Effects of whey or maltodextrin addition during production on physical quality of white cheese powder during storage.
There is an increasing demand for cheese as a food ingredient, especially as a flavoring agent. One of the most important cheese flavoring agents is cheese powder. To obtain an intense cheese flavor, ripened cheese is used as a raw material in cheese powder but this increases production costs. Moreover, use of natural cheese decreases the physical quality of powder because of its high fat content. In this study, we evaluated opportunities to use whey or maltodextrin for improving the physical quality of powders in production of white cheese powder. We produced cheese powders with 3 different formulations-control (CON), whey-added (WACP), and maltodextrin-added (MACP)-and determined the effects of formulation on cheese powder quality. Physical quality parameters such as color, densities, reconstitution properties, free fat content, particle morphology, and sensory characteristics were investigated. The different cheese powders were stored for 12 mo at 20°C and we evaluated the effect of storage on powder quality. Addition of maltodextrin to cheese powder formulations significantly improved their physical quality. The densities and reconstitution properties of cheese powder were increased and free fat content was decreased by use of maltodextrin. The MACP particles were spherical with a uniform distribution and larger particle sizes, whereas CON and WACP particles were wrinkled, irregular shaped with deep surface dents, and variable in size. Although caking was observed in scanning electron micrographs after 12 mo of storage, it was not detected by sensory panelists. The color of cheese powders changed very slowly during storage but browning was detected. The results of this study show that it is possible to use maltodextrin or whey in production of white cheese powder to reduce production costs and improve the physical quality of powders.


An Analysis of the FDA MAUDE Database and the Search for Cobalt Toxicity in Class 3 Johnson & Johnson/DePuy Metal-on-Metal Hip Implants.
This study was designed to determine whether systemic cobalt toxicity as an adverse event could be documented using the Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience (MAUDE) database for cobalt-chromium containing hip implant recipients. Class 3 Johnson & Johnson (J&J)/DePuy devices were chosen for analysis because of the large number of adverse event reports related to their Pinnacle and ASR XL Acetabular hip replacement systems. A secondary goal was to characterize the reporters who are populating the information in the MAUDE database and to evaluate the quality of the data and information submitted. Using FDA MAUDE downloadable data files, 83,528 adverse event medical device narrative reports were identified with the product code of KWA (Prosthesis, Hip, Semiconstrained [Metal Uncemented Acetabular Component]) for J&J/DePuy (KWA Text File). These are class 3 devices and devices with known high failure rates. The ASR XL Acetabular hip replacement Systems and Pinnacle fall into this category. This group of implants was chosen because implant failure is associated with elevated cobalt levels. Two additional subfiles were created from Free Text records in the narrative reports containing key words that indicated a chromium or cobalt (CrCo) device and another for key words indicating elevated levels of cobalt or toxicity. These files were then searched for symptoms of systemic cobalt toxicity with Microsoft Excel using key words pertaining to symptom categories of: cognitive/memory loss, tremor, neuropathy, depression, auditory symptoms, visual symptoms, cardiac, and thyroid disease. Reports are submitted to the FDA at the device component level. It was common for multiple reports to be submitted for a single device. It was not possible to differentiate systemic versus local symptoms for adverse event reports in the neuropathy category. This category was not analyzed. The number of adverse event reports in the other categories ranged from 119 to 16 for the J&J/DePuy KWA Text File and 59 to 4 in the file of records having key words indicating potential elevation of CrCo or toxicity. Cardiac, visual, and auditory conditions were most frequently reported. With the possible exception of cardiomyopathy, the numbers of these reports are far below the prevalence expected in the general population of comparable age. The content of the MAUDE database records often contained little objective data. We found less than 4% of 14,714 records, which indicated cobalt elevation or toxicity contained units for quantitative measurement. There was also frequent use of nondescript, all-encompassing words and phrases such as "mental anguish," found in 321 KWA Text File records. Manufacturers submitted more than 99% of the reports and the most common reporter occupation was attorney, found in 42.24% of the 83,550 J&J/DePuy KWA Reporter File records. Physician was the reporter's occupation in 20.48% of reports but seldom reported directly to the FDA. We were not able find in the FDA MAUDE database meaningful warning signs to support the contention that chromium-cobalt-containing Class 3 J&J and DePuy hip implants caused systemic neurological or thyroid symptoms in patients. The incidence of reported cardiomyopathy was rare but frequent enough to be cause of concern. The redaction of most patient data along with the nonstructured nature of data entry would be expected to hinder the identification of warning signs. Even identification of the type of device could not be consistently carried out. In addition, the FDA needs to implement a methodology to identify and group all reports from a single device implanted into a patient, so duplication of event counting would not occur. Of 83,550 J&J/DePuy KWA Reporter File records, we found only two physician reports sent directly to the FDA. Almost all reports are submitted by manufacturers and are most commonly authored by attorneys. A standard of care needs to be set for physicians to report medical device adverse events to the FDA.


Truncated Product Methods for Panel Unit Root Tests.
This paper proposes two new panel unit root tests based on Zaykin et al. (2002)'s truncated product method. The first one assumes constant correlation between p-values and the second one uses sieve bootstrap to allow for general forms of cross-section dependence in the panel units. Monte Carlo simulation shows that both tests have reasonably good size and are powerful in cases of some very large p-values. The proposed tests are applied to a panel of real GDP and inflation density forecasts, resulting in evidence that professional forecasters may not update their forecast precision in an optimal Bayesian way.


Details of the intralingual topography and morphology of the lingual nerve.
The lingual nerve supplies the tongue with trigeminal sensory fibers and sensory fibers that originate from the chorda tympani. The aim of this study was to investigate, by dissection, the anatomical features of the lingual nerve at the level of the tongue and to correlate the findings with existing data. Six human adult cadavers dissected bilaterally and 6 specimens of tongue-pharynx-larynx from autopsied adult cadavers were studied. The lingual nerve gives off its terminal branches at the anterior border of the hyoglossus muscle where the anastomotic loops between the lingual and hypoglossal nerves are found. Two morphological types of terminal division of the lingual nerve were seen: a single primary trunk or two primary trunks, a medial one distributed in the middle third of the tongue and a lateral one for the anterior third of the tongue. The primary terminal branches of the lingual nerve were located on the outer surface of the genioglossus muscle, forming a nervous layer over the deep artery of the tongue. The following emerged from the primary trunk(s): thin branches for the ipsilateral mucosa of the ventral surface of the tongue and 4-9 thick secondary trunks, with palisade disposition and translingual courses that followed the outer surface of the genioglossus muscle towards the dorsal mucosa of the ipsilateral part of the tongue, anterior to the circumvallate papillae.


Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments.
The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments.


Prioritization of Patients for Publicly Funded IVF in Ontario: A Survey of Fertility Centres.
On December 21, 2015, Ontario began funding one cycle of IVF for any Ontarian under age 43, with a program cap of 5000 cycles per year, which is below expected demand. Our objective was to determine how fertility clinics are prioritizing patients for limited-funded IVF cycles. An electronic survey was emailed to medical directors of all 25 fertility clinics providing funded IVF in Ontario. From January to March 2016, 22 (88%) of the clinics responded. All reported providing access to funded IVF, and 100% already had a wait list. Eight clinics prioritized patients on a first-come, first-served basis; two used a lottery; 11 reported using multiple patient factors to determine priority for funding; and one declined to answer. Of the clinics reporting multiple factors, the five most common factors were first-come, first-served (90.9%); older aged patients (81.8%); patients about to lose their funding eligibility (63.6%); duration of infertility (36.3%); and duration at current clinic (36.3%). There is variation in how patients are prioritized for publicly funded IVF in Ontario. Some clinics have chosen to prioritize patients in a first-come, first-served manner, whereas others have chosen to prioritize patients based on multiple factors that would favour older patients. This is the first study providing the public and government insight on how the new fertility program has been implemented by individual clinics. This information is important for patients to understand their own chances of receiving a funded IVF cycle because this may vary depending on individual clinics.


The impact of urbanization on mood disorders: an update of recent evidence.
Mood disorders are highly prevalent and represent a leading cause of global disability. Urbanization holds great public health implications spanning various environmental, lifestyle behavioural, economic and social domains. Underlying risk factors for mood disorders are heterogeneous but the psychiatric literature has extended beyond individual-level risk, to account for population-level environment and social-related precursors to mental ill health. This review summarizes recent studies published since 2017 examining the impact of urbanization and associated environmental, social and lifestyle risks for mood disorders, specifically depression. All identified studies examined depression or subclinical mood-related symptomatology. Recent evidence suggests individuals residing in urban areas experience increased risk of depression. Mechanistic pathways include increased exposure to noise, light and air pollution, poor quality housing, reduced diet quality, physical inactivity, economic strain and diminished social networks. The role of the gut microbiome in the development of mood disorders represents a novel research domain expected to hold potential for the psychiatric and environmental field. Further research is needed to extrapolate the relationship between increased sedentary lifestyles and technology use and depression in urban societies. Recent evidence highlights the complexity and reciprocity of underlying driving factors in the relationship between urbanization and mood disorders. Future epidemiological research should continue to untangle such complexity. There was a dearth of evidence relating to urbanization and mood disorders other than depression. Future research should identify the unique experiences of vulnerable subgroups who experience disproportionate increased risk of adverse health experiences associated with urbanization.


Metabolic alterations in normal and streptozotocin-diabetic rats in vivo: influence of prolonged starvation.
We studied the influence of prolonged starvation on carbohydrate metabolism in streptozotocin-diabetic rats compared with normal rats. In streptozotocin (STZ)-diabetic rats, the plasma glucose concentration decreased gradually during prolonged starvation, while it did not change in normal rats. In normal rats, glycogen depletion in the liver occurred within 24 hr of starvation, while in STZ-diabetic rats, glycogen content did not change even after 72 hr of starvation. Impaired glucose tolerance and glycogen deposition in response to oral administration of glucose were observed in STZ-diabetic rats compared with normal animals. STZ-diabetic animals generally had lower glycogen synthase and phosphorylase activities compared with normal rats during starvation. In normal animals, there is a significant correlation between the plasma concentration of free fatty acids and 3-hydroxybutyrate. On the basis of these findings, metabolic alterations in chemically-induced diabetic animals were discussed.


Pilot clinical trial with a new beta 2-sympathomimetic bronchodilator, mabuterol.
An open pilot study was performed on 10 patients with chronic, reversible, obstructive lung disease and known good response to beta 2-bronchodilators. The effects of 40, 60 and 80 micrograms 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) given orally and of 0.4 mg fenoterol (aerosol) were measured on airway resistance, thoracic gas volume, pulse rate and blood pressure. Side effects, ECG and laboratory values were recorded. Mabuterol was found to have a good, clinically useful, bronchodilating effect and to possess excellent tolerability at doses of 40-60 micrograms.


A fairness assessment of mobility-based COVID-19 case prediction models.
In light of the outbreak of COVID-19, analyzing and measuring human mobility has become increasingly important. A wide range of studies have explored spatiotemporal trends over time, examined associations with other variables, evaluated non-pharmacologic interventions (NPIs), and predicted or simulated COVID-19 spread using mobility data. Despite the benefits of publicly available mobility data, a key question remains unanswered: are models using mobility data performing equitably across demographic groups? We hypothesize that bias in the mobility data used to train the predictive models might lead to unfairly less accurate predictions for certain demographic groups. To test our hypothesis, we applied two mobility-based COVID infection prediction models at the county level in the United States using SafeGraph data, and correlated model performance with sociodemographic traits. Findings revealed that there is a systematic bias in models' performance toward certain demographic characteristics. Specifically, the models tend to favor large, highly educated, wealthy, young, and urban counties. We hypothesize that the mobility data currently used by many predictive models tends to capture less information about older, poorer, less educated and people from rural regions, which in turn negatively impacts the accuracy of the COVID-19 prediction in these areas. Ultimately, this study points to the need of improved data collection and sampling approaches that allow for an accurate representation of the mobility patterns across demographic groups.


Topical ophthalmic fourth-generation fluoroquinolones: Appropriate use and cost considerations.
The utilization and refill rates of topical ophthalmic fourth-generation fluoroquinolones among physicians, as well as the associated costs, were studied. A large data set of retrospective pharmacy prescription claims was obtained from multiple plans, including commercial managed care organizations, Medicaid, and Medicare. The data included the number and cost of all new and refill prescriptions for six months for gatifloxacin 0.3% and moxifloxacin 0.5% by physician specialty. New prescription and refill data were also analyzed from a state Medicaid plan to determine if similar trends existed. Primary care physicians wrote approximately 7,000 (7.7%) gatifloxacin and 84,000 (92.3%) moxifloxacin prescriptions, with pediatricians accounting for 4,000 (5.1%) gatifloxacin and 75,000 (94.9%) moxifloxacin prescriptions. Eye care physicians accounted for a similar amount of prescriptions for each antibiotic during the same period. The total cost of prescriptions for all primary care practitioners was approximately $170,000 for gatifloxacin and $2.5 million for moxifloxacin; prescriptions written by pediatricians accounted for $110,000 for gatifloxacin and $2.2 million for moxifloxacin. Prescription drug claims from payers using pharmacy benefit management companies during a six-month period indicated that the numbers of prescriptions written for gatifloxacin and moxifloxacin were similar among eye care physicians, but primary care physicians wrote a greater number of prescriptions for moxifloxacin. Analysis of claims to a Medicaid database revealed an increase in the prescriptions written by primary care physicians for moxifloxacin after its addition to the drug formulary.


A review on the 40th anniversary of the first regulation of drinking water disinfection by-products.
Water disinfection, primarily by chlorination, is one of the greatest achievements of public health. However, more than half a century after its introduction, studies in the 1970s reported that (a) chlorine interacted with organic matter in the water to form disinfection by-products (DBPs); (b) two DBPs, chloroform and bromoform, both trihalomethanes (THMs), were rodent carcinogens; (c) three brominated THMs were mutagenic; in six studies chlorinated drinking waters in the United States and Canada were mutagenic; and (d) in one epidemiological study there was an association between bladder cancer mortality and THM exposure. This led the U.S. Environmental Protection Agency to issue its first DBP regulation in 1979. Forty years later, >600 DBPs have been characterized, 20/22 have been shown to be rodent carcinogens, >100 have been shown to be genotoxic, and 1000s of water samples have been found to be mutagenic. Data support a hypothesis that long-term dermal/inhalation exposure to certain levels of the three brominated THMs, as well as oral exposure to the haloacetic acids, combined with a specific genotype may increase the risk for bladder cancer for a small but significant population group. Improved water-treatment methods and stricter regulations have likely reduced such risks over the years, and further reductions in potential risk are anticipated with the application of advanced water-treatment methods and wider application of drinking water regulations. This 40-year research effort is a remarkable example of sustained cooperation between academic and government scientists, along with public/private water companies, to find answers to a pressing public health question.


[Objective need for cancer prevention in the Czech Republic and Europe, and the state thereof].
There is no doubt today of the need for cancer prevention. The growing incidence of cancer itself provides a sufficient justification for prevention programmes. A review of literature presented in this paper also documents the strong background of evidence-based cancer prevention programmes. The article also provides a critical analysis of the current status of primary cancer prevention and cancer screening in the Czech Republic in contrast with available international comparisons. Relevant international data have been obtained from the regularly repeated "Health at a Glance" studies (published by the OECD). Although the Czech Republic is one of the countries with the highest cancer burden in Europe, it has failed to develop and support a cancer prevention policy on a central level, and this also applies to smoking prevention. The Czech population needs an effective national strategy for the support of cancer prevention, as well as a strategy which would ensure equitable cancer care in terms of both quality and correct indication; a strategy which would be sustainable for at least 10 to 15 years to come.Key words: oncology - screening - risk factor - prevention - population burden This study was supported by the project 36/14//NAP "Development and implementation of methodology for the evaluation of effectiveness of personalised invitations of citizens to cancer screening programmes" as part of the pro-gram-me of the Czech Ministry of Health "National action plans and conceptions". The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE "uniform requirements" for biomedical papers.


Effect of Platelet-derived P-selectin on Neutrophil Recruitment in a Mouse Model of Sepsis-induced Acute Kidney Injury.
Acute kidney injury (AKI) is a severe disease in critically ill patients. Neutrophil infiltration into kidney was associated with the development of AKI, and P-selectin may be involved in the process of neutrophil recruitment in kidney. This study aimed to explore the potential effect of platelet-derived P-selectin on neutrophil recruitment in a mouse model of sepsis-induced AKI. A total of 30 C57BL/6 male mice were divided into five groups (n = 6 in each): sham group, sepsis group, anti-Ly6G group, anti-P-selectin group, and platelet depletion group. Sepsis was induced by cecal ligation and puncture. Serum creatinine concentration and platelet activity were measured by biochemical detector and flow cytometry, respectively. Histological and pathological features were analyzed using hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining, respectively. Myeloperoxidase (MPO) activity was detected with MPO assay. Unpaired t-test was used for data analysis. Serum creatinine increased significantly in septic group compared to sham group (2.68 ± 0.27 mg/dl vs. 0.82 ± 0.19 mg/dl, t = 12.06, P = 0.0000) but attenuated in antibodies-treated animals compared to septic group (anti-Ly6G: 1.62 ± 0.30 mg/dl vs. 2.68 ± 0.27 mg/dl, t = 5.76, P = 0.0004; anti-P-selectin: 1.76 ± 0.31 mg/dl vs. 2.68 ± 0.27 mg/dl, t = 4.92, P = 0.0012; and platelet depletion: 1.93 ± 0.29 mg/dl vs. 2.68 ± 0.27 mg/dl, t = 4.14, P = 0.0032). Platelet amount significantly decreased compared to sham group (658.20 ± 60.64 × 109/L vs. 822.00 ± 48.60 × 109/L, t = 4.71, P = 0.0015) in septic mice, especially in platelet depletion group (240.80 ± 44.98 × 109/L vs. 822.00 ± 48.60 × 109/L, t = 19.63, P = 0.0000). P-selectin activity was significantly increased in septic group compared to sham group (16.54 ± 1.60% vs. 1.90 ± 0.29%, t = 15.64, P = 0.0000) but decreased significantly in platelet depletion group compared to septic group (3.62 ± 0.68% vs. 16.54 ± 1.60%, t = 12.89, P = 0.0002). IHC analysis shown that neutrophil infiltration increased in septic mice compared to sham group (36.67 ± 3.79% vs. 9.17 ± 1.61%, t = 11.58, P = 0.0003) and function-blocked groups (anti-Ly6G: 36.67 ± 3.79% vs. 15.33 ± 1.53%, t = 9.05, P = 0.0008; anti-P-selectin: 36.67 ± 3.79% vs. 21.33 ± 1.53%, t = 6.51, P = 0.0029; and platelet depletion: 36.67 ± 3.79% vs. 23.33 ± 3.06%, t = 4.75, P = 0.0090). MPO increased significantly in septic group compared to control (49.73 ± 1.83 ng/mg prot vs. 13.04 ± 2.16 ng/mg prot, t = 19.03, P = 0.0000) but decreased in function-blocked groups compared to septic group (anti-Ly6G: 26.52 ± 3.86 ng/mg prot vs. 49.73 ± 1.83 ng/mg prot, t = 9.59, P = 0.0000; anti-P-selectin: 33.06 ± 6.75 ng/mg prot vs. 49.73 ± 1.83 ng/mg prot, t = 4.85, P = 0.0013; and platelet depletion: 33.37 ± 2.25 ng/mg prot vs. 49.73 ± 1.83 ng/mg prot, t = 5.33, P = 0.0007). Platelets-derived P-selectin may be involved in the development of septic AKI through inducing neutrophil infiltration into kidney.


Effect of hydroxyurea on foetal haemoglobin in myeloproliferative & myelodysplastic syndromes.
The effect of hydroxyurea on foetal haemoglobin (HbF) levels was evaluated in 36 patients of myeloproliferative and myelodysplastic disorders. In 17 (47.2%) patients, HbF levels increased from 1.40 +/- 1.17 to 3.03 +/- 1.97 per cent after 4 wk therapy with hydroxyurea. In the responders this increase was highly significant (P less than 0.001). The rise in the HbF levels after hydroxyurea therapy was significant in patients with chronic myeloid leukaemia but not in the other groups.


Infection Source and Epidemiology of Nontuberculous Mycobacterial Lung Disease.
Nontuberculous mycobacteria (NTM) are ubiquitous organisms that are generally found not only in the natural environment but also in the human engineered environment, including water, soil, and dust. These organisms can form biofilms and can be readily aerosolized because they are hydrophobic owing to the presence of the lipid-rich outer membrane. Aerosolization and subsequent inhalation were the major route of NTM lung disease. Water distribution systems and household plumbing are ideal habit for NTM and the main transmission route from natural water to household. NTM have been isolated from drinking water, faucets, pipelines, and water tanks. Studies that used genotyping have shown that NTM isolates from patients are identical to those in the environment, that is, from shower water, showerheads, tap water, and gardening soil. Humans are likely to be exposed to NTM in their homes through simple and daily activities, such as drinking, showering, or gardening. In addition to environmental factors, host factors play an important role in the development of NTM lung disease. The incidence and prevalence of NTM lung disease are increasing worldwide, and this disease is rapidly becoming a major public health problem. NTM lung disease is associated with substantially impaired quality of life, increased morbidity and mortality, and high medical costs. A more comprehensive understanding of the infection source and epidemiology of NTM is essential for the development of new strategies that can prevent and control NTM infection.


Effects of particulate air pollution on the respiratory health of subjects who live in three areas in Kanpur, India.
In this study, the authors assessed the relationship between daily changes in respiratory health and particulate levels with diameters of (a) less than 10 microm (PM10) and (b) less than 2.5 microm (PM2.5) in Kanpur, India. The subjects (N = 91) were recruited from 3 areas in Kanpur: (1) Indian Institute of Technology (Kanpur), which was a relatively clean area; (b) Vikas Nagar, a typical commercial area; and (c) finally, the residential area of Juhilal Colony. All subjects resided near to air quality monitoring sites. Air quality and peak expiratory flow rate samplings were conducted for 39 d. Once during the sampling period, lung-function tests (i.e., forced expiratory volume in 1 s, forced vital capacity) were performed on each subject. Subjects who resided at the clean site performed at predicted (i.e., acceptable) values more often than did subjects who lived at the remaining 2 sites. Subjects who lived at all 3 sites demonstrated a substantial average deficit in baseline forced vital capacity and forced expiratory volume in 1 s values. The authors used a statistical model to estimate that an increase of 100 microg/m3 of the pollutant PM10 could reduce the mean peak expiratory flow rate of an individual by approximately 3.2 l/min.


[Long-Term Effect of Fulvestrant for Locally Advanced Breast Cancer in an Elderly Patient - A Case Report].
We report an elderly patient with locally advanced breast cancer who received long-term fulvestrant therapy.The patient was a 75-year-old woman who presented with a right breast lump.She noticed the tumor 4 years and 6 months ago, but she had not visited any hospital.However, her daughter brought her to our hospital.The tumor was 73mm in diameter.A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma, positive for estrogen receptor(ER)and progesterone receptor(PgR), and negative for HER2/neu.The Ki-67 positive cell index was 20%.We performed a whole- body checkup, and confirmed the diagnosis as T4cN1M0, Stage III B.She initiated endocrine therapy by letrozole(2.5 mg/ day).After 1 year and 6months, tumor marker levels increased.We changed the endocrine therapy to fulvestrant(500mg/ month).For the next 2 years and 6 months, this therapy was effective.Her axillary lymph node metastases disappeared and tumor size decreased(60%).She underwent muscle-preserving mastectomy plus axillary lymph node dissection.The pathological diagnosis from the resected surgical specimen was confirmed as invasive ductal carcinoma, positive for ER and PgR, and negative for HER2/neu protein expression.The surgical margins were negative, and there was no metastasis in the lymph nodes.She was administered adjuvant endocrine therapy.Four years after surgery, she was well without metastasis.


Probing nanocrystalline grain dynamics in nanodevices.
Dynamical structural defects exist naturally in a wide variety of solids. They fluctuate temporally and hence can deteriorate the performance of many electronic devices. Thus far, the entities of these dynamic objects have been identified to be individual atoms. On the other hand, it is a long-standing question whether a nanocrystalline grain constituted of a large number of atoms can switch, as a whole, reversibly like a dynamical atomic defect (that is, a two-level system). This is an emergent issue considering the current development of nanodevices with ultralow electrical noise, qubits with long quantum coherence time, and nanoelectromechanical system sensors with ultrahigh resolution. We demonstrate experimental observations of dynamic nanocrystalline grains that repeatedly switch between two or more metastable coordinate states. We study temporal resistance fluctuations in thin ruthenium dioxide (RuO2) metal nanowires and extract microscopic parameters, including relaxation time scales, mobile grain sizes, and the bonding strengths of nanograin boundaries. These material parameters are not obtainable by other experimental approaches. When combined with previous in situ high-resolution transmission electron microscopy, our electrical method can be used to infer rich information about the structural dynamics of a wide variety of nanodevices and new two-dimensional materials.


Comparative oxidation of hemoglobins A and S.
The mutant hemoglobin S (HbS) previously was reported to undergo accelerated autooxidation during incubation in vitro. However, subsequent observations have raised the possibility that this might be explained by adventitious association of molecular iron with HbS, rather than reflecting an inherent property of HbS. Using purified HbA and HbS obtained from genotypic HbAS donors, we found that the observed oxidation rate of HbS, but not of HbA, is indeed exaggerated by adventitious iron. This result suggests a preferential partitioning of molecular iron to HbS over HbA, which was further supported by experimentation. However, after elimination of this effect, there still remains a significant increase in inherent autooxidation rate for HbS. Physiologic oxidants (superoxide, peroxide, hydroxyl radical) and various Fe(III) chelates all stimulate oxidation of oxyHb, but they do so equivalently for HbA and HbS. Nevertheless, these mechanisms also would contribute to excessive biologic oxidation of HbS because the cytoplasm of sickle red blood cells, unlike that of normal cells, would be exposed to abnormal amounts of oxidants and low-molecular-weight iron compounds.


Prospective longitudinal patient-reported outcomes of swallowing following intensity modulated proton therapy for oropharyngeal cancer.
With an enlarging population of long-term oropharyngeal cancer survivors, dysphagia is an increasingly important toxicity following oropharynx cancer treatment. While lower doses to normal surrounding structures may be achieved with intensity modulated proton therapy (IMPT) compared to photon-based radiation, the clinical benefit is uncertain. Seventy-one patients with stage III/IV oropharyngeal cancer (AJCC 7th edition) undergoing definitive IMPT on a longitudinal prospective cohort study who had completed the MD Anderson Dysphagia Inventory (MDADI) at pre-specified time points were included. The majority of patients had HPV-positive tumors (85.9%) and received bilateral neck radiation (81.4%) with concurrent systemic therapy (61.8%). Mean composite MDADI scores decreased from 88.2 at baseline to 59.6 at treatment week 6, and then increased to 74.4 by follow up week 10, 77.0 by 6 months follow up, 80.5 by 12 months follow up, and 80.1 by 24 months follow up. At baseline, only 5.6% of patients recording a poor composite score (lower than 60), compared to 61.2% at treatment week 6, 19.1% at follow up week 10, 13.0% at 6 months follow up, 13.5% at 1 year follow up, and 11.1% at 2 years follow up. Patient reported outcomes following IMPT for oropharyngeal cancer demonstrates decreased swallowing function at completion of treatment with relatively rapid recovery by 10 weeks follow up and steady improvement through 2 years. The results are comparable to similar longitudinal studies of photon-based radiotherapy for oropharynx cancer, and suggest that IMPT confers no additional excess toxicity related to swallowing.


Circular causality.
The problem of disentangling complex dynamic systems is addressed, especially with a view to identifying those variables that take part in the essential qualitative behaviour of systems. The author presents a series of reflections about the methods of formalisation together with the principles that govern the global operation of systems. In particular, a section on circuits, nuclei, and circular causality and a rather detailed description of the analytic use of the generalised asynchronous logical description, together with a brief description of its synthetic use (OreverseO logic). Some basic rules are recalled, such as the fact that a positive circuit is a necessary condition of multistationarity. Also, the interest of considering as a model, rather than a well-defined set of differential equations, a variety of systems that differ from each other only by the values of constant terms is emphasised. All these systems have a common Jacobian matrix and for all of them phase space has exactly the same structure. It means that all can be partitioned in the same way as regards the signs of the eigenvalues and thus as regards the precise nature of any steady states that might be present. Which steady states are actually present, depends on the values of terms of order zero in the ordinary differential equations (ODEs), and it is easy to find for which values of these terms a given point in phase space is steady. Models can be synthesised first at the level of the circuits involved in the Jacobian matrix (that determines which types and numbers of steady states are consistent with the model), then only at the level of terms of order zero in the ODE's (that determines which of the steady states actually exist), hence the title 'Circular casuality'.


The treatment of cervical intraepithelial neoplasia.
Treatment of cervical intraepithelial neoplasia, both squamous and glandular, is based on the premise that this condition may ultimately progress to invasive cancer. Treatments have evolved in a conservative direction resulting in reduced morbidity yet also achieving satisfactory control of disease. As yet there is no way in which those cases that have malignant potential can be distinguished from those that do not. Satisfactory management is dependent upon the exclusion of an invasive process. Cytologic, colposcopic and histologic confirmation of preinvasion are therefore natural precedents to management.


A simple method for the determination of organochlorine pollutants and the enantiomers in oil seeds based on matrix solid-phase dispersion.
A simple, rapid and effective method was developed based on matrix solid-phase dispersion (MSPD) for the determination of organochlorine pollutants including sixteen organochlorine pesticides (OCPs) and seven polychlorinated biphenyls (PCBs) in oil seeds (peanuts and soybeans). Among the organochlorine pollutants selected, α-HCH, heptachlor, o,p'-DDT, o,p'-DDD, trans-chlordane and cis-chlordane were chiral and their enantiomers were determined by GC-ECD with a chiral column. The MSPD procedure was optimized focusing on the type and amount of dispersion sorbent, co-column sorbent and eluting solvent. Under the optimized condition, good recoveries were obtained in the range of 68.9-103.3% with relative standard deviations (RSD) values below 16.1% in all cases. LODs and LOQs were in range of 0.1-2.0ngg(-1) and 0.4-6.7ngg(-1) respectively. In summary, the method set up was qualified to be used for the determination of the pollutants and the enantiomers in oil seeds.


[Relationship between the operation time of multiple fractures with system inflammation changes and clinical outcomes].
To investigate the relationship between the operation time of femur shaft fracture with post-operation system inflammation changes and clinical outcomes for those multiple fractures. This investigation was designed as a prospective, nonrandomized cohort study. From April 2005 to August 2007, all 78 hospitalized patients were divided into 3 groups by an inclusion criteria: multiple fractures with opened fracture of femur shaft (group A, n = 26), multiple fractures with closed fracture of femur shaft (group B, n = 23), single closed fracture of femur shaft (group C, n = 29). In the group A, damage control orthopaedics (DCO) procedure were performed. In the group B and C, all the femur shaft fractures were performed intramedullary nail fixation early (< 24 h). From serially sampled venous blood, inflammatory reaction index were estimated by measured the concentration of IL-6, TNF-alpha surround the operation, and the conditions of multiple organs were estimated by assayed PaO2/FiO2, total bilirubin (TBIL), creatinine (Cr) levels, the postoperation complication rates were analyzed among each groups. The extent of inflammation changes, multiple organs damage conditions and postoperation complication rates were compared and analyzed among the 3 groups. In the group A, the median increase values of IL-6,TNF-alpha after the secondary surgery were 59 ng/L and 85 ng/L, whereas they were 154 ng/L and 250 ng/L respectively in the group B, there was a significant difference between the 2 groups (P < 0.01). In addition, the median increase values of IL-6, TNF-alpha after the first surgery in group A and in group C were both significantly less than group B (P < 0.01). Correspondingly, the abnormal rates of PaO2/ FiO2, TBIL, Cr levels occurred in the group B were all greater than group A after the 2 surgery procedures (P < 0.05), and in the aspects of average ventilation days, ICU staying days, duration of positive fluid balance (input/output > 500 ml/24 h), the group B were all greater than group A after the second surgery ( P < 0.01). Compared with group A after the first surgery, group B showed a longer average ventilation days, but it had no significant difference in average ICU stay days and duration of positive fluid balance. In addition, for group C, all the aspects above were less than group B (P < 0.01). Concerned with the complications after surgery in each groups, fat embolism and MODS rate between group A and B had no significant difference (11.5% vs 13.0% ,P > 0.05), but higher than which of group C (P < 0.01). The early intramedullary nail fixation of femur shaft fracture in multiple fractures may lead to a significant system inflammation changes, and may develop the subclinical changes of multiple organs. However, these changes are less in those surgery procedures later performed, namely intramedullary nail fixation of femur shaft fracture in multiple fractures as a primary definitive treatment has a potential risk, and should be carefully evaluated.


Platelets: balancing the septic triad.
In this issue of Blood, de Stoppelaar et al further unravel the relevance of platelets in a mouse model of pneumonia-derived sepsis by illustrating how platelets dynamically modulate infection and the inflammatory response.


On-pump cardiac surgery in a conscious patient using a thoracic epidural anesthesia--an ultra fast track method.
To demonstrate the applicability and efficacy of spontaneous ventilation during cardiac surgery. From March 1999 through December 2002, 129 awake patients were operated on; 90 on-pump and 39 off-pump. A thoracic epidural space blockage was performed one hour prior to an incision being made at the Th 2-Th 4 level. Medial approach was used and the hanging drop method was routinely employed for epidural space detection. There were 82 male and 47 female patients with a mean age of 64.5 years. Forty two cases were aortic valve replacement, 32 patients underwent on-pump coronary artery bypass grafting (CABG), 12 underwent mitral valve replacement, 27 patients were indicated for sternal wound reexploration, 12 for off-pump CABG, one for aortic valve replacement with aortic arch reconstruction and aortic valve replacement together with CABG was performed three times. There were ten conversions to general anesthesia and there was no death. Mean duration of the stay in the intensive care unit was 7.2 hours and in the hospital 5.1 days. We did not observe low cardiac output syndrome, stroke, renal insufficiency or pulmonary dysfunction in patients who sufficiently underwent thoracic epidural anesthesia. Less pain at assessments was demonstrated (Visual Analgetic Score=3.3). The recent interest in rapid recovery and early out-patient care of patients after cardiac surgery has prompted investigations into the use of neuraxial analgesia for these procedures. The above mentioned technique would be beneficial for patients with preoperative pulmonary dysfunction and may be particularly useful in endoscopic cardiac surgery. (Tab. 1, Fig. 2, Ref. 18.)


CORRELATION OF FINE STRUCTURE AND PHYSIOLOGY OF THE INNERVATION OF SMOOTH MUSCLE IN THE GUINEA PIG VAS DEFERENS.
An electron microscope study of the innervation of smooth muscle of the guinea pig vas deferens was undertaken in order to find a structural basis for recent electrophysiological observations. The external longitudinal muscle coat was examined in transverse section. Large areas of the surfaces of adjacent muscle cells were 500 to 800 A apart. Closer contacts were rare. A special type of close contact suggested cytoplasmic transfer between neighbouring cells. Groups of non-myelinated axons from ganglia at the distal end of the hypogastric nerve ramified throughout the muscle. Some small axon bundles and single axons lay in narrow fissures within closely packed muscle masses. Many axons contained "synaptic vesicles." About 25 per cent of the muscle fibres in the plane of section were within 0.25 micro of a partly naked axon; of these 15 per cent were within 500 A of the axon, and about 1 per cent made close contact (200 A) with a naked axon. It is unlikely that every muscle fibre is in close contact with an axon, and it is not possible for every fibre to have many such contacts. Muscle fibres are probably activated by both diffusion of transmitter from naked portions of axons a fraction of a micron distant, and electrotonic spread of activity from neighbouring cells.


Visible light-induced synthesis of 3,4-diarylthiophenes from 3,4-diaryl-2,5-dihydrothiophenes.
Using a catalytic amount of platinum(II) terpyridyl complex 3, 3,4-diarylthiophenes (2a-f) could be synthesized from 3,4-diaryl-2,5-dihydrothiophenes (1a-f) under visible light (λ > 450 nm) irradiation in degassed CH(3)CN. Spectroscopic study and product analysis reveal that the reaction is initiated by photoinduced electron transfer from 3,4-diaryl-2,5-dihydrothiophenes to platinum(II) complex 3, leading to the formation of 3,4-diarylthiophenes.


The limitation of mitral echocardiography in combined mitral lesions.
In combined mitral stenosis and incompetence, the mitral echocardiogram is able to estimate the degree of mitral stenosis (i. e. mitral valve area) without being able to detect or quantify mitral incompetence. A diastolic closure rate of 20 mm/sec or less does not exclude significant mitral incompetence as claimed by others. Cardiac catheterization is still necessary in mitral stenosis, where concominant mitral incompetence is suspected clinically, to confirm its presence and quantify its degree.


Impact of Teachers' Practices on Students' Reading Comprehension Growth in Guatemala.
This article discusses an educational intervention, with a strong emphasis on reading development in a bilingual context, in the Western Highlands of Guatemala (WH), a highly disadvantaged region, where the majority of the population is of Mayan origin and primary education is poor. The majority of the students in the Western Highlands speak a Mayan language as their mother tongue, yet they are generally taught in Spanish. We assisted in the development and implementation of a bilingual/intercultural education model including teacher training at the university level and bilingual materials development. Implementation included education for administrators and teacher coaching. For this intervention, aimed at improving reading outcomes, we report data for the first 3 years of implementation, and offer insights for system-wide interventions in low-resource areas.


Outcomes of antiretroviral therapy in Vietnam: results from a national evaluation.
Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam's national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations. Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART. Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data. Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4-76.5, median age 30, interquartile range [IQR]: 26-34, 62.0% reported a history of intravenous drug use, CI: 58.6-65.3). Median baseline CD4 cell count was 78 cells/mm(3) (IQR: 30-162) and 30.4% (CI: 25.8-35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8-89.9), 84.0% (CI: 81.8-86.0), 78.8% (CI: 75.7-81.6), and 74.6% (CI: 69.6-79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45-153), 142 (IQR: 78-217), 213 (IQR: 120-329), and 254 (IQR: 135-391) cells/mm(3). Patients who were PWID showed significantly poorer retention. The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.


Intercellular junctions between the follicle cells and oocytes of Xenopus laevis.
During development, the oocytes of Xenopus laevis establish junctional contact with the follicle cells enveloping them. These junctions have alternatively been described as desmosomes and as gap junctions. In this paper the morphology of these junctions has been examined in gonadotropin-stimulated and unstimulated animals at all stages of development. Contact between the oocyte and follicle cell plasma membranes is visible in stage I oocytes as thickenings in the membranes, separated by intercellular spaces of 20nm or greater. By stage III in unstimulated oocytes and stage II in gonadotropin-stimulated oocytes, intermembrane spaces at these junctional contacts are often reduced to 2 to 7 nm in width. These narrow intermembrane spaces persist through early stage IV, with greater frequency of occurrence in oocytes taken from hormonally stimulated animals. The closeness of these junctional contacts, and the permeability of the junctional spaces to intercellular tracer substances, supports the evidence that these are gap junctions.


N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2.
SARS-CoV-2 has been spreading around the world for the past year. Recently, several variants such as B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma), which share a key mutation N501Y on the receptor-binding domain (RBD), appear to be more infectious to humans. To understand the underlying mechanism, we used a cell surface-binding assay, a kinetics study, a single-molecule technique, and a computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and a slower dissociation rate. Atomic force microscopy (AFM)-based single-molecule force microscopy (SMFS) consistently quantified the interaction strength of RBD with the mutation as having increased binding probability and requiring increased unbinding force. Molecular dynamics simulations of RBD-ACE2 complexes indicated that the N501Y mutation introduced additional π-π and π-cation interactions that could explain the changes observed by force microscopy. Taken together, these results suggest that the reinforced RBD-ACE2 interaction that results from the N501Y mutation in the RBD should play an essential role in the higher rate of transmission of SARS-CoV-2 variants, and that future mutations in the RBD of the virus should be under surveillance.


lncRNA DLX6-AS1 Promotes Proliferation of Laryngeal Cancer Cells by Targeting the miR-26a/TRPC3 Pathway.
Laryngeal cancer is the most prevalent tumor type in head and neck cancers. Early diagnosis is considered as an important strategy for improving prognosis. The lncRNA DLX6-AS1 has been shown to modulate tumor phenotypes in several types of cancer, but the role of DLX6-AS1 in laryngeal cancer and its concrete mechanisms are not clear. Tissue samples from laryngeal cancer patients and corresponding clinical data were used for detailed analysis. The laryngeal cancer cell lines HEp-2 and Tu-177 were studied. Cell proliferation, ROS production, mitochondrial respiratory function, intracellular and mitochondrial calcium influx were assessed. Western blotting, quantitative RT-PCR and luciferase assays were used to analyze the interactions. A xenografted tumor model was established to analyze the effects of DLX6-AS1 on tumor growth in vivo. lncRNA DLX6-AS1 had increased expression in tumor tissues compared with adjacent normal tissues and in higher clinical stages compared with lower stages, which was associated with poor prognosis. In detail, DLX6-AS1 knockdown decreased cell proliferation and affected key mitochondrial metabolic parameters in both HEp-2 and Tu-177 cells. Moreover, DLX6-AS1 knockdown suppressed TRPC3-mediated mitochondrial calcium uptake and ROS production. Furthermore, miR-26a functioned as a link between these two molecules, as it could be absorbed by DLX6-AS1 and thus regulated the levels of TRPC3. Finally, the DLX6-AS1/miR-26a/TRPC3 axis modulated laryngeal cancer proliferation both in vitro and in vivo. This study provides new evidence that a novel lncRNA, DLX6-AS1, regulates mitochondrial calcium homeostasis, respiration and tumor proliferation via modulating the miR-26a/TRPC3 axis in laryngeal cancer.


Hyperlipidemia: a risk factor for chronic allograft dysfunction.
While the early results of renal transplantation have improved in the last years, but the long-term allograft survival have not improved to the same extent. The major cause of these graft losses is chronic allograft dysfunction (CAD). The pathogenesis of CAD is complex and results from a interaction of immune and nonimmune factors. Between these non-immunological related factors there are two cardiovascular risk factors, hypertension and especially hyperlipidemia, that have been implicated in the development and progression of CAD. Lipid profile abnormalities are very prevalent in renal transplant patients. In last years several authors have reported an association between different lipid profile alterations and CAD. We conducted an observational study in our group to determine the relationship between different lipid disturbances and CAD. The hypertriglyceridemia and the Lp(a)>30 mg/dL before and after transplantation were, between the lipid abnormalities, the two independent risk factors for CAD in a multivarite analysis.


Acute lithiasic cholecystitis, pseudoneoplastic form, a cause of conversion for laparoscopic cholecystectomy.
Acute lithiasic cholecystitis represents one of the most frequent pathologies of the digestive tract, most often requiring emergency surgical treatment. The prevalence of this condition increases with age and it affects women the most. Laparoscopic cholecystectomy is the preferred surgical treatment, as it diminishes postoperatory pain, it reduces the hospitalization period and medical and social costs, and it also provides a rapid postoperatory recovery. We present the case of an elder female patient, who presented with complex symptoms and signs, suggesting both lithiasic cholecystitis and a gallbladder neoplastic condition. Although there was preferred a laparoscopic cholecystectomy, the presence of an inflammatory process with intense sclerous reaction in the hepatocystic triangle led the conversion of laparoscopic cholecystectomy into an open, classical one. Due to the inflammatory process, the common bile duct (CBD) could not be explored. The subsequent practicing of a cholangiography on the drain tube highlighted the presence of an obstacle in the end zone of the CBD, which could not be removed until the second surgical intervention. The histopahological exams - from frozen sections to immunohistochemistry - had a crucial role in deciding patient's surgical management. The good evolution of the case and the final postoperatory result confirmed that the therapeutic manner chosen for this case was the appropriate one.


Effects of kanamycin administration to poultry on the proliferation of drug-resistant Salmonella.
Four experiments were conducted to examine the relationship between antibiotic administration to poultry and the in vivo proliferation of Salmonellae. The frequency of isolation of drug-resistant transconjugant S. arizonae from the livers of chicks inoculated per os with multiply drug-resistant Escherichia coli and drug-sensitive S. arizonae was directly related to the concentration of kanamycin administered to the chicks in their drinking water. Kanamycin administration was also associated with a significant (P less than .05) increase in the frequency of isolation of drug-resistant transconjugant S. typhimurium from the intestines and livers of poults inoculated with drug-sensitive S. typhimurium and multiply drug-resistant E. coli. Kanamycin administration significantly reduced the spread of drug-sensitive S. typhimurium to the livers of poults inoculated only with that strain. These experiments demonstrate that antibiotic administration to poultry can enhance the proliferation of drug-resistant Salmonella.


In-situ magnetization/heating electron holography to study the magnetic ordering in arrays of nickel metallic nanowires.
Magnetic nanostructures of different size, shape, and composition possess a great potential to improve current technologies like data storage and electromagnetic sensing. In thin ferromagnetic nanowires, their magnetization behavior is dominated by the competition between magnetocrystalline anisotropy (related to the crystalline structure) and shape anisotropy. In this way electron diffraction methods like precession electron diffraction (PED) can be used to link the magnetic behavior observed by Electron Holography (EH) with its crystallinity. Using off-axis electron holography under Lorentz conditions, we can experimentally determine the magnetization distribution over neighboring nanostructures and their diamagnetic matrix. In the case of a single row of nickel nanowires within the alumina template, the thin TEM samples showed a dominant antiferromagnetic arrangement demonstrating long-range magnetostatic interactions playing a major role.


MEK1 and AKT2 mutations in Japanese lung cancer.
Recently, to identify potential somatic mutations in genes of epidermal growth factor receptor (EGFR) signaling pathway, MEK1 gene mutation at exon 2 and mutation of the AKT2 (v-akt murine thymoma viral oncogene homologue 2) gene at kinase domain have been reported in non-small cell lung cancer. We investigated the MEK1 mutation (n = 280) and AKT2 mutation (n = 273) in surgically treated non-small cell lung cancer cases. The presence or absence of MEK1 mutation (exon 2) and AKT2 mutation at kinase domain was analyzed by direct sequences. MEK1 mutation (K57K) was found from 1 of 280 patients with lung cancer (0.4%) and detected only one case (0.4%) of AKT2 mutation (R371H) in our cohort. MEK1 mutation was exclusive with EGFR, K-ras, and B-raf mutations at kinase domain. However, AKT2 mutation was coexisted with EGFR and PIK3CA mutations. This study demonstrated that mutation in the kinase domain of AKT2 and MEK1 exon 2 mutation occurred in a small fraction of Japanese lung cancers.


[Correlation of changes in various enzymologic and immunologic indices and electrocardiotopographic findings in myocardial infarction complicated by true cardiogenic shock and acute left ventricular failure].
A total of 112 myocardial infarction survivors with the uncomplicated and the complicated (genuine cardiogenic shock, acute left ventricular insufficiency) course of the disease were followed up to study and correlate the activity of creatine phosphokinase (CPK), its MB isoenzyme, titres of the complement binding antibodies to CPK and the cardiac muscle and also electrocardiotopographic parameters. The time of the appearance, maximum elevation and normalization of the parameters under study did not depend on the presence or absence of complications. Genuine cardiogenic shock was characterized by higher values of CPK, MB CPK, as well as by a greater extent and depth of the necrotic and peri-infarction zones, as judged by the electrocardiotopogram , and lower increase in the titres of antibodies to CPK and the myocardium. Acute left ventricular insufficiency was associated with higher CPK activity and more elevated titres of antibodies to the latter with the greater extent and depth of the ischemic lesion as compared to the necrotic one. Significantly enhanced enzymic levels in the first case were of cardiac and in the second of extracardiac origin.


Stroke risk in arthritis: A systematic review and meta-analysis of cohort studies.
Stroke is a major contributor to the global burden of disease. Although numerous modifiable risk factors (RF) for stroke have been identified, some remain unexplained. Increasing studies have investigated stroke risk in arthritis, but their results are inconsistent. We aimed to synthesize, quantify, and compare the risk of stroke for the major types of arthritis in cohort studies by using a systematic review and meta-analysis approach. We searched Chinese and English databases to identify relevant studies from inception to April 30, 2020. Only studies adjusting at least for age and sex were included. We calculated pooled effect estimates for relative risk (RR) and 95% confidence interval (CI) and identified potential sources of heterogeneity and publication bias. A total of 1,348 articles were retrieved, and after an preliminary screening of titles and abstracts, 69 were reviewed for full text, and finally, 32 met the criteria for meta-analysis. Stroke risk in arthritis was significantly increased in studies adjusting for age and sex (RR = 1.36, 95% CI: 1.27-1.46) and for at least one traditional risk factor (RR = 1.40, 95% CI: 1.28-1.54). The results of studies stratified by stroke subtype were consistent with the main finding (ischemic stroke: RR = 1.53, 95% CI: 1.32-1.78; hemorrhagic stroke: RR = 1.45, 95% CI: 1.15-1.84). In subgroup analysis by arthritis type, stroke risk was significantly increased in rheumatoid arthritis (RR = 1.38, 95% CI: 1.29-1.48), ankylosing spondylitis (RR = 1.49, 95% CI: 1.25-1.77), psoriatic arthritis (RR = 1.33, 95% CI: 1.22-1.45), and gout (RR = 1.40, 95% CI: 1.13-1.73) but not osteoarthritis (RR = 1.03, 95% CI: 0.91-1.16). Age and sex subgroup analyses indicated that stroke risk was similar by sex (women: RR = 1.47, 95% CI: 1.31-1.66; men: RR = 1.44, 95% CI: 1.28-1.61); risk was higher with younger age (<45 years) (RR = 1.46, 95% CI: 1.17-1.82) than older age (≥65 years) (RR = 1.17, 95% CI: 1.08-1.26). Stroke risk was increased in multiple arthritis and similar between ischemic and hemorrhagic stroke. Young patients with arthritis had the highest risk.


Development of a Label-Free Immunosensor for Clusterin Detection as an Alzheimer's Biomarker.
Clusterin (CLU) has been associated with the clinical progression of Alzheimer's disease (AD) and described as a potential AD biomarker in blood plasma. Due to the enormous attention given to cerebrospinal fluid (CSF) biomarkers for the past couple of decades, recently found blood-based AD biomarkers like CLU have not yet been reported for biosensors. Herein, we report the electrochemical detection of CLU for the first time using a screen-printed carbon electrode (SPCE) modified with 1-pyrenebutyric acid N-hydroxysuccinimide ester (Pyr-NHS) and decorated with specific anti-CLU antibody fragments. This bifunctional linker molecule contains succinylimide ester to bind protein at one end while its pyrene moiety attaches to the carbon surface by means of π-π stacking. Cyclic voltammetric and square wave voltammetric studies showed the limit of detection down to 1 pg/mL and a linear concentration range of 1-100 pg/mL with good sensitivity. Detection of CLU in spiked human plasma was demonstrated with satisfactory recovery percentages to that of the calibration data. The proposed method facilitates the cost-effective and viable production of label-free point-of-care devices for the clinical diagnosis of AD.


Optimizing double emulsion process to decrease the burst release of protein from biodegradable polymer microspheres.
The process parameters such as the compositions of inner and outer aqueous phase and emulsification technique of the primary emulsion were optimized to decrease the burst release of BSA from biodegradable polymer microspheres in double emulsion method. It was found that diminished burst release of -14% was achieved for the microspheres produced by formulations, where no phosphate was present in the inner water phase (non-buffered system). Primary emulsion made by probe sonication rather than homogenization or mechanical stirring led to microspheres with insignificant burst effect. Microspheres obtained using 0.1% aqueous Tween 80 solution as the outer aqueous phase, frequently exhibit reduced burst effect of 2.7%. Low microsphere yield (52.1%), however, was observed. Microsphere yield was, therefore, enhanced by addition of additive such as sodium chloride, glucose or mannitol into the outer aqueous phase. Decrease in BSA entrapment was observed in the presence of sodium chloride, but reduction in entrapment efficiency was observed in the case of glucose. Burst release increased from 2.7% to 9.5% or 3.4% as 2.5% sodium chloride or 7.5% glucose was added into the outer aqueous phase respectively. Marked burst release (>20%) was observed in the presence of additive of higher concentration independent of sodium chloride or glucose. As far as surfactant type was concerned, diminished burst was found when PVP or Tween 80 rather than PVA was utilized as the surfactant during microsphere preparation. In addition to PLGA, the copolymers of L-lactide (LLA) and dimethyl trimethylene carbonate (DTC) or trimethylene carbonate (TMC) were also evaluated. Insignificant burst effect was found for the microspheres composed of DTC or TMC copolymers.


Electro-optic chaos system with time delay signature concealment based on XOR operation and multi-bit PRBS.
A novel chaos system with XOR operations and multi-bit PRBS is proposed to improve the sequence complexity and the security of the classic electro-optic intensity chaos system. Through the bifurcation diagram and permutation entropy analysis, the PE can be increased to 0.99. The key space is enlarged because additional DSP parameters and PRBS are introduced. The impacts of ADC/DAC characteristics and PRBS characteristics are analyzed in detail. The simulation results show that the time delay signature can be concealed with the appropriate DSP parameters.


Substrate recognition by the protein disulfide isomerases.
Protein folding in the endoplasmic reticulum is often associated with the formation of native disulfide bonds. Their primary function is to stabilize the folded structure of the protein, although disulfide bond formation can also play a regulatory role. Native disulfide bond formation is not trivial, so it is often the rate-limiting step of protein folding both in vivo and in vitro. Complex coordinated systems of molecular chaperones and protein folding catalysts have evolved to help proteins attain their correct folded conformation. This includes a family of enzymes involved in catalyzing thiol-disulfide exchange in the endoplasmic reticulum, the protein disulfide isomerase (PDI) family. There are now 17 reported PDI family members in the endoplasmic reticulum of human cells, but the functional differentiation of these is far from complete. Despite PDI being the first catalyst of protein folding reported, there is much that is still not known about its mechanisms of action. This review will focus on the interactions of the human PDI family members with substrates, including recent research on identifying and characterizing their substrate-binding sites and on determining their natural substrates in vivo.


Comparison of two pathological processing methods for large endoscopic submucosal dissection (ESD) specimens.
Accurate histopathological evaluation of the endoscopic submucosal dissection (ESD) specimens is essential for clinicians to guide further triage and management. This study aimed to report a novel processing technique for large ESD (≥4 cm) specimens. 92 patients with colorectal neoplasms who had undergone ESD were included. 46 ESD specimens were treated with conventional handling process, while the rest 46 cases were given the optimised method. Macrobiocassettes and L-shaped embedding moulds were applied in the optimised method. We evaluated the efficacy of this improved procedure in terms of the number of paraffin blocks, storage space and time consumption of pathological assessment. The average diameter of ESD specimens was 4.5±0.4 cm and 4.7±0.5 cm in the control and test group (p=0.023), respectively. In control group, 398 paraffin blocks of 46 cases were obtained. With the same cases number and larger lesion size, only 276 blocks were achieved in test group (p<0.001). As for the storage space, the total volume of paraffin blocks and slides (4554.0 cm3 and 1207.5 cm3) of optimised method was significantly reduced compared with the control group (6208.8 cm3 and 1741.3 cm3) (p=0.001, p<0.001). In addition, the optimised method was superior to the conventional one in shortening time consumption of pathological assessment (164.5 min and 269.0 min, p<0.001). The optimised technique not only reduced the workload and storage space, but also facilitated accurate pathological assessment.


Surgical treatment of Candida albicans spondylodiscitis.
Spinal infection poses a demanding diagnostic and treatment problem for which a multidisciplinary approach with spine surgeons, radiologists, and infectious disease specialists is required. Infections are usually caused by bacterial microorganisms, although fungal infections can also occur. Most patients with spinal infections diagnosed in the early stages can be successfully managed conservatively with antibiotics, bed rest, and spinal braces. In cases of gross or pending instability, progressive neurological deficits, failure of conservative treatment, spinal abscess formation, severe symptoms indicating sepsis, and failure of previous conservative treatment, surgical treatment is required. A 64-year-old male presented to the Outpatient Department with a complaint of pain in bilateral upper extremities for 4 months. The pain was shooting in type, radiating to bilateral arms, forearms, and hands with no aggravating and relieving factors. He is a known case of carcinoma pyriform sinus for which he underwent various cycles of chemotherapy. Ten years later, a tracheostomy was performed for laryngeal edema, and again, an endoscopic gastrostomy was performed due to feeding difficulties. He then developed fever and cervical pain along with pain in the bilateral upper extremities. An infectious etiology was suspected for which multiple antibiotics were started with no positive response. An MRI was performed, which was suggestive of spondylodiscitis probably of tubercular origin. A biopsy was done to confirm the diagnosis, following which antitubercular (HRZE) therapy was started. He was also treated with Duloxetine and gabapentin, which resulted in minor improvements. Subsequent MRIs showed diffuse involvement of the multiple cervical vertebrae along with cord compression. Two stages of anterior corpectomy followed by posterior instrumentation were done. Following the procedure, the patient developed an infection, which was managed with antibiotics. The titanium implant was not removed. A muscle graft was planned with the pectoralis muscle and flap closure was done. The tissue was also sent for Gram stain, AFB stain, and GeneXpert, which showed normal findings. Finally, in tissue culture, Candida albicans was isolated. On performing the enzyme immunoassay test, it was found to be Aspergillus (Galactomannan antigen) positive as well. Antitubercular treatment was stopped. Then, he was managed with an antifungal, oral voriconazole, for the duration of 1 and a half years. Patients diagnosed with Candida spondylodiscitis tend to have favorable outcomes, likely linked to timely identification, thorough surgical debridement, and proper azole medication. Our case achieved success by promptly identifying and confirming it through tissue culture, detecting spinal cord compression, decompressing it, and initiating specific antifungal treatment. A delay in commencing antifungal therapy has been associated with poorer outcomes, especially in neurological health. Our patient received voriconazole for a full year, suggesting that favorable outcomes are achievable for fungal spondylodiscitis with swift and appropriate surgery and antifungal medication. In summary, evaluation for fungal infection is essential in all cases of unexplained spinal infection in immunocompromised patients, regardless of presentation. If the antifungal treatment proves ineffective, a surgical approach is typically employed for the management of fungal spondylodiscitis. Our report details a successful case of fungal spondylodiscitis treated with a surgical approach and highlights the potential for a fungal infection to be a causative factor in noncompressive myelopathy, which may be sometimes mistaken for radiation myelitis.


Multiple vesicular morphologies in AB/AC diblock copolymer complexes through hydrogen bonding interactions.
We report for the first time multiple vesicular morphologies in block copolymer complexes formed in aqueous media via hydrogen bonding interactions. A model AB/AC diblock copolymer system consisting of polystyrene-block-poly(acrylic acid) (PS-b-PAA) and polystyrene-block-poly(ethylene oxide) (PS-b-PEO) was examined using transmission electron microscopy, small-angle X-ray scattering, and dynamic light scattering. The complexation and morphological transitions were driven by the hydrogen bonding between the complementary binding sites on PAA and PEO blocks of the two diblock copolymers. Upon the addition of PS-b-PEO, a variety of bilayer aggregates were formed in PS-b-PAA/PS-b-PEO complexes including vesicles, multilamellar vesicles (MLVs), thick-walled vesicles (TWVs), interconnected compound vesicles (ICCVs), and irregular aggregates. Among these aggregates, ICCVs were observed as a new morphology. The morphology of aggregates was correlated with respect to the molar ratio of PEO to PAA. At [EO]/[AA] = 0.5, vesicles were observed, while MLVs were obtained at [EO]/[AA] = 1. TWVs and ICCVs were formed at [EO]/[AA] = 2 and 6, respectively. When [EO]/[AA] reached 8 and above, only irregular aggregates appeared. These findings suggest that complexation between two amphiphilic diblock copolymers is a viable approach to prepare polymer vesicles in aqueous media.


Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors.
Men diagnosed with clinically localized prostate cancer have a number of treatment options available, including watchful waiting, radical prostatectomy and radiation therapy. With the widespread use of serum prostate specific antigen (PSA) testing, prostate cancers are being diagnosed earlier in their natural history, with many tumors being small and of little health risk to the patient, at least in the short term. To better counsel men diagnosed with prostate cancer, we developed a statistical model that accurately predicts the presence of small moderately differentiated, confined cancer based on clinical variables (serum PSA, clinical stage, prostate biopsy Gleason grade and ultrasound volume) and variables derived from the analysis of systematic biopsies. The analysis included 409 patients diagnosed by systematic needle biopsy with clinical stages T1c or T2a N0 or NX and M0 or MX prostate cancer who were treated solely with radical prostatectomy at 1 of 2 institutions. Additional biopsy features included number and percentage of biopsy cores involved with cancer and high grade cancer, in addition to total length of biopsy cores involved. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume and without poorly differentiated elements. Logistic regression was used to construct several prediction models and the resulting nomograms. Overall 80 (20%) of the patients had indolent cancer. The nomogram predicted the presence of an indolent cancer with discrimination (area under the receiver operating characteristics curves) for various models ranging from 0.64 to 0.79. Calibration of the models appeared good. Nomograms incorporating pretreatment variables (clinical stage, Gleason grade, PSA and the amount of cancer in a systematic biopsy specimen) can predict the probability that a man with prostate cancer has an indolent tumor. These nomograms have good discriminatory ability and calibration, and may benefit the patient and clinician when the various treatment options for prostate cancer are being considered.


Pharmacologic enhancement of rat skin flap survival with topical oleic acid.
This study was instituted to investigate in a rat model the effect of topical coadministration of the penetration enhancer oleic acid (10% by volume) and RIMSO-50 (medical grade dimethyl sulfoxide, 50% by volume) on rat skin flap survival. A rectangular abdominal skin flap (2.5 x 3 cm) was surgically elevated over the left abdomen in 40 nude rats. The vein of the flap's neurovascular pedicle was occluded by placement of a microvascular clip, and the flap was resutured with 4-0 Prolene to its adjacent skin. At the end of 8 hours, the distal edge of the flap was reincised to gain access to the clips and the clips were removed. After resuturing of the flap's distal edge to its adjacent skin, the 40 flaps were randomly divided into four groups. Group 1 (control) flaps were treated with 5 g of saline, group 2 (dimethyl sulfoxide) flaps were treated with 2.7 g of dimethyl sulfoxide (50% by volume), group 3 flaps (oleic acid) were topically treated with 0.45 g of oleic acid (10% by volume), and group 4 (dimethyl sulfoxide plus oleic acid) flaps were treated with a mixture of 0.45 g of oleic acid (10% by volume) and 2.7 g of dimethyl sulfoxide (50% by volume) diluted in saline. Each flap was topically treated with 5 ml of drug-soaked gauze for 1 hour immediately after clip removal to attenuate reperfusion injury. Thereafter, drug was applied topically once daily for 4 more days. Digital photographs of each flap were then taken on day 6 and the flaps were then harvested. The percentage of skin survival in each flap was determined by computerized morphometry and planimetry. The mean surviving area of group 3 (oleic acid-treated flaps) was 23.60 +/- 4.19 percent and was statistically higher than that in group 1 (control, saline-treated flaps) at 7.20 +/- 2.56 percent. The mean surviving area of group 2 (dimethyl sulfoxide-treated flaps) at 18.00 +/- 5.23 percent and group 4 (oleic acid- and dimethyl sulfoxide-treated flaps) at 9.90 +/- 3.44 percent did not achieve statistically higher mean surviving areas than controls. A topical solution of oleic acid (10% by volume) caused a statistically significant increase in the survival of rat abdominal skin flaps relative to controls. Dimethyl sulfoxide and the two experimental drugs together did not increase the percentage of flap survival when given as a single 5-ml dose released from a surgical sponge at reperfusion for 1 hour and then daily for a total of 5 days. The reasons for the lack of response are unknown but may have included the technical difficulty of delivering an adequate dose of dimethyl sulfoxide topically and immiscibility between dimethyl sulfoxide and oleic acid. Further studies may be warranted.


Clinical application of the enzyme immunoassay for pancreatic oncofetal antigen.
Pancreatic oncofetal antigen (POA) purified by us has been detected in sera of patients with carcinoma of the pancreas by the micro-Ouchterlony method. In an attempt to improve the sensitivity and clinical usefulness of the serum POA assay, we established an enzyme immunoassay for POA and reported the results with this method. In this study, we investigated serum POA levels in pancreatic cancer and other diseases. The tissue localization of this POA in the pancreas was also studied. For the establishment of the enzyme immunoassay, an anti-POA-F(ab')2 fragment prepared from absorbed antiserum was conjugated with beta-D-galactosidase. The solid-phase "sandwich" principle was used. The normal upper limit of the serum POA level was defined as 400 units/ml. Among 60 patients with pancreatic cancer, 44 had elevated levels (73.3%). Of 22 cases with chronic pancreatitis, 4 had elevated levels (18.2%). In malignant diseases other than pancreatic cancer, elevated levels of serum POA were seen in 17.6% to 48.5% of the patients, most of whom had only slightly elevated levels. These results indicate that enzyme immunoassay for POA is clinically useful for making a diagnosis of pancreatic cancer. Immunoperoxidase staining showed POA to be found at the apical surface of ductular cells in fetal pancreas, at the luminal surface of glandular structures in pancreatic cancer tissue, and also at the luminal surface of the small duct in normal pancreas. Thus it is suggested that a high level of serum POA in patients with pancreatic cancer is derived from pancreatic cancer tissue.


Hemoperitoneum during continuous ambulatory peritoneal dialysis: a possible complication of radiation induced peritoneal injury.
Hemoperitoneum requiring surgical exploration developed in association with an indwelling chronic peritoneal dialysis catheter. Major intra-abdominal hemorrhage in continuous ambulatory peritoneal dialysis (CAPD) has not been previously reported. Radiation therapy for carcinoma of the bladder and subsequent radiation induced peritoneal injury appears to have predisposed this patient to develop catheter-related trauma and hemorrhage. Antecedent radiation therapy with its possible deleterious effects on the peritoneal membrane may subject potential CAPD patients to unique risks and should be considered in the decision to choose CAPD as a form of treatment for end stage renal disease.


Structural and functional diversity among amyloid proteins: Agents of disease, building blocks of biology, and implications for molecular engineering.
Amyloids have long been associated with protein dysfunction and neurodegenerative diseases, but recent research has demonstrated that some organisms utilize the unique properties of the amyloid fold to create functional structures with important roles in biological processes. Additionally, new engineering approaches have taken advantage of amyloid structures for implementation in a wide variety of materials and devices. In this review, the role of amyloid in human disease is discussed and compared to the functional amyloids, which serve a largely structural purpose. We then consider the use of amyloid constructs in engineering applications, including their utility as building blocks for synthetic biology and molecular engineering. Biotechnol. Bioeng. 2017;114: 7-20. © 2016 Wiley Periodicals, Inc.


A diagrammatic formulation of the kinetic theory of fluctuations in equilibrium classical fluids. IV. The short time behavior of the memory function.
Using a recently developed diagrammatic formulation of the kinetic theory of fluctuations in liquids, we investigate the short time behavior of the memory function for density fluctuations in a classical atomic fluid. At short times, the memory function has a large contribution that is generated by the repulsive part of the interatomic potential. We introduce a small parameter that is a measure of the softness of the repulsive part of the potential. The diagrams in the memory function that contribute to lowest order in that small parameter are identified and summed to give an explicit expression for the dominant contribution to the memory function at short times. The result leads to a theory for fluids with continuous potentials that is similar to the Enskog theory for hard sphere fluids.


The response surface optimization of exopolysaccharide produced by Weissella confusa XG-3 and its rheological property.
The response surface methodology (RSM) was used to optimize the exopolysaccharide (EPS) production by a lactic acid bacteria (LAB) Weissella confusa XG-3. Two-level factorial design screened three significantly influencing factors sucrose, initial pH and sodium acetate. Central composite design (CCD) predicted under the condition of sucrose 80.1 g L-1, initial pH 5.8 and sodium acetate 3.7 g L-1, the maximal EPS yield obtained a 2.9-fold increase, reaching 97.5 ± 1.1 g L-1. This maximal value was far exceeding EPS production by other W. confusa species strains reported so far. The results suggested that W. confusa XG-3 had a potential for large-scale EPS production. The rheological properties of XG-3 EPS was further investigated. It was a typical non-Newtonian fluid, exhibiting pseudo-plastic behavior. The EPS concentration and temperature exerted positive and negative impact on apparent viscosity, respectively. The XG-3 EPS maintained relatively higher viscosity at moderate pH (6-8). The intrinsic viscosity [η] was 409.7 (25 °C) and 201.7 (35 °C), which was relevant to temperature but irrelevant to EPS concentration. This EPS efficiently coagulated sucrose-supplemented milk in a concentration-dependent manner. These results indicated that XG-3 EPS had an applicable potential in food processing fields especially dairy products.


Irritable bowel syndrome in psychiatric perspectives: a comprehensive review.
We comprehensively reviewed the irritable bowel syndrome (IBS) in terms of pathogenesis, psychiatric implications, general management and appropriate role of antidepressants, in particular selective serotonin uptake inhibitors (SSRIs) in the treatment of IBS. English language papers cited in MEDLINE and PychInfo from January 2000 to July 2006 were searched with a combination of the following key words: irritable bowel syndrome, 5-HT, pathogenesis, comorbid, psychiatry, treatment, psychotropic drugs, antidepressant, selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and sertraline), tricyclic antidepressants, review, meta-analysis and placebo. The papers on IBS describing the clinical features, pathophysiology, evaluation, management, and clinical trials [randomised placebo-controlled trial (RCT), open-label study or case report] were selected for this review. Further literatures were also detected from references of the identified papers. The epidemiology, diagnostic criteria, pathophysiology, general management, bidirectional comorbidity, summary of currently available RCTs and open-label studies investigating antidepressant efficacy (focusing on SSRIs), and suggestions for SSRI use in IBS were relevantly synthesised based on through review of identified data. This article summarised an up-to-date clinical overview of IBS in psychiatric perspectives as well as to position a current role of SSRIs in the treatment of IBS. From this review, the routine use of SSRIs for IBS treatment cannot be conclusive due to a paucity of RCTs, although a handful of RCTs suggested a potentially beneficial effect of SSRIs over placebo.


Identification of cancer stem cell subpopulations of CD34(+) PLC/PRF/5 that result in three types of human liver carcinomas.
CD34(+) stem cells play an important role during liver development and regeneration. Thus, we hypothesized that some human liver carcinomas (HLCs) might be derived from transformed CD34(+) stem cells. Here, we determined that a population of CD34(+) cells isolated from PLC/PRF/5 hepatoma cells (PLC) appears to function as liver cancer stem cells (LCSCs) by forming HLCs in immunodeficient mice with as few as 100 cells. Moreover, the CD34(+) PLC subpopulation cells had an advantage over CD34(-) PLCs at initiating tumors. Three types of HLCs were generated from CD34(+) PLC: hepatocellular carcinomas (HCCs); cholangiocarcinomas (CC); and combined hepatocellular cholangiocarcinomas (CHCs). Tumors formed in mice transplanted with 12 subpopulations and 6 progeny subpopulations of CD34(+) PLC cells. Interestingly, progenies with certain surface antigens (CD133, CD44, CD90, or EPCAM) predominantly yielded HCCs. CD34(+) PLCs that also expressed OV6 and their progeny OV6(+) cells primarily produced CHC and CC. This represents the first experiment to demonstrate that the OV6(+) antigen is associated with human CHC and CC. CD34(+) PLCs that also expressed CD31 and their progeny CD31(+) cells formed CHCs. Gene expression patterns and tumor cell populations from all xenografts exhibited diverse patterns, indicating that tumor-initiating cells (TICs) with distinct antigenic profiles contribute to cancer cell heterogeneity. Therefore, we identified CD34(+) PLC cells functioning as LCSCs generating three types of HLCs. Eighteen subpopulations from one origin had the capacity independently to initiate tumors, thus functioning as TICs. This finding has broad implications for better understanding of the multistep model of tumor initiation and progression. Our finding also indicates that CD34(+) PLCs that also express OV6 or CD31 result in types of HLCs. This is the first report that PLC/PRF/5 subpopulations expressing CD34 in combination with particular antigens defines categories of HLCs, implicating a diversity of origins for HLC.


Modulation of molecular imprints in the antigen-experienced B cell repertoire by rituximab.
Transient B cell depletion by rituximab has recently gained more importance in the treatment of rheumatic disorders. Nevertheless, little is known about the reemerging B cells. We analyzed dynamic changes in the repopulating B cells, particularly the postswitch B cells, and studied the mutational patterns of Ig genes in antigen-experienced B cells. Five patients with active rheumatoid arthritis (RA) were treated with rituximab. In 3 patients, B cell receptor (BCR) gene analysis was performed before treatment and during B cell recovery using genomic DNA. In 2 patients, B cell subsets were studied during the early recovery phase using single-cell technology. For comparison, immunophenotyping of B cell subsets was performed. Early B cell recovery was marked by a relatively expanded population of highly mutated B cells, which were correlated with B cells with a plasmablast phenotype on comparative immunophenotyping. Analysis of the mutational pattern in these cells revealed increased RGYW/WRCY (where R = A/G, Y = C/T, and W = A/T) hotspot targeting (44% before rituximab versus 59% after) and elevated ratios of replacement to silent mutations within the complementarity-determining regions in Ig genes (1.87 before rituximab versus 2.67 after; P < or = 0.0025). Our findings show that rituximab leads to qualitative changes in the imprints of highly mutated, antigen-experienced BCRs, representing the result of selection, whereas molecular processes such as Ig V rearrangements are not affected by this treatment.


AN AUDIT OF THE CURRENT PRACTICES OF AIRWAY MANAGEMENT IN PATIENTS UNDERGOING SURGERY FOR ATLANTO-AXIAL DISLOCATION IN A SINGLE INSTITUTION.
Patients with atlanto axial dislocation (AAD) undergo stabilisation procedures under general anesthesia. Airway management in these patients is difficult as cervical spine movements during laryngoscopy can worsen spinal cord damage. Though multiple airway devices are used to intubate the trachea of these patients, there is no evidence of superiority of one technique over another. This retrospective study was designed to audit the practice of airway management during surgery for AAD over a 5 year period, starting from 2006 till 2011. Patients' demographics, airway intervention techniques, types of surgical procedures, postoperative neurological and respiratory deterioration were recorded from the case files. Association between the types of airway interventions and the postoperative neurological and respiratory deterioration were analysed. One hundred and six patients underwent surgery for AAD during the study period. Sixty one percent of the patients were intubated with the help of a fiberoptic bronchoscope (FOB) and among them 15% received general anesthesia to facilitate FOB. Eighteen patients developed neurological deterioration and 15 patients developed respiratory weakness requiring ventilation postoperatively. Congenital AAD patients had higher chances for extubation at the end of surgery when intubated using FOB (p = 0.007). Among the AAD patients, female gender had significantly higher incidence of neurological deterioration compared to males. In the current audit, there was no correlation between the perioperative variables and postoperative respiratory and neurological deterioration. Most of the respiratory problems occurred between 2-5 postoperative days stressing the need for extended intensive postoperative monitoring of these patients.


Low back pain among nurses: a follow-up beginning at entry to the nursing school.
A prospective cohort. To investigate the prevalence of back pain from entering the nursing school through 5 years in nursing and the determinants and modifiers of back pain and disability. Physical loading, psychologic characteristics, and several other factors have been associated with back pain at work in earlier studies. Because of the lack of the prework entry morbidity data, the nature of the associations between these exposures and the symptoms is unclear. That previous back pain is a predictor of later pain underlines the importance to have pre-employment data in investigations of the role of exposures at work. Female nursing students (n = 174) were followed for 7.5 years. Data on constitutional and behavioral factors, occupational exposures, and back-related symptoms and disability were collected. Back pain was grouped into "sciatic," "sudden," or "other" and related disability. The lifetime cumulative prevalence of back pain increased from 31% at entry to nursing school to 72% at the end of the school and further to 82% after 5 years as a nurse. The 1-year prevalence of any back pain was 54% for the first year in nursing school, 57% for the first year as a nurse, and 64% for the fifth year as a nurse. In multivariate analyses, other back pain and related disability as a nurse were associated with back pain history at the entry to nursing school (odds ratio, 7.1; 95% confidence interval, 1.5-34; and 3.6; 1.2-11, respectively), and working in twisted/bent positions (odds ratio, 6.2; 95% confidence interval, 1.7-23; and 7.5; 2.9-20, respectively). Sudden back pain was not associated with any of the studied risk factors. Sciatic back pain was associated only with working positions (odds ratio, 6.9; 95% confidence interval, 2.1-23). Lifetime prevalence of back pain increased sharply during nursing school but slowly after that. Back pain at entering the nursing school was a predictor for back-related pain and disability. Self- reported occupational physical work load was associated with back pain and related disability. The nature of the association is unclear, but it is likely that back pain is exacerbated during nursing.


[The age dynamics of characteristics of metabolism of lipids and carbohydrates in male youths of the North-East of Russia.]
The purpose of study is to evaluate age dynamics of biochemical indices in male youths permanently residing in the Magadan oblast. Material and methods. The study was carried out concerning indices of lipids and glucose in blood of 174 male youths aged from 17 to 20-21 years in the Magadan oblast. The detection of main indices of lipid and carbohydrate profiles was implemented using portable biochemical and carbohydrate express-analyzer CardioChek PA (USA) by analyzing capillary blood sampled from finger on an empty stomach after 10-12 hours after last food intake. The mathematical models of age alterations of main indices of lipid carbohydrate profile were made on the basis of implemented analysis. It resulted in regression equations describing relationships between indices of total cholesterol, low density lipoproteins, high density lipoproteins, level of glycemia and age characteristics of the examined. Conclusion. The character of alterations of most of analyzed indices of biochemical profile indicates availability of aged shifts to area of their increasing already in youth period of ontogenesis. It is established that values of indices of lipid profile in examined groups were within limits of accepted reference values, approaching the lower limit of the norm. The evaluation of metabolism of carbohydrates in male youths of Magadan established that in representatives of all age groups the given indicator is at the higher limit of reference range normoglycemia with increasing in the elder age group. At that, the study revealed a rather significant percentage of male youths with hyperglycemia manifestations in condition of carbohydrate metabolism (25%-29% in total sampling of the examined). The developed regression models indicate occurrence of a significant age conditionality of increasing of content of total cholesterol, low density lipoproteins, concentration of glucose in blood. The values of high density lipoproteins have no effect of age criteria.


Evaluation of a buried vertical well leachate recirculation system for municipal solid waste landfills.
Vertical liquids addition systems have been used at municipal landfills as a leachate management method and to enhance biostabilization of waste. Drawbacks of these systems include a limitation on pressurized injection and the occurrence of seepage. A novel vertical well system that employed buried wells constructed below a lift of compacted waste was operated for 153 days at a landfill in Florida, USA. The system included 54 wells installed in six clusters of nine wells connected with a horizontally-oriented manifold system. A cumulative volume of 8430 m3 of leachate was added intermittently into the well clusters over the duration of the project with no incidence of surface seeps. Achievable average flow rates ranged from 9.3 × 10-4 m3 s-1 to 14.2 × 10-4 m3 s-1, which was similar to or greater than flow rates achieved in a previous study using traditional vertical wells at the same landfill site. The results demonstrated that pressurized liquids addition in vertical wells at municipal solid waste landfills can be achieved while avoiding typical operational and maintenance issues associated with seeps.


Facilitation of patient involvement in care: development and validation of a scale.
The authors describe the development and validation of the Facilitation of Patient Involvement Scale, a 9-item measure of the degree to which patients perceive that their physicians actively facilitate or encourage them to be involved in their own healthcare. They first assessed the unidimensionality of the measure, conducting factor analysis in a pilot study of 236 individuals. Subsequently, they assessed the scale's reliability and validity with additional samples of 333, 338, 44, and 84 participants. Reliability of the scale was very high, with average Cronbach's alpha levels of .91. To test the validity of the scale, they used correlational and multiple regression analyses. The findings indicated that patients' satisfaction with their medical encounters was associated with patients' perceptions of facilitation; that perceptions of facilitation were also moderately correlated with general adherence patterns and preferred communication styles; and that patient age, gender, and education level were not relevant to perceptions that healthcare professionals promote patients' involvement in their own care.