Part II. Clinical evaluation of toric hydrophilic contact lenses.
Five toric hydrogel contact lenses have been approved for marketing by the FDA and several more await final approval in the near future. Clinical use of these special design lenses for correction of astigmatism has increased during the past year, improvements in lens design and fabrication are taking place, but problems remain. Analysis of the reasons for fitting failures show that lens quality and axis mislocation are the primary causes of lens performance failures.


Non accidental repeated lithium poisoning in a child: The role of hair analysis.
Non accidental intoxication due to child abuse is rare and its frequency is likely underestimated because it is difficult to diagnose. Here, we report a case of voluntary repeated exposure to lithium in an infant, for whom the clinical manifestations were convulsions. Toxicological analysis was very helpful for documenting lithium exposure during the assumed period of time. Interpreting the results of hair analysis, a simple and minimally invasive examination, is tricky at this age, but it can facilitate the differentiation of acute versus chronic exposure. Although infrequent and underestimated, lithium should be considered as a cause of intoxication in a previously healthy child with acute seizure.


Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus.
To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive "trophic" (15 mL/kg/d) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus. Infants were eligible for the study if they were 23(1/7)-30(6/7) weeks' gestation, weighed 401-1250 g at birth, received maximum enteral volumes ≤60 mL/kg/d, and were about to be treated with indomethacin or ibuprofen. A standardized "feeding advance regimen" and guidelines for managing feeding intolerance were followed at each site (N = 13). Infants (N = 177, 26.3 ± 1.9 weeks' mean ± SD gestation) were randomized at 6.5 ± 3.9 days to receive "trophic" feeds ("feeding" group, n = 81: indomethacin 80%, ibuprofen 20%) or no feeds ("fasting [nil per os]" group, n = 96: indomethacin 75%, ibuprofen 25%) during the drug administration period. Maximum daily enteral volumes before study entry were 14 ± 15 mL/kg/d. After drug treatment, infants randomized to the "feeding" arm required fewer days to reach the study's feeding volume end point (120 mL/kg/d). Although the enteral feeding end point was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the 2 groups. There were no differences between the 2 groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation, or other neonatal morbidities. Infants required less time to reach the feeding volume end point if they were given "trophic" enteral feedings when they received indomethacin or ibuprofen treatments.


Transparent Intracellular Sensing Platform with Si Needles for Simultaneous Live Imaging.
Vertically ordered Si needles are of particular interest for long-term intracellular recording owing to their capacity to infiltrate living cells with negligible damage and minimal toxicity. Such intracellular recordings could greatly benefit from simultaneous live cell imaging without disrupting their culture, contributing to an in-depth understanding of cellular function and activity. However, the use of standard live imaging techniques, such as inverted and confocal microscopy, is currently impeded by the opacity of Si wafers, typically employed for fabricating vertical Si needles. Here, we introduce a transparent intracellular sensing platform that combines vertical Si needles with a percolated network of Au-Ag nanowires on a transparent elastomeric substrate. This sensing platform meets all prerequisites for simultaneous intracellular recording and imaging, including electrochemical impedance, optical transparency, mechanical compliance, and cell viability. Proof-of-concept demonstrations of this sensing platform include monitoring electrical potentials in cardiomyocyte cells and in three-dimensionally engineered cardiovascular tissue, all while conducting live imaging with inverted and confocal microscopes. This sensing platform holds wide-ranging potential applications for intracellular research across various disciplines such as neuroscience, cardiology, muscle physiology, and drug screening.


Extracellular proton release by stimulated neutrophils.
We have tried to elucidate the mechanism of phagosome acidification in human neutrophils. Assuming that phenomena occurring at the plasma membrane reflect reactions in the phagocytic vacuoles, we have stimulated human neutrophils with agents that induce a "respiratory burst," and we have measured the release of protons into the extracellular medium. Phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine and serum-opsonized zymosan particles each caused a rapid release of protons, concomitant with the increase in oxygen consumption. The stimulated release of protons was strictly coupled to the increase respiration of the cells, because inhibition of the respiration of either anaerobiosis, chlorpromazine, or glycolytic inhibitors also inhibited the release of protons. Also, in the presence of the above-mentioned stimulating agents, neutrophils from three patients with chronic granulomatous disease enhanced neither respiration not proton release. In normal cells, the ratio of deltaH+/-deltaO2 was 1.04 +/- 0.19 (mean +/ SD, n = 13). The mechanism of this proton release is not clear. The amount of lactic and carbonic acid produced by stimulated neutrophils was inadequate to explain the amount of protons released. Perhydroxyl radicals were also ruled out as the source of the protons. Because the cells did not release measurable amounts of phosphate ions, a phosphate-hydroxyl-ion antiport was also excluded. Finally, the lack of any effect of uncouplers renders it unlikely that a respiration-driven proton gradient is built up across the plasma membrane.


How we decide what to eat: Toward an interdisciplinary model of gut-brain interactions.
Everyday dietary decisions have important short-term and long-term consequences for health and well-being. How do we decide what to eat, and what physiological and neurobiological systems are involved in those decisions? Here, we integrate findings from thus-far separate literatures: (a) the cognitive neuroscience of dietary decision-making, and (b) growing evidence of gut-brain interactions and especially influences of the gut microbiome on diet and health outcomes. We review findings that suggest that dietary decisions and food consumption influence nutrient sensing, homeostatic signaling in the gut, and the composition of the gut microbiome. In turn, the microbiome can influence host health and behavior. Through reward signaling pathways, the microbiome could potentially affect food and drink decisions. Such bidirectional links between gut microbiome and the brain systems underlying dietary decision-making may lead to self-reinforcing feedback loops that determine long-term dietary patterns, body mass, and health outcomes. This article is categorized under: Economics > Individual Decision-Making Psychology > Brain Function and Dysfunction Psychology > Reasoning and Decision Making.


Effect of length and cross-bridge attachment on Ca2+ binding to cardiac troponin C.
The sensitivity of skinned cardiac muscle bundles to Ca2+ is a function of sarcomere length. Ca2+ sensitivity is increased as fiber length is extended along the ascending limb of the force-length curve and it has been suggested that this phenomenon makes a major contribution to the steep force-length relationship that exists in living cardiac muscle. To gain greater insight into the mechanism behind the length dependence of Ca2+ sensitivity isotopic measurements of Ca2+ binding to detergent-extracted bovine, ventricular muscle bundles were made under conditions in which troponin C was the only major Ca2+ binding species. Experiments were designed to determine whether 1) Ca2+-troponin C affinity varies in the sarcomere length range corresponding to the ascending limb of the force-length curve, and 2) Ca2+ binding correlates with length per se or with changes in the number of length-dependent cross-bridge attachments. Measurements were made of Ca2+ binding in the rigor and relaxed states. The latter state was produced by suppressing actin-myosin interaction with the phosphate analogue, sodium vanadate. After vanadate treatment it is possible to obtain a complete Ca2+ saturation curve in the presence of physiological MgATP concentrations and at constant sarcomere length. The results show that the binding of Ca2+ to the regulatory site of cardiac troponin C is length dependent but this length dependence is actually a dependence on the number of attached cross bridges.


The biology of fracture repair.
Fracture healing or bone regeneration has been described histologically, histochemically, biochemically, physiologically, biophysically, and biomechanically. However, these various descriptive analyses do not answer the following all-important questions: What is the inductor(s) that incites cells to start forming bone at the fracture site? What are the responding cells that serve as progenitor cells for the osteoblasts and chondroblasts that appear in the interfragmentary gap? Do factors exist that are required to maintain the regenerating process to its conclusion? Until answers to these questions are found in the laboratory, we will not know "how" bone heals or regenerates itself.


Association of the Type of Toy Used During Play With the Quantity and Quality of Parent-Infant Communication.
The early language environment of a child influences language outcome, which in turn affects reading and academic success. It is unknown which types of everyday activities promote the best language environment for children. To investigate whether the type of toy used during play is associated with the parent-infant communicative interaction. Controlled experiment in a natural environment of parent-infant communication during play with 3 different toy sets. Participant recruitment and data collection were conducted between February 1, 2013, and June 30, 2014. The volunteer sample included 26 parent-infant (aged 10-16 months) dyads. Fifteen-minute in-home parent-infant play sessions with electronic toys, traditional toys, and books. Numbers of adult words, child vocalizations, conversational turns, parent verbal responses to child utterances, and words produced by parents in 3 different semantic categories (content-specific words) per minute during play sessions. Among the 26 parent-infant dyads, toy type was associated with all outcome measures. During play with electronic toys, there were fewer adult words (mean, 39.62; 95% CI, 33.36-45.65), fewer conversational turns (mean, 1.64; 95% CI, 1.12-2.19), fewer parental responses (mean, 1.31; 95% CI, 0.87-1.77), and fewer productions of content-specific words (mean, 1.89; 95% CI, 1.49-2.35) than during play with traditional toys or books. Children vocalized less during play with electronic toys (mean per minute, 2.9; 95% CI, 2.16-3.69) than during play with books (mean per minute, 3.91; 95% CI, 3.09-4.68). Parents produced fewer words during play with traditional toys (mean per minute, 55.56; 95% CI, 46.49-64.17) than during play with books (mean per minute, 66.89; 95% CI, 59.93-74.19) and use of content-specific words was lower during play with traditional toys (mean per minute, 4.09; 95% CI, 3.26-4.99) than during play with books (mean per minute, 6.96; 95% CI, 6.07-7.97). Play with electronic toys is associated with decreased quantity and quality of language input compared with play with books or traditional toys. To promote early language development, play with electronic toys should be discouraged. Traditional toys may be a valuable alternative for parent-infant play time if book reading is not a preferred activity.


T-cells of virus-infected mice produce a lymphokine which activates the autoreactivity of intact mouse lymphocytes.
The role of lymphokines was estimated in induction of autoreactive T-cells during Langat virus infection in mice. It was shown that in vitro cultured splenocytes from virus-infected animal containing autoreactive lymphocytes (ARL) spontaneously produce a lymphokine which is capable to activate the autoreactivity of lymphocytes derived from the spleen of intact syngeneic mice. The capacity of this lymphokine to activate the autoreactivity of acceptor cells within 2 hr was demonstrated by local graft-versus host reaction (GVHR) in the donor-recipient system. According to their surface markers (theta-antigen expression, absence of immunoglobulins) the lymphokine activating autoreactivity (LAA) producers may belong to T-lymphocyte population. Autoreactivity could be induced by the lymphokine only if the LAA producers and acceptors were compatible by the major histocompatibility complex antigens.


