Obstetric outcome of Bangladeshi women in east London.
To study the obstetric outcome of women of Bangladeshi origin in comparison with the white caucasian population in East London. A retrospective study of 16718 pregnancies over a five year period (1987-1991). An East London teaching hospital district. Six thousand four hundred and sixty Bangladeshi women compared with 7592 white caucasian women. Maternal: antenatal complications; induction and augmentation rates; analgesia and anaesthesia; instrumental delivery and caesarean section rates; third stage complications. Fetal: gestation and weight at birth; perinatal mortality rates. The following statistically significant findings were noted: Bangladeshi women had a longer reproductive age span and were of greater parity including grand multiparity. They suffered fewer antenatal complications except for gestational diabetes. They had lower induction rates and, among the parous group, lower augmentation rates. During labour they required less analgesia but more commonly had general anaesthesia for caesarean section deliveries. They required instrumental delivery less often but there was no difference in overall caesarean section rate for the two groups. However, overall Bangladeshi women had a lower elective caesarean section rate, although parous Bangladeshi women had a higher emergency section rate. In the third stage there were no differences in the complication rates for the nulliparous women, however the parous Bangladeshi women had a higher postpartum haemorrhage rate and a lower perineal repair rate consistent with their higher parity. Whilst preterm births were more common in Bangladeshi women, significant prematurity (less than 28 weeks gestation) was less common. Similarly, although Bangladeshi babies weighed less at birth, they had fewer babies weighing less than 1500 grammes. There was no statistically significant difference in the perinatal mortality rate between the two groups, being 8.1 per thousand births overall. Whilst there was a statistically insignificant decline in death rates over the five-year period, between the groups there was no consistent difference. Pregnant Bangladeshi women in East London constitute a relatively high parity, low risk population who have less obstetric intervention and yet manage an equivalent (or better) perinatal outcome compared to their white caucasian neighbours.


Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities.
To explore associations between psychiatric symptoms and cerebral magnetic resonance imaging abnormalities in low-birth-weight adolescents, 55 very low-birth-weight (<or=1500 gm), 54 term small for gestational age (birth weight <10th centile) and 66 term control adolescents (birth weight >or=10th centile) were assessed at 14-15 years of age. Outcome measures were Schedule for Affective Disorders and Schizophrenia for School-Age Children, Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Autism Spectrum Screening Questionnaire, and qualitatively assessed cerebral magnetic resonance images. The very low-birth-weight group manifested increased prevalence of psychiatric symptoms and disorders compared with controls (P < 0.001), especially symptoms of attention-deficit/hyperactivity disorder, and high frequency of ventricular dilatation, white matter reduction, thinning of corpus callosum, and gliosis (P < 0.01 vs controls). The Attention-Deficit/Hyperactivity Disorder Rating Scale score was significantly associated with white matter reduction and thinning of corpus callosum in this group. The term small for gestational age group had increased prevalence of psychiatric symptoms compared with control subjects, but not more frequent abnormalities on cerebral magnetic resonance imaging. In conclusion, attention-deficit/hyperactivity disorder symptoms were significantly associated with white matter reduction and thinning of corpus callosum in very low-birth-weight adolescents. No associations were found for other psychiatric symptoms and brain abnormalities in any of the groups.


Fe/Ni bimetal and nitrogen co-doped porous carbon fibers as electrocatalysts for oxygen reduction reaction.
In this work, oxygen reduction reaction (ORR) electrocatalysts Fe/Ni bimetal and nitrogen co-doped porous carbon fibers (Fex/Niy-NPCF), derived from electrospun nanofiber, have been prepared. In order to optimize the ORR performance of one dimension (1D) catalysts, SiO2 were used as template to create the hierarchical porous structure. The morphology of Fex/Niy-NPCF was investigated by scanning electron microscope (SEM) and transmission electron microscope (TEM). By adjusting the ratio of iron and nickel, the influence of the trace of secondary-metal doping in electrocatalyst on catalytic activity was deeply studied. The electrochemical measurements suggested that the trace of secondary-metal doping was good for increasing the half-wave potential of electrocatalyst. The optimized Fe28/Ni2-NPCF exhibited an excellent catalytic activity with an onset potential of 0.96 V and a half-wave potential of 0.88 V, which are comparable to that of the benchmark 20 wt% Pt/C. This excellent catalytic performance was derived from secondary-metal doping and abundant pore structure.


Inhibitory Activities of Pyrazolo-Oxazine Heterocyclic Derivatives.
Despite several reports and reviews addressing the biological significance of pyrazoles and oxazines, no comprehensive work on the pyrazolo oxazine fused ring system has been published so far. We report all biological evaluations on pyrazolo-oxazine derivatives in this mini-review to provide an avenue for medicinal and pharmacological researchers to conduct further in-depth exploration.


Implications of XRCC1, XPD and APE1 gene polymorphism in North Indian population: a comparative approach in different ethnic groups worldwide.
Identifying risk factors for human cancers should consider combinations of genetic variations and environmental exposures. Several polymorphisms in DNA repair genes have impact on repair and cancer susceptibility. We focused on X-ray repair cross-complementing group 1 (XRCC1), Xeroderma pigmentosum D (XPD) and apurinic/apyrimidinic endonuclease (APE1) as these are most extensively studied in cancer. Present study was conducted to determine distribution of XRCC1 C26304T, G27466A, G23591A, APE1 T2197G and XPD A35931C gene polymorphisms in North Indian population and compare with different populations globally. PCR-based analysis was conducted in 209 normal healthy individuals of similar ethnicity. Allelic frequencies in wild type of XRCC1 C26304T were 91.1% C(Arg); G27466A 62.9% G(Arg); G23591A 60.3% G(Arg); APE1 T2197G 75.1% T(Asp) and XPD A35931C 71.8% A(Lys). The variant allele frequency were 8.9% T(Trp) in XRCC1 C26304T; 37.1% A(His) in G27466A; 39.7% A(Gln) in G23591A; 24.9% G(Glu) in APE1 and 28.2% C(Gln) in XPD respectively. We further compared frequency distribution for these genes with various published studies in different ethnicity. Our results suggest that frequency in these DNA repair genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.


A deep-blue OLED-based biochip for protein microarray fluorescence detection.
Integrated biochips exploit a multi-disciplinary approach to produce portable point-of-care medical diagnostic systems that uncouple diagnosis from centralized laboratories. These portable devices are cost effective and have several advantages including broader accessibility to health care worldwide. Fluorescence detection of a disease-specific probe excited by an optical source is one of the most diffused methods for quantitative analysis on biochips. Here we designed and characterized a miniaturized biochip based on a novel deep-blue organic light-emitting diode. The molecular design of the diode was optimized to excite a fluorophore-conjugated antibody and tested on a protein microarray configuration with good sensitivity and specificity. These findings will be instrumental for the development of next generation point-of-care biochips.


Identification of the ferredoxin interaction sites on ferredoxin-dependent glutamate synthase from Synechocystis sp. PCC 6803.
Based on in silico docking methods, five amino acids in glutamate synthase (Gln-467, His-1144, Asn-1147, Arg-1162, and Trp-676) likely constitute key binding residues in the interface of a glutamate synthase:ferredoxin complex. Although all interfacial mutants studied showed the ability to form a complex under low ionic strength, these docking mutations showed significantly less ferredoxin-dependent activities, while still retaining enzymatic activity. Furthermore, isothermal titration calorimetry showed a possible 1:2 molar ratio between the wild-type glutamate synthase and ferredoxin. However, each of our interfacial mutants showed only a 1:1 complex with ferredoxin, suggesting that the mutations directly affect the glutamate synthase:ferredoxin heterodimer interface.


Green-light-responsive metal-organic frameworks for colorectal cancer treatment.
Herein, the synthetic methods for preparation of a novel light-responsive metal-organic framework (MOF) UiO-AZB-F are outlined. Upon irradiation with green light, the framework demonstrates controlled release of chemotherapeutic drug cargo with simultaneous breakdown into low toxicity small molecule components.


The Specifics of Neovascularization of Wound Defects in the Oral Mucosa during Its Regeneration under a Piezoelectric Polymer Membrane.
We studied restoration of microvessels in the oral mucosa wound defects under a polymer piezoelectric membrane (group 2) and without it (group 1). The control group included animals with intact mucosa. On day 3, the expression of the vascular endothelial growth factor (VEGF) increased in all experimental groups, while the expression of CD34 increased only in group 2, which attested to intensive neoangiogenesis. On day 7, we observed a decrease in VEGF expression and an increase in CD34 expression that was more pronounced in group 2, which reflected the beginning of blood vessels maturation. More rapid formation and maturation of blood vessels in group 2 was confirmed by electron microscopy: on day 7, endothelial cells with mature organelles and signs of active transcapillary exchange were seen. On day 12, the immature blood vessels still predominated in group 1, while in group 2, the expression of angiogenesis markers decreased though remained above the control, which created prerequisites for the complete restoration of wound area vascularization in group 2. In group 1, the expression of VEGF and CD34 was significantly below the control, which attested to the development of poorly vascularized scar tissue.


Ethyl α-l-sorboside.
Ethyl l-sorboside, C8H16O6, was prepared from the rare sugar l-sorbose, C6H12O6, and crystallized. It was confirmed that ethyl l-sorboside formed α-pyran-ose with a 2 C 5 conformation. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming a three-dimensional network. The unit-cell volume of the title ethyl α-l-sorboside is 940.63 Å3 (Z = 4), which is about 194.69 Å3 (26.1%) bigger than that of l-sorbose [745.94 Å3 (Z = 4)].


Glucose phosphorylation and dephosphorylation in chicken liver.
1. Glucokinase was absent from chicken liver and only the low Km hexokinases, inhibited by AMP, ADP but not ATP, were present. 2. The Km of chicken liver glucose-6-phosphatase for glucose-6-phosphate was reduced from 5.65 to 3.75 mM following starvation, and the enzyme was inhibited by glucose. 3. Starvation of chickens for 24 hr slightly lowered the hexokinase activity and doubled glucose-6-phosphatase activity; it did not change subcellular distribution of the enzymes. Oral glucose rapidly restored the activities to fed values. 4. It was concluded that glucose uptake into, and efflux from, chicken hepatocytes, was regulated by the activity and kinetic characteristics of glucose-6-phosphatase and by the glucose-6-phosphate concentration, and that the hexokinases had little regulatory function.


Effect of Metabolite Extract of Streptomyces hygroscopicus subsp. hygroscopicus on Plasmodium falciparum 3D7 in Vitro.
Malaria eradication has been complicated by the repeated emergence of antimalarial drug resistances. We aimed to determine whether a metabolite extract of Streptomyces hygrocopicus subsp. hygroscopicus could decrease the viability of Plasmodium falciparum 3D7 in vitro. S. hygroscopicus subsp. hygroscopicus isolates were inoculated and fermented on the ISP4 medium. The fermented S. hygroscopicus was mixed with ethylacetate 1:5 (v/v), and the solvent phase was evaporated. Several concentrations of isolated extract was added to the P. falciparum 3D7 culture containing trophozoite and schizont stages in 24 wells plates when the degree of parasite-infected erythrocytes reached 5%, then incubated for 8 hours. DNA parasite density was measured using flow cytometry, parasite degree and morphology were observed under microscopic by Giemsa-stained smears. The metabolite extract affected the morphology of almost all of parasite asexual stages. Schizonts and trophozoites failed to grow and appeared damaged with pycnotic cores and loss of cytoplasmic content. At 8 hours there was a significant decrease in DNA parasite density in culture exposed to 2.6 mg/ml and 13 mg/ml (P = 0.002; P = 0.024) of the extract. The degree of parasite-infected erythrocytes was decreased from the beginning of exposure (0.02 mg/ml of the extract). There was a significant inverse correlation between the concentration of extract and the degree of parasite-infected erythrocytes as well as the density of DNA parasite (r = -0.772, P = 0.000; r =-0.753; P =0.000). Metabolite extract of S. hygroscopicus subsp. hygroscopicus causes morphological damage, decreases the degree of parasite-infected erythrocytes and the DNA density of P. falciparum 3D7 in vitro.


Searching for mechanisms of action of antimicrobials.
Although development of antimicrobial resistance by bacteria is a natural phenomenon, the antibiotic resistance crisis is a reality that leads us in a gap of antimicrobial alternatives on therapeutics. Considering this cruel reality and committed to contribute to look for new antibacterial agents, this manuscript presents a review of easy laboratory methods that evaluate the mode of action of compounds, since it is a basic requirement for the discovery and development of new drugs. The literature was screened by searching the keywords "mode of action", "antibiotic", "antimicrobial activity", "inhibition mode", "method" and "bacteria" in Pubmed, Scopus, Science Direct and BVS in a period of time from 2000 to 2019. This review demonstrates the wide variety of methods that can be employed in research on mechanisms of action of antibacterial substances. Therefore, we compiled different protocols (presented in the supplementary material), available in the literature, with the purpose of facilitating the start of experiments.


Jacalin: isolation, characterization, and influence of various factors on its interaction with human IgA1, as assessed by precipitation and latex agglutination.
An IgA1-specific lectin, Jacalin, was isolated from dried seeds of the jackfruit, Artocarpus integrifolia, by affinity binding to IgA1-Sepharose and elution with D-galactose. Jacalin is a glycoprotein with two non-covalently bound subunits (15 and 18 K). Interactions between Jacalin and human Igs were studied by precipitation in gel and in solution, and by agglutination of IgA1-coated latex by Jacalin. Jacalin precipitated only with IgA1-containing samples, including monomers, polymers, monoclonal, polyclonal and secretory IgA1, but not IgA2 of both A2m(1) and A2m(2) allotypes, nor with IgG1, 2, 3 and 4, IgM, IgD, and IgE; after neuraminidase treatment, only IgA1 and IgD were precipitated. Jacalin had a relatively broad pH range of activity in both precipitation and agglutination of IgA1-latex. Bivalent metal cations (Ca, Mg, Mn, Cu, Zn, Co, Cd), EDTA, Triton X-100, Tween-20, Na deoxycholate and ionic strength did not influence these reactions. Na dodecylsulphate, guanidine and urea inhibited the reactions whereas NP-40 rather enhanced them. Among 39 types of sugar tested, 10 displayed inhibitory activity, decreasing in the following order: p-nitrophenyl-alpha-D-galactopyranoside, 1-O-methyl-alpha-D-galactopyranoside, D-melibiose, p-nitrophenyl-beta-D-galactopyranoside, GalNAc, stachyose, 1-O-methyl-alpha-D-mannopyranoside, D-galactose, D-galactosamine and 1-O-methyl-alpha-D-glucopyranoside. IgA1, treated with neuraminidase or not, but not the other human Igs, was also an excellent inhibitor of agglutination, being more powerful than the best sugars studied. Only neuraminidase-treated IgD was also inhibitory, but less so than IgA1. Jacalin preferentially bound to alpha-linked non-reducing D-galactose. The configuration of OH-groups at C-2, C-4 and C-6 of D-galactose was important for the reaction. Jacalin recognizes terminal Gal beta 1-3GalNac-, as in the IgA1-hinge, and/or GalNAc-, but not Gal beta 1-4GlcNAc-, nor Gal beta 1-6GlcNAc-, nor their sialylayted extensions. Latex agglutination and its inhibition assay are particularly well suited for the study of these lectin-glycoprotein interactions.


Do breast cancer patients have a gender preference when choosing a breast surgeon?
There is a paucity of data on breast cancer (BC) patients' gender preferences when it comes to choosing their surgeon, unlike in other specialties like gynaecology and obstetrics, where women tend to prefer a female physician. The aim of this trial was to examine if there are any gender preferences in women with BC at the time of choosing their breast surgeon. A cross-sectional, observational and descriptive study with 528 patients, older than 18 years, at the Breast Department 'Servicio Oncológico Hospitalario del Instituto Venezolano de los Seguros Sociales', from January to June 2022. We applied an anonymous questionnaire to evaluate patients' gender preferences when it comes to choosing their breast surgeon. The average age of the patients was 56 ± 11 years. 89.4% did not have gender preferences, whereas 6.5% and 4.1% chose to be treated by female surgeons and male surgeons, respectively. The most important characteristics chosen by the patients when they decided to choose their breast surgeon were experience (75%), knowledge (54%) and hospital-based (41%). Personal and professional skills are the most important factors when it comes to patients choosing their breast surgeon, gender does not have any impact on expertise or competence.


A comprehensive program in asbestos hazard surveillance and education.
The surveillance program of asbestos workers at the Long Beach Naval Shipyard consists of a variety of clinical examinations and consultations; educational efforts targeted toward individual patients and groups; environmental measurement; maintenance of pertinent monographic and periodic literature; and records and report maintenance.


Self-concept, emotion and memory performance in schizophrenia.
The "self-reference effect" describes better memory for material someone has related to one's self previously. Schizophrenia can affect aspects of the inner self such as own thoughts or actions. Schizophrenia symptoms, therefore, might not only have an influence on the self-concept, including the self-attribution of positive or negative personality traits, but also reduce the self-reference effect. 15 schizophrenia patients and 15 matched healthy controls were asked to decide on positive and negative personality traits across three separate conditions: self-evaluation, other evaluation (of an intimate person), and during a lexical control task, respectively. An unannounced recognition task followed. Patients revealed a negative bias in the evaluation of themselves and of the well-known other person. The reference to a person (oneself, close other) increased later recognition performance. However, patients with schizophrenia revealed an overall decreased recognition performance. The amount of patients' passivity symptoms, i.e., an increase in the permeability of their "self-other boundary", correlated negatively with their recognition performance for previously self-referred characteristics and traits referred to the intimate other. This was not the case for lexically processed stimuli or an increase of negative symptoms. Our data underline the necessity of taking into account symptom subgroups when dealing with specific cognitive dysfunctions in schizophrenia.


Tuberculosis Infection among Non-US-Born Persons and Persons ≥60 Years of Age, United States, 2019-2020.
We examined tuberculosis (TB) infection results for the United States from the 2019-2020 National Health and Nutrition Examination Survey. Over this period, 10% of non-US-born persons and 7% of those >60 years of age tested positive for TB infection. These results provide up-to-date information on TB infection among study subpopulations.


MutSα and MutSβ as size-dependent cellular determinants for prime editing in human embryonic stem cells.
Precise genome editing in human pluripotent stem cells (hPSCs) has potential applications in isogenic disease modeling and ex vivo stem cell therapy, necessitating diverse genome editing tools. However, unlike differentiated somatic cells, hPSCs have unique cellular properties that maintain genome integrity, which largely determine the overall efficiency of an editing tool. Considering the high demand for prime editors (PEs), it is imperative to characterize the key molecular determinants of PE outcomes in hPSCs. Through homozygous knockout (KO) of MMR pathway key proteins MSH2, MSH3, and MSH6, we reveal that MutSα and MutSβ determine PE efficiency in an editing size-dependent manner. Notably, MSH2 perturbation disrupted both MutSα and MutSβ complexes, dramatically escalating PE efficiency from base mispair to 10 bases, up to 50 folds. Similarly, impaired MutSα by MSH6 KO improved editing efficiency from single to three base pairs, while defective MutSβ by MSH3 KO heightened efficiency from three to 10 base pairs. Thus, the size-dependent effect of MutSα and MutSβ on prime editing implies that MMR is a vital PE efficiency determinant in hPSCs and highlights the distinct roles of MutSα and MutSβ in its outcome.


Adherens Junctions Revisualized: Organizing Cadherins as Nanoassemblies.
This Perspective considers how classical cadherin cell-cell adhesion receptors are organized at the nanoscale to generate lateral clusters. Recent advances in optical microscopy reveal that clustering constitutes a general feature of cadherin organization, but one that takes diverse forms. Here we consider the molecular mechanisms responsible for cadherin clustering and their functional implications. We frame our discussion in light of what is known about how nanoscale organization is conferred upon the plasma membrane, through protein-protein interactions, regulation of the cortical actin cytoskeleton, and the lipid environment of the membrane.


Korean nurses' perspectives regarding handoffs.
Nursing handoffs are communicative routines in most nursing units. The handoff is critical to the continuity and safety of patient care. Negative perceptions of handoffs could hinder efficient communication between nurses. This study identified the perceptions of nurses' handoffs in Korea. A descriptive survey was employed. The population included nurses who worked in a general ward in 201 hospitals with more than 300 beds. 27.9% responded that the current handoff method needed to be changed and 75.8% had no handoff-related guideline. "Handoffs are frequently interrupted by outsiders' visits" was the most frequent problem expressed. Variables associated with a perceived need for change in handoff methods were age, handoff method, and preparation time for handoffs. Nurses recognized that handoffs were frequently interrupted by external factors and consumed too much time. Therefore, a standardized handoff method is needed to ensure the accuracy of information.


Sex Differences and Estrous Influences on Oxytocin Control of Food Intake.
Central oxytocin potently reduces food intake and is being pursued as a clinical treatment for obesity. While sexually dimorphic effects have been described for the effects of oxytocin on several behavioral outcomes, the role of sex in central oxytocin modulation of feeding behavior is poorly understood. Here we investigated the effects of sex, estrous cycle stage, and female sex hormones (estrogen, progesterone) on central oxytocin-mediated reduction of food intake in rats. Results show that while intracerebroventricular (ICV) oxytocin potently reduces chow intake in both male and female rats, these effects were more pronounced in males than in females. We next examined whether estrous cycle stage affects oxytocin's food intake-reducing effects in females. Results show that ICV oxytocin administration significantly reduces food intake during all estrous cycle stages except proestrous, suggesting that female sex hormones may modulate the feeding effects of oxytocin. Indeed, additional results reveal that estrogen, but not progesterone replacement, in ovariectomized rats abolishes oxytocin-mediated reductions in chow intake. Lastly, oxytocin receptor mRNA (Oxtr) quantification (via quantitative PCR) and anatomical localization (via fluorescent in situ hybridization) in previously established sites of action for oxytocin control of food intake revealed comparable Oxtr expression between male and female rats, suggesting that observed sex and estrous differences may be based on variations in ligand availability and/or binding. Overall, these data show that estrogen reduces the effectiveness of central oxytocin to inhibit food intake, suggesting that sex hormones and estrous cycle should be considered in clinical investigations of oxytocin for obesity treatment.


Some effects of chlorambucil on nuclear protein phosphorylation in the Yoshida ascites sarcoma.
The ability of nuclei, isolated from Yoshida ascites sarcoma cells, to phosphorylate nuclear proteins in the presence of [gamma-32P]ATP has been investigated. Comparisons were made between a strain sensitive to the effects of the alkylating agent, chlorambucil, with a corresponding resistant strain both before and after drug-treatment of tumour-bearing animals. There was no gross quantitative differences between the drug-sensitive and-resistant untreated cells but treatment resulted in increased levels in the sensitive strain. Qualitative differences were seen before treatment in the phosphorylation pattern of the tris-saline-soluble nuclear sap fraction. The high molecular weight species in the fraction from sensitive cells showed phosphorylations which were absent, or present at very low levels, in the corresponding fraction from drug-resistant cells. Changes were observed in the tris-saline-soluble and non-histone protein fractions from drug-sensitive cells following treatment of tumour-bearing animals. Only minor alterations in patterns of phosphorylation were seen in fractions from drug-resistant cells.


Mother to infant transmission of hepatitis C virus infection.
Eight women with chronic hepatitis C virus (HCV) infection during pregnancy gave birth to 11 children. Five of these children had elevated ALT, but only two had increased levels in more than one sample. All children tested before 6 months of age were positive for anti-HCV at most up to 7 months of age and then became negative. One child with a maximum ALT level of 8.4 mukat/l however, regained anti-HCV positivity at 12 months of age, and a liver biopsy at 21 months of age showed resolving hepatitis. Passively acquired HCV antibodies are obviously found in newborns of anti-HCV-positive mothers with chronic hepatitis. In 1 of 11 children, active anti-HCV production and concomitant liver disease suggested mother to infant transmission of hepatitis C virus infection.


Fc receptor-mediated transcytosis of IgG-coated liposomes across epithelial barriers.
Drug carriers such as liposomes are not readily transported across cellular barriers that constitute epithelia. However, certain epithelia (rabbit yolk sac endoderm and enterocytes of suckling rat gut proximal small intestine) are well known to transcytose maternal IgG by Fc receptor-mediated endocytic events. We have shown that coating liposomes with appropriate IgG enhances their transport across these epithelia, as measured both by radioactivity indicative of liposomal membrane or entrapped 125I-PVP and [3H]inulin, and by the hypoglycemic effect of entrapped insulin. It is suggested that these transported liposomes follow a pathway of transcytosis in clathrin-coated vesicles, thus escaping lysosomal degradation.


Composite waste recycling: Predictive simulation of the pyrolysis vapours and gases upgrading process in Aspen plus.
Waste generation is one of the greatest problems of present times, and the recycling of carbon fibre reinforced composites one big challenge to face. Currently, no resin valorisation is done in thermal fibre recycling methods. However, when pyrolysis is used, additional valuable compounds (syngas or H2-rich gas) could be obtained by upgrading the generated vapours and gases. This work presents the thermodynamic and kinetic multi-reaction modelling of the pyrolysis vapours and gases upgrading process in Aspen Plus software. These models forecast the theoretical and in-between scenario of a thermal upgrading process of an experimentally characterised vapours and gases stream (a blend of thirty-five compounds). Indeed, the influence of temperature (500 °C-1200 °C) and pressure (ΔP = 0, 1 and 2 bar) operating parameters are analysed in the outlet composition, residence time and possible reaction mechanisms occurring. Validation of the kinetic model has been done comparing predicted outlet composition with experimental data (at 700 °C and 900 °C with ΔP = 0 bar) for H2 (g), CO (g), CO2 (g), CH4 (g), H2O (v) and C (s). Kinetic and experimental results show the same tendency with temperature, validating the model for further research. Good kinetic fit is obtained for H2 (g) (absolute error: 0.5 wt% at constant temperature and 0.3 wt% at variable temperature) and H2O (v) shows the highest error at variable T (8.8 wt%). Both simulation and experimental results evolve towards simpler, less toxic and higher generation of hydrogen-rich gas with increasing operating temperature and pressure.


Combination effect on HIV infection in vitro of soluble CD4 and HIV-neutralizing antibodies.
In combination with HIV gp120 V3-loop antibody, two carbohydrate specific neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding (1B1) both displayed antagonism.


Meta-analytic approaches for examining complexity and heterogeneity in studies of adolescent development.
In the field of adolescent development, meta-analysis offers valuable tools for synthesizing and assessing cumulative research evidence on the effectiveness of programs, practices, and policies intended to promote healthy adolescent development. When examining the impact of a program implemented across multiple primary studies, variation is often observed in the methodological attributes of those primary studies, such as their implementation methods, program components, participant characteristics, outcome measurement, and the systems in which programs are deployed. Differences in methodological attributes of primary studies represented in a meta-analysis, referred to as complexity, can yield variation in true effects across primary studies, which is described as heterogeneity. We discuss heterogeneity as a parameter of interest in meta-analysis, introducing and demonstrating both graphical and statistical methods for evaluating the magnitude and impact of heterogeneity. We discuss approaches for presenting characteristics of heterogeneity in meta-analytic findings, and methods for identifying and statistically controlling for aspects of methodological complexity that may contribute to variation in effects across primary studies. Topics and methods related to assessing and explaining heterogeneity were contextualized in the field of adolescent development using a sample of primary studies from a large meta-analysis examining the effectiveness of brief alcohol interventions for youth. We highlighted approaches currently underutilized in the field and provided R code for key methods to broaden their use. By discussing various heterogeneity statistics, visualizations, and explanatory methods, this article provides the applied developmental researcher a foundational understanding of complexity and heterogeneity in meta-analysis.


Newman's theory of health applied in family caregiving in Canada.
This study was conducted using an innovative mode of heuristic inquiry within the context of Newman's theory of health as expanding consciousness. Twelve caregiving families of persons who were diagnosed with schizophrenia participated in the study. In accordance with Newman's theory of health as praxis, the majority of the participants in the study recognized their patterns of the whole. As a result, they reported understanding and acceptance of their relative's mental illness.


The rule of law: Natural, human, and divine.
In this paper we compare two different contexts-the legal and the scientific-in which the concept of law is prominent. We argue that the acute philosophical awareness, in the early modern period, of the difficulties surrounding the law concept in the scientific context, and the various responses to these difficulties, are rooted in an earlier tradition of jurisprudential concerns over the concept of natural law in its legal sense. We seek to show, further, that each one of the various philosophical accounts of the concept of natural law (in both of its senses) is embedded in a metaphysical and theological context, so that different visions of God yield different accounts of the meaning of the natural law idiom in science as well as legal theory.


Do prognosis and clinicopathological features differ in young early-stage breast cancer?
Breast cancer is the most frequently detected cancer and the leading cause of cancer-related death in women. Although it is mostly seen in older patients, breast cancer affects women aged 24 to >70 years, with poorer prognosis in young patients. Young age remains a controversial topic in the literature. This study aimed to identify subtype differences and the effect of age on early-stage breast cancer outcomes. A total of 300 consecutive patients underwent surgery between 2011 and 2015 for early-stage breast cancer. Of these, 248 were eligible for this study and were divided into three groups: group Y (aged ≤35 years), group M (aged >35 and ≤45 years), and group E (aged >45 years). The clinical and pathological features and data related to recurrence, metastasis, and death were recorded. No statistical differences were found between groups regarding histopathological features except for higher histological grade and Ki-67 levels in group M. Additionally, group Y recorded no progression (recurrence or metastasis) or death. Disease-free survival was 117.8 months (95% CI 111.8-123.8) for group M, which was significantly shorter than that for group E (p < 0.001). Additionally, the hazard ratio (HR) for progression from group M to group E was 10.21 with significant difference (p = 0.003, 95% CI 2.26-46.08). However, the HR of group Y to group E was 0.04, without significance (p = 0.788, 95% CI 0.18-345 × 106). The overall 5-year survival was 100% in group Y, 98.8% in group M, and 99.3% in group E, without significance. A very young age cannot be considered an independent risk factor for poor prognosis. Rather than age, histological grade and Ki-67 index are more important factors in early-stage breast cancer.


Management of Ureteral Stent Discomfort in Contemporary Urology Practice.
Ureteral stents are used ubiquitously in routine urological practice, and despite their long-standing clinical use, stent associated urinary symptoms and pain continue to be of significant concern for patients. Therefore, we reviewed contemporary randomized controlled trials and meta-analyses investigating the alleviation of urinary stent symptoms. A thorough search of randomized controlled trials and meta-analyses of pharmacotherapeutic means of alleviating urinary stent symptoms was conducted and reviewed. Efforts were made to evaluate the quality of studies based on methodology and tools used to assess symptoms. Our search resulted in 16 published reports that fit our criteria. Of these randomized controlled trials 13 involved oral agents while 3 studies evaluated intravesical therapies. Specific pharmacological classes that were assessed included nonsteroidal anti-inflammatory drugs, anesthetics, alpha-antagonists, anticholinergics and paralytics. The majority of randomized controlled trials evaluated the role of alpha-antagonists, which ultimately produced the most compelling evidence of a reduction in stent associated lower urinary tract symptoms and pain. The randomized controlled trials involving anticholinergic agents have produced inconsistent results. Stent associated symptoms are a significant source of dissatisfaction for patients undergoing urological procedures. Numerous agents have been studied and uroselective alpha-antagonists have most consistently demonstrated a significant reduction in symptoms.


Fluoride removal in batch and column systems using bonechar produced in a top-lit updraft drum gasifier and furnace.
Hundreds of millions of people are exposed to excessive levels of fluoride in drinking water, predominately in low-resource communities. Activated alumina is recognized as the best available technology for fluoride removal from drinking water by the United States Environmental Protection Agency, but it has substantial economic and environmental costs. Bonechar is a more environmentally friendly and potentially lower cost alternative adsorbent. Here, fluoride adsorption from groundwater (pH 8.1 ± 0.2) by activated alumina was compared with bonechar primarily produced from bovine bones at peak heating temperatures between 400 and 1100 °C in a modular top-lit updraft drum (TLUD) stove (using a bone-wood mixture) and furnace. TLUD and furnace bonechar produced at peak heating temperatures 650-1000 °C and 400-800 °C, respectively, outperformed activated alumina in batch tests (i.e., required smaller doses to achieve 90% fluoride removal). The impact of using bovine versus swine bones to produce bonechar had a negligible impact on fluoride adsorption. A wide range of peak heating temperatures in the TLUD achieved by varying primary air flow rates and fuel selection (e.g., bone-to-wood mass ratios) produced efficient fluoride adsorbents. This finding demonstrates that a TLUD can be a robust, operationally flexible production system. Fluoride removal by TLUD and furnace bonechars showed strong, negative correlations (R2 ≥0.88) with organic matter content. Bonechar pilot column tests indicated that the mass transfer zone was captured (i.e., immediate fluoride breakthrough was not observed) at an empty bed contact time (EBCT) of 5 min, increasing EBCT to 30 min had a minimal impact on adsorption efficiency, and intermittent operation (3-10 d shut-off periods) decreased effluent fluoride concentrations. Furnace bonechars produced at peak heating temperatures 400-700 °C outperformed activated alumina in pilot columns. Differences in adsorption efficiencies in batch and column tests were associated with the linearity of fluoride adsorption. A theoretical model quantifying adsorption linearity with Freundlich 1/n values was able to predict adsorber performance solely based on batch test data.


Transition from standard robotic prostatectomy to Retzius-sparing prostatectomy: feasibility and early outcomes.
Retzius-sparing robotic-assisted radical prostatectomy (rsRARP) has gained popularity due to superior early continence outcomes compared to standard robotic prostatectomy (sRARP). We evaluate the results of a single surgeon who transitioned from sRARP to rsRARP and compare oncologic and functional outcomes. We retrospectively reviewed all prostatectomies performed by a single surgeon between June 2018 and October 2020. Perioperative, oncologic, and functional data were collected and analyzed. Patients who underwent sRARP were compared with those who underwent rsRARP. Both groups contained 37 consecutive patients each. Preoperative patient characteristics and biopsy results were similar between the two groups. Perioperative outcomes were significant for longer operative room time and higher proportion of T3 tumors in the rsRARP group. Thirty-day complication and readmission rates were similar between groups. There was no difference in early oncologic outcomes, