms in both intent-to-treat (ITT) and per-protocol populations. Baseline demographic, behavioral and clinical characteristics were balanced across study arms. Nearly 80% of participants were under 35 years of age. Median follow-up time was 21 months and the retention rate was over 93%. There were 471 first chlamydia infections, 247 in the intervention arm and 224 in the control arm with an overall incidence of 6.2/100 woman-years (wy) (relative hazard (RH) 1.11, 95% Confidence Interval (CI): 0.93-1.33; p = 0.25) and 192 first gonococcal infections, 95 in the intervention arm and 97 in the control arm with an overall incidence of 2.4/100wy (RH 0.98, 95%CI: 0.74-1.30; p = 0.90). Per protocol results indicated that when diaphragm adherence was defined as "always use" since the last visit, there was a significant reduction in the incidence of GC infection among women randomized to the intervention arm (RH 0.61, 95%CI: 0.41-0.91, P = 0.02). There was no difference by study arm in the rate of acquisition of CT or GC. However, our per-protocol results suggest that consistent use of the diaphragm may reduce acquisition of GC. ClinicalTrials.gov NCT00121459.


Lateral Extra-articular Tenodesis with Iliotibial Band Using Knotless All-Suture Anchor Femoral Fixation.
Common injuries, such as anterior cruciate ligament (ACL) tears, can result in both anterior and rotational instability of the knee. An arthroscopic anterior cruciate ligament reconstruction (ACLR) method has been shown to be effective in restoring anterior translational stability, but this could be followed by persistent rotational instability by means of residual pivot shifts or repeat instability episodes. Alternative techniques, such as a lateral extraarticular tenodesis (LET), has been proposed as a technique for preventing persistent rotational instability following ACLR. This article presents a case of a LET using an autologous central slip of iliotibial (IT) band with fixation to the femur using a 1.8-mm knotless all-suture anchor.


Detection of Chlamydia trachomatis inside spermatozoa using flow cytometry: Effects of antibiotic treatment (before and after) on sperm count parameters.
There is increasing evidence that Chlamydia trachomatis (CT) infection can directly affect male fertility. However, only few have investigated the effects of CT on semen parameters, and mostly with inconclusive results. The main aims of this study were to identify CT inside spermatozoa, and the possible pre and post antibiotic treatment effects on the overall semen parameters. We developed a flow cytometric method for the detection of CT inside spermatozoa (SPI™). Briefly, sperm cells were fixed, membrane permeabilized and DNA was loosened using DNAse. Sperm cells were incubated with a primary monoclonal antibody against CT and with a secondary fluorescent antibody (vs primary), and analysed using a flow cytometer. Of 2415 infertile individuals, 48.61% were found positive for CT. 170 CT+ samples were included in the CT antibiotic treatment study. 78.82% (134/170) of the CT+ showed a significant reduction in the percentage of the iCT infected spermatozoa after the antibiotic treatment; 59.70% (80/134) decreased to non-detectable levels. Spermcount data were also recorded. Spermatozoa morphology (normal and teratozoospermia index, TZI) and motility (fast progressive and non-progressive spermatozoa) were statistically significant altered in CT+ pre-treatment vs control group. CT antibiotic treatment showed statistically significant effects on normal spermatozoa morphology, mid-piece and tail defects, and TZI. The study demonstrated that semen flow cytometric analysis of semen could be a valuable tool for faster and accurate identification of individuals with asymptomatic CT infection. It also identified a positive effect of antibiotic therapy on semen parameters, that could help males with infertility.


Non-vascularized free toe phalanx transplantation in the treatment of symbrachydactyly and constriction ring syndrome.
Forty-eight patients underwent a total number of 113 non-vascularized free toe phalanx transplantations for congenital short digits between 1975 and 2003, a mean number of 2.3 transplanted phalanges per patient. The mean age at the time of initial surgery was 3.6 years (range 6 months to 21 years). The follow-up time ranged from 4 months to 14 years with a mean of 6 years. Sixty-four phalanges showed radiographically measured growth, 22 phalanges showed signs of resorption, while 27 phalanges showed neither growth nor resorption. Resorption increased with patient age. Three patients developed donor site problems. The optimum timing for initial surgery is as early as possible because of the safer and greater growth potential and less resorption of the transplanted phalanges. Non-vascularized free toe phalanx transplantations offer a simple and safe method of lengthening with a significant improvement of hand function.


Tumours of the thalamic region. A retrospective study of 27 cases.
Twenty seven patients with thalamic tumours were evaluated retrospectively in the Neurosurgical Clinic of the University Hospital in Groningen between 1969 and 1983. The diagnosis was based on neuroradiological studies. The authors recommend stereotactic biopsy of thalamic tumours followed by irradiation in selected cases.


Hydrogen Bonding, π-Stacking, and Aurophilic Interactions in Two Dicyanoaurate(I)-Based Manganese(II) Complexes with Auxiliary Bis-Pyridine Ligands.
The relevance of hydrogen-bonding, π-π stacking and aurophilic interactions in the solid-state of two new heterobimetallic (AuI -MnII ) complexes is analyzed in this manuscript. They are discrete complexes of formulae [Mn(bipy)2 (H2 O){Au(CN)2 }][Au(CN)2 ] and [Mn(dmbipy)2 {Au(CN)2 }] ⋅ H2 O, (bipy=2,2'-bipyridine and dmbipy=5,5'-dimethyl-2,2'-bipyridine), which are based on dicyanidoaurate(I) groups and 2,2'-bipyridyl-like co-ligands. They have been synthesized in good yields and X-ray characterized. In both compounds, aurophilic, OH⋅⋅⋅N hydrogen bonding and π-π interactions governed the supramolecular assemblies in the solid state. These contacts with special emphasis on the aurophilic interactions have been studied using density functional theory calculations and characterized using the quantum theory of atoms-in-molecules and the noncovalent interaction plot. The aurophilic contacts have been also rationalized from an orbital point of view using the natural bond orbital methodology, evidencing stabilization energies up to 5.7 kcal/mol. Moreover, the interaction energies have been decomposed using the Kitaura-Morokuma energy decomposition analysis, confirming the importance of electrostatic and orbital effects.


Amundsen, Nansen, and the question of science: dramatizing historical research on the polar heroic.
Recent historical research reveals a much greater role than previously assumed for science in the polar activities of Fridtjof Nansen and Roald Amundsen. Science-based polar exploration was what first linked these two men; Amundsen's subsequent turn to sport and sensation dampened their relationship. These insights and other new perspectives about heroic period of polar exploration are being transformed by the author into a drama for stage that will have its world premier in Norway in December 2011. The play attempts to use imaginatively the art and craft of theatre to diffuse insight from historical scholarship.


Preclinical and clinical development of a dengue recombinant subunit vaccine.
This review focuses on a dengue virus (DENV) vaccine candidate based on a recombinant subunit approach which targets the DENV envelope glycoprotein (E). Truncated versions of E consisting of the N-terminal portion of E (DEN-80E) have been expressed recombinantly in the Drosophila S2 expression system and shown to have native-like conformation. Preclinical studies demonstrate that formulations containing tetravalent DEN-80E adjuvanted with ISCOMATRIX™ adjuvant induce high titer virus neutralizing antibodies and IFN-γ producing T cells in flavivirus-naïve non-human primates. The preclinical data further suggest that administration of such formulations on a 0, 1, 6 month schedule may result in higher maximum virus neutralizing antibody titers and better durability of those titers compared to administration on a 0, 1, 2 month schedule. In addition, the virus neutralizing antibody titers induced by adjuvanted tetravalent DEN-80E compare favorably to the titers induced by a tetravalent live virus comparator. Furthermore, DEN-80E was demonstrated to be able to boost virus neutralizing antibody titers in macaques that have had a prior DENV exposure. A monovalent version of the vaccine candidate, DEN1-80E, was formulated with Alhydrogel™ and studied in a proof-of-principle Phase I clinical trial by Hawaii Biotech, Inc. (NCT00936429). The clinical trial results demonstrate that both the 10 μg and 50 μg formulations of DEN1-80E with 1.25 mg of elemental aluminum were immunogenic when administered in a 3-injection series (0, 1, 2 months) to healthy, flavivirus-naïve adults. The vaccine formulations induced DENV-1 neutralizing antibodies in the majority of subjects, although the titers in most subjects were modest and waned over time. Both the 10 μg DEN1-80E and the 50 μg DEN1-80E formulations with Alhydrogel™ were generally well tolerated.


Non-Invasive Cerebral Autoregulation Monitoring During Awake Carotid Endarterectomy Identifies Clinically Significant Brain Ischaemia.
The aim was to evaluate the potential of near infrared spectrometry (NIRS) monitoring enhanced by autoregulation parameters to detect clamp ischaemia during awake carotid endarterectomy (CEA). This was a prospective, hypothesis generating, single centre observational study. Fifty-nine consecutive patients with carotid artery stenosis, of whom 15 (25%) were symptomatic, were enrolled. The patients underwent awake CEA with NIRS monitoring. Regional oxygen saturation (rSO2), relative tissue haemoglobin concentration (rTHb), and mean arterial blood pressure were captured by ICM + software (University of Cambridge Enterprise, Cambridge, UK). The cerebral oxygenation index (COx) and haemoglobin volume index (HVx) were calculated continuously. Two groups were formed depending on neurological symptoms: a symptomatic group with shunt insertion (shunt) and an asymptomatic group (no shunt). Eight patients (14%) became symptomatic and needed intra-operative shunting. The decrease in ipsilateral rSO2 was higher in the shunt group (13.5% vs. 5.3%) and rTHB increased on the non-operated side (+0.05 ± 0.01; p = .016). In symptomatic patients no significant change in rTHB was found during clamping, whereas in asymptomatic patients there was a bilateral increase (ipsilateral: + 0.06 [p = .022]; contralateral: + 0.06 [p = .010]). In asymptomatic patients, ipsilateral COx decreased after clamping (-0.06 ± 0.02; p = .024), indicating functional autoregulation. In symptomatic patients, ipsilateral COx increased to 0.32 (+0.19 ± 0.05; p = .048), indicating loss of autoregulation. Accordingly, pooled ipsilateral and contralateral data showed increasing HVx and COx in symptomatic patients (HVx, p < .001; COx, p = .039). In addition to a drop in rSO2, the loss of autoregulatory capacity may be useful in identifying clinically significant clamping ischaemia during CEA under general anaesthesia and may allow optimisation of blood pressure management during awake CEA.


Upregulation of the long noncoding RNA UCA1 affects the proliferation, invasion, and survival of hypopharyngeal carcinoma.
Several long noncoding RNAs (lncRNAs) are involved in oncogenesis. Our microarray analysis showed that numerous lncRNAs are dysregulated in hypopharyngeal squamous cell carcinoma (HSCC) tumor tissues as compared with normal tissues. Among those lncRNAs, urothelial carcinoma-associated 1 (UCA1) has been found to have an oncogenic role in HSCC. We confirmed the upregulation of UCA1 in HSCC by assessing its expression levels in a cohort of 53 patient tumors and paired non-tumor samples. In addition, we found that high UCA1 expression was significantly associated with advanced T category, late clinical stage, greater lymphatic invasion, and worse prognosis. Furthermore, in vitro experiments demonstrated that UCA1 functioned as an oncogene by promoting the proliferation and invasion and preventing the apoptosis of HSCC cells. Taken together, our findings for the first time identify the role of UCA1 as a tumor promoter and a pro-metastatic factor in HSCC, demonstrating that UCA1 is a potential prognostic biomarker and therapeutic target in HSCC.


Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases.
The current study evaluated the effect of bevacizumab added to fluoropyrimidine-plus-oxaliplatin (5FU/OX) chemotherapy for colorectal liver metastases (CLM) on the pathologic response and nontumorous liver histology. A total of 105 consecutive patients treated preoperatively with 5FU/OX chemotherapy with (n = 62) or without (n = 43) bevacizumab were analyzed. The response to chemotherapy was evaluated by pathologic analysis of tumor viability (percentage of viable tumor in relation to tumor surface area). The incidence and grade of hepatic sinusoidal dilation were also investigated. Bevacizumab-containing regimens significantly reduced the degree of tumor viability compared with 5FU/OX-only chemotherapy (32.9% vs 45.3%; P = .02). After stratification according to the magnitude of tumor viability, a higher proportion of patients treated with bevacizumab than without had <25% residual viable tumor cells (45% vs 23%; P = .02). However, the addition of bevacizumab to 5FU/OX did not appear to increase the incidence of complete pathologic response (11.3% vs 11.6%; P = .59). The incidence and severity of sinusoidal dilation was lower in patients treated with bevacizumab than in those treated with 5FU/OX only (any grade: 27.4% vs 53.5%; moderate or severe: 8.1% vs 27.9%; both P < .01). In patients treated with 5FU/OX chemotherapy, bevacizumab improves the pathologic response, as demonstrated by a reduction of the degree of tumor viability, and reduces the incidence and severity of hepatic injury. This retrospective study provides additional evidence supporting the use of bevacizumab in combination with 5FU/OX for CLM.


A review of geographic variation and Geographic Information Systems (GIS) applications in prescription drug use research.
While understanding geography's role in healthcare has been an area of research for over 40 years, the application of geography-based analyses to prescription medication use is limited. The body of literature was reviewed to assess the current state of such studies to demonstrate the scale and scope of projects in order to highlight potential research opportunities. To review systematically how researchers have applied geography-based analyses to medication use data. Empiric, English language research articles were identified through PubMed and bibliographies. Original research articles were independently reviewed as to the medications or classes studied, data sources, measures of medication exposure, geographic units of analysis, geospatial measures, and statistical approaches. From 145 publications matching key search terms, forty publications met the inclusion criteria. Cardiovascular and psychotropic classes accounted for the largest proportion of studies. Prescription drug claims were the primary source, and medication exposure was frequently captured as period prevalence. Medication exposure was documented across a variety of geopolitical units such as countries, provinces, regions, states, and postal codes. Most results were descriptive and formal statistical modeling capitalizing on geospatial techniques was rare. Despite the extensive research on small area variation analysis in healthcare, there are a limited number of studies that have examined geographic variation in medication use. Clearly, there is opportunity to collaborate with geographers and GIS professionals to harness the power of GIS technologies and to strengthen future medication studies by applying more robust geospatial statistical methods.


Detailed characterization of particle emissions due to thermal failure of batteries with different cathodes.
Sufficient levels of thermal, electrical, mechanical, or electrochemical abuse can cause thermal runaway in lithium-ion batteries, leading to the release of electrolyte vapor, combustible gas mixtures, and high-temperature particles. Particle emissions due to thermal failure of batteries may cause serious pollution of the atmosphere, water sources, and soil as well as enter the human biological chain through crops, posing a potential threat to human health. Furthermore, high-temperature particle emissions may ignite the flammable gas mixtures produced during the thermal runaway process, resulting in combustion and explosions. This research focused on determining the particle size distribution, elemental composition, morphology, and crystal structure of particles released from different cathode batteries after thermal runaway. Accelerated adiabatic calorimetry tests were performed on a fully charged Li(Ni0.3Co0.3Mn0.3)O2 battery (NCM111), Li(Ni0.5Co0.2Mn0.3)O2 battery (NCM523), and Li(Ni0.6Co0.2Mn0.2)O2 battery (NCM622). Results of all three batteries indicate that particles with a diameter less than or equal to 0.85 mm exhibit an increase in volume distribution followed by a decrease in volume distribution as the diameter increases. F, S, P, Cr, Ge, and Ge were detected in particle emissions with mass percentages ranging from 6.5% to 43.3%, 0.76-1.20%, 2.41-4.83%,1.8-3.7%, and 0-0.14%, respectively. When present in high concentrations, these may have negative impacts on human health and the environment. In addition, the diffraction patterns of the particle emissions were approximately the same for NC111, NCM523, and NCM622, with emissions primarily composed of Ni/Co elemental, graphite, Li2CO3, NiO, LiF, MnO, and LiNiO2. This study can provide important insights into the potential environmental and health risks associated with particle emissions from thermal runaway in lithium-ion batteries.


Effects of chemical modifications of Pa-11, a phospholipase A2 from the venom of Australian king brown snake (Pseudechis australis), on its biological activities.
Pa-11, a phospholipase A2 isolated from the venom of an Australian elapid snake Pseudechis australis, was chemically modified and its enzymic, neuromuscular and lethal activities were studied. Carboxymethylation of Met-8 gave a derivative with 2% of the enzymic activity and less than 3% of the lethal activity of native Pa-11; it had about 5% of the original ability to block directly and indirectly stimulated mouse phrenic nerve-hemidiaphragm preparations. Nitrophenylsulfenylation of tryptophanyl residues at positions 31 and 69 caused loss of all activities. Amidination of all 14 lysyl residues gave a derivative with 41% and 16% of the enzymic and lethal activities, respectively, but with less than 5% of the original neuromuscular blocking activity. Mono-carbamoylation of lysyl residues at positions 58, 63, 81 and 85 was achieved. The most abundant derivative, 58-carbamoyl-lysine Pa-11 was enzymically 130% and lethally 100% as active as native Pa-11, but it had only about 20% of the native's neuromuscular activity in vitro. 63-Carbamoyl-lysine Pa-11 had 10% of the enzymic and 20% of the lethal activities, respectively; however, it retained at least 50% of its ability to block neuromuscular transmission in vitro, while losing most of its activity to block directly stimulated muscle contractions. 81- and 85-Carbamoyl derivatives have the same enzymic and lethal activities as the original protein, but the 85 derivative had less than 10% of the native neuromuscular activity. Hence, modifications of lysine residues at positions 58, 63 and 85 seem to be particularly significant in altering the neuromuscular, but not enzymic, activity of Pa-11, perhaps by altering the ability of the toxin to bind to its target on nerve and muscle membranes. Modification at position 63 appeared to lead to a dissociation of effects on neuromuscular transmission and directly on muscle cells.


Specialized dermatological-rheumatological patient management improves diagnostic outcome and patient journey in psoriasis and psoriatic arthritis: a four-year analysis.
Management of psoriasis patients with arthralgia suffering from suspected psoriatic arthritis (PsA) requires an interdisciplinary approach involving dermatologists and rheumatologists. The aim of the study was to analyze the specialized dermatological-rheumatological management of these patients before and after foundation of a PsA center. A retrospective cohort study of all dermatological-rheumatological consultations during two periods was conducted. Period one, from April 1st, 2016 to February 28th, 2018 versus period two, from March 1st, 2018 to January 31st, 2020, after foundation of a PsA center. Clinical data on patient characteristics including psoriasis subtypes, clinical symptoms and signs, disease activity scores, classification criteria and comorbidities as well as patient journey were extracted and analyzed. Four hundred four consultations were studied. Close collaboration in a PsA center lead to a relevantly shortened patient journey concerning rheumatological complaints: period 1: median (IQR): 36.0 (10.0-126.0) months, period 2: median (IQR): 24.0 (6.0-60.0) months. Established scores and classification criteria such as GEPARD or CASPAR did not assist in diagnosis of PsA. Arthralgia (p = 0.0407), swollen joints (p = 0.0151), morning stiffness (p = 0.0451) and dactylitis (p = 0.0086) helped to distinguish between osteoarthritis and PsA. Clinical signs and symptoms, scores and classification criteria usually assessed were less helpful than expected in diagnosis of PsA. Close collaboration in a specialized PsA center yielded the fastest way of diagnosis.


[Acute pituitary failure as the presentation of a prolactin cell adenoma during a pregnancy made possible by bromocriptine (author's transl)].
A 21-year-old woman had sterility due to amenorrhoea-galactorrhoea with hyperprolactinaemia and hypoplastic ovaries. The sella turcica was asymmetrical but tomograms were suggestive of a congenital appearance. There was no suprasellar expansion. Treatment with bromocriptine and HMG resulted in pregnancy. Acute pituitary failure occurred at the 10th week, revealing an adenoma. The pregnancy proceeded to term after hypophysectomy. This complication, the first reported under the effects of bromocriptine, may serve as a reminder of the precautions to be taken during pregnancy in a hyperprolactinaemic woman.


Adenovirus-mediated expression of heparin cofactor II inhibits thrombin-induced cellular responses in fibroblasts and vascular smooth muscle cells.
Heparin cofactor II functions as a physiological inhibitor of thrombin activity. The rate of inactivation of thrombin by heparin cofactor II is increased in the presence of dermatan sulfate, which is produced by fibroblasts or smooth muscle cells. To elucidate the role of heparin cofactor II in the extravascular cells, we induced expression of heparin cofactor II in cultured human fibroblasts or vascular smooth muscle cells using adenovirus-mediated gene transfer. After infection of adenovirus vector, these cells secreted heparin cofactor II protein into culture medium. The expressed heparin cofactor II formed the complex with exogenous thrombin and inhibited the proteolytic activity of thrombin. Expression of heparin cofactor II by infection of adenovirus vector inhibited thrombin-induced tissue-type plasminogen activator and interleukin-6 releases from fibroblasts and thrombin-induced interleukin-6 release from vascular smooth muscle cells. These findings show that fibroblasts and vascular smooth muscle cells expressing heparin cofactor II are resistant to thrombin-induced cellular responses.


End-of-Study Results for the Ladder Phase 2 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.
To report the end-of-study results from the Ladder clinical trial of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). Multicenter, randomized, active treatment-controlled phase 2 clinical trial. Patients diagnosed with nAMD with a documented response to anti-vascular endothelial growth factor treatment who received study treatment (N = 220). Patients were randomized 3:3:3:2 to treatment with the PDS filled with ranibizumab 10-mg/ml, 40-mg/ml, and 100-mg/ml formulations or monthly intravitreal ranibizumab 0.5-mg injections. End-of-study results for the time to first meeting refill criteria (first refill), mean change from baseline for best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. At study end, the mean time on study was 22.1 months (range, 10.8-37.6 months) for all PDS patients. Median time to first refill was 8.7 months, 13.0 months, and 15.8 months, and 28.9%, 56.0%, and 59.4% of patients went 12 months or longer without meeting refill criteria in the PDS 10-mg/ml, 40-mg/ml, and 100-mg/ml treatment arms, respectively. At month 22, the observed mean BCVA change from baseline was ‒4.6 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒2.3 ETDRS letters, +2.9 ETDRS letters, and +2.7 ETDRS letters in the PDS 10-mg/ml, 40-mg/ml, 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg treatment arms, respectively. At month 22, the observed mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg treatment arms. No new safety signals were detected during the additional follow-up. Over a mean of 22 months on study, vision and anatomic outcomes were comparable between the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms, with a lower total number of ranibizumab treatments with the PDS. The Ladder end-of-study findings were consistent with the primary analysis, and the PDS generally was well tolerated throughout the entire study period. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision.


Relationship between the duration of G1 period of eukaryotic cell cycle and age-associated changes in the expression of cyclin D1 and nuclear receptors.
The relationship between the duration of G(1) phase of eukaryotic cell cycle and age of cell donor was studied. The relationship of these processes with age-specific changes in the expression of cyclin D1 and nuclear receptors was traced. Obvious changes in the dynamics of expression of cyclin and nuclear receptors were detected in cells from donors of different age.


The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic.
Background: Levothyroxine (LT4) is the mainstay of therapy for hypothyroidism. Yet, despite physician efforts at dose titration, some patients remain hypothyroid on LT4 doses in excess of weight-based calculations, a condition known as refractory hypothyroidism. The LT4 absorption test (LT4AT) has been proposed to have utility in these patients by enabling distinction of LT4 malabsorption from pseudomalabsorption, a condition of intentional nonadherence. Given its rare use in clinical practice, we reviewed our institution's experience with the LT4AT to assess its impact on management of refractory hypothyroidism. Methods: We reviewed the charts of 16 patients diagnosed with refractory hypothyroidism and who had completed the LT4AT between January 2015 to January 2019. The primary aim was to determine the utility of this test in distinguishing LT4 malabsorption from pseudomalabsorption. Secondary aims were to determine whether the results of this test impacted physicians' management decisions, as well as to report on clinical outcomes at follow-up. Our LT4AT is a six-hour test wherein patients receive a weight-based dose of LT4 followed by serial measurements of total thyroxine (TT4) and thyrotropin (TSH). Percentage absorption is calculated using the following formula, with normal absorption being ≥60%: [Formula: see text] Results: Percentage absorption was calculated in 13 of 16 patients due to lack of TT4 data for 3 patients. Absorption was impaired in one patient (% absorbed = 0), who had known causes of malabsorption. The remaining 12 patients had normal absorption by hour 4 of the test (% absorption 60-158) in conjunction with upward TT4 trends. Clinical follow-up ranged from 1 to 32 months (median 6.5 months), with 11 patients having follow-up data. Six of these had normal or suppressed TSH values at most recent follow-up, and four had improved but persistent TSH elevations. The one said patient with malabsorption improved with intravenous LT4. Conclusions: The LT4AT can provide valuable information for distinguishing malabsorption from pseudomalabsorption. Our findings support the combined use of calculated percentage absorptions with TT4 trends for at least a four-hour time frame when making determinations regarding absorption.


Interaction of HIV-1 reverse transcriptase with modified oligonucleotide primers containing 2'-O-beta-D-ribofuranosyladenosine.
Modified synthetic oligodeoxyribonucleotides containing 2'-O-beta-D-ribofuranosyladenosine were used as primers in the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase. The degree of elongation of the primers depends on the position of the additional ribose unit, its presence in the specific position of the primer (-4) (and only in it) completely preventing elongation. Computer-modeled binding of the modified primers to the active site of reverse transcriptase demonstrated that steric hindrances arising from the interaction of the additional ribose residue with the reverse transcriptase region 262-270 interacting with the minor groove of the DNA substrate prevents elongation in the above mentioned case.


Planning and evaluating community oral health programs.
Community oral-health programs focus primarily on populations, including those who do not seek oral health care. Planning these programs should include involvement of the community, broadly defined to include individuals and organizations that represent those who can help design and implement it and those who could be affected by it. This article provides an overview of systematic approaches to planning and evaluating community oral health programs. Such approaches help ensure that stakeholders agree on the purpose of the program, work toward its success, and contribute toward its continuous improvement.


Relation Between Pulmonary Venous Flow and Left Atrial Pressure During Percutaneous Mitral Valve Repair With the MitraClip.
Pulmonary venous (PV) flow may provide valuable information in terms of the severity of mitral regurgitation and left atrial (LA) pressure. We sought to find PV flow determinants of LA pressure during MitraClip procedure. We analyzed 575 PV flows in 290 patients using transesophageal echocardiography before and after MitraClip procedure. We measured peak systolic velocity (Sv), diastolic velocity (Dv), systolic velocity time integral (Svti), diastolic velocity time integral (Dvti), and those systolic to diastolic ratio as PV flow parameters. Systolic PV flow velocity was lower than diastolic PV flow velocity before the procedure, but systolic PV flow velocity markedly increased after the procedure. Peak Sv/Dv ratio and Svti/Dvti ratio after the procedure were significantly higher than those before the procedure (peak Sv/Dv; 1.06 [inter-quartile range (IQR) 0.73 to 1.34] vs 0.32 [IQR 0.03 to 0.55], p <0.001, Svti/Dvti; 1.06 [IQR 0.76 to 1.61] vs 0.26 [IQR 0.02 to 0.51], p <0.001). Peak Sv/Dv ratio and Svti/Dvti ratio were negatively correlated with mean LA pressure and LA pressure V wave, respectively (peak Sv/Dv ratio; r = -0.50 and r = -0.59, Svti/Dvti ratio; r = -0.47 and r = -0.58, p <0.001). In receiver operating characteristics curve assessing the ability of PV flow to predict mean LA pressure ≥20 mm Hg after the successful procedure, the area under the curve of peak Sv/Dv ratio was 0.76 (p <0.001). Peak Sv/Dv ratio <0.98 best predicted LA pressure ≥20 mm Hg with 77% sensitivity and 71% specificity. In conclusion, systolic PV flow velocity immediately increased in response to mitral regurgitation reduction during MitraClip procedure. PV flow velocity, specifically systolic to diastolic ratio, was useful to evaluate invasively determined LA pressure.


A comparative study of serum effusion albumin gradient and Light's criteria to differentiate exudative and transudative pleural effusion.
The incidence of pleural effusion is approximately one million per year. For diagnosing and treatment plan, pleural effusions have to be classified into transudate and exudate. If the diagnosis is not appropriate, it may result in severe complications. The established criterion for differentiating exudates from transudates is Light's criteria. But there were some false positive results in case of transudative effusions when Light's criteria were used. This study was done to determine the accuracy of serum effusion albumin gradient (SEAG) when compared to Light's criteria in differentiating transudates and exudates. It is a prospective observational study. In the present study, the sample size is 66 patients, in whom the SEAG was used for the classification of pleural effusions with a cut-off value of 1.2 g/dl. All the blood samples were collected and biochemical parameters like total protein, albumin, and LDH were analyzed in both serum and pleural fluid using XL 640 fully automated random access analyzer. Results were analyzed using SPSS software version 20. 20 of 22 transudates and 41 of 44 exudates were classified correctly using SEAG. The diagnostic accuracy of SEAG (92.42%) is better than Light's criteria (87.87%) in differentiating both transudative and exudative effusions. The SEAG is superior to Light's criteria in identifying the transudative effusions. It is also observed that Light's criteria identified exudative effusions better than SEAG.


Cohort dominance rank and "robbing and bartering" among subadult male long-tailed macaques at Uluwatu, Bali.
Robbing and bartering is a habitual behavior among free-ranging long-tailed macaques (Macaca fascicularis) at a single site in Bali, Indonesia. The behavior consists of three main elements: (1) a macaque takes an item from a human; (2) the macaque maintains possession of the item; then (3) the macaque releases or hands off the item after accepting a food offer from a human. In this paper, we analyze data on individual variation in robbing and bartering among subadult males in relation to dominance rank. Using focal animal sampling we collected 197 observation hours of data on 13 subadult males from two groups (6 from Celagi; 7 from Riting) at the Uluwatu temple site from May 2017 to March 2018, recording 44 exchanges of items for food from 92 total robberies following 176 total attempts. We also measured dominance rank using interaction data from our focal animals. Dominance rank was strongly positively correlated with robbery efficiency in Riting, but not Celagi, meaning that more dominant Riting subadult males exhibited fewer overall robbery attempts per successful robbery. We suggest the observed variation in robbing and bartering practices indicates there are crucial, yet still unexplored, social factors at play for individual robbing and bartering decisions.


Watch out for reporter gene assays with Renilla luciferase and paclitaxel.
Luminescence-based reporter gene assays are widely used in biochemistry. Signals from reporter genes (e.g., firefly luminescence) are usually normalized to signals from constantly luminescing luciferases such as Renilla luciferase. This normalization step can be performed by modern luminometry devices automatically providing final results. Here we demonstrate paclitaxel to strikingly enhance Renilla luminescence, thereby potentially flawing results from reporter gene assays. In consequence, these data advocate for careful examination of raw data and militate against automatic data processing.


Selective losses of large immune complexes during density gradient ultracentrifugation and an approach for prevention of these losses.
Substantial amounts (12.3-40.0%) of model immune complexes became nonspecifically adsorbed to centrifuge tubes during sucrose density gradient ultracentrifugation, and the adsorbed complexes were therefore unavailable for subsequent detection by the C1q solid-phase assay. The adsorption was greater for heavier immune complexes; thus detection of large-latticed complexes was impaired more than detection of small-latticed complexes. Loss of complexes could be prevented by incorporation of 0.05% polyoxyethylene (20) sorbitan monolaurate (Tween 20) into sucrose density gradient solutions and precoating tubes with gelatin. Tween 20 did not alter the immune complex lattice and did not prevent detection of immune complexes by the C1q solid-phase assay. Similar selective losses of immune complexes occurred when serum specimens from 2 patients with circulating immune complexes were analyzed by sucrose density gradient ultracentrifugation; the nonspecific adsorption of serum immune complexes which occurred during ultracentrifugation could be prevented by precoating centrifuge tubes with gelatin and incorporating 0.05% Tween 20 into sucrose gradients.


[Blood glucose level as a criterion for surgical stress during ataralgesia and sodium nitroprusside hypotension during the surgical treatment of cerebral arterial aneurysms].
Test for stress-induced hyperglycemia showed that deep sodium nitroprusside-controlled arterial hypotension in ataralgesia is a powerful stress-producing factor. Additional neurovegetative inhibition by administration of small doses of ganglioblocking agent pentamine is suggested for the prevention hypotension-induced stress.


Guns in the Home and the Possibility of Aggressive Tendencies: Exploring a Community Sample of Adolescents in Low-Income Communities.
Firearm violence has been the second leading cause of death among adolescents and young adults in the United States since 2000 and is a major public health concern. But firearms may be related to less lethal forms of violence as well. Here we examine the relationship between the presence of a gun in the home and several behavioral and psychosocial measures related to aggression and violence among adolescents using data from a community-based survey of nearly 2,000 youths living in low-income neighborhoods. Our results indicate that adolescents living in homes where a gun is present display more aggressive attitudes and behaviors than their counterparts living in homes with no gun present. More research is needed to better understand the mechanisms underlying the relationships, but they may relate to a weapon's effect or social learning.


Dietary Garcinia cambogia does not modify skin properties of mice with or without excessive sucrose intake.
The influence of 3.3% Garcinia cambogia extract on the properties of mouse skin with or without 10% sucrose water loading was investigated. Mice (7-week-old) were given free access to a control diet or a diet containing Garcinia cambogia extract. They were also given water alone or both water and sucrose water. Their skin was compared by both biochemical and histological methods. The collagen and triacylglycerol contents were not significantly different among the four groups. Similarly, electron microscopy revealed no differences in the thickness of the dermis layer or the subcutaneous tissue layer. Mice given the diet containing Garcinia cambogia tended to have a reduced total number of adipocytes, but not significantly. These results suggest that Garcinia cambogia supplementation for at least 4 weeks does not induce a negative effect on skin properties in mice irrespective of excessive sucrose intake.


A circular RNA, circPTPN14, increases MYC transcription by interacting with FUBP1 and exacerbates renal fibrosis.
Fibrosis is a relentlessly progressive and irreversible cause of organ damage, as in chronic kidney disease (CKD), but its underlying mechanisms remain elusive. We found that a circular RNA, circPTPN14, is highly expressed in human kidneys with biopsy-proved chronic interstitial fibrosis, mouse kidneys subjected to ischemia/reperfusion (IR) or unilateral ureteral obstruction (UUO), and TGFβ1-stimulated renal tubule epithelial cells (TECs). The intrarenal injection of circPTPN14 shRNA alleviated the progression of fibrosis in kidneys subjected to IR or UUO. Knockdown of circPTPN14 in TECs inhibited TGFβ1-induced expression of profibrotic genes, whereas overexpressing circPTPN14 increased the profibrotic effect of TGFβ1. The profibrotic action of circPTPN14 was ascribed to an increase in MYC transcription. The binding of circPTPN14 to the KH3 and KH4 domains of far upstream element (FUSE) binding protein 1 (FUBP1) enhanced the interaction between FUBP1 and FUSE domain, which was required for the initiation of MYC transcription. In human kidneys (n = 30) with biopsy-proved chronic interstitial fibrosis, the expression of circPTPN14 positively correlated with MYC expression. Taken together these studies show a novel mechanism in the pathogenesis of renal fibrosis, mediated by circPTPN14, which can be a target in the diagnosis and treatment of CKD.


Virus-like particles presenting flagellin exhibit unique adjuvant effects on eliciting T helper type 1 humoral and cellular immune responses to poor immunogenic influenza virus M2e protein vaccine.
Current licensed adjuvants including aluminum hydroxide (alum) bias immune responses toward T helper type 2 (Th2) immune responses. We tested whether virus-like particles presenting flagellin (Flag VLP) exhibit adjuvant effects on eliciting Th1 type immune responses and improving the efficacy of poor immunogenic tandem repeat M2e (M2e5x) protein vaccine against influenza virus. Co-immunization of mice with Flag VLP and M2e5x protein vaccine induced significantly higher levels of IgG2a isotype (Th1) antibodies in sera and mucosal sites, effector CD4+ T cells secreting IFN-γ and granzyme B, and more effective lung viral clearance and protection compared to alum adjuvant. Flag VLP stimulated primary macrophages and dendritic cells to secrete inflammatory cytokines, which is partially dependent on the Toll-like receptor 5. This study provides insight into developing effective vaccine adjuvants.


Human genetics and sleep behavior.
Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research.


HCV selection and HVR1 evolution in a chimpanzee chronically infected with HCV-1 over 12 years.
To study hepatitis C virus (HCV) selection and hypervariable region-1 (HVR1) evolution in a chimpanzee chronically infected with HCV-1 over 12 years after inoculation with a human factor VIII concentrate contaminated with HCV. From the inoculum, the earliest chimpanzee plasma and 12 annual plasma samples, HCV fragments including HVR1 were amplified followed by cloning and sequencing. Five HCV subtypes - 1a, 1b, 2a, 2b, 3a - and multiple 1a strains were identified in the inoculum. Two 1a strains were found in the earliest chimpanzee sample, while a single HCV-1 strain was detected in the 12 annual samples. None of the chimpanzee sequences were identical to those found in the inoculum. Over 12 years, HVR1 patterns changed irregularly, but a few patterns showed identical nucleotide or amino acid sequences. In the last three years, the variety of HVR1 patterns decreased, while the proportion of major patterns increased. These corresponded to a higher virus load and a lower number of amino acid substitutions. Simultaneously, the HVR1 sequences became more similar to the consensus sequence of the 1a subtype. HCV selection was observed from the inoculum to the inoculated chimpanzee and from the early acute hepatitis to the persistent chronic infection. The selection occurred at three levels: among subtypes after transmission, among isolates during acute hepatitis and among quasispecies in chronic infection.


Effects of high-dose alacepril on left atrial pressure and central aortic pressure in awake dogs with mitral valve regurgitation.
The purpose of this study was to clarify how alacepril in amounts greater than those recommended on the product labeling approved by drug regulatory agencies affects left atrial pressure (LAP) and central aortic pressure in dogs with experimentally induced mitral valve regurgitation (MR). Six healthy Beagle dogs were surgically induced for MR and received alacepril at either 1.5mg/kg/12-h (3.0mg/kg/day) or 3.0mg/kg/12-h (6.0mg/kg/day) per one administration for seven days. After a four-week washout period, another dosage was administrated as a crossover study. Dogs were randomised to receive 3.0mg/kg/day or 6.0mg/kg/day first. LAP and central systolic (SAP), mean (MAP), and diastolic (DAP) aortic pressure were measured for 24-h before and during the administration of alacepril. The earliest decreases in SAP, MAP, and DAP with 6.0mg/kg/day were observed on days 4, 4, and 5, respectively. With 3.0mg/kg/day, the earliest decrease in DAP was observed on day 7. The maximum LAP was decreased on days 5 and 7 with 6.0mg/kg/day. The mean LAP was decreased on day 7 with 6.0mg/kg/day. In conclusion, the administration of alacepril at 6.0mg/kg/day reduced the LAP and central aortic pressure within several days.


Pulsed Doppler echocardiographic detection of the origin of musical murmurs in a case of pacemaker implantation.
We report a case of systolic and diastolic musical murmurs that developed 4 years after DDD pacemaker implantation. Echocardiographic examination disclosed no evidence of serious pacemaker-related complications. Pulsed Doppler examination with a sample volume at the right ventricular portion of a pacemaker lead showed prominent harmonic signals. The timing of the signals was consistent with that of musical murmurs. We considered vibration of the pacemaker lead as a possible origin of the musical murmurs. Systolic and diastolic musical murmurs can develop without serious cause in a patient with a transvenous pacemaker. Pulsed Doppler examination was useful in detecting the origin of musical murmurs.


Effects of Women's Body Satisfaction, Emotional Eating, and Race on Short-, Mid-, and Long-term Weight Loss.
To improve understanding of psychosocial factors, their changes, and racial differences with implications for behavioral obesity treatments. Women with obesity of White (n = 64) and Black (n = 33) racial groups participated in cognitive-behavioral community-based obesity treatment and were assessed on body satisfaction, emotional eating, and weight changes over 3, 6, 12, and 24 months via mixed-model repeated-measures analysis of variance and stepwise multiple regression analyses. Baseline body satisfaction scores were significantly higher (P < 0.001) in Black participants. White participants had significantly higher (P = 0.04) emotional eating scores. Significant overall improvements (P < 0.001) in body satisfaction, emotional eating, and weight were found, with weight reduction significantly greater (P = 0.05) among the White women. Weight reductions were significantly predicted by changes in body satisfaction and emotional eating (R2 = 0.12-0.20, P < 0.01). When racial group was entered into the analyses, the explained variance in weight change over 6 and 12 months significantly increased (P < 0.05). Findings suggest addressing body satisfaction, emotional eating, and racial differences by adjusting obesity treatment targets could improve outcomes. Research-to-practice needs include a control group and further identification/elucidation of other psychosocial and economic factors that might affect outcomes.


Cloning and sequencing of the cDNA encoding the murine mammary gland long-form prolactin receptor.
The nucleotide sequence of a 1992-bp cDNA encoding the long form of the murine mammary prolactin receptor (PRL-R) has been determined. The deduced 68-kDa protein has high sequence identity with long forms of prolactin receptors from rat ovary and rabbit mammary gland.


Physiological responses of the southern king crab, Lithodes santolla (Decapoda: Lithodidae), to aerial exposure.
The recent demand for live seafood has made Lithodes santolla a potential candidate for the live crab market. Since live transport implies long aerial exposure times, the present study determined the tolerance of L. santolla to aerial exposure and also explored the physiological status of L. santolla after six different aerial exposure times: 0, 10, 20, 30, 40 and 50h. No mortalities were recorded during emersion periods shorter than 40 h, however, all hemolymph parameters were modulated by aerial exposure. Hemolymph dissolved oxygen and pH were inversely related with the aerial exposure time (-0.016 mg L(-1) h(-1) and -0.018 h(-1), respectively), while oxyhemocyanin and hemolymph protein were positively correlated (0.006 mmol L(-1) h(-1) and 0.487 mg mL(-1) h(-1), respectively). Oxygen consumption at re-immersion was affected by aerial exposure time, with low values in animals emersed for longer than 30 h. We postulate that the unexpected high tolerance of L. santolla to aerial exposure is mainly related to adaptations to hypoxia, developed to overcome hypoxic events in their natural environment in deep water. The present findings are not only important for understanding L. santolla's physiology, but also provide the first evaluation of the potential marketing of southern king crab as live seafood.


Detection of Migrainous Infarction with Formal Visual Field Testing: A Case Report.
Cerebrovascular accidents (CVA) of the posterior circulation are a rare complication of migraine, and present with atypical CVA symptomatology. A 49-year-old-male presented with complaint of persistent visual aura and resolved mild cephalgia. His exam corroborated his reported incomplete left inferior quadrantanopia, and was confirmed by immediate formal optometry evaluation. Occipital CVA was confirmed on admission. Migrainous strokes of posterior circulation should be considered as a potential diagnosis in any headache patient with persistent visual aura. This case suggests that incorporation of formal visual field testing in the emergent setting can shorten the time required for diagnosis in certain circumstances.