Marital abuse and psychological well-being among women in the southern region of Jordan.
The purpose of this study was to examine the relationship between marital abuse and psychological well-being among women in the southern region of Jordan. A descriptive correlational design was used to collect data from a randomly selected sample of 915 women in the southern region of Jordan. Data collected were related to forms of marital abuse and six domains of psychological well-being. The analysis showed that women have moderate to high level of psychological well-being. The prevalence of ever being abused during the past 12 months ranged from 3.2% (n = 25) for being threatened with a knife to 45.1% (n = 348) for their husbands being unconcerned about them while they were sick. There were significant differences in marital abuse related to having ever had school education (χ(2) = 8.56, df = 2, p = .014). All forms of marital abuse were highly correlated (p < .01). Self-acceptance and environmental mastery domains of psychological well-being had negative and significant correlation with all forms of marital abuse (p < .01). DISCUSSION OF CONCLUSION: Health professionals in health care centers need to assess for marital abuse and its consequence on women's health. Interventions should emphasize promotion of psychological well-being and the factors that influence women empowerment.


Degradation of 3,5-dichlorophenol by UV-C photolysis and UV-C-activated persulfate oxidation process in pure water and simulated tertiary treated urban wastewater.
UV-C and UV-C/peroxydisulfate (PS) treatments of 3,5-dichlorophenol (3,5-DCP), a model industrial pollutant, were comparatively investigated in two different water matrices namely distilled water (DW) and simulated treated urban wastewater (SWW). The treatment performance of the selected treatment processes was comprehensively examined by following changes in 3,5-DCP, dissolved organic carbon (DOC), PS consumption, Cl- release, aromatic/aliphatic degradation products and acute toxicities towards the marine photobacterium Vibrio fischeri and freshwater microalga Pseudokirchneriella subcapitata. The treatability of 2 mg/L (12.3 µM) 3,5-DCP in DW was investigated under different operating conditions such as initial PS concentrations (0.00-1.00 mM) and pH values (3-11) at a fixed light intensity (0.5 W/L). Increasing the pH and PS concentration exhibited positive effects on 3,5-DCP degradation. Even 10 mg/L 3,5-DCP was completely degraded with UV-C/PS treatment in 40 min in the presence of 0.03 mM PS at pH 6.3 accompanied with 95% DOC removal that was achieved after 120 min treatment. The second-order rate constant of 3,5-DCP (10 mg/L) with SO4⋅- was determined as 1.77×109 M-1s-1 using competition kinetics. Cl- release and formation of hydroquinone were evidences of 3,5-DCP degradation involving SO4⋅-. 3,5-DCP (2 mg/L) was also subjected to UV-C and UV-C/PS treatments in SWW. 3,5-DCP (100% after 60 min) and in particular DOC (26% after 120 min treatment) removal efficiencies observed in DW decreased dramatically in SWW. The original and UV-C/PS-treated samples were non-toxic towards Vibrio fischeri; however, Pseudokirchneriella subcapitata toxicity increased from 20% to 47% through 80 min UV-C/PS treatment of 3,5-DCP.


Estimating the price at which hepatitis C treatment with direct-acting antivirals would be cost-saving in Japan.
In Japan, 1.5-2 million people are chronically infected with hepatitis C virus (HCV) infection. New direct-acting antiviral agents (DAA) offer an unprecedented opportunity to cure HCV. While the price of HCV treatment decreased recently in most countries, it remains one of the highest in Japan. Our objective was to evaluate the cost-effectiveness of HCV treatment in patients of different age groups and to estimate the price at which DAAs become cost-saving in Japan. A previously developed microsimulation model was adapted to the Japanese population and updated with Japan-specific health utilities and costs. Our model showed that compared with no treatment, the incremental cost-effectiveness ratio (ICER) of DAAs at a price USD 41,046 per treatment was USD 9,080 per quality-adjusted life year (QALY) gained in 60-year-old patients. HCV treatment became cost-effective after 9 years of starting treatment. However, if the price of DAAs is reduced by 55-85% (USD 6,730 to 17,720), HCV treatment would be cost-saving within a 5 to 20-year time horizon, which should serve to increase the uptake of DAA-based HCV treatment. The payers of health care in Japan could examine ways to procure DAAs at a price where they would be cost-saving.


Applying Visual Research Methods in Pharmacy Education.
Objective. To explore the use of a qualitative visual research method, analysis of Lifenets, to understand students' conceptions of their social and material worlds. Methods. The Lifenet View model and drawing exercise invites students to create a cognitive map of the self in social and material contexts. Ninety-five undergraduate students enrolled in an online undergraduate human development course created Lifenet drawings depicting their connections to people, places, and things at two points in time: the present and the distant future. They also wrote essays describing their drawings. Researchers used an inductive analytical process to identify patterns in the set of drawings, developing a coding taxonomy used to systematically analyze the data. Results. Results offered insights into participants' current self-perceptions and their expectations for the future. Analysis of Lifenets allowed researchers to document and gain insight into participants' perspectives on their current relationships, career aspirations, and assumptions about aging. While students often depicted strong ties to family, friends, and religious entities, few students expressed ties to the secular institutions that define civic and professional life. Conclusion. The Lifenet View exercise may provide instructors with a way to better understand students' social circumstances and to identify and address specific gaps in the professional education curriculum. Use of the Lifenet View exercise in the pharmacy curriculum could provide valuable opportunities for career exploration and expanded cultural awareness of self and others.


A Simple Index for Nonalcoholic Steatohepatitis-HUFA-Based on Routinely Performed Blood Tests.
Background and objectives: Data suggests that nearly 30% of the general population have steatosis and up to 5% of this population develops nonalcoholic steatohepatitis (NASH). Liver biopsy is still considered to be the gold standard for the diagnosis of NASH. Great effort is being made toward the identification of sensitive diagnostic tests that do not involve invasive procedures to address a common concern in patients with the nonalcoholic fatty liver disease-whether they have NASH or simple steatosis. We aimed to investigate the independent predictors and develop a non-invasive, easy-to-perform, low-cost set of parameters that may be used in clinical practice to differentiate simple steatosis from NASH. Methods: А cross-sectional study of nonalcoholic fatty liver disease (NAFLD) patients divided into two groups: group I-simple steatosis (SS) and group II-biopsy-proven NASH. Strict inclusion criteria and stepwise analysis allowed the evaluation of a vast number of measured/estimated parameters. Results: One hundred and eleven patients were included-82 with simple steatosis and 29 with biopsy-proven NASH. The probability of NASH was the highest when homeostatic model assessment of insulin resistance (HOMA-IR) was above 2.5, uric acid above 380 µmol/L, ferritin above 100 µg/L and ALT above 45 U/L. An acronym of using first letters was created and named the HUFA index. This combined model resulted in an area under the receiver operator characteristic curve (AUROC) of 0.94, provided sensitivity, specificity, positive predictive value and a negative predictive value for NASH of 70.3%, 95.1%, 83.1% and 90.0%, respectively. Conclusion: We suggest a simple non-invasive predictive index HUFA that encompasses four easily available parameters (HOMA-IR, uric acid, ferritin and ALT) to identify patients with NASH, which may reduce the need for a liver biopsy on a routine basis in patients with NAFLD.


Predicting reports of unmet expectations among rheumatology patients.
Approximately 25% of patients report unmet expectations after their doctor visits. In a longitudinal study of rheumatology patients, we examined whether changes in health status could predict unmet expectations. Arthritis patients (n = 177) responded to 2 surveys (baseline and 6-month followup). Both surveys contained questions on health status (functional status, pain, helplessness, psychological status) and visit duration. The followup survey contained questions on postvisit unmet expectations. Factors associated with unmet expectations were determined. Fifty-eight patients (33%) reported unmet expectations, most often for information (47%) and new medications (31%). Unmet expectations were more common among patients with greater baseline helplessness (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.0-3.6) and short doctor visits at followup (OR 5.6, 95% CI 2.4-13.1). Unmet expectations were less common among those experiencing a decline in pain (OR 0.3, 95% CI 0.1-0.9). Attention to the patient's level of pain and helplessness and duration of the visit may limit reports of unmet expectations.


Healthcare cost and loss of productivity in a Canadian population of patients with and without lupus nephritis.
To compare the healthcare cost and loss of productivity in patients with systemic lupus erythematosus (SLE) with (LN) and without lupus nephritis (lupus nephritis-negative, LNN). Patients were classified into those with active (ALN and ALNN) and inactive disease (ILN and ILNN). Patients reported on visits to healthcare professionals and use of diagnostic tests, medications, assistive devices, alternative treatments, hospital emergency visits, surgical procedures, and hospitalizations as well as loss of productivity in the 4 weeks preceding enrollment. Enrollment was 141 patients, 79 with LN and 62 LNN. Patients with LN were more likely to visit rheumatologists and nephrologists, undergo diagnostic tests, and had higher costs for medications than patients who were LNN. The annual healthcare cost averaged $CAN 12,597 ± 9946 for patients with LN and $10,585 ± 13,149 for patients who were LNN, a difference of $2012 (95% CI -$2075, $6100). Patients with ALN had more diagnostic tests and surgical procedures, contributing to a significantly higher annual direct cost ($14,224 ± 10,265) compared to patients with ILN ($9142 ± 8419) and a difference of $5082 (95% CI $591, $9573). The healthcare cost was not different between patients with ALNN and patients with ILNN. In patients with LN and patients who were LNN, < 50% were employed and on average missed 6.5-9 days of work per month. The loss of productivity was significantly higher for caregivers of patients with LN than caregivers of patients who were LNN. Healthcare cost and loss of productivity were similar between patients with LN and patients who were LNN; the loss of productivity for caregivers is higher for patients with LN; and the healthcare cost is greater in ALN than in ILN.


Insulin-producing cells are bi-potential and differentiatorsprior to proliferation in early human development.
To investigate the differentiation and migration of endocrine cells to form the pancreatic islets of Langer-hans in early human development. Embryonic pancreas of 6-14 wk gestation was observed using immunocytochemistry methods in early human development. Insulin and glucagon are expressed in the same epithelium cells in the pancreas. In addition, in-sulin-producing cells also secrete somatostatin in early human embryonic development and these insulin-pro-ducing cells also express nestin. Pancreatic duct epithelial cells that can produce insulin in early human development are pre-cursors and still have the potential to differentiate other endocrine cells. These progenitors have differen-tiated before migration from primary ductal epithelium to form the pancreatic islets.


Dissecting causal associations of type 2 diabetes with 111 types of ocular conditions: a Mendelian randomization study.
Despite the well-established findings of a higher incidence of retina-related eye diseases in patients with diabetes, there is less investigation into the causal relationship between diabetes and non-retinal eye conditions, such as age-related cataracts and glaucoma. We performed Mendelian randomization (MR) analysis to examine the causal relationship between type 2 diabetes mellitus (T2DM) and 111 ocular diseases. We employed a set of 184 single nucleotide polymorphisms (SNPs) that reached genome-wide significance as instrumental variables (IVs). The primary analysis utilized the inverse variance-weighted (IVW) method, with MR-Egger and weighted median (WM) methods serving as supplementary analyses. The results revealed suggestive positive causal relationships between T2DM and various ocular conditions, including "Senile cataract" (OR= 1.07; 95% CI: 1.03, 1.11; P=7.77×10-4), "Glaucoma" (OR= 1.08; 95% CI: 1.02, 1.13; P=4.81×10-3), and "Disorders of optic nerve and visual pathways" (OR= 1.10; 95% CI: 0.99, 1.23; P=7.01×10-2). Our evidence supports a causal relationship between T2DM and specific ocular disorders. This provides a basis for further research on the importance of T2DM management and prevention strategies in maintaining ocular health.


Prognostic value of pre-treatment CT texture analysis in combination with change in size of the primary tumor in response to induction chemotherapy for HPV-positive oropharyngeal squamous cell carcinoma.
To determine the additive value of quantitative radiomic texture features in predicting progression in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) based on pre-treatment CT. Retrospective analysis of a single-center cohort of adult patients enrolled in a response-adapted radiation volume de-escalation trial treated with induction chemotherapy. Texture analysis of HPV-positive OPSCC was performed via primary tumor site contouring on pre-treatment contrast-enhanced CT scans. Percent change in size of the tumor in response to induction chemotherapy based on RECIST 1.1 criteria and progression free survival were clinically determined for this cohort. Receiver operating characteristic (ROC) analysis was performed to compare the accuracy of percent change in tumor size after induction chemotherapy with a combination of change in tumor size and radiomic texture features for predicting tumor progression. Radiomic texture analysis of the primary tumors in 38 patients with OPSCC depicted on pre-treatment neck CT scans using skewness and entropy in combination with percent change in tumor size after induction chemotherapy yielded a statistically significant increase in accuracy for predicting tumor progression over change in tumor size alone, with an area under the curve of 0.80 versus 0.56 (one-tailed P=0.0087). This pilot study suggests that disease progression in patients with HPV-positive OPSCC is more accurately predicted using a combination of texture features on pre-treatment CT scans, along with change in tumor size compared to change in tumor size alone and could therefore serve as a radiomic texture signature.


Biosorption of lead ion by lactic acid bacteria and the application in wastewater.
Through the study of biosorption of Pb2+ by lactic acid bacteria, two strains called CN-011 and CN-005 with high tolerance and great adsorption to lead were screened. The minimum bactericidal concentration of lead ions for both CN-011 and CN-005 was 1.45 mmol/L. The optimal culture conditions for the removal of 30 mg/L lead ions were achieved by culturing lactic acid bacteria at an initial pH of 7.0, 37 °C and 120 rpm for 48 h. The adsorption rate of CN-011 and CN-005 for Pb2+ were 85.95% and 86.78%, respectively. In simulated wastewater samples, the average adsorption rate of Pb2+ was 73.38% for CN-011 and 74.15% for CN-005. The mechanism of biosorption was characterized by Fourier Transform infrared spectroscopy, Scanning Electron Microscope-Energy Dispersive Spectrometer, X-ray Photoelectron Spectroscopy, which revealed that Pb2+ mainly reacted with hydroxyl ions in peptidoglycan or polysaccharide, and carboxylate radical in teichoic acid or protein on the surface of lactic acid bacteria cell wall. The deposits produced on the bacterial surface were identified as lead oxide and lead nitrate.


Oncomirs - microRNAs with a role in cancer.
MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.


Surface modification of T-lymphocytes observed during rosetting.
Scanning electron microscopy has been used to characterize alterations of lymphocyte surface topology that occur on contact with erythrocytes during the rosetting reaction. Molt-4 cells, a line of leukemic human lymphocytes, defined as T-cells through their ability to form rosettes with sheep erythrocytes, were used for this. Unreacted Molt-4 cells exhibit surfaces that are virtually smooth and carry few microvilli. In contrast, Molt-4 cells in rosettes display a time-dependent modification of surface topology, characterized by the emergence of numerous, long microvilli, particularly in areas of red cell contact.


Highly Reliable 3D Channel Memory and Its Application in a Neuromorphic Sensory System for Hand Gesture Recognition.
Brain-inspired neuromorphic computing systems, based on a crossbar array of two-terminal multilevel resistive random-access memory (RRAM), have attracted attention as promising technologies for processing large amounts of unstructured data. However, the low reliability and inferior conductance tunability of RRAM, caused by uncontrollable metal filament formation in the uneven switching medium, result in lower accuracy compared to the software neural network (SW-NN). In this work, we present a highly reliable CoOx-based multilevel RRAM with an optimized crystal size and density in the switching medium, providing a three-dimensional (3D) grain boundary (GB) network. This design enhances the reliability of the RRAM by improving the cycle-to-cycle endurance and device-to-device stability of the I-V characteristics with minimal variation. Furthermore, the designed 3D GB-channel RRAM (3D GB-RRAM) exhibits excellent conductance tunability, demonstrating high symmetricity (624), low nonlinearity (βLTP/βLTD ∼ 0.20/0.39), and a large dynamic range (Gmax/Gmin ∼ 31.1). The cyclic stability of long-term potentiation and depression also exceeds 100 cycles (105 voltage pulses), and the relative standard deviation of Gmax/Gmin is only 2.9%. Leveraging these superior reliability and performance attributes, we propose a neuromorphic sensory system for finger motion tracking and hand gesture recognition as a potential elemental technology for the metaverse. This system consists of a stretchable double-layered photoacoustic strain sensor and a crossbar array neural network. We perform training and recognition tasks on ultrasonic patterns associated with finger motion and hand gestures, attaining a recognition accuracy of 97.9% and 97.4%, comparable to that of SW-NN (99.8% and 98.7%).


Genistein and Glyceollin Effects on ABCC2 (MRP2) and ABCG2 (BCRP) in Caco-2 Cells.
The goal of the present study was to determine the effects of glyceollins on intestinal ABCC2 (ATP Binding Cassette C2, multidrug resistance protein 2, MRP2) and ABCG2 (ATP Binding Cassette G2, breast cancer resistance protein, BCRP) function using the Caco-2 cell intestinal epithelial cell model. Glyceollins are soy-derived phytoestrogens that demonstrate anti-proliferative activity in several sources of cancer cells. 5 (and 6)-carboxy-2',7'-dichloroflourescein (CDF) was used as a prototypical MRP2 substrate; whereas BODIPY-prazosin provided an indication of BCRP function. Comparison studies were conducted with genistein. Glyceollins were shown to inhibit MRP2-mediated CDF transport, with activity similar to the MRP2 inhibitor, MK-571. They also demonstrated concentration-dependent inhibition BCRP-mediated efflux of BODIPY-prazosin, with a potency similar to that of the recognized BCRP inhibitor, Ko143. In contrast, genistein did not appear to alter MRP2 activity and even provided a modest increase in BCRP efflux of BODIPY-prazosin. In particular, glyceollin inhibition of these two important intestinal efflux transporters suggests the potential for glyceollin to alter the absorption of other phytochemicals with which it might be co-administered as a dietary supplement, as well as alteration of the absorption of pharmaceuticals that may be administered concomitantly.


Isolation and characterization of an endo-beta-galactosidase from Bacteroides fragilis.
Six strains of Bacteroides fragilis were examined and all found to produce endo-beta-galactosidase, an enzyme that hydrolyses internal beta-galactosidic linkages of oligosaccharides belonging to the poly-N-acetyl-lactosamine series, with the common structure GlcNAc beta 1 leads to 3Gal beta 1 leads to 4GlcNAc/Glc. The enzyme was produced without the addition of an inducer such as keratan sulphate. It was purified 7000-fold from the culture supernatant and obtained with a yield 4-10-fold greater than from sources described previously. The specificity of the enzyme towards bovine corneal keratan sulphate, milk oligosaccharides and the glycolipids lacto-N-neotetraosylceramide and lacto-N-tetraosylceramide closely resembled that of the endo-beta-galactosidase isolated from Escherichia freundii. A novel observation was that both enzymes hydrolysed the type 2 sequence, Gal beta 1 leads to 4GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc, at about twice the rate of the type 1 isomer, Gal beta 1 leads to 3GlcNAc beta 1 leads to 3Gal beta 1 leads to 4Glc. Because of the ease of purification of the enzyme and high yield in the absence of contaminating glycosidases and proteinases, Bacteroides fragilis is a valuable source of endo-beta-galactosidase for the structural analysis of carbohydrate chains.


Design of an improved surgical instrument for the removal of bladder tumours.
The aim of this work was to design an add-on instrument that could potentially decrease the recurrence of non-muscle invasive bladder cancer. The current surgical approach permits spilled tumour cells to disseminate within the bladder, re-implant and cause tumour recurrence. An add-on instrument has been designed in the form of an opening cone intended to provide space for surgery and yet reduce tumour cell spillage and dissemination. A prototype was manufactured using the shape memory metal Nitinol which was activated using an electrical current to facilitate opening and supplemented with latex to provide a sealed environment. The prototype was tested in comparable surgical conditions utilising porcine bladder wall and blue dye to simulate tumour cells. It was demonstrated that the vast majority of dye was retained within the device, supporting the proposed aim.


The worldwide association between television viewing and obesity in children and adolescents: cross sectional study.
Studies exploring the effect of television viewing on obesity throughout childhood are conflicting. Most studies have been confined to single high-income countries. Our aim was to examine the association between television viewing habits and Body Mass Index (BMI) in adolescents and children in a multicentre worldwide sample. In the International Study of Asthma and Allergies in Children Phase Three, adolescents aged between 12 and 15 years completed questionnaires which included questions on television viewing habits, height and weight. Parents/guardians of children aged between 5 and 8 years completed the same questionnaire on behalf of their children. The questionnaire asked "During a normal week, how many hours a day (24 hours) do you (does your child) watch television?" Responses were categorised as; "short" (<1 hour), "moderate" (1 to ≤3 hours), "long" (3 to ≤5 hours) and "prolonged" (>5 hours). 207,672 adolescents from 37 countries and 77,003 children from 18 countries provided data. Daily television viewing in excess of one hour was reported in 89% of adolescents and 79% of children. Compared with adolescents in the short viewing group, those in the moderate, long and prolonged groups had BMIs that were 0.14 kg/m(2), 0.21 kg/m(2), 0.30 kg/m(2) and 0.08 kg/m(2), 0.16 kg/m(2) and 0.17 kg/m(2) larger for females and males respectively (both P<0.001). Compared with children in the short viewing group, those in the moderate, long and prolonged groups had BMIs that were 0.24 kg/m(2), 0.34 kg/m(2), 0.36 kg/m(2) and 0.19 kg/m(2), 0.32 kg/m(2) and 0.36 kg/m(2) larger for females and males respectively (both P<0.001). Increased television viewing hours were positively associated with BMI in both adolescents and children with an apparent dose response effect. These findings extend the evidence that television viewing contributes to increased BMI in childhood.


IBD-related mental health disorders: where do we go from here?
Inflammatory bowel disease is a complex and debilitating disease which is known to cause mental burden for patients. Even though few studies look at mental health disease in this cohort of patients, there is growing evidence of a correlation between disease activity and prevalence of mental health conditions such as anxiety, depression and post-traumatic stress disorder. In this literature review, the relationship between inflammatory bowel disease and mental health disorders is explored, with an emphasis on recognition, screening and therapeutic options and special considerations for these complex comorbidities. The relationship between medical and psychological disease is not often considered and less well understood and there is a need for further research in these fields. Patients would have much to gain both medically and psychologically from a multidisciplinary approach to this chronic disease association.


Colon cancer associated genes exhibit signatures of positive selection at functionally significant positions.
Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by ~180 Million Years (MY) of independent evolution between these species. For a given set of human disease related genes, it is therefore important to determine if functional equivalency has been retained between species. In this study we test the hypothesis that cancer associated genes have different patterns of substitution akin to adaptive evolution in different mammal lineages. Our analysis of the current literature and colon cancer databases identified 22 genes exhibiting colon cancer associated germline mutations. We identified orthologs for these 22 genes across a set of high coverage (>6X) vertebrate genomes. Analysis of these orthologous datasets revealed significant levels of positive selection. Evidence of lineage-specific positive selection was identified in 14 genes in both ancestral and extant lineages. Lineage-specific positive selection was detected in the ancestral Euarchontoglires and Hominidae lineages for STK11, in the ancestral primate lineage for CDH1, in the ancestral Murinae lineage for both SDHC and MSH6 genes and the ancestral Muridae lineage for TSC1. Identifying positive selection in the Primate, Hominidae, Muridae and Murinae lineages suggests an ancestral functional shift in these genes between the rodent and primate lineages. Analyses such as this, combining evolutionary theory and predictions - along with medically relevant data, can thus provide us with important clues for modeling human diseases.


[Evaluation of capacity for informed consent in psychiatric and neurological patients--proposal of a stepwise decisional procedure].
Evaluation of capacity for informed consent in psychiatric and neurological patients is assuming increasing importance in clinical practice. After a brief description of legal aspects, a procedural algorithm is presented for evaluation of capacity concerning consent of patients in medical treatment and procedures. This evaluation is based on the investigation and documentation of understanding, voluntariness, and decisional capacity. Relevant deficits of only one of these components in the evaluative procedure exclude capacity for informed consent. The outlined approach is compared with international proposals and discussed with regard to its application in clinical practice.


A Comparison of Visualizations for Identifying Correlation over Space and Time.
Observing the relationship between two or more variables over space and time is essential in many domains. For instance, looking, for different countries, at the evolution of both the life expectancy at birth and the fertility rate will give an overview of their demographics. The choice of visual representation for such multivariate data is key to enabling analysts to extract patterns and trends. Prior work has compared geo-temporal visualization techniques for a single thematic variable that evolves over space and time, or for two variables at a specific point in time. But how effective visualization techniques are at communicating correlation between two variables that evolve over space and time remains to be investigated. We report on a study comparing three techniques that are representative of different strategies to visualize geo-temporal multivariate data: either juxtaposing all locations for a given time step, or juxtaposing all time steps for a given location; and encoding thematic attributes either using symbols overlaid on top of map features, or using visual channels of the map features themselves. Participants performed a series of tasks that required them to identify if two variables were correlated over time and if there was a pattern in their evolution. Tasks varied in granularity for both dimensions: time (all time steps, a subrange of steps, one step only) and space (all locations, locations in a subregion, one location only). Our results show that a visualization's effectiveness depends strongly on the task to be carried out. Based on these findings we present a set of design guidelines about geo-temporal visualization techniques for communicating correlation.


Effect of thyroxine administration on the IGF/IGF binding protein system in neonatal and adult thyroidectomized rats.
The effects of different doses of thyroxine (T(4)) delivered by injection or s.c. pellet implantation on alterations of the IGF/IGF binding protein (IGFBP) system were studied in neonatal and adult thyroidectomized (Tx) rats. Body weight, blood glucose, plasma insulin, TSH and GH and pituitary GH content, as well as serum IGF-I, IGF-II, IGFBP-1, -2 and -3 and their liver mRNA expression were assayed. Pellet implantation with the smaller dose of T(4) (1.5 microg/100 g body weight (b.w.) per day) in Tx neonatal rats decreased serum IGF-I, -II and the 30 kDa complex of IGFBPs (IGFBP-1 and -2), and increased serum IGFBP-3. Only the larger dose of T(4) (3 microg/100 g b.w. per day) recovered liver mRNA expression of IGF-I and ensured euthyroid status as shown by the normalized levels of plasma TSH. The rapid increase of body weight and serum GH after T(4) administration indicated a high sensitivity to T(4) during the neonatal period. Serum and liver mRNA expression of IGFs and plasma insulin and GH recovered in adult Tx rats after pellet implantation of 1.75 microg/100 g b.w. per day throughout 10 days. The continuous replacement of T(4) by pellet seems to be the most suitable method for thyroid rehabilitation. A very good correlation was found between insulin and IGF-II in Tx neonates treated with T(4) but not between insulin and IGF-I in Tx adults. IGFBP-2 seems to be up-regulated by T(4) deprivation in neonatal and adult rats. Finally, a good correlation as well as a partial correlation were found between IGFs and thyroid hormones in both neonatal and adult Tx populations, suggesting a direct effect in vivo of T(4) on the hepatic secretion of IGFs, as previously suggested in vitro.


Acute liver failure.
Acute liver failure (ALF) (sometimes referred to as fulminant hepatic failure) is a clinical syndrome from a variety of causes resulting from rapid loss in hepatocyte function, typically associated with coagulopathy and encephalopathy in a patient without preexisting liver disease or cirrhosis. Cerebral edema is a cardinal feature and may produce uncal herniation, yielding brain stem compression and death. The typical interval from onset of symptoms to onset of encephalopathy is 1 to 2 weeks, but cases evolving more slowly, up to 6 months, may still be included in the definition. ALF is rare, affecting 2000 patients annually in the United States, and comprises ∼7% of liver transplants annually. Currently, in the United States, acetaminophen accounts for ∼50% of all cases of ALF, but other etiologies include hepatitis, drug-induced liver injury, autoimmune hepatitis. Prior to the availability of liver transplantation (LT), mortality of ALF was extremely high, often exceeding 90%; most common causes of death were multiorgan failure, hemorrhage, infection, and cerebral edema. Fortunately, survival has improved considerably in the last 3 decades (overall survival now exceeds 60%). In large part, this improved survival reflects the option of LT but also reflects the high frequency of acetaminophen toxicity as a cause of ALF. In fact, most patients with ALF are not candidates for LT. Critical care of patients with ALF is key to their survival, and decisions must sometimes be made with inadequate information. We review standard practices (medical, pharmacological, and LT) and new research initiatives and findings for this interesting but vexing orphan disease. Particular attention will be paid to practical matters for clinicians to consider in approaching the ALF patient.


[New developments in the hormonal treatment of breast cancer in postmenopausal women].
Nowadays the role of the hormonotherapy in the treatment of breast cancer in postmenopausal women is well established. The benefit of tamoxifen is demonstrated in the adjuvant setting as well as in the treatment of advanced breast cancer. After tamoxifen failure the hormonosensitive patients can be offered a second and a third hormonal treatment. The developments of new hormonotherapies recently or shortly put at the disposal of oncologists, such as new antiestrogens or selective estrogen receptors modulators (SERM), new steroidal and nonsteroidal aromatase inhibitors and antiprogestins are reviewed as well as the recent data on the use of tamoxifen in the primary prevention of breast cancer. The principal characteristics and the potential therapeutic uses of these agents are reviewed in the treatment and prevention of breast cancer in postmenopausal patients.


NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY TRANSHITAL ESOPHAGECTOMY IN LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: IMPACT OF PATHOLOGICAL COMPLETE RESPONSE.
Multimodal therapy with neoadjuvant chemoradiotherapy, followed by esophagectomy has offered better survival results, compared to isolated esophagectomy, in advanced esophageal cancer. In addition, patients who have a complete pathological response to neoadjuvant treatment presented greater overall survival and longer disease-free survival compared to those with incomplete response. To compare the results of overall survival and disease-free survival among patients with complete and incomplete response, submitted to neoadjuvant chemoradiotherapy, with two therapeutic regimens, followed by transhiatal esophagectomy. Retrospective study, approved by the Research Ethics Committee, analyzing the medical records of 56 patients with squamous cell carcinoma of the esophagus, divided into two groups, submitted to radiotherapy (5040 cGY) and chemotherapy (5-Fluorouracil + Cisplatin versus Paclitaxel + Carboplatin) neoadjuvants and subsequently to surgical treatment, in the period from 2005 to 2012, patients. The groups did not differ significantly in terms of gender, race, age, postoperative complications, disease-free survival and overall survival. The 5-year survival rate of patients with incomplete and complete response was 18.92% and 42.10%, respectively (p> 0.05). However, patients who received Paclitaxel + Carboplatin, had better complete pathological responses to neoadjuvant, compared to 5-Fluorouracil + Cisplatin (47.37% versus 21.62% - p = 0.0473, p <0.05). There was no statistical difference in overall survival and disease-free survival for patients who had a complete pathological response to neoadjuvant. Patients submitted to the therapeutic regimen with Paclitaxel and Carboplastin, showed a significant difference with better complete pathological response and disease progression. New parameters are indicated to clarify the real value in survival, from the complete pathological response to neoadjuvant, in esophageal cancer.


Occludin regulates glucose uptake and ATP production in pericytes by influencing AMP-activated protein kinase activity.
Energetic regulation at the blood-brain barrier is critical for maintaining its integrity, transport capabilities, and brain demands for glucose. However, the underlying mechanisms that regulate these processes are still poorly explored. We recently characterized the protein occludin as a NADH oxidase and demonstrated its influence on the expression and activation of the histone deacetylase SIRT-1. Because SIRT-1 works in concert with AMP-activated protein kinase (AMPK) (AMPK), we investigated the impact of occludin on this metabolic switch. Here we show that in blood-brain barrier pericytes, occludin promotes AMPK expression and activation, influencing the expression of glucose transporters GLUT-1 and GLUT-4, glucose uptake, and ATP content. Furthermore, occludin expression, AMP-dependent protein kinase activity, and glucose uptake were altered under inflammatory (TNFα) and infectious (HIV) conditions. We also show that pericytes share glucose and mitochondria with astrocytes, and that occludin levels modify the ability of pericytes to share those energetic resources. In addition, we demonstrate that murine mitochondria can be transferred from live brain microvessels to energetically impaired human astrocytes, promoting their survival. Our findings demonstrate that occludin plays an important role in blood-brain barrier pericyte metabolism by influencing AMPK protein kinase activity, glucose uptake, ATP production, and by regulating the ability of pericytes to interact metabolically with astrocytes.


Social Exchange and Sexual Behavior in Young Women's Premarital Relationships in Kenya.
Transactional sex, or the exchange of money and gifts for sexual activities within nonmarital relationships, has been widely considered a contributing factor to the disproportionate prevalence of HIV/AIDS among young women in sub-Saharan Africa. This study applied social exchange theory to premarital relationships in order to investigate the linkages between a variety of young women's resources-including employment and material transfers from male partners-and sexual behaviors. Data on the first month of premarital relationships (N=551 relationships) were collected from a random sample of young adult women ages 18-24 in Kisumu, Kenya, using a retrospective life history calendar. Consistent with the hypotheses, results showed that young women's income increases the likelihood of safer sexual activities, including delaying sex and using condoms consistently. Material transfers from the male partner displayed the opposite effect, supporting the view that resources obtained from within the relationship decrease young women's negotiating power.


Weight Loss and Alzheimer's Disease in Down Syndrome.
Virtually all adults with Down syndrome (DS) develop Alzheimer's disease (AD) pathology, but research gaps remain in understanding early signs of AD in DS. The goal of the present study was to determine if unintentional weight loss is part of AD in DS. The specific aims were to: 1) examine relation between chronological age, weight, AD pathology, and AD-related cognitive decline were assessed in a large cohort of adults with DS, and 2) determine if baseline PET amyloid-β (Aβ) and tau PET status (-versus+) and/or decline in memory and mental status were associated with weight loss prior to AD progression. Analyses included 261 adults with DS. PET data were acquired using [11C] PiB for Aβ and [18F] AV-1451 for tau. Body mass index (BMI) was calculated from weight and height. Direct measures assessed dementia and memory. Clinical AD status was determined using a case consensus process. Percent weight decline across 16-20 months was assessed in a subset of participants (n = 77). Polynomial regressions indicated an 0.23 kg/m2 decrease in BMI per year beginning at age 36.5 years, which occurs alongside the period during which Aβ and tau increase and memory and mental status decline. At a within-person level, elevated Aβ, decline in memory and mental status were associated with higher percent weight loss across 16-20 months. Unintentional weight loss occurs alongside Aβ deposition and prior to onset of AD dementia, and thus may be a useful sign of AD in DS.


Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation.
In the synovial cells of patients with RA, activation of the nuclear factor-kappaB (NF-kappaB) pathway results in the transactivation of a multitude of responsive genes that contribute to the inflammatory phenotype, including TNF-alpha from macrophages, matrix metalloproteinases from synovial fibroblasts and chemokines that recruit immune cells to the inflamed pannus. This is largely a consequence of activation of the 'canonical' NF-kappaB pathway that involves heterodimers of p50/p65. Whilst much information on the role of NF-kappaB in inflammation has been gleaned from genetic deficiency of the respective genes in mice, important differences exist in the signalling networks between human and murine immune cells and immortalized cell lines. Despite these differences at the molecular level, the importance of NF-kappaB in inflammation is undisputed and inhibition of the pathway is widely believed to have great potential as a therapeutic target in RA. Commercial effort has gone into developing inhibitors of NF-kappaB activation. However, inhibition of the NF-kappaB activation can result in an exacerbation of inflammation if TNF-alpha production by macrophages is not controlled. It will be important that such inhibitors are carefully monitored before their long-term use in chronic inflammatory conditions such as RA.


Experiential Avoidance and Bordering Psychological Constructs as Predictors of the Onset, Relapse and Maintenance of Anxiety Disorders: One or Many?
To investigate (a) the incremental predictive validity of experiential avoidance over and above bordering psychological constructs (i.e., rumination, worry, neuroticism and anxiety sensitivity) in predicting onset, relapse and maintenance of anxiety disorders; and (b) whether these related constructs can be represented by a single, higher-order latent factor with similar predictive power as the separate psychological constructs while offering a more parsimonious predictive model. Longitudinal cohort study with repeated assessments after 4 years in a sample of 2157 adults aged 18-65, consisting of 1614 persons with past or current anxiety disorder (Panic Disorder with or without Agoraphobia, Social Anxiety Disorder, Generalized Anxiety Disorder, Agoraphobia without panic) according to the Composite Interview Diagnostic Instrument (CIDI) and 543 controls. Experiential avoidance (Acceptance and Action Questionnaire-I) manifested substantial overlap with bordering cognitive constructs. Experiential avoidance and anxiety sensitivity both uniquely predicted maintenance of anxiety disorders and neuroticism uniquely predicted relapse of anxiety disorders, over and above the effect of the other cognitive constructs. Moreover, a latent factor of psychological vulnerability loaded strongly on each of these psychological constructs. This latent factor predicted onset, maintenance and relapse of anxiety disorders. The tendency to frequently experience strong negative emotions, to evaluate these experiences as aversive and to engage in avoidant coping strategies may constitute a transdiagnostic factor predictive of anxiety disorders. Further developing and testing of interventions targeting transdiagnostic construct underlying anxiety and mood disorders seem warranted.


Immunity to avian infectious bronchitis.
Avian infectious bronchitis is recognized clinically as a respiratory disease in its only natural host,the chicken, but the virus is disseminated throughout other systems by a viraemia with localization especially in the kidney and oviduct. The sensitivity or instability of the antigenic and immunogenic properties of the virus under laboratory stress or natural influences complicates the selection of seed virus for vaccines. Modified or attenuated active virus vaccines induce greater protection against subsequent infection than do inactive virus vaccines. Maternal antibody is effective in providing passive immunity for about two weeks after the chick is hatched. Immunoglobulins induced by primary infection or by vaccination are IgG effective for neutralization of virus by circulating antibody, and presumably secretory IgA in the respiratory tract, with the latter being more effective as evidenced by protection of the trachea against reinfection. The level of humoral antibody is not necessarily correlative with immunity based on chicken protection tests against challenge with virulent virus. A true carrier status apparently does not result from primary infection but it has been suggested that the chicken may possibly become an immune carrier.


Single residue substitutions that change the gating properties of a mechanosensitive channel in Escherichia coli.
MscL is a channel that opens a large pore in the Escherichia coli cytoplasmic membrane in response to mechanical stress. Previously, we highly enriched the MscL protein by using patch clamp as a functional assay and cloned the corresponding gene. The predicted protein contains a largely hydrophobic core spanning two-thirds of the molecule and a more hydrophilic carboxyl terminal tail. Because MscL had no homology to characterized proteins, it was impossible to predict functional regions of the protein by simple inspection. Here, by mutagenesis, we have searched for functionally important regions of this molecule. We show that a short deletion from the amino terminus (3 amino acids), and a larger deletion of 27 amino acids from the carboxyl terminus of this protein, had little if any effect in channel properties. We have thus narrowed the search of the core mechanosensitive mechanism to 106 residues of this 136-amino acid protein. In contrast, single residue substitutions of a lysine in the putative first transmembrane domain or a glutamine in the periplasmic loop caused pronounced shifts in the mechano-sensitivity curves and/or large changes in the kinetics of channel gating, suggesting that the conformational structure in these regions is critical for normal mechanosensitive channel gating.


Balbiani ring induction in phosphate metabolism.
Balbiani rings (BR), giant puffs in Chironomus larval salivary glands, code for giant secretory proteins. As shown earlier, the normally dominant BR2 is turned off with its putative translation product during exposure of larvae to compounds that diminish the stores of P(i). A BR6 develops from a compact chromosome band, and a new giant protein appears in the secretion as the major component. We have determined the sequence of cloned DNA fragments representative for large parts of BR1 and BR2 (normally active) and the inducible BR6. There is an excess of positive charges and high contents of serine/threonine in the coded amino acid composition for the BR1 and BR2 sequences. The coded amino acid sequence for the BR6 clone shares homologies with the others but has an excess of negative charges and lacks serine/threonine. This suggested that the P(i) effects observed earlier could be related to differences in phosphorylation between the normal proteins and the BR6 product. This could be confirmed by measurements of phosphorylation, which occurs in the normal giant proteins mainly at seryl residues. P export with giant secretory protein is normally quantitatively important. Thus, BR6 activation should decrease P loss when P(i) pools are lowered because of inducer action.


[Update on neurosurgical treatment for obsessive compulsive disorder].
Responses to pharmacotherapy and psychotherapy in obsessive-compulsive disorder (OCD) range from 60 to 80% of cases. However, a subset of OCD patients do not respond to adequately conducted treatment trials, leading to severe psychosocial impairment. Stereotactic surgery can be indicated then as the last resource. Five surgical techniques are available, with the following rates of global post-operative improvement: anterior capsulotomy (38-100%); anterior cingulotomy (27-57%); subcaudate tractotomy (33-67%); limbic leucotomy (61-69%), and central lateral thalamotomy/anterior medial pallidotomy (62.5%). The first technique can be conducted as a standard neurosurgery, as radiosurgery or as deep brain stimulation. In the standard neurosurgery neural circuits are interrupted by radiofrequency. In radiosurgery, an actinic lesion is provoked without opening the brain. Deep brain stimulation consists on implanting electrodes which are activated by stimulators. Literature reports a relatively low prevalence of adverse events and complications. Neuropsychological and personality changes are rarely reported. However, there is a lack of randomized controlled trials to prove efficacy and adverse events/complication issues among these surgical procedures. Concluding, there is a recent development in the neurosurgeries for severe psychiatric disorders in the direction of making them more efficacious and safer. These surgeries, when correctly indicated, can profoundly alleviate the suffering of severe OCD patients.


Inner ear anomaly of three-dimensional computed tomography: computed tomographic attenuation and image changes.
With regard to image diagnosis of inner ear anomalies, three-dimensional computed tomography (3D-CT) is useful in obtaining very realistic images that are unmatched by 2D-CT. Unlike the step scanning in the existing 2D-CT, in helical 3D-CT, scanning is performed in a spiral motion by continuously rotating the scanner and moving the table along the body axis at a constant speed. As a result, data obtained by this CT are continuous and very smooth curves can be obtained. Among the data, the CT attenuation determines the quality of the final 3D images. In the present paper, the usefulness of 3D-CT was investigated in a case with Mondini-type inner ear malformation.


Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations.
To define molecular mechanisms underlying the clinical spectrum of epilepsy and movement disorder in individuals with de novo mutations in the GNAO1 gene. We identified all GNAO1 mutations reported in individuals with epilepsy (early infantile epileptiform encephalopathy 17) or movement disorders through April 2016; 15 de novo mutant alleles from 25 individuals were introduced into the Gαo subunit by site-directed mutagenesis in a mammalian expression plasmid. We assessed protein expression and function in vitro in HEK-293T cells by Western blot and determined functional Gαo-dependent cyclic adenosine monophosphate (cAMP) inhibition with a coexpressed α2A adrenergic receptor. Of the 15 clinical GNAO1 mutations studied, 9 show reduced expression and loss of function (LOF; <90% maximal inhibition). Six other mutations show variable levels of expression but exhibit normal or even gain-of-function (GOF) behavior, as demonstrated by significantly lower EC50 values for α2A adrenergic receptor-mediated inhibition of cAMP. The GNAO1 LOF mutations are associated with epileptic encephalopathy while GOF mutants (such as G42R, G203R, and E246K) or normally functioning mutants (R209) were found in patients with movement disorders with or without seizures. Both LOF and GOF mutations in Gαo (encoded by GNAO1) are associated with neurologic pathophysiology. There appears to be a strong predictive correlation between the in vitro biochemical phenotype and the clinical pattern of epilepsy vs movement disorder.


The relationship between rearfoot, tibial and hip kinematics in individuals with patellofemoral pain syndrome.
Excessive rearfoot eversion is thought to be a risk factor for patellofemoral pain syndrome development, based on theoretical rationale linking it to greater tibial internal rotation and hip adduction. This study aimed to establish the relationship of rearfoot eversion with tibial internal rotation and hip adduction during walking in individuals with and without patellofemoral pain syndrome. Twenty-six individuals with patellofemoral pain syndrome and 20 controls (18-35years) participated. Each underwent instrumented three-dimensional motion analysis during over-ground walking. Pearson's correlation coefficients (r) were calculated to establish the relationship of rearfoot eversion with tibial internal rotation and hip adduction (peak and range of motion). Greater peak rearfoot eversion was associated with greater peak tibial internal rotation in the patellofemoral pain syndrome group (r=0.394, P=0.046). Greater rearfoot eversion range of motion was associated with greater hip adduction range of motion in the patellofemoral pain syndrome (r=0.573, P=0.002) and control (r=0.460, P=0.041) groups; and greater peak hip adduction in the control group (r=0.477, P=0.033). Associations between greater rearfoot eversion and greater hip adduction indicate that interventions targeted at the foot or hip in individuals with patellofemoral pain syndrome may have similar overall effects on lower limb motion and clinical outcomes. The relationship between rearfoot eversion and tibial internal rotation identified in the patellofemoral pain syndrome group may be related to aetiology. However, additional prospective research is needed to confirm this.


Urinary phthalate metabolite concentrations and hot flashes in women from an urban convenience sample of midlife women.
Phthalate exposure is associated with altered reproductive function, but little is known about associations of phthalate exposure with risk of hot flashes. To investigate associations of urinary phthalate metabolite levels with four hot flash outcomes in midlife women. A cross-sectional study of the first year of a prospective cohort of midlife women, the Midlife Women's Health Study (2006-2015), a convenience sample from an urban setting. 728 multi-racial/ethnic pre- and perimenopausal women aged 45-54 years. Women completed questionnaires about hot flash experience and provided 1-4 urine samples over four consecutive weeks that were pooled for analysis. Phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates: ƩPhthalates; DEHP: ƩDEHP), exposure sources (plastics: ƩPlastic; personal care products: ƩPCP), and modes of action (anti-androgenic: ƩAA). Covariate-adjusted logistic regression models were used to assess associations of continuous natural log-transformed phthalate metabolite concentrations with hot flash outcomes. Analyses were conducted to explore whether associations differed by menopause status, body mass index (BMI), race/ethnicity, and depressive symptoms. Overall, 45% of women reported a history of hot flashes. Compared to women who never experienced hot flashes, every two-fold increase in ƩPlastic was associated with 18% (OR: 1.18; 95%CI: 0.98, 1.43) and 38% (OR: 1.38; 95%CI: 1.11, 1.70) higher odds of experiencing hot flashes in the past 30 days and experiencing daily/weekly hot flashes, respectively. Some associations of phthalates with certain hot flash outcomes differed by menopause status, BMI, race/ethnicity, and depressive symptoms. This study suggests that phthalates are associated with hot flash experience and may impact hot flash risk in women who are susceptible to experiencing hot flashes.


Robotic Total Pancreatectomy: A Novel Pancreatic Head-First Approach (with Video).
The development of the Da Vinci robotic platform has drastically altered the paradigm of minimal invasive pancreatic surgery. However, the evidence of robotic total pancreatectomy (RTP) is still limited. Here we report an alternative approach of RTP, starting with pancreatoduodenectomy (the pancreatic head-first approach). The patient was a 55-year-old female with a diagnosis of diffuse PNET in the head, body, and tail of the pancreas. The da Vinci Xi robotic system was used for RTP. Our technique of RTP consists of three steps: (1) pancreatoduodenectomy, (2) (en bloc) distal pancreatectomy, and (3) reconstructions. The operative time was 490 min with an estimated blood loss of 100 ml. The postoperative course was uneventful, and the patient was discharged on postoperative day 10. RTP is a technically challenging procedure; however, the pancreatic head-first approach of RTP has several advantages.


Habitat degradation increases stress-hormone levels during the breeding season, and decreases survival and reproduction in adult common lizards.
The allostatic load model describes how individuals maintain homeostasis in challenging environment and posits that costs induced by a chronic perturbation (i.e., allostatic load) are correlated to the secretion of glucocorticoids, such as corticosterone. Habitat perturbations from anthropogenic activities are multiple and functional responses to those are still unclear. Here, we manipulated the habitat quality in 24 semi-natural populations of the common lizard during 1 year. We tested the predictions of the allostatic load model that habitat degradation should increase baseline corticosterone levels, and should induce concomitant physiological changes, such as lipid mobilization and lower immunocompetence, and demographic changes, such as lower body growth, survival and/or reproductive performances. Our results highlight stage-dependent effects of habitat degradation on physiological traits during the breeding season: adult lizards had higher baseline corticosterone levels and yearling lizards had a lower inflammatory response than adults, whereas juveniles had higher circulating lipid levels than yearlings and adults without concomitant change in corticosterone levels. In addition, habitat degradation reduced the performances of adults but not of juveniles: in low habitat quality populations, adult males had a lower survival and females had a smaller fecundity. These results are in accordance with the allostatic load model given that allostatic load was detected only during the season and in life stages of maximal energy expenditure. This underlines the importance to account for individual energy requirements to better understand demographic responses to habitat perturbation.


Recommendations for optimization of fortified and blended food aid products from the United States.
Fortified blended foods (FBFs) were introduced into the Food for Peace program (also known as US Public Law 480) in the 1960s. Minimal changes have since been made to their formulations. A Food Aid Quality Enhancement Project to assess the nutritional adequacy of FBFs for vulnerable populations was conducted, and the findings indicate that FBFs do not meet the nutritional needs of infants and young children between the ages of 6 and 24 months. Improvements are also needed for FBFs intended for school-aged children and adults. Two separate products would better meet the varying nutritional needs of diverse groups of beneficiaries. Proposed here is a two-step strategy for better addressing the needs of today's food aid beneficiaries: 1) improving FBFs for general distribution to households, schools, and emergency settings, with potential efficiencies gained in manufacturing and formulation to reduce costs; 2) developing new products for infants and young children, which would deliver the nutrient density required for growth and development.


Determining salt concentrations for equivalent water activity in reduced-sodium cheese by use of a model system.
The range of sodium chloride (salt)-to-moisture ratio is critical in producing high-quality cheese products. The salt-to-moisture ratio has numerous effects on cheese quality, including controlling water activity (a(w)). Therefore, when attempting to decrease the sodium content of natural cheese it is important to calculate the amount of replacement salts necessary to create the same a(w) as the full-sodium target (when using the same cheese making procedure). Most attempts to decrease sodium using replacement salts have used concentrations too low to create the equivalent a(w) due to the differences in the molecular weight of the replacers compared with salt. This could be because of the desire to minimize off-flavors inherent in the replacement salts, but it complicates the ability to conclude that the replacement salts are the cause of off-flavors such as bitter. The objective of this study was to develop a model system that could be used to measure a(w) directly, without manufacturing cheese, to allow cheese makers to determine the salt and salt replacer concentrations needed to achieve the equivalent a(w) for their existing full-sodium control formulas. All-purpose flour, salt, and salt replacers (potassium chloride, modified potassium chloride, magnesium chloride, and calcium chloride) were blended with butter and water at concentrations that approximated the solids, fat, and moisture contents of typical Cheddar cheese. Salt and salt replacers were applied to the model systems at concentrations predicted by Raoult's law. The a(w) of the model samples was measured on a water activity meter, and concentrations were adjusted using Raoult's law if they differed from those of the full-sodium model. Based on the results determined using the model system, stirred-curd pilot-scale batches of reduced- and full-sodium Cheddar cheese were manufactured in duplicate. Water activity, pH, and gross composition were measured and evaluated statistically by linear mixed model. The model system method accurately determined the concentrations of salt and salt replacer necessary to achieve the same a(w) as the full-sodium control in pilot-scale cheese using different replacement salts.


Frequency-dependent conspecific attraction to food patches.
In many ecological situations, resources are difficult to find but become more apparent to nearby searchers after one of their numbers discovers and begins to exploit them. If the discoverer cannot monopolize the resources, then others may benefit from joining the discoverer and sharing their discovery. Existing theories for this type of conspecific attraction have often used very simple rules for how the decision to join a discovered resource patch should be influenced by the number of individuals already exploiting that patch. We use a mechanistic, spatially explicit model to demonstrate that individuals should not necessarily simply join patches more often as the number of individuals exploiting the patch increases, because those patches are likely to be exhausted soon or joining them will intensify future local competition. Furthermore, we show that this decision should be sensitive to the nature of the resource patches, with individuals being more responsive to discoveries in general and more tolerant of larger numbers of existing exploiters on a patch when patches are resource-rich and challenging to locate alone. As such, we argue that this greater focus on underlying joining mechanisms suggests that conspecific attraction is a more sophisticated and flexible tactic than currently appreciated.


Esophageal atresia, tracheomalacia and arterial compression: role of aortopexy.
Between 1985 and 1990, we treated 46 cases of esophageal atresia in the pediatric surgery department in Marseille. In 17 of these patients atresia was associated with tracheomalacia. The most common respiratory manifestations were acute apneic attacks, cyanotic spells and recurring pneumopathy. The underlying cause was arterial compression of the airways by the innominate artery in 6 cases, the aortic arch in 2 cases, and a common origin of the innominate and left carotid arteries in 2 cases. Eleven patients underwent surgery to relieve arterial compression: suspension of the aorta from the under surface of the sternum (10 cases) and reimplantation of the innominate artery (1 case). Results in terms of tracheal caliber and symptomatic relief were excellent in 10 cases including 1 case requiring redo, and poor in 1 case. For diagnosis, our experience shows the importance of endoscopy, nuclear magnetic resonance and recognition of gastroesophageal reflux which is often associated (9/11). The role of tracheomalacia is discussed. On the basis of our results and those previously reported, aortopexy appears to be an effective surgical technique in patients with esophageal atresia presenting respiratory complications due to arterial compression.


Pain control.
There are two components to the perception of pain; the 'sensory' and the 'reactive'. Psychological factors control the latter. Pain research is rapidly advancing: the discovery of endorphins and opioid receptors, the appreciation of the psychological component of pain and the multidisciplinary approach to chronic pain are major advances. Pain can be classified as acute or chronic. Acute pain is easy to diagnose, the cause of pain obvious and the treatment logical, chronic pain has a greater psychological component, is difficult to diagnose and treatment is often empirical. Methods of pain control include drugs, injection techniques, electro stimulation, non invasive therapies, denervation procedures and palliative procedures. A multidisciplinary approach and a combination of methods is necessary to treat chronic pain. Spinal opioids, radiofrequency thermocoagulation, intrapleural bupivacaine, cryoanalgesia and patient controlled analgesia are recent advances in pain control. However, most pain can be controlled adequately with simple methods; what is essential is the interest and commitment of the physician towards achieving optimum therapeutics.


Insights and advances in chronic urticaria: a Canadian perspective.
In the past few years there have been significant advances which have changed the face of chronic urticaria. In this review, we aim to update physicians about clinically relevant advances in the classification, diagnosis and management of chronic urticaria that have occurred in recent years. These include clarification of the terminology used to describe and classify urticaria. We also detail the development and validation of instruments to assess urticaria and understand the impairment on quality-of-life and the morbidity caused by this disease. Additionally, the approach to management of chronic urticaria now focuses on evidence-based use of non-impairing, non-sedating H1-antihistamines given initially in standard doses and if this is not effective, in up to 4-fold doses. For urticaria refractory to H1-antihistamines, omalizumab treatment has emerged as an effective, safe option.


Demographic factors associated with joint supplement use in dogs from the Dog Aging Project.
Osteoarthritis (OA) is one of the most prevalent age-related chronic conditions that afflict companion dogs, and multiple joint supplements are available to prevent or treat OA, though the efficacy of these treatments is controversial. While the demographic factors that are associated with OA diagnosis are well established, the factors that are associated with joint supplement use are not as well studied. Using data collected from the Dog Aging Project, we analyzed owner survey responses regarding joint supplement administration and OA diagnosis for 26,951 adult dogs. In this cross-sectional analysis, logistic regression models and odds-ratios (OR) were employed to determine demographic factors of dogs and their owners that were associated with joint supplement administration. Forty percent of adult dogs in our population were given some type of joint supplement. Perhaps not surprisingly, dogs of older age, larger size, and those that were ever overweight were more likely to receive a joint supplement. Younger owner age, urban living, owner education, and feeding commercial dry food were associated with a reduced likelihood of administration of joint supplements to dogs. Interestingly, mixed breed dogs were also less likely to be administered a joint supplement (OR: 0.73). Dogs with a clinical diagnosis of OA were more likely to receive a joint supplement than those without a reported OA diagnosis (OR: 3.82). Neutered dogs were more likely to have a diagnosis of OA, even after controlling for other demographic factors, yet their prevalence of joint supplement administration was the same as intact dogs. Overall, joint supplement use appears to be high in our large population of dogs in the United States. Prospective studies are needed to determine if joint supplements are more commonly administered as a preventative for OA or after an OA clinical diagnosis.


[Current treatment strategies for sigmoid diverticulitis].
Treatment of colonic diverticular disease has evolved over the past years. Most episodes are simple and can be successfully treated with antibiotics alone. For complicated diverticulitis, a strong trend is developing towards less invasive therapies including interventional radiology and laparoscopic lavage in an effort to avoid the morbidity and discomfort of a diverting colostomy. Based on a better understanding of the natural history of the disease, the indication to prophylactic colectomy after a few episodes of simple diverticulitis has been seriously challenged. For those patients who need a colectomy, single port laparoscopy, NOTES and transanal specimen extraction are being proposed. However larger studies are needed to confirm the hypothetical advantages of these evolving techniques.


Regulation of hepatic synthesis and secretion of cholesterol and glycerolipids in animals maintained in different nutritional states.
The distribution of newly synthesized and exogenous fatty acids and of newly synthesized cholesterol between cellular and very-low-density lipoprotein (VLDL) lipids was studied in hepatocytes derived from animals fed on a normal diet or on diets supplemented with polyunsaturated fat or sucrose. Phospholipid synthesis from either exogenous or endogenous (biosynthetic) fatty acids was unaffected by nutritional state. Cholesterol synthesis was decreased in the fat-fed animals, but sucrose feeding had no significant effect. In all nutritional states, newly synthesized rather than exogenous fatty acids were better substrates for phospholipid synthesis. In all groups, compared with newly synthesized triacylglycerol, smaller proportions of newly synthesized phospholipid and cholesterol were secreted as VLDLs. This was confirmed in intact animals by using Triton WR-1339. Newly synthesized phospholipid formed a greater proportion of the VLDL glycerolipid in the fat-fed than in the normal or sucrose-fed animals. In all groups, phospholipids labelled from endogenous fatty acids were secreted in preference to those labelled from exogenous fatty acids.


Dysgeusia related to urinary obstruction from benign prostatic disease: a case control and qualitative study.
Anecdotal reports suggest that dysgeusia may be related to a variety of systemic factors, including bladder outflow obstruction. This is a hospital-based case-controlled study involving 111 patients who were admitted to urological wards for transurethral resection of the prostate for benign prostatic disease with age- and sex-matched control of 137 subjects. We used a semi-structured questionnaire by a trained interviewer at admission (preoperative), at the postoperative period and at follow-up between 4-6 months (median 5 months). Analysis used unpaired t-test and chi(2) test. The incidence of dysgeusia was 22% in the study group and 13% in the control group (P=N.S.). However, strikingly, the dysgeusia in the study group was relieved promptly by relief of urinary obstruction in 100% of cases and did not return within the follow-up period. The mechanism of the dysgeusia associated with dysuria in benign prostatic disease is unknown, but we suggest that the dysgeusia could be from the stress of dysuria or due to a release of an unknown chemical from the urinary tract or an overflow of neural impulse from pontine/cortical micturition centres to the taste centres. An association between dysgeusia and dysuria has not been described before.


Favorable Adaptation during SARS-CoV-2-Pandemic as Told by Student-Athletes-A Longitudinal and Behavioral Study.
(1) Background: The aim was to explore the impact of adaptive responses (resilience factors) on student-athletes' behaviors during a stressful period of life during the SARS-CoV-2-pandemic of 2020 and 2021. (2) Methods: A constructivist-based grounded theory (CGT) was used guided by a biopsychosocial approach. Based on purposeful sampling, 22 male and female student-athletes were divided into four focus group interviews (FGI) seven months after the outbreak of the SARS-CoV-2-pandemic (October 2020) and 18 of these were followed up by FGI seven months later (May 2021). The mean age was 17.65 and they represented golf and handball. (3) Results: The CGT contained four main categories seven months after the SARS-CoV-2-pandemic outbreak: Social support, Self-discipline, Physical practice and recovery and Management of everyday life. Fourteen months after the SARS-CoV-2-pandemic outbreak, four additional main categories emerged: More extensive social support, Belief in the future, Self-awareness and Responsibility and problem-solving. (4) Conclusions: The CTG suggests that student-athletes' favorable adaptations to the stressful SARS-CoV-2-pandemic period 2020-2021 are based on a gradually developed ability to take responsibility for one's own actions, insight into the importance of deepened social interaction, belief in a positive post-COVID future and increased awareness of physical activity and its relation to perceived health.


LCAT Enzyme Replacement Therapy Reduces LpX and Improves Kidney Function in a Mouse Model of Familial LCAT Deficiency.
Familial LCAT deficiency (FLD) is due to mutations in lecithin:cholesterol acyltransferase (LCAT), a plasma enzyme that esterifies cholesterol on lipoproteins. FLD is associated with markedly reduced levels of plasma high-density lipoprotein and cholesteryl ester and the formation of a nephrotoxic lipoprotein called LpX. We used a mouse model in which the LCAT gene is deleted and a truncated version of the SREBP1a gene is expressed in the liver under the control of a protein-rich/carbohydrate-low (PRCL) diet-regulated PEPCK promoter. This mouse was found to form abundant amounts of LpX in the plasma and was used to determine whether treatment with recombinant human LCAT (rhLCAT) could prevent LpX formation and renal injury. After 9 days on the PRCL diet, plasma total and free cholesterol, as well as phospholipids, increased 6.1 ± 0.6-, 9.6 ± 0.9-, and 6.7 ± 0.7-fold, respectively, and liver cholesterol and triglyceride concentrations increased 1.7 ± 0.4- and 2.8 ±0.9-fold, respectively, compared with chow-fed animals. Transmission electron microscopy revealed robust accumulation of lipid droplets in hepatocytes and the appearance of multilamellar LpX particles in liver sinusoids and bile canaliculi. In the kidney, LpX was found in glomerular endothelial cells, podocytes, the glomerular basement membrane, and the mesangium. The urine albumin/creatinine ratio increased 30-fold on the PRCL diet compared with chow-fed controls. Treatment of these mice with intravenous rhLCAT restored the normal lipoprotein profile, eliminated LpX in plasma and kidneys, and markedly decreased proteinuria. The combined results suggest that rhLCAT infusion could be an effective therapy for the prevention of renal disease in patients with FLD.


Calcium hydroxide dressing residues after different removal techniques affect the accuracy of Root-ZX apex locator.
This study compared the ability of several techniques to remove calcium hydroxide (CH) from the root canal and determined the influence of CH residues on the accuracy of the electronic apex locator. Root canals of 90 human maxillary lateral incisors with confirmed true working length (TWL) were prepared and filled with CH. The teeth were randomly assigned to one of the experimental groups according to the CH removal technique (n = 14): 0.9% saline; 0.9% saline + master apical file (MAF); 17% ethylenediamine tetraacetic acid (EDTA); 17% EDTA + MAF; 5.25% sodium hypochlorite (NaOCl); 5.25% NaOCl + MAF. Six teeth were used as negative control. After CH removal, the electronic working length was measured using Root-ZX (Morita Corp.) and compared with TWL to evaluate Root-ZX accuracy. All specimens were sectioned longitudinally, and the area of remaining CH (CH) and total canal area were measured using imaging software. The EDTA + MAF and NaOCl + MAF groups showed better CH removal than other groups (p < 0.05). Root-ZX reliability to prevent overestimated working length to be > 85% within a tolerance of ± 1.0 mm (p < 0.05). There was strong negative correlation between amount of CH residues and EAL accuracy (r = -0.800 for ± 0.5 mm; r = -0.940 for ± 1.0 mm). The mechanical instrumentation improves the CH removal of irrigation solutions although none of the techniques removed the dressing completely. Residues of CH medication in root canals affected the accuracy of Root-ZX adversely.


An essential role for Polycomb Repressive Complex 2 in the mouse ovary.
Polycomb repressive complex 2 (PRC2) catalyses the repressive epigenetic modification of histone 3 lysine 27 tri-methylation (H3K27me3) and functions as a key epigenetic regulator during embryonic development. PRC2 is known to regulate the development of a range of tissues by transcriptional silencing of genes that control cell differentiation, but its roles in female germline and ovarian development remain unknown. Using a mouse model with hypomorphic embryonic ectoderm development (EED) function that reduced H3K27me3 in somatic and germ cells, we found that PRC2 was required for survival, with more than 95% of female animals dying before birth. Although surviving adult EED hypomorphic females appeared morphologically similar to controls and were fertile, Eedhypo/hypo adult ovaries were abnormal, with altered morphology characterised by abnormal follicles. Early Eedhypo/hypo and control fetal ovaries were morphologically similar, and germ cells entered meiosis normally. Immunofluorescent analyses of somatic and germline markers indicated that ovarian development in Eedhypo/hypo ovaries was similar to heterozygous and WT controls. However, TUNEL analyses revealed higher rates of apoptosis in the ovarian surface epithelium, and transcriptional analyses revealed changes in genes regulating epithelial and steroidogenic cell differentiation, possibly foreshadowing the defects observed in adult ovaries of hypomorphic females. While it was possible to analyse early-mid fetal ovarian development, postnatal stages were inaccessible due to the high level of lethality during late fetal stages. Despite this limitation, the data we were able to obtain reveal a novel role for EED in the ovary that is likely to alter ovarian development and ovarian function in adult animals.


The Importance of Accounting for Movement When Relating Neuronal Activity to Sensory and Cognitive Processes.
A surprising finding of recent studies in mouse is the dominance of widespread movement-related activity throughout the brain, including in early sensory areas. In awake subjects, failing to account for movement risks misattributing movement-related activity to other (e.g., sensory or cognitive) processes. In this article, we (1) review task designs for separating task-related and movement-related activity, (2) review three "case studies" in which not considering movement would have resulted in critically different interpretations of neuronal function, and (3) discuss functional couplings that may prevent us from ever fully isolating sensory, motor, and cognitive-related activity. Our main thesis is that neural signals related to movement are ubiquitous, and therefore ought to be considered first and foremost when attempting to correlate neuronal activity with task-related processes.


[Detection of cytomegalovirus antibody activity in intravenous preparations of immunoglobulins with parallel-line method].
The study demonstrated a possibility to detect specific anti-CMV antibody activity in intravenous preparations of immunoglobulins by qualitative immunoenzyme analysis using parallel-line method. Independently of production technology, specificity, and the activity level, the preparations had a dose-response curve that was parallel to that of a standard sample with five-point linearity at double-step dilution. This makes it possible to use the test system DS-ELISA-ANTI-CMV-G to detect anti-CMV antibody activity in ready-for-use preparations.


Salmochelin, the long-overlooked catecholate siderophore of Salmonella.
Salmochelin is a C-glucosylated enterobactin produced by Salmonella species, uropathogenic and avian pathogenic Escherichia coli strains, and certain Klebsiella strains. It was the first glucosylated siderophore described. The glucosylation has been interpreted as a bacterial evasion mechanism against the mammalian catecholate siderophore-binding protein siderocalin (NGAL-lipocalin). The synthesis, excretion, and uptake of salmochelin requires five genes, iroBCDEN, and also the enterobactin biosynthesis and utilization system. Some salmochelin-producing strains also secrete microcins, which possess a C-terminal, linear glucosyl-enterobactin moiety. These microcins recognize the catecholate siderophore receptors IroN, Cir, Fiu, and FepA, and may inhibit the growth of competitors for catecholate siderophores.


Percutaneous image-guided sternal biopsy: a cross-institutional retrospective review of diagnostic yield and safety in 50 cases.
Image-guided sternal biopsy may be technically daunting given the immediately subjacent critical structures. There is a paucity of literature describing technique, safety, and efficacy. This study aims to quantify the diagnostic yield and safety of image-guided sternal biopsies. Secondary aims include (1) describing the preferred approach/technique and (2) identifying imaging features and disease entities associated with higher and lower diagnostic yields. A retrospective review of 50 image-guided sternal biopsies performed at two quaternary care centers from 2000 to 2019 was performed. Recorded lesion-related variables included as follows: location, density, extraosseous extension, and size. Recorded variables from electronic medical records included as follows: patient demographics, histologic or microbiological diagnosis, and complications. Recorded technique-related variables included as follows: needle obliquity, type, and gauge; biopsy core number and length; and modality. Of the 50 biopsies, 88.0% resulted in a definitive histologic diagnosis. Six biopsies were non-diagnostic. The majority of biopsies were performed under computed tomography (88.0%), followed by ultrasound (12.0%). Tumor was the most common biopsy indication (90.0%), followed by infection (10.0%). Of the diagnostic biopsies indicated for tumor, 88.9% were malignant. Seventy-four percent of the lesions were predominantly lytic. Fifty percent of lesions had extraosseous extension. Lesion locations were as follows: manubrium (48.0%), sternal body (48.0%), and sternomanubrial joint (4.0%). No minor or major, acute, or delayed procedure-related complications were encountered. Image-guided sternal biopsy is an efficacious and safe method of obtaining a definitive histologic diagnosis regardless of lesion-specific features or location.