The SAPHO syndrome: a single-center study of 41 adult patients.
The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) is a rare disease and only a few series have been published about it. We describe the experience of a rheumatology department with a focus on the therapeutic aspects. All cases of SAPHO fulfilling the Benhamou criteria and seen between 1992 and 2013 in our unit were retrospectively included. Forty-one patients (11 men and 30 women) were included. The average age was 45 years (20-80 yrs) at the time of diagnosis. Nineteen patients had palmoplantar pustulosis, 3 had psoriasis vulgaris, 3 had severe acne, and 15 had no dermatological involvement. Bone symptoms involved mainly the anterior chest wall (n = 28, 68%), followed by the spine (n = 16, 39%) and sacroiliac joints (n = 12, 29%). Four patients had peripheral osteitis and 2 had mandibular osteitis. Ten patients had peripheral arthritis affecting mainly the knees and wrists. None of the 36 patients tested was HLA-B27-positive. At least a partial response was achieved with colchicine, methotrexate, or sulfasalazine in 0/6, 2/4, and 1/6 of patients, respectively. Antibiotic therapy (azithromycin, n = 7; doxycycline, n = 2) was effective in 2/9 patients. Pamidronate was prescribed in 26 patients with bone involvement and 18/22 patients evaluable at 6 months responded to this therapy. Two patients were treated with tumor necrosis factor blockers: 1 with infliximab and 1 with adalimumab, followed by etanercept. Based on our experience, SAPHO can be diagnosed in the elderly. It was not associated with HLA-B27. Soft tissue involvement was common and the bisphosphonates were generally effective on bone involvement.


Transcriptional profiling of polycythemia vera identifies gene expression patterns both dependent and independent from the action of JAK2V617F.
To understand the changes in gene expression in polycythemia vera (PV) progenitor cells and their relationship to JAK2V617F. Messenger RNA isolated from CD34(+) cells from nine PV patients and normal controls was profiled using Affymetrix arrays. Gene expression change mediated by JAK2V617F was determined by profiling CD34(+) cells transduced with the kinase and by analysis of leukemia cell lines harboring JAK2V617F, treated with an inhibitor. A PV expression signature was enriched for genes involved in hematopoietic development, inflammatory responses, and cell proliferation. By quantitative reverse transcription-PCR, 23 genes were consistently deregulated in all patient samples. Several of these genes such as WT1 and KLF4 were regulated by JAK2, whereas others such as NFIB and EVI1 seemed to be deregulated in PV by a JAK2-independent mechanism. Using cell line models and comparing gene expression profiles of cell lines and PV CD34(+) PV specimens, we have identified panels of 14 JAK2-dependent genes and 12 JAK2-independent genes. These two 14- and 12-gene sets could separate not only PV from normal CD34(+) specimens, but also other MPN such as essential thrombocytosis and primary myelofibrosis from their normal counterparts. A subset of the aberrant gene expression in PV progenitor cells can be attributed to the action of the mutant kinase, but there remain a significant number of genes characteristic of the disease but deregulated by as yet unknown mechanisms. Genes deregulated in PV as a result of the action of JAK2V617F or independent of the kinase may represent other targets for therapy.


Opt-out bloodborne virus screening: a cross-sectional observational study in an acute medical unit.
Recent treatment developments for HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV) have greatly improved prognoses. Current screening practices are mainly risk based and are suboptimal. Improved efforts are critically needed to identify persons with these viruses. The aims of this study were to assess the feasibility of an opt-out bloodborne virus (BBV) screening programme in an acute medical unit (AMU) and to describe the prevalence of HIV, HBV and HCV in this population. This was a cross-sectional observational study in the AMU of a tertiary referral hospital in Galway, a city in the west of Ireland. 1936 patients entered the study; 54% were male, mean age was 53.1 years (SD 19.6). During the study period, all patients attending the AMU aged ≧16 years who were having bloods drawn and who had the ability to verbally consent for an additional blood sample met the inclusion criteria for the study. Over 44 weeks, 1936/4793 (40.4%) patients consented to BBV panel testing. Diagnosed prevalence rates for HIV, HBV and HCV were 0.5/1000, 2/1000 and 1.5/1000, respectively. There was one HIV-positive result; the patient was already engaged in care. Four patients tested positive for HBV surface antigen; one new diagnosis, one previously lost to follow-up and two already engaged in care. Three patients had active HCV infection; two had been lost to follow-up and are now linked back into services. BBV testing uptake of 40.4% is higher than previous studies in AMU settings that used opt-in strategies, but lower than expected, possibly due to not incorporating testing into routine practice. The diagnosed prevalence of HBV is notable as little data currently exist about its prevalence in Ireland. These data are valuable in order to inform further prevention strategies for these infections in low-prevalence settings.


[Occurrence characteristics and molecular genetic basis of pod shattering in soybean].
Pod shattering is a natural property of wild soybean (Glycine soja) for propagation and also a major cause of yield loss in cultivated soybean (Glycine max L. Merr). Thus, studies on occurrence characteristics and molecular genetic basis of pod shattering in soybean can provide insights into both molecular mechanisms and potential application in legume crop improvement. In this review, we summarize the occurrence features and phenotypic identification methods of pod shattering based on analysis of the cellular microstructure of shattering-resistant soybean pod. We also introduced the identification and breeding of shattering-resistant germplasms, the progress of molecular genetic studies on shattering-resistant phenotype in soybean as well as perspectives on future studies of pod-shattering trait and application in crop improvement.


Specialist health visitor-led weight management intervention in primary care: exploratory evaluation.
This paper is a report of an exploratory study to evaluate the effectiveness and acceptability of a specialist health visitor-led weight management clinic in primary care. Tackling obesity is a global health priority. Whilst there is evidence to support a role for primary healthcare professionals in its management, provision in England varies widely. Using designated 'obesity specialists' is an approach warranting further investigation. In 2003-2004, patients with a body mass index of 30 or more received a specialist health visitor-led intervention based on the Jan Felgens 'I2E2' model. Clinical outcome data and self-reported dietary consumption data were collected at weeks 1, 13, 27 and 52. Quantitative and qualitative data on patient acceptability of the clinic were collected at week 26. Eighty-nine patients attended the clinic. Mean body weight and body mass index and systolic and diastolic blood pressure decreased over time by statistically significant amounts. There was a non-significant decrease in fasting blood sugar over time, but approximately one in 10 patients with undiagnosed diabetes were identified. No statistically significant change was evident for cholesterol levels. Mean self-reported weekly consumption of cakes, desserts and snacks decreased and that of fruit and vegetables increased, each by statistically significant amounts. Participants found the clinic highly acceptable and identified the specialist health visitor as fundamental to its success. A partnership approach to weight management through which patients are empowered to make sustainable lifestyle changes now needs to be tested in a multi-centre randomized controlled trial.


A Comparative In Vitro Sensitivity Study of "Ceftriaxone-Sulbactam-EDTA" and Various Antibiotics against Gram-negative Bacterial Isolates from Intensive Care Unit.
A rapid increase in multidrug-resistant (MDR) strains is being seen across the globe especially in the Southeast Asian region, including India. Carbapenems and colistin form the mainstay of treatment against gram-negative pathogens, especially extended-spectrum beta-lactamase (ESBL)- and metallo-beta-lactamse (MBL)-producing isolates. However, due to increased resistance to carbapenems and toxicity of colistin, especially in intensive care units (ICUs), carbapenem-sparing antibiotics like ceftriaxone-sulbactam-EDTA (CSE) combination needs to be evaluated. Bacterial isolates cultured from various clinical samples from all ICUs for a period of 9 months were evaluated. Bacterial identification was performed by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) and antibiotic susceptibility testing were performed by disk diffusion and E test method. Antibiogram of various antibiotics was noted. Extended-spectrum beta-lactamase- and MBL-producing bacteria were identified by phenotypic methods. Antibiotic sensitivity results of CSE were compared with the comparator drugs like colistin, carbapenems, and tigecycline in Enterobacteriaceae, Acinetobacter spp., and Pseudomonas spp. along with ESBL and MBL producers. A total of 2,760 samples of blood, cerebrospinal fluid (CSF), respiratory samples, tissue, and pus were collected from ICUs with maximum isolates from pus (37%) followed by respiratory samples (31%) and blood (27%). Escherichia coli and Klebsiella pneumoniae were the predominant gram-negative pathogens accounting for 56% of the isolates followed by Acinetobacter spp. (23%) and Pseudomonas spp. (15%). Extended-spectrum beta-lactamase screening was positive for 57% (1,069/1,877) isolates; whereas 43% (732/1,877) were MBL producers. According to the antibiotic susceptibility results, CSE was the most effective antibiotic showing 94% sensitivity for carbapenem-sensitive Enterobacteriaceae and 97% for carbapenem-resistant Acinetobacter and Pseudomonas spp. Among the other drugs, colistin was found to be the most effective showing almost 95% sensitivity in both the Enterobacteriaceae and non-Enterobacteriaceae group (both ESBL + OXA/NDM). Ceftriaxone-sulbactam-EDTA was also found much more effective (95%) as compared to Colistin (89%) toward ESBL- and MBL-producing strains of Enterobacteriaceae and non-Enterobacteriaceae group. Among the carbapenems, imipenem was the most effective drug against Enterobacteriaceae showing 34% sensitivity and ertapenem proved to be least effective. In our present study, CSE emerged as a potent antibacterial agent against MDR gram-negative infections; both for ESBL as well as MBL producers. Hence, in light of present study, we strongly recommend inclusion of CSE in routine sensitivity panel and may be used as a carbapenem- and colistin-sparing drug and a promising option against ESBL and MBL producers especially in ICU. Singh S, Sahu C, Patel SS, Singh A, Yaduvanshi N. A Comparative In Vitro Sensitivity Study of "Ceftriaxone-Sulbactam-EDTA" and Various Antibiotics against Gram-negative Bacterial Isolates from Intensive Care Unit. Indian J Crit Care Med 2020;24(12):1213-1217.


Diet quality in middle-aged and older women with and without body weight dissatisfaction: results from a population-based national nutrition survey in Switzerland.
Body weight dissatisfaction is associated with unhealthy dietary behaviours in young adults, but data are scarce regarding how this relationship evolves with age. The objectives of the present study were to assess the prevalence of body weight dissatisfaction and the association between body weight dissatisfaction, nutrient intake and diet quality in middle-aged and older women. We used data of a population-based sample of 468 middle-aged (50-64 y/o) and older (65-75 y/o) women, extracted from the cross-sectional 2014-15 Swiss National Nutrition Survey. Body weight dissatisfaction was assessed by questionnaire. Dietitians assessed dietary intakes using two non-consecutive computer-assisted multi-pass 24-h dietary recalls and performed anthropometric measurements. Nutrient intakes were calculated and compared with national dietary guidelines, and diet quality scored with the 2010 Alternate Healthy Eating Index (2010-AHEI). 41⋅1 % of women reported body weight dissatisfaction, and 49⋅8 % wanted to lose weight. Body weight dissatisfaction was associated with weight loss desire and a higher body mass index (BMI; P < 0⋅001). Women with body weight dissatisfaction consumed significantly less carbohydrates and dietary fibres, even when BMI was controlled for (P < 0⋅05). They also fell short of national dietary guidelines for magnesium and iron. Body weight dissatisfied women obtained lower 2010-AHEI scores than satisfied women (β -4⋅36, 95 % CI -6⋅78, -1⋅93). However, this association disappeared when the BMI was introduced in the equation. This highlights the importance of targeting both body dissatisfaction and unhealthy eating in obesity prevention and treatment at all ages.


Evaluation of efficacy of entomopathogenic nematodes against larvae of Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae).
The blowfly Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae) is the primary agent of cutaneous myiasis of sheep in northern Europe, southern Africa, Australia and New Zealand. As the application of chemicals has several disadvantages, alternative control measures of traumatic myiasis of livestock must be developed. In this study, the use of entomopathogenic nematodes (EPNs) as potential biocontrol agents against second instar larvae of Lucilia sericata was considered. The following nematode species were tested: Heterorhabditis bacteriophora (IS 5, HHU 1, Hmol, HNC 1, HAZ 36, Hbrecon, HHU 2, HAZ 29, HHP 88, HHU 3, HHU 4 and HGua), Steinernema intermedia, NC513 strain of S. glaserii, S. anomali, S. riobrave, Steinernema sp. and 5 strains of S. feltiae (22, Vija Norway, HU 1, scp, and IS 6). None of the examined EPN species or strains showed larvicidal efficacy at 37 degrees C (no killing effect was observed in the case of the two heat-tolerant strains--H. bacteriophora and S.feltiae) against L. sericata larvae. At lower temperatures (20 degrees C and 25 degrees C) only strains of S. feltiae were found to be active. The overall odds ratios calculated for L. sericata maggots to contract S. feltiae nematode infection show significant (p < 0.05) effect only in the case of strains HU 1, 22 and IS 6. In the case of strains HU 1 and 22 parasitic forms of S. feltiae could be detected in the dead larvae of L. sericata. Strain IS 6 (and also Vija Norway at 20 degrees C) penetrated and killed fly larvae, but only adult forms of the nematode occurred in the cadavers.


TNF-α antagonism with etanercept enhances penile NOS expression, cavernosal reactivity, and testosterone levels in aged rats.
Erectile dysfunction (ED) has been reported to be associated with inflammation. This study investigated the effects of tumor necrosis factor alpha (TNF-α) inhibitor etanercept on penile neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) expressions, testosterone concentrations, neurogenic and endothelium-dependent relaxations of corpus cavernosum (CC), and circulating and cavernosal levels of inflammatory markers in aged rats. Animals were separated into control, aged, and etanercept-treated aged groups. Aged rats displayed significantly increased serum and cavernosal TNF-α, C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule (ICAM-1) levels, and decreased penile nNOS and eNOS expressions and serum testosterone levels compared with controls. In etanercept-treated aged group, NOS expressions were similar to that of the control group. The circulating and cavernosal concentrations of TNF-α, CRP, MCP-1, ICAM-1, and testosterone were also normalized by etanercept. Neurogenic and endothelium-dependent relaxant responses significantly decreased in aged rats and etanercept treatment markedly improved these relaxation responses. Our findings indicate that aging decreases penile NOS expression, neurogenic and endothelium-dependent relaxations of CC, and also suppresses serum testosterone levels by inducing inflammatory response that may contribute to the development of ED. TNF-α antagonism may be a novel strategy to treat aging-associated ED.


[Vitamin D and reproductive health].
Vitamin D insufficiency and deficiency in women with infertility is more common than in the population. However, we still do not know the exact mechanisms for the participation of vitamin D in the regulation of reproductive function. The purpose of this study is to analyze actual literature data on the role of vitamin D in the regulation of reproductive system and its influence on using of assisted reproductive technologies for the treatment of infertility. A search was carried out for literary sources published in the NSBI database PubMed, Medline, and others with a search depth of up to 20 years. 135 sources on this topic were studied, of which 54 were included in the analysis. The review presents data obtained in animal studies, in vitro and in clinical studies. Thus, the absence of vitamin D resulted in a dramatical decrease in fertility in both female and male rats and mice, due to the development of hypocalcemia. In vitro studies describe its involvement in the receptive transformation of the endometrium and in the regulation of the immune response during embryo implantation. However, clinical studies often show conflicting results. There is no unequivocal data on the effect of vitamin D levels on spermogram parameters, but a decrease in the pregnancy rate was shown when ovulation was induced in pairs, where a vitamin D deficiency was revealed in men. A meta-analysis published in 2017 showed a decrease in the pregnancy and live birth rate in women with low levels of vitamin D after the use of assisted reproductive technologies (ART). It was not possible to establish whether this decrease depends on oocyte quality or endometrium. There is an opportunity that the effect of vitamin D deficiency on fertility will not come with all forms of infertility. For example, in women with anovulation due to polycystic ovary syndrome, vitamin D deficiency is demonstrated to decrease pregnancy rate in ovulation induction cycles and in ART. Such relationship was not found in women with unexplained infertility.Thus, the role of vitamin D in the pathogenesis of infertility requires further study, as well as the possibilities of therapy in order to increase the effectiveness of infertility treatment methods and assisted reproductive technology programs.


Cell cycle regulators in Drosophila: downstream and part of developmental decisions.
The molecular identification of an evolutionarily conserved set of cell cycle regulators in yeast, Xenopus egg extracts, and vertebrate cell culture has opened up a new perspective for understanding the mechanisms that regulate cell proliferation during metazoan development. Now we can study how the crucial regulators of eukaryotic cell cycle progression, the various cyclin/cdk complexes (for a recent review see Nigg (1995) BioEssays 17, 471-480), are turned on or off during development. In Drosophila, this analysis is most advanced, in particular in the case of the rather rigidly programmed embryonic cell cycles that generate the cells of the larvae. In addition, this analysis has revealed how the mitotic cycle is transformed into an endocycle which allows the extensive growth of larvae and oocytes. In contrast, we know little about cyclin/cdk regulation during the imaginal proliferation that generates the cells of the adult. Nevertheless, we will also consider this second developmental phase with its conspicuous regulative character, because it will be of great interest for the analysis of the molecular mechanisms that integrate growth and proliferation during development.


Time-resolved Assessment of Drying Plants by Brillouin and Raman Spectroscopies.
Raman and Brillouin spectroscopy enable non-invasive assessment of chemical and elastic properties of biomaterials, respectively. In this report, Brillouin micro-spectroscopy was used for the time-resolved analysis of elastic properties of Populus and Geranium leaves, while Raman micro-spectroscopy was employed for the assessment of their chemical variation during drying. Spectroscopic assessment of elastic and chemical properties can improve our understanding of mechano-chemical changes of plants in response to environmental stress and pathogens at the microscopic cellular level. This report demonstrates the potential of multimodal optical sensing and imaging of plants as an emerging technique for the quantitative assessment of agricultural crops.


Numerical schemes for solving and optimizing multiscale models with age of hepatitis C virus dynamics.
Age-structured PDE models have been developed to study viral infection and treatment. However, they are notoriously difficult to solve. Here, we investigate the numerical solutions of an age-based multiscale model of hepatitis C virus (HCV) dynamics during antiviral therapy and compare them with an analytical approximation, namely its long-term approximation. First, starting from a simple yet flexible numerical solution that also considers an integral approximated over previous iterations, we show that the long-term approximation is an underestimate of the PDE model solution as expected since some infection events are being ignored. We then argue for the importance of having a numerical solution that takes into account previous iterations for the associated integral, making problematic the use of canned solvers. Second, we demonstrate that the governing differential equations are stiff and the stability of the numerical scheme should be considered. Third, we show that considerable gain in efficiency can be achieved by using adaptive stepsize methods over fixed stepsize methods for simulating realistic scenarios when solving multiscale models numerically. Finally, we compare between several numerical schemes for the solution of the equations and demonstrate the use of a numerical optimization scheme for the parameter estimation performed directly from the equations.


Longitudinal trends in use and costs of targeted therapies for common cancers in Taiwan: a retrospective observational study.
Some targeted therapies have improved survival and overall quality of cancer care generally, but these increasingly expensive medicines have led to increases in pharmaceutical expenditure. This study examined trends in use and expenditures of antineoplastic agents in Taiwan, and estimated market shares by prescription volume and costs of targeted therapies over time. We also determined which cancer types accounted for the highest use of targeted therapies. This is a retrospective observational study focusing on the utilisation of targeted therapies for treatment of cancer. The monthly claims data for antineoplastic agents were retrieved from Taiwan's National Health Insurance Research Database (2009-2012). We calculated market shares by prescription volume and costs for each class of antineoplastic agent by cancer type. Using a time series design with Autoregressive Integrated Moving Average (ARIMA) models, we estimated trends in use and costs of targeted therapies. Among all antineoplastic agents, use of targeted therapies grew from 6.24% in 2009 to 12.29% in 2012, but their costs rose from 26.16% to 41.57% in that time. Monoclonal antibodies and protein kinase inhibitors contributed the most (respectively, 23.84% and 16.12% of costs for antineoplastic agents in 2012). During 2009-2012, lung (44.64% of use; 28.26% of costs), female breast (16.49% of use; 27.18% of costs) and colorectal (12.11% of use; 13.16% of costs) cancers accounted for the highest use of targeted therapies. In Taiwan, targeted therapies are increasingly used for different cancers, representing a substantial economic burden. It is important to establish mechanisms to monitor their use and outcomes.


Risk factors and clinical outcomes of cytomegalovirus diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation.
This study aims to evaluate the risk factors and prognosis for CMV diseases in hematologic malignancy patients without hematopoietic stem-cell transplantation (HSCT). We performed a case-control study (1:2) between 2012 and 2022. Adults with pathologic-confirmed CMV diseases (n=60) among hematologic malignancy patients were matched and compared to whom without CMV disease. Lymphoma was the most common underlying malignancy, and gastrointestinal tract involvement was the most common CMV disease. In the case group, high-dose steroid administration and transfusion within one month before diagnosis were higher (p<0.001). Steroid administration (aOR=5.78; 95% confidence interval: 1.25-26.68, p=0.024), red blood cell transfusion within one month (aOR=14.63; 2.75-77.76, p=0.002), low BMI (aOR=13.46, 2.07-87.45, p=0.006), and hypoalbuminemia (aOR=26.48, 5.93-118.17, p<0.001) were independent risk factors associated with CMV disease. The 30-day mortality was higher in the case group and CMV disease was significantly associated with all-cause mortality (aOR=14.41, 3.23-64.31, p<0.001). In hematologic malignancy patients without HSCT, risk factors for CMV organ disease included high-dose steroid administration and RBC transfusion within one month, low BMI, and hypoalbuminemia. Overall mortality was significantly higher with CMV disease, and CMV disease occurrence was a significant risk factor for mortality.


Mechanism of hydroxylation at C-22 during the biosynthesis of ecdysteroids in the locust Schistocerca gregaria.
1. The fates of the 22-pro-R and 22-pro-S hydrogen atoms of cholesterol during the biosynthesis of ecdysteroids in the ovaries of Schistocerca gregaria were investigated. 2. Two stereospecifically labelled cholesterol species, obtained by incubating 3R,2R- and 3R,2S-[2-14C, 2-3H]mevalonic acid with rat liver preparations, were administered, in turn, to maturing adult female locusts and the radiolabelled ecdysteroid conjugates isolated from the eggs. Enzymic hydrolysis of the conjugates yielded free ecdysteroids, from which ecdysone was purified. 3. Derivative formation and oxidation at C-22 of both ecdysone samples indicated that the 22-pro-R and 22-pro-S hydrogen atoms of cholesterol were stereospecifically eliminated and retained respectively during ecdysteroid formation. This indicates that C-22 hydroxylation in ecdysone biosynthesis is direct and occurs with retention of configuration.


1H homonuclear editing of rat brain using semiselective pulses.
We have used a semiselective Hahn spin-echo sequence of the form (1331)-tau-(2662)-tau-AQ, delivered by a surface coil to obtain high-resolution 1H NMR spectra from the brains of intact dead rats. This sequence gave suppression of the tissue water resonance by a factor of 80,000 when tau = 68 ms. Delivery of a frequency-selective Dante pulse train to the alpha-CH resonance of lactate at 4.11 ppm, simultaneously with the 2662 refocusing pulse, altered the j-modulation in the spin-coupled beta-CH3 protons. Subtraction of this spectrum from one in which the Dante was ineffective gave an edited spectrum containing only the beta-CH3 resonance of lactate at 1.31 ppm. When the position of the Dante was shifted to 3.78 ppm to selectively invert the alpha-CH protons of alanine, an edited spectrum of alanine was obtained.


Is orthorexic behavior common in the general public? A large representative study in Germany.
Orthorexia is described as a strict, health-oriented eating pattern with clinically significant impairment in everyday life. Its prevalence varied widely in previous studies due to heterogenous assessment procedures. Determinants for the eating pattern and its prevalence have not been investigated in larger representative studies. A population-based telephone survey in Germany was conducted in n = 1007 participants. The Dusseldorf Orthorexia Scale with a cut-off of 30 was used to assess orthorexic behavior. Determinants of orthorexia, including personal BMI, depressive symptoms Patient Health Questionnaire and socio-demographic variables were analyzed in multivariate regression. The prevalence of orthorexic behavior was 6.9%. A higher rate of orthorexic behavior was observed in heavier, less educated, vegetarian and more depressed participants; in multivariate analysis only associations to lower educational attainment, a vegetarian diet and depressive symptoms remained. No gender or age differences were observed. The study results show that orthorexic behavior may indeed by associated with significant strain and psychological distress. Current debates on the criteria of clinical significance of orthorexic behavior call for new instruments and further investigations, to elicit the prevalence of people with orthorexic behavior that classifies as a pathological eating disorder. Level V: descriptive study.


Type 1 reaction, neuritis and disability in leprosy. What is the current epidemiological situation?
Type 1 reaction is one of the major causes of nerve damage in leprosy patients leading to disabilities of varying severity. Though this complication of leprosy has been extensively described, we still know very little of its natural history and of the factors which may predispose to it. This paper examines the descriptive and analytic epidemiology of these reactions in leprosy. We find that they vary greatly in clinical expression, time of onset, duration and severity, which has important implications for the way they are handled in the context of leprosy-control programmes. We review the various risk factors that have been suggested over the last 30 years and the evidence of their utility in identifying 'high-risk' patients is assessed. We then review the specific aspects of neuritis and disability in leprosy and examine the contribution of Type 1 reaction to leprosy-associated disabilities. The prospects for early detection and prevention of Type 1 reaction are examined in the light of current knowledge, both at research and at the leprosy control level.


Systemic administration of recombinant interleukin 2 stimulates in vivo lymphoid cell proliferation in tissues.
Recent work in our laboratory has demonstrated that the repeated injections of high doses of recombinant interleukin 2 (IL 2) can dramatically reduce the number of established pulmonary and hepatic metastases and the growth of intradermal tumors in a variety of murine tumor models. We have thus undertaken studies to define the mechanisms underlying these in vivo effects of IL 2. Using an in vivo DNA-labeling technique in which we employed 5-[125I]iodo-2'-deoxyuridine (125IUdR), we examined the in vivo cell proliferation in the tissues of mice treated with IL 2. A proliferation index (PI) was calculated by dividing the raw counts per minute (cpm) of tissues in IL 2-treated mice by the cpm in corresponding tissues of control animals. At an IL 2 dose of 6000 U given i.p. three times a day, the highest 125IUdR incorporation was seen in the lungs, liver, spleen, kidneys, and mesenteric lymph nodes (PI = 6.9, 6.9, 5.1, 7.1, 24.6, respectively, at 5 days). The amount of lymphoid proliferation in these organs was a direct function of the dose of IL 2 administered. Other tissues including thymus, intestines, skin, and hind limb showed no significant increase in 125IUdR uptake even after host treatment with the highest doses of IL 2. Blood and brain demonstrated intermediate incorporation of the radiolabel. Preirradiation of the host largely eliminated the proliferative response to IL 2. Histologic studies of normal and irradiated mice receiving IL 2 corroborated the result of the 125IUdR findings. In normal IL 2-treated mice, large collections of activated lymphoid cells were seen, most prominently in the lungs, liver, and kidneys, whereas markedly decreased lymphoid proliferation was evident histologically in preirradiated mice. A fluorescein-labeled monoclonal antibody directed against the Thy-1.2 surface determinant was used to identify these dividing cells in frozen tissue sections as T lymphoid cells. Activated lymphocytes isolated from the lungs, liver, spleen, and mesenteric lymph nodes of IL 2-treated mice demonstrated significant lysis of a fresh murine sarcoma target in short-term 51Cr-release assays. These studies demonstrate that the systemic administration of recombinant IL 2 causes in vivo activation and proliferation of host lymphoid cells and has important implications for the adoptive immunotherapy of tumors.


90-degree light scattering by the Menger sponge fractal.
Selection rules for the 90 degrees light scattering by the Menger sponge fractal were derived by the group theory based on the symmetry of its localized electromagnetic eigenmodes. The light scattering spectra were calculated by the finite-difference time-domain method and compared with the eigenfrequencies of the localized modes obtained from the dipole radiation spectra. Their correspondence is quite good and supports the accuracy of the numerical calculation and the correctness of the selection rules. It was also shown that the scattering spectra are background free and the quality factor of the localized modes can be obtained from the spectral width of the scattering peaks. Thus the 90 degrees light scattering is a powerful method for the investigation of the Menger sponge fractal.


Paternal heterochromatin formation in human embryos is H3K9/HP1 directed and primed by sperm-derived histone modifications.
The different configurations of maternal and paternal chromatin, acquired during oogenesis and spermatogenesis, have to be rearranged after fertilization to form a functional embryonic genome. In the paternal genome, nucleosomal chromatin domains are re-established after the protamine-to-histone exchange. We investigated the formation of constitutive heterochromatin (cHC) in human preimplantation embryos. Our results show that histones carrying canonical cHC modifications are retained in cHC regions of sperm chromatin. These modified histones are transmitted to the oocyte and contribute to the formation of paternal embryonic cHC. Subsequently, the modifications are recognized by the H3K9/HP1 pathway maternal chromatin modifiers and propagated over the embryonic cleavage divisions. These results are in contrast to what has been described for mouse embryos, in which paternal cHC lacks canonical modifications and is initially established by Polycomb group proteins. Our results show intergenerational epigenetic inheritance of the cHC structure in human embryos.


[Substitution of dexamethasone for dexamphetamine due to their written and spoken similarity].
We present a 15-year-old girl and an 11-year-old boy who were prescribed dexamphetamine for treatment of Attention Deficit Hyperactivity Disorder (ADHD), and who subsequently presented with symptoms indicative of Cushing's syndrome. It turned out that both children had taken high doses of dexamethasone instead of dexamphetamine due to an error made by the pharmacist. The diagnosis of exogenous Cushing's syndrome is easily made. However, it is a serious condition with possibly severe and persistent complications. The substitution of dexamethasone for dexamphetamine has been described before. Both doctors and pharmacists should be aware of this possible error.


Global gene regulation in tomato plant (Solanum lycopersicum) responding to vector (Bactericera cockerelli) feeding and pathogen ('Candidatus Liberibacter solanacearum') infection.
Different responses are elicited in tomato plants by Bactericera cockerelli harboring or not the pathogen 'Candidatus Liberibacter solanacearum'. 'Candidatus Liberibacter solanacearum' (Lso) has emerged as a major pathogen of crops worldwide. This bacterial pathogen is transmitted by Bactericera cockerelli, the tomato psyllid, to solanaceous crops. In this study, the transcriptome profiles of tomato (Solanum lycopersicum) exposed to B. cockerelli infestation and Lso infection were evaluated at 1, 2 and 4 weeks following colonization and/or infection. The plant transcriptional responses to Lso-negative B. cockerelli were different than plant responses to Lso-positive B. cockerelli. The comparative transcriptome analyses of plant responses to Lso-negative B. cockerelli revealed the up-regulation of genes associated with plant defenses regardless of the time-point. In contrast, the general responses to Lso-positive B. cockerelli and Lso-infection were temporally different. Infected plants down-regulated defense genes at week one while delayed the up-regulation of the defense genes until weeks two and four, time points in which early signs of disease development were also detected in the transcriptional response. For example, infected plants regulated carbohydrate metabolism genes which could be linked to the disruption of sugar distribution usually associated with Lso infection. Also, infected plants down-regulated photosynthesis-related genes potentially resulting in plant chlorosis, another symptom associated with Lso infection. Overall, this study highlights that tomato plants induce different sets of genes in response to different stages of B. cockerelli infestation and Lso infection. This is the first transcriptome study of tomato responses to B. cockerelli and Lso, a first step in the direction of finding plant defense genes to enhance plant resistance.


Hippocampal regulation of context-dependent neuronal activity in the lateral amygdala.
Pavlovian fear conditioning is a robust and enduring form of emotional learning that provides an ideal model system for studying contextual regulation of memory retrieval. After extinction the expression of fear conditional responses (CRs) is context-specific: A conditional stimulus (CS) elicits greater conditional responding outside compared with inside the extinction context. Dorsal hippocampal inactivation with muscimol attenuates context-specific CR expression. We have previously shown that CS-elicited spike firing in the lateral nucleus of the amygdala is context-specific after extinction. The present study examines whether dorsal hippocampal inactivation with muscimol disrupts context-specific firing in the lateral amygdala. We conditioned rats to two separate auditory CSs and then extinguished each CS in separate and distinct contexts. Thereafter, single-unit activity and conditional freezing were tested to one CS in both extinction contexts after saline or muscimol infusion into the dorsal hippocampus. After saline infusion, rats froze more to the CS when it was presented outside of its extinction context, but froze equally in both contexts after muscimol infusion. In parallel with the behavior, lateral nucleus neurons exhibited context-dependent firing to extinguished CSs, and hippocampal inactivation disrupted this activity pattern. These data reveal a novel role for the hippocampus in regulating the context-specific firing of lateral amygdala neurons after fear memory extinction.


Sentinel Surveillance for Expedited Partner Therapy Prescriptions Using Pharmacy Data, in 2 New York City Neighborhoods, 2015.
Expedited partner therapy (EPT) for Chlamydia trachomatis (Ct) is the practice of providing Ct-infected patients with medication, or prescription (prescription-EPT) to deliver to their sex partners without first examining those partners. New York City (NYC) providers commonly use prescription-EPT, yet NYC pharmacists report only occasional receipt of EPT prescriptions. This project assessed the frequency of EPT prescriptions filled in 2 NYC neighborhoods. The 2 NYC facilities reporting the most frequent use of prescription-EPT were identified from Ct provider case reports and contacted to ascertain their EPT practices. Providers at the first facility (facility 1) prescribed two 1-g doses of azithromycin, including sex partner treatment on the index patient's electronic prescription. Providers at the second facility (facility 2) gave patients paper prescriptions for sex partners. We reviewed prescriptions filled in 2015 for azithromycin, 1 or 2 g at pharmacies near these facilities; prescriptions indicating partner therapy were classified "EPT prescriptions". Facility 1 providers submitted 112 Ct case reports indicating prescription-EPT, compared with 114 submitted by facility 2 providers. Twelve of 26 identified pharmacies agreed to participate. At 7 pharmacies near facility 1, we found 61 EPT prescriptions from facility 1 and 37 from other facilities. At 5 pharmacies near facility 2, we found only 1 EPT prescription from facility 2 and 3 from other facilities. Expedited partner therapy prescriptions were received in NYC pharmacies near to EPT-prescribing facilities, but with great variability and at a lower frequency than suggested by provider case reports. Provider EPT prescribing practices may impact the likelihood that partners receive medication and should be further evaluated.


Thrombocytopenia associated with transcatheter closure of giant patent ductus arteriosus.
Thrombocytopenia occasionally occurs following the closure of some giant patent ductus arteriosus cases. Unfortunately, there is no associated research describing the associated risk factors for thrombocytopenia post-procedure. We reviewed all patients who received occluders with sizes ≥10/12 mm between January 2013 and June 2019. All the data and information on the characteristics of the patients and their follow-up were recorded. Univariate analysis, receiver operating characteristic curves, and linear regression were used to analyse the risk factors for thrombocytopenia and the predictors of hospitalisation stay. Finally, 32 patients (17.5%) suffered from thrombocytopenia. Univariate analysis revealed the ratio between occluder disc size (mm) and body weight (kg) (1.71 ± 0.51 versus 1.35 ± 0.53) as an independent predictive factor for thrombocytopenia, and the area under the curve of the ratio of occluder size and body weight for predicting thrombocytopenia post-closure was 0.691 (95% confidence interval: 0.589-0.792, p = 0.001). The best cut-off value for the ratio of occluder size and weight was 1.5895, with a sensitivity and specificity of 68.8 and 66.9%, respectively. Each unit of the ratio of occluder size and body weight predicted an average hospitalisation stay of 2.856 days (95% confidence interval: 1.380-4.332). Treatment with medication did not reduce the hospitalisation stay or benefit platelet restoration. Once the ratio of occluder size and body weight is greater than 1.6, thrombocytopenia always exists. Every unit of the ratio of occluder size and body weight represents an additional 3 days of hospitalisation. Treatment does not reduce the duration of hospitalisation.


Spatiotemporal Dynamics of Highly Pathogenic Avian Influenza Subtype H5N8 in Poultry Farms, South Korea.
Highly pathogenic avian influenza (HPAI), a zoonotic disease, is a major threat to humans and poultry health worldwide. In January 2014, HPAI virus subtype H5N8 first infected poultry farms in South Korea, and 393 outbreaks, overall, were reported with enormous economic damage in the poultry industry. We analyzed the spatiotemporal distribution of HPAI H5N8 outbreaks in poultry farms using the global and local spatiotemporal interaction analyses in the first (January to July 2014) and second (September 2014 to June 2015) outbreak waves. The space-time K-function analyses revealed significant interactions within three days and in an over-40 km space-time window between the two study periods. The excess risk attributable value (D0) was maintained despite the distance in the case of HPAI H5N8 in South Korea. Eleven spatiotemporal clusters were identified, and the results showed that the HPAI introduction was from the southwestern region, and spread to the middle region, in South Korea. This spatiotemporal interaction indicates that the HPAI epidemic in South Korea was mostly characterized by short period transmission, regardless of the distance. This finding supports strict control strategies such as preemptive depopulation, and poultry movement tracking. Further studies are needed to understand HPAI disease transmission patterns.


Laparoscopic Versus Open Partial Nephrectomy for Stage T1a of Renal Tumors.
Partial nephrectomy is the gold standard treatment for small kidney masses. Data on the comparison oflaparoscopic (LPN) versus open partial nephrectomy (OPN) are based on retrospective studies. Thus, we plannedto compare these two techniques in a prospective trial. The study population consisted of patients over 18 years old with single renal mass of≤ 4 cm. Patients were divided into two groups considering their preference. Study arms were matched accordingto age, gender, tumor size and location and renal nephrometry score. Mean operation time, warm ischemia time,hospital stay, peri-operative complications and changes in glomerular filtration rate (GFR) after 1 month were recordedand compared in two groups. Patients' satisfaction score, visual analogue scale and narcotics use to controlpost-operative pain were also studied. 34 and 31 patients underwent LPN and OPN, respectively. There was no significant difference betweenOPN and LPN regarding hospital stay (4.1 versus 4.6 days; P = .37), mean hemoglobin drop (2.17 and 1.96 g/dL;P = .62), changes in GFR and positive margin (1 versus 3 p=.40). LPN was accompanied with longer mean surgerytime (180 min versus 127 minutes; P < .001) and higher rate of urologic complications (P = .04); nevertheless,patient satisfaction rate was higher (P = .02) and dose of narcotics necessary for controlling post-operative painwas lower (P = .04) in LPN. This clinical trial shows that LPN has some benefits over OPN, including decreased post-operativepain and higher patient satisfaction. However, extra caution should be considered in the issue of tumor margin andurinary leakage in LPN.


Effects of using text message interventions for the management of musculoskeletal pain: a systematic review.
Musculoskeletal pain is the greatest cause of disability worldwide. Owing to its increasing prevalence and burden, the importance of affordable treatments has been highlighted. Text message interventions are accessible, low cost, and effective in promoting healthy behaviour and managing chronic diseases. However, little is known about their role in musculoskeletal pain. This systematic review was conducted to appraise the literature on the effects of text messages (as an intervention or a component of an intervention) compared with any control on pain and function in people with musculoskeletal pain (PROSPERO: CRD42018117371). MEDLINE, EMBASE, CINAHL, Cochrane, and PEDro databases were searched from inception to April 2020. Keywords relating to musculoskeletal pain, text messages, and randomised controlled trials were combined. Methodological quality was assessed using the PEDro score. Of the 12,022 studies identified, 11 were included, with a mean PEDro score of 5.4/10 points (SD 1.3). Pooled analyses were not performed because of heterogeneity of interventions and clinical characteristics. When text messages were added to and compared with usual care, some positive effects were found only on treatment adherence. Although small and inconsistent, some positive effects were reported for pain intensity, function, care-seeking behaviour, adherence, and quality of life when text messages were added to multicomponent interventions. Moreover, text message and telephone counselling interventions had similar effects on function. Overall included studies were of limited methodological quality and heterogeneous. However, our results indicate potential benefits of text messages in the treatment of musculoskeletal pain, which need to be confirmed in future trials.


Animal models of drug craving.
Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive-motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving.


Gender empowerment, inequalities and the prevalence of adult female obesity: An empirical analysis using new data, 1990-2013.
Aims: Do gender inequality and gender discrimination explain female obesity? Discrimination denies access to choose and constrains agency. Scope: Using the Global Burden of Disease data on overweight and obesity share of the adult female population for almost 160 countries over a 24-year period, we find that female empowerment has no effect on the population share that is overweight, but it reduces the obese share of women. The substantive impact is, however, slight and the results are not robust to testing a sample of only developing countries. Political freedoms for women in general, however, show positive effects on the prevalence of obesity, results that are again substantively meagre. Higher levels of income inequality and a measure of health inequality predict lower levels of female obesity independently of the controls, which raises some doubt about large arguments linking generalized inequality to obesogenic environments. Results: In so far as our measures of female empowerment capture greater access to rights and agency, they are poor predictors of the prevalence of obesity. The results suggest that local-level idiosyncrasies matter a lot more than do macro-level factors. Conclusions: Any conclusion should be treated tentatively given the short temporal domain examined here and uncertainties in the data. While promoting rights and equity for women are still intrinsically valuable and moral, the task of reducing obesity per se may require more targeted public action promoting healthier lifestyles and consumption among vulnerable groups.


Mortality of chrome leather tannery workers and chemical exposures in tanneries.
A retrospective mortality analysis was conducted in a cohort of 9,365 individuals employed as of 1940 in two chrome leather tanneries in the United States and followed to the end of 1982. Vital status as of the closing date was determined for over 95% of the cohort. Potential hazardous workplace exposures varied with department and included nitrosamines, chromate pigments, benzidine-based direct dyestuffs, formaldehyde, leather dust, and aromatic organic solvents. Mortality from all causes combined was lower than expected for each tannery, the standardized mortality ratio being 81 for one and 93 for the other. Deaths from cancer of each site, including the lung, were also lower than expected compared to those of either the population of the United States or of local state rates. A significant excess of deaths was observed, however, due to accidental causes in one tannery and cirrhosis of the liver, suicide, and alcoholism in the other. These excesses did not appear to be causally associated with occupational exposures. The findings of this study are consistent with those of the only other mortality investigation of leather tannery employees.


Deriving protein binding-corrected chemical concentrations for in vitro testing.
Extracellular chemical concentrations are considered physiologically relevant for in vitro testing and are evaluated in traditional in vitro systems using cell culture media containing 5%-10% fetal bovine serum (FBS). However, depending on the physicochemical properties, and in vitro testing conditions, cells could be exposed to variable unbound extracellular concentrations. If in vitro unbound concentrations are not calculated, it is challenging to distinguish the chemical potency and concentration-driven responses. In this study, one- and two-protein binding models were used to estimate protein binding corrected chemical concentrations of various chemicals for in vitro testing. As ceftizoxime, moxifloxacin, and nicotine have low protein binding affinity, the in vitro protein binding in 5%-10% FBS is less than 5% and can be considered negligible. However, protein binding of moderate and highly protein-bound chemicals must be corrected for as the in vitro unbound concentrations in 5%-10% FBS containing cell culture media will vary over a range of chemical concentrations. In vitro pharmacological and toxicological assessments must incorporate protein binding-adjusted in vitro concentrations to ensure physiologically relevant exposures. A user-friendly Excel spreadsheet is provided to help bench scientists calculate protein binding-corrected chemical concentrations for in vitro testing.


The Patient's Experience of Ocular Melanoma in the US: A Survey of the Ocular Melanoma Foundation.
Ocular melanomas threaten patients with early death, visual handicap, and loss of the eye. The aims of this study were to identify aspects of care that patients with ocular melanoma considered most important and to determine whether patients felt their needs had been adequately addressed. A cross-sectional study including US ocular melanoma patients and their caregivers. An online survey of US ocular melanoma patients was designed and conducted by the Ocular Melanoma Foundation. The cohort included 180 patients with uveal melanoma and 4 with conjunctival melanoma. Median follow-up was 3 years. A third of patients reported that their uveal melanoma had initially been diagnosed as a nevus. Most uveal melanomas were treated with brachytherapy. Almost 50% of patients had no genetic tumor analysis. Screening methods reported most commonly were computed tomography and liver function tests. Metastatic disease developed in 11% of patients. Few patients (13.3%) reported an offer of psychological support. Most dissatisfaction was with lack of advice on financial aspects of care and lack of psychological counseling, with women tending to express more dissatisfaction with care. Many patients complained about the way ophthalmologists delivered bad news to them. This patients' perspective highlights directions for research, education, and other measures to improve the care of patients with ocular melanoma in the US and elsewhere.


Predicting Monomers for Use in Polymerization-Induced Self-Assembly.
We report an in silico method to predict monomers suitable for use in polymerization-induced self-assembly (PISA). By calculating the dependence of LogPoct /surface area (SA) on the length of the growing polymer chain, the change in hydrophobicity during polymerization was determined. This allowed for evaluation of the capability of a monomer to polymerize to form self-assembled structures during chain extension. Using this method, we identified five new monomers for use in aqueous PISA via reversible addition-fragmentation chain transfer (RAFT) polymerization, and confirmed that these all successfully underwent PISA to produce nanostructures of various morphologies. The results obtained using this method correlated well with and predicted the differences in morphology obtained from the PISA of block copolymers of similar molecular weight but different chemical structures. Thus, we propose this method can be utilized for the discovery of new monomers for PISA and also the prediction of their self-assembly behavior.


High-resolution genome-wide mapping of AHR and ARNT binding sites by ChIP-Seq.
The aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) activated complex regulates genes in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR has also emerged as a potential therapeutic target for the treatment of human diseases and different cancers, including breast cancer. To better understand AHR and ARNT signaling in breast cancer cells, we used chromatin immunoprecipitation linked to high-throughput sequencing to identify AHR- and ARNT-binding sites across the genome in TCDD-treated MCF-7 cells. We identified 2594 AHR-bound, 1352 ARNT-bound, and 882 AHR/ARNT cobound regions. No significant differences in the genomic distribution of AHR and ARNT were observed. Approximately 60% of the cobound regions contained at least one core an aryl hydrocarbon response element (AHRE), 5'-GCGTG-3'. AHR/ARNT peak density was the highest within 1 kb of transcription start sites (TSS); however, a number of AHR/ARNT cobound regions were located as far as 100 kb from TSS. De novo motif discovery identified a symmetrical variation of the AHRE (5'-GTGCGTG-3'), as well as FOXA1 and SP1 binding motifs. Microarray analysis identified 104 TCDD-responsive genes where 98 genes were upregulated by TCDD. Of the 104 regulated genes, 69 (66.3%) were associated with an AHR- or ARNT-bound region within 100 kb of their TSS. Overall our study identified AHR/ARNT cobound regions across the genome, revealed the importance but not absolute requirement for an AHRE in AHR/ARNT interactions with DNA, and identified a modified AHRE motif, thereby increasing our understanding of AHR/ARNT signaling pathway.


Differentially-dimensioned furrow formation by zygotic gene expression and the MBT.
Despite extensive work on the mechanisms that generate plasma membrane furrows, understanding how cells are able to dynamically regulate furrow dimensions is an unresolved question. Here, we present an in-depth characterization of furrow behaviors and their regulation in vivo during early Drosophila morphogenesis. We show that the deepening in furrow dimensions with successive nuclear cycles is largely due to the introduction of a new, rapid ingression phase (Ingression II). Blocking the midblastula transition (MBT) by suppressing zygotic transcription through pharmacological or genetic means causes the absence of Ingression II, and consequently reduces furrow dimensions. The analysis of compound chromosomes that produce chromosomal aneuploidies suggests that multiple loci on the X, II, and III chromosomes contribute to the production of differentially-dimensioned furrows, and we track the X-chromosomal contribution to furrow lengthening to the nullo gene product. We further show that checkpoint proteins are required for furrow lengthening; however, mitotic phases of the cell cycle are not strictly deterministic for furrow dimensions, as a decoupling of mitotic phases with periods of active ingression occurs as syncytial furrow cycles progress. Finally, we examined the turnover of maternal gene products and find that this is a minor contributor to the developmental regulation of furrow morphologies. Our results suggest that cellularization dynamics during cycle 14 are a continuation of dynamics established during the syncytial cycles and provide a more nuanced view of developmental- and MBT-driven morphogenesis.


Proteome-Wide Profiling of Cellular Targets Modified by Dopamine Metabolites Using a Bio-Orthogonally Functionalized Catecholamine.
Selective death of midbrain dopaminergic neurons is a hallmark pathology of Parkinson's disease (PD), but the molecular mechanisms that initiate the cascade of events resulting in neurodegeneration in PD remain unclear. Compelling evidence suggests that dysregulation of dopamine (DA) induces neuronal stress and damage responses that are operative processes in striatal degeneration preceding PD-like symptoms. Improper DA sequestration to vesicles raises cytosolic DA levels, which is rapidly converted into electrophilic dopaquinone species (DQs) that react readily with protein nucleophiles forming covalent modifications that alter the native structure and function of proteins. These so-called DA-protein adducts (DPAs) have been reported to play a role in neurotoxicity, and their abundance with respect to neurodegeneration has been linked to clinical and pathological features of PD that suggest that they play a causal role in PD pathogenesis. Therefore, characterizing DPAs is a critical first step in understanding the susceptibility of midbrain dopaminergic neurons during PD. To help achieve this goal, we report here a novel DA-mimetic (DAyne) containing a biorthogonal alkyne handle that exhibits a reactivity profile similar to DA in aqueous buffers. By linking DPAs formed with DAyne to a fluorescent reporter molecule, DPAs were visualized in fixed cells and within lysates. DAyne enabled global mapping of cellular proteins affected by DQ modification and their bioactive pathways through enrichment. Our proteomic profiling of DPAs in neuronal SH-SY5Y cells indicates that proteins susceptible to DPA formation are extant throughout the proteome, potentially influencing several diverse biological pathways involved in PD such as endoplasmic reticulum (ER) stress, cytoskeletal instability, proteotoxicity, and clathrin function. We validated that a protein involved in the ER stress pathway, protein disulfide isomerase 3 (PDIA3), which was enriched in our chemoproteomic analysis, is functionally inhibited by DA, providing evidence that dysregulated cellular DA may induce or exacerbate ER stress. Thus, DAyne provided new mechanistic insights into DA toxicity that may be observed during PD by enabling characterization of DPAs generated reproducibly at physiologically relevant quinone exposures. We anticipate our design and application of this reactivity-based probe will be generally applicable for clarifying mechanisms of metabolic quinone toxicity.


The 1952 outbreak of encephalitis in California; epidemiologic aspects.
For the most part, epidemiologic phenomena observed in the outbreak of encephalitis in 1952 accorded with patterns that had been apparent in previous years. Ninety-seven per cent of the 414 laboratory-confirmed cases of western equine and St. Louis encephalitis in humans occurred in the 20 Central Valley counties. The cases of western equine encephalomyelitis in horses were generally scattered over the state. In the Central Valley most of the cases in horses were in animals less than two years of age; elsewhere the incidence was higher in older horses.There were no laboratory-confirmed cases of western equine or St. Louis encephalitis in humans earlier than June or later than October. In 1952 there were far more cases of western equine than of St. Louis encephalitis-a departure from the pattern in the previous seven years when there were about as many of one as of the other. No known satisfactory index is available for the prediction of the extent or type of outbreaks in humans. Approximately one-third of the cases of western equine encephalitis were in patients less than one year of age, whereas there were no cases of the St. Louis disease in patients that young.The incidence of western equine encephalitis in persons under 5 years of age was about the same for girls as for boys. In higher age brackets, males with western equine encephalitis outnumbered females 2 to 1. The corresponding ratio for St. Louis encephalitis was only 1.2 to 1.


Preoperative thrombocytopenia and outcomes of hepatectomy for hepatocellular carcinoma.
Platelet count is known to be an indirect indicator of portal hypertension but is not a part of the model for end-stage liver disease (MELD) score or the Child-Pugh score for risk stratification in hepatobiliary surgery. Data from 2097 hepatic resections for hepatocellular carcinoma (HCC) were evaluated from 2005-2012 using the National Surgical Quality Improvement Program database. Patient demographics, morbidity, and mortality were evaluated. Median age and body mass index were 64 y and 26.5 kg/m(2), respectively. Majority of the patients had American Society of Anesthesiologists ≥3 (78.1%) and median MELD score was 7. On multivariate analysis, thrombocytopenia (platelet count <150/nL) and severe thrombocytopenia (platelet count <100/nL) were independently associated with an increased risk of mortality (odds ratio [OR], 1.79; P = 0.024 and OR, 4.19; P < 0.001), cardiopulmonary complications (OR, 1.61; P = 0.009 and OR, 1.96; P = 0.018), need for blood transfusion (OR, 1.35; P = 0.05 and OR, 1.60; P = 0.05), septic complications (OR, 1.53; P = 0.025 and OR, 1.96; P = 0.016), reintubation (OR, 1.91; P = 0.004 and OR, 2.64; P = 0.003), and renal insufficiency and/or failure (OR, 2.48; P = 0.001 and OR, 4.96; P < 0.001), respectively. Thrombocytopenia, which is an indirect indicator for portal hypertension, is significantly associated with adverse outcomes after hepatectomy, independent of the MELD score. Platelet count should be integrated into the selection criteria for hepatic resections for HCC.


RARE NON-SURGICAL RELATED MASSIVE SPONTANEOUS SUPRACHOROIDAL HEMORRHAGE. A CASE REPORT.
We present two rare cases of non-surgical-related massive spontaneous suprachoroidal hemorrhage. The first case was a 73-year-old male with uncontrolled hypertension, who presented with left vision loss, only able to perceive light, with very high intraocular pressure (IOP) and blood pressure (BP), 68 mmHg and 196/106 mmHg, respectively. Ocular examination showed a limited fundus view, and the B-scan revealed near kissing suprachoroidal hemorrhage. The second case was a 59-year-old male, post valve replacement surgery on life-long warfarin, who presented with hand movement vision and IOP of 47 mmHg. The B-scan showed massive submacular and suprachoroidal hemorrhage with therapeutic range International Normalized Ratio (INR). Suprachoroidal hemorrhage is one of the rare complications that can be seen in any ocular surgery. However, spontaneous suprachoroidal hemorrhage is a rarer disease. Most of the reported cases are associated with underlying medical conditions. Thus prevention is crucial. This involves ophthalmologists, physicians and general practitioners in managing this group of patients with associated risk factors, for better recognition of this devastating ocular complication in which early detection may reduce ocular morbidity.


Analyses of radioactive aerosols to support accurate internal dose assessments at Chin-Shan nuclear power plant.
Studies of the physical and chemical properties of radioactive aerosols produced in different work environments were made at Chin-Shan nuclear power plant in Taiwan. These properties, including particle mass- and activity-size distributions, elemental and radionuclide compositions, and solubility lung class, are essential for the assessment of internal dose equivalents from the inhalation of radioactive aerosols. Several practices and environments studied include thermal arc cutting, grinding, sandblasting, and noble gas progeny. For physical analyses, cascade impactors, scanning electron microscopy with energy-dispersive x-ray analysis, inductively coupled plasma atomic emission spectrometry, and neutron activation analysis were applied. For chemical analyses, the solubility lung class was determined, in vitro, with the measurement of aerosol dissolution rates in simulated biological fluids. Results of these analyses were used to calculate the annual limit on intake, the derived air concentration, and committed dose equivalents for radiological protection against radioactive aerosols produced at Chin-Shan nuclear power plant.


Health-related quality of life of unrelated bone marrow donors in Japan.
To promote bone marrow donation, both the safety and well-being of healthy unrelated volunteer donors must be protected. This prospective cohort study evaluated donors' health-related quality of life (HRQOL) and identified factors associated with it. Using the Medical Outcomes Study Short Form 36 Health Survey (SF-36) before bone marrow harvesting (BMH), and again 1 week and 3 months after the donors' discharge, we evaluated HRQOL of 565 donors (329 men, 236 women) registered with the Japan Marrow Donor Program (JMDP). We also examined the data routinely collected by the JMDP, such as BMH-related problems and other demographic and medical variables, to determine whether such data could be used to predict donors' HRQOL after discharge. Mean scores of all pre-BMH SF-36 subscales showed better functioning than the national norm. One week after discharge, mean scores on physical functioning (PF) and role-physical (RP) subscales, indicative of physical states, and bodily pain (BP) were approximately 1 SD lower than the national norm; however, mental health (MH) and general health perception (GH) remained above normal; the most frequent BMH-related problems were pain at the donation site and lower back pain, which were associated with lower PF, RP, and BP scores. Female gender and duration of procedure predicted lower PF, RP, and BP. Three months after discharge, mean scores of all SF-36 subscales had returned to baseline levels. These data show that the adverse effects of BMH on donors' HRQOL are transient and can be minimized by better management of pain.


Age-Dependent Modifications of AMPA Receptor Subunit Expression Levels and Related Cognitive Effects in 3xTg-AD Mice.
GluA1, GluA2, GluA3, and GluA4 are the constitutive subunits of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), the major mediators of fast excitatory transmission in the mammalian central nervous system. Most AMPARs are Ca(2+)-impermeable because of the presence of the GluA2 subunit. GluA2 mRNA undergoes an editing process that results in a Q-R substitution, a key factor in the regulation of AMPAR Ca(2+)-permeability. AMPARs lacking GluA2 or containing the unedited subunit are permeable to Ca(2+) and Zn(2+). The phenomenon physiologically modulates synaptic plasticity while, in pathologic conditions, leads to increased vulnerability to excitotoxic neuronal death. Given the importance of these subunits, we have therefore evaluated possible associations between changes in expression levels of AMPAR subunits and development of cognitive deficits in 3xTg-AD mice, a widely investigated transgenic mouse model of Alzheimer's disease (AD). With quantitative real-time PCR analysis, we assayed hippocampal mRNA expression levels of GluA1-4 subunits occurring in young [3 months of age (m.o.a.)] and old (12 m.o.a) Tg-AD mice and made comparisons with levels found in age-matched wild type (WT) mice. Efficiency of GluA2 RNA editing was also analyzed. All animals were cognitively tested for learning short- and long-term spatial memory with the Morris Water Maze (MWM) navigation task. 3xTg-AD mice showed age-dependent decreases of mRNA levels for all the AMPAR subunits, with the exception of GluA2. Editing remained fully efficient with aging in 3xTg-AD and WT mice. A one-to-one correlation analysis between MWM performances and GluA1-4 mRNA expression profiles showed negative correlations between GluA2 levels and MWM performances in young 3xTg-AD mice. On the contrary, positive correlations between GluA2 mRNA and MWM performances were found in young WT mice. Our data suggest that increases of AMPARs that contain GluA1, GluA3, and GluA4 subunits may help in maintaining cognition in pre-symptomatic 3xTg-AD mice.


Interaction of artemisinin and its derivatives with human serum albumin studied using spectroscopies and molecular modeling methods.
The interactions of artemisinins including artemisinin, dihydroartemisinin, artemether and artesunate with human serum albumin (HSA) were studied by fluorescence spectroscopy, UV-Vis absorption spectroscopy, synchronous fluorescence, three-dimensional fluorescence, circular dichroism (CD) and molecular modeling. Results obtained from analysis of fluorescence spectrum and fluorescence intensity indicated that the artemisinins had a strong ability to quench the intrinsic fluorescence of HSA through a static quenching procedure. Furthermore, the association constants K a and the corresponding thermodynamic parameters ΔH, ΔG and ΔS at various temperatures were also calculated. Based on the mechanism of Förster's non-radiative energy transfer theory, the distance between the acceptors and HSA were found. In addition, alteration of the secondary structure of HSA in the presence of the artemisinins was tested by CD spectroscopy. Molecular modeling revealed that the artemisinins were bounded in the large hydrophobic cavity of the site I of HSA.


Omics studies for comprehensive understanding of immunoglobulin A nephropathy: state-of-the-art and future directions.
Immunoglobulin A nephropathy (IgAN) is the most common worldwide primary glomerulonephritis with a strong autoimmune component. The disease shows variability in both clinical phenotypes and endpoints and can be potentially subdivided into more homogeneous subtypes through the identification of specific molecular biomarkers. This review focuses on the role of omics in driving the identification of potential molecular subtypes of the disease through the integration of multilevel data from genomics, transcriptomics, epigenomics, proteomics and metabolomics. First, the identification of molecular biomarkers, including mapping of the full spectrum of common and rare IgAN risk alleles, could permit a more precise stratification of IgAN patients. Second, the analysis of transcriptomic patterns and their modulation by epigenetic factors like microRNAs has the potential to increase our understanding in the pathogenic mechanisms of the disease. Third, the specificity of urinary proteomic and metabolomic signatures and the understanding of their functional relevance may contribute to the development of new non-invasive biomarkers for a better molecular characterization of the renal damage and its follow-up. All these approaches can give information for targeted therapeutic decisions and will support novel clinical decision making. In conclusion, we offer a framework of omic studies and outline barriers and potential solutions that should be used for improving the diagnosis and treatment of the disease. The ongoing decade is exploiting novel high-throughput molecular technologies and computational analyses for improving the diagnosis (precision nephrology) and treatment (personalized therapy) of the IgAN subtypes.


INDUCED ANTIBODIES THAT REACT IN VITRO WITH SEDIMENTABLE CONSTITUENTS OF NORMAL AND NEOPLASTIC TISSUE CELLS : PRESENCE OF THE ANTIBODIES IN THE BLOOD OF RABBITS CARRYING VARIOUS TRANSPLANTED CANCERS.
Antibodies were found in the blood of certain rabbits carrying one or another of four transplanted cancers (Brown-Pearce and V2 carcinomas; RSI and Kato sarcomas) which will fix complement in vitro in mixture with saline extracts of various normal and neoplastic rabbit tissues-including liver, kidney, spleen, and the four tumors mentioned-and chick embryo tissue as well. These antibodies, which have been called induced tissue antibodies, are similar to the natural antibodies previously described (2) in that they react with those constituents of the various tissue cells that prove readily sedimentable in the high speed centrifuge; they differ from the natural antibodies in being absent from the blood of normal rabbits and in withstanding 65 degrees C. for 30 minutes. Certain quantitative differences suggest that the induced tissue antibodies have somewhat various affinities, depending in part upon the type of neoplasm carried by the host. They may perhaps be consequent on antigenic differences between the sedimentable constituents of the tumor cells and those of the new hosts; for they were not found in the blood of rabbits carrying papillomas and cancers composed of the animals' own cells, and not in that of rabbits in which multiple vaccinia or fibroma virus lesions had recently regressed. The characters of the sedimentable constituents of normal and neoplastic tissue cells, as revealed thus far by chemical, morphological, and serological studies, have recently been discussed (2,8). In this relation, it has seemed essential to recognize the induced antibodies here described, particularly since they may complicate serological studies aimed at disclosing distinctive sedimentable substances in tissue cells. In an associated paper experiments are reported which bear upon the relation between the induced tissue antibodies and an antibody that reacts specifically with a distinctive sedimentable constituent of Brown-Pearce carcinoma cells (7).


Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates.
No treatment is currently available for mucopolysaccharidosis (MPS) IIIB, a neuropathic lysosomal storage disease caused by autosomal recessive defect in α-N-acetylglucosaminidase (NAGLU). In anticipation of a clinical gene therapy treatment for MPS IIIB in humans, we tested the rAAV9-CMV-hNAGLU vector administration to cynomolgus monkeys (n=8) at 1E13 vg/kg or 2E13 vg/kg via intravenous injection. No adverse events or detectable toxicity occurred over a 6-month period. Gene delivery resulted in persistent global central nervous system and broad somatic transduction, with NAGLU activity detected at 2.9-12-fold above endogenous levels in somatic tissues and 1.3-3-fold above endogenous levels in the brain. Secreted rNAGLU was detected in serum. Low levels of preexisting anti-AAV9 antibodies (Abs) did not diminish vector transduction. Importantly, high-level preexisting anti-AAV9 Abs lead to reduced transduction in liver and other somatic tissues, but had no detectable impact on transgene expression in the brain. Enzyme-linked immunoabsorbent assay showed Ab responses to both AAV9 and rNAGLU in treated animals. Serum anti-hNAGLU Abs, but not anti-AAV9 Abs, correlated with the loss of circulating rNAGLU enzyme. However, serum Abs did not affect tissue rNAGLU activity levels. Weekly or monthly peripheral blood interferon-γ enzyme-linked immunospot assays detected a CD4(+) T-cell (Th-1) response to rNAGLU only at 4 weeks postinjection in one treated subject, without observable correlation to tissue transduction levels. The treatment did not result in detectable CTL responses to either AAV9 or rNAGLU. Our data demonstrate an effective and safe profile for systemic rAAV9-hNAGLU vector delivery in nonhuman primates, supporting its clinical potential in humans.


Dynamic PET simulator via tomographic emission projection for kinetic modeling and parametric image studies.
To develop and evaluate a fast and simple tool called dpetstep (Dynamic PET Simulator of Tracers via Emission Projection), for dynamic PET simulations as an alternative to Monte Carlo (MC), useful for educational purposes and evaluation of the effects of the clinical environment, postprocessing choices, etc., on dynamic and parametric images. The tool was developed in matlab using both new and previously reported modules of petstep (PET Simulator of Tracers via Emission Projection). Time activity curves are generated for each voxel of the input parametric image, whereby effects of imaging system blurring, counting noise, scatters, randoms, and attenuation are simulated for each frame. Each frame is then reconstructed into images according to the user specified method, settings, and corrections. Reconstructed images were compared to MC data, and simple Gaussian noised time activity curves (GAUSS). dpetstep was 8000 times faster than MC. Dynamic images from dpetstep had a root mean square error that was within 4% on average of that of MC images, whereas the GAUSS images were within 11%. The average bias in dpetstep and MC images was the same, while GAUSS differed by 3% points. Noise profiles in dpetstep images conformed well to MC images, confirmed visually by scatter plot histograms, and statistically by tumor region of interest histogram comparisons that showed no significant differences (p < 0.01). Compared to GAUSS, dpetstep images and noise properties agreed better with MC. The authors have developed a fast and easy one-stop solution for simulations of dynamic PET and parametric images, and demonstrated that it generates both images and subsequent parametric images with very similar noise properties to those of MC images, in a fraction of the time. They believe dpetstep to be very useful for generating fast, simple, and realistic results, however since it uses simple scatter and random models it may not be suitable for studies investigating these phenomena. dpetstep can be downloaded free of cost from https://github.com/CRossSchmidtlein/dPETSTEP.


Performance of osteopathic medical school graduates on the American Osteopathic Board of Internal Medicine certifying examinations 1985 to 1994.
This study examined the trends in the medical knowledge of osteopathic internal medicine residents in American Osteopathic Association-approved residency programs during a recent 10-year period and compared these trends with the declining medical knowledge observed for internal medicine residents graduated from allopathic medical schools and trained in allopathic residency programs. These results demonstrate a similar pattern of declining medical knowledge that appears to have leveled off during the past few years of the study. These trends occurred among candidates from both large and smaller training institutions. Various factors may have contributed to these observations.


Repair of 8-oxo-7,8-dihydroguanine in prokaryotic and eukaryotic cells: Properties and biological roles of the Fpg and OGG1 DNA N-glycosylases.
Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases. In prokaryotic and eukaryotic cells, 8-oxoG is primarily repaired by the base excision repair pathway (BER) initiated by a DNA N-glycosylase, Fpg and OGG1, respectively. In Escherichia coli, Fpg cooperates with MutY and MutT to prevent 8-oxoG-induced mutations, the "GO-repair system". In Saccharomyces cerevisiae, OGG1 cooperates with nucleotide excision repair (NER), mismatch repair (MMR), post-replication repair (PRR) and DNA polymerase η to prevent mutagenesis. Human and mouse cells mobilize all these pathways using OGG1, MUTYH (MutY-homolog also known as MYH), MTH1 (MutT-homolog also known as NUDT1), NER, MMR, NEILs and DNA polymerases η and λ, to prevent 8-oxoG-induced mutations. In fact, mice deficient in both OGG1 and MUTYH develop cancer in different organs at adult age, which points to the critical impact of 8-oxoG repair on genetic stability in mammals. In this review, we will focus on Fpg and OGG1 proteins, their biochemical and structural properties as well as their biological roles. Other DNA N-glycosylases able to release 8-oxoG from damaged DNA in various organisms will be discussed. Finally, we will report on the role of OGG1 in human disease and the possible use of 8-oxoG DNA N-glycosylases as therapeutic targets.


Urinary microRNAome in healthy cats and cats with pyelonephritis or other urological conditions.
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level. miRNAs have been found in urine and have shown diagnostic potential in human nephropathies. Here, we aimed to characterize, for the first time, the feline urinary miRNAome and explore the use of urinary miRNA profiles as non-invasive biomarkers for feline pyelonephritis (PN). Thirty-eight cats were included in a prospective case-control study and classified in five groups: healthy Control cats (n = 11), cats with PN (n = 10), cats with subclinical bacteriuria or cystitis (SB/C, n = 5), cats with ureteral obstruction (n = 7) and cats with chronic kidney disease (n = 5). By small RNA sequencing we identified 212 miRNAs in cat urine, including annotated (n = 137) and putative novel (n = 75) miRNAs. The 15 most highly abundant urinary miRNAs accounted for nearly 71% of all detected miRNAs, most of which were previously identified in feline kidney. Ninety-nine differentially abundant (DA) miRNAs were identified when comparing Control cats to cats with urological conditions and 102 DA miRNAs when comparing PN to other urological conditions. Tissue clustering analysis revealed that the majority of urine samples clustered close to kidney, which confirm the likely cellular origin of the secreted urinary miRNAs. Relevant DA miRNAs were verified by quantitative real-time PCR (qPCR). Eighteen miRNAs discriminated Control cats from cats with a urological condition. Of those, seven miRNAs were DA by both RNAseq and qPCR methods between Control and PN cats (miR-125b-5p, miR-27a-3p, miR-21-5p, miR-27b-3p, miR-125a-5p, miR-17-5p and miR-23a-3p) or DA between Control and SB/C cats (miR-125b-5p). Six additional miRNAs (miR-30b-5p, miR-30c, miR-30e-5p, miR-27a-3p, miR-27b-39 and miR-222) relevant for discriminating PN from other urological conditions were identified by qPCR alone (n = 4) or by both methods (n = 2) (P<0.05). This panel of 13 miRNAs has potential as non-invasive urinary biomarkers for diagnostic of PN and other urological conditions in cats.


Readability and Comprehensibility of Patient Information Leaflets for Antidiabetic Medications in Qatar.
Background:The readability and comprehensibility of the patient information leaflets (PILs) provided with antidiabetic medications are of questionable standards; this issue negatively affects adherence to drug therapy, especially in patients with limited literacy skills. Objective: To evaluate the readability and comprehensibility of PILs supplied with medications used for the treatment of type 2 diabetes mellitus in Qatar. Methods: All PILs of the antidiabetic medications in Qatar were evaluated using the Flesch Reading Ease (FRE) score for readability. The Flesch-Kincaid Grade Level, Gunning-Fog Index, and SMOG Grading were used to estimate the comprehensibility of PILs in terms of school grade levels. Results: A total of 45 PILs were evaluated: 32 (71.1%) PILs of brand-name products and 13 (28.9%) for generics. Nine (20%) of the PILs were in English only; 8 (17.8%) were in English, Arabic, and French; and 28 (62.2%) were in English and Arabic. The mean FRE score was 37.71 (±15.85), and the most readable PIL had FRE score of 62. The mean scores for the comprehensibility evaluations were 10.96 (±2.67), 15.02 (±2.52), and 11.41 (±1.6) for the Flesch-Kincaid Grade Level, Gunning-Fog Index, and SMOG Grading, respectively. The most commonly used antidiabetic medication was metformin with 1372.9 (±552.9) as PILs' mean number of words. Conclusion: Only 2.2% of PILs had acceptable readability scores. All PILs could be comprehended by at least an 11th grade student, which exceeds the recommended grade level for health-related materials. Approximately 20% of these PILs were in English only and were not readable by most patients.


Impact of makeup on remote-PPG monitoring.
Camera-based remote photoplethysmography (remote-PPG) enables contactless measurement of blood volume pulse from the human skin. Skin visibility is essential to remote-PPG as the camera needs to capture the light reflected from the skin that penetrates deep into skin tissues and carries blood pulsation information. The use of facial makeup may jeopardize this measurement by reducing the amount of light penetrating into and reflecting from the skin. In this paper, we conduct an empirical study to thoroughly investigate the impact of makeup on remote-PPG monitoring, in both the visible (RGB) and invisible (Near Infrared, NIR) lighting conditions. The experiment shows that makeup has negative influence on remote-PPG, which reduces the relative PPG strength (AC/DC) at different wavelengths and changes the normalized PPG signature across multiple wavelengths. It makes (i) the pulse-rate extraction more difficult in both the RGB and NIR, although NIR is less affected than RGB, and (ii) the blood oxygen saturation extraction in NIR impossible. To the best of our knowledge, this is the first work that systematically investigate the impact of makeup on camera-based remote-PPG monitoring.


Effects of human neutrophil elastase and Pseudomonas aeruginosa proteinases on human respiratory epithelium.
It has been suggested that proteinase enzymes could play an important role in the pathogenesis of chronic bronchial infections including bronchiectasis and cystic fibrosis (CF). Because Pseudomonas aeruginosa frequently colonizes the respiratory tract in bronchiectasis and CF, we examined the in vitro effects of human neutrophil elastase (HNE) and proteinase enzymes produced by P. aeruginosa (elastase: PE; alkaline proteinase: PAP) on the ciliary beat frequency (CBF) and ultrastructure of human nasal ciliated respiratory epithelium. HNE (500 micrograms/ml) progressively reduced CBF and caused marked epithelial disruption; lower concentrations (100 and 20 micrograms/ml) also caused epithelial disruption but without slowing CBF. The effects of HNE (500 micrograms/ml) were completely abolished by adding alpha 1-antitrypsin (5 mg/ml). There was no synergy between HNE and pyocyanin, a product of P. aeruginosa which slows CBF. PE in phosphate-buffered saline also caused epithelial disruption without slowing CBF; however, PE in medium containing divalent metal ions caused CBF slowing as well as epithelial disruption at 100 micrograms/ml. PAP (500 micrograms/ml) had almost no effect on ciliated epithelium. The effects of HNE and PE on nasal and bronchial epithelium obtained from the same patient were similar. Light and transmission electron microscopy revealed that HNE and PE were cytotoxic and caused detachment of epithelial cells from neighboring cells and the basement membrane. There was cytoplasmic blebbing of the cell surface and mitochondrial damage; however, no increase of abnormalities in the ultrastructure of cilia on living cells was seen. These results support the hypothesis that HNE and PE contribute to the delayed mucociliary clearance and epithelial damage that is observed in patients with chronic bronchial infection.


Combined pubic rami and sacral osteoporotic fractures: a prospective study.
Pelvic osteoporotic fractures (POFs) are often associated with considerable morbidity and mortality mainly as a result of infections and cardiovascular events. Patients usually need prolonged institutionalization, rehabilitation, and follow-up, with a high rate of dependency and cost. The most common sites of POFs include the pubic rami, sacrum, ilium, and acetabulum. Combined pubic rami (PROFs) and sacral osteoporotic fractures (SOFs) have been reported, mostly in retrospective studies, describing the mechanism of injury and incidence. The aim of this study was to evaluate the association between PROFs and SOFs and to assess the effect of combined PROFs and SOFs on patients' mobility, discharge destination, and length of stay. We prospectively studied 67 patients with low-impact PROFs and/or SOFs. There were 54 (80.4%) female and 13 (19.6%) male patients, and the average age was 87.5 (range 65-96) years. All patients were assessed by the fracture liaison service. Patients had magnetic resonance imaging or bone scan when there was history of low back pain following the injury or lumbosacral tenderness on clinical examination. The mean length of stay for all patients was 45 (± 35) days. Mortality rate was 10.4%. A significant relationship was found between low back pain and a positive finding of sacral fracture. Patients with combined PROFs and SOFs showed significantly longer length of stay than those with isolated PROFs. The presence of low back pain and tenderness in patients who had low-impact pelvic injuries was highly suggestive of the presence of an associated SOF. There was a high association between sacral and PROFs. The length of stay of patients with PROFs associated with sacral osteoporotic fractures was significantly longer than that of patients with PROFs only. Therefore, we recommend considering the high association between SOFs and PROFs in planning the management and rehabilitation of patients with POFs.


[Labile iron pool formation in rat's blood under rhabdomyolysis].
The labile nonheme iron pool formation in blood under glycerol induced rhabdomyolysis in rats has been investigated. This iron is not included in transferrin, thereby it is redox-active. Rhabdomyolysis was caused by intramuscular injection of 50% glycerol in a dose of 10 ml/kg. In the first day it has been registered that the blood plasma free heme content increased 10 times and the liver heme-oxigenase activity increased 6 times. Plasma redox-active iron pool formation has been registered by EPR method. Such iron was absent in the control group. This iron pool content in the interval from the 1st to the 6st day was more than 2 mg/l and significantly higher than the transferrin iron level. The plasma iron pool unshielded by transferrin may be one of oxidative stress causes.


The effect of spatial frequency on perceptual learning of inverted faces.
We investigated the efficacy of training adults to recognize full spectrum inverted faces presented with different viewpoints. To examine the role of different spatial frequencies in any learning, we also used high-pass filtered faces that preserved featural information and low-pass filtered faces that severely reduced that featural information. Although all groups got faster over the 2 days of training, there was more improvement in accuracy for the group exposed to full spectrum faces than in the two groups exposed to filtered faces, both of which improved more modestly and only when the same faces were shown on the 2 days of training. For the group exposed to the full spectrum range and, to a lesser extent, for those exposed to high frequency faces, training generalized to a new set of full spectrum faces of a different size in a different task, but did not lead to evidence of holistic processing or improved sensitivity to feature shape or spacing in inverted faces. Overall these results demonstrate that only 2h of practice in recognizing full-spectrum inverted faces presented from multiple points of view is sufficient to improve recognition of the trained faces and to generalize to novel instances. Perceptual learning also occurred for low and high frequency faces but to a smaller extent.


Age at menarche of university students in Bangladesh: secular trends and association with adult anthropometric measures and socio-demographic factors.
Age at menarche has been shown to be an important indicator for diseases such as breast cancer and ischaemic heart disease. The aim of the present study was to document secular trends in age at menarche and their association with anthropometric measures and socio-demographic factors in university students in Bangladesh. Data were collected from 995 students from Rajshahi University using a stratified sampling technique between July 2004 and May 2005. Trends in age at menarche were examined by linear regression analysis. Multiple regression analysis was used to assess the association of age at menarche with adult anthropometric measures and various socio-demographic factors. The mean and median age of menarche were 13.12+/-1.16 and 13.17 years, respectively, with an increasing tendency among birth-year cohorts from 1979 to 1986. Menarcheal age was negatively associated with BMI (p<0.01), but positively associated with height (p<0.05). Early menarche was especially pronounced among students from urban environments, Muslims and those with better educated mothers. Increasing age at menarche may be explained by improved nutritional status among Bangladeshi populations. Early menarche was associated with residence location at adolescence, religion and mother's education.


Contaminant concentrations in Illinois mink and otter.
: Mink and otters are valuable wildlife resources and management efforts in North America and Europe have been directed towards re-establishing extirpated populations or expanding existing populations. The similarity of otter and mink habits and trophic status may allow inferences about the suitability of the habitat that is occupied by one species (mink) for the other species that is absent (otter). Remnant otter populations in Illinois have not expanded even though suitable habitat appears to be available and is occupied by mink. Low contaminant concentrations in tissues of mink trapped in a habitat where otters are not found and metal and organochlorine concentrations in tissues of otters incidentally collected by the Illinois Department of Natural Resources, suggest that environmental contaminants should not hinder natural expansion of otters in Illinois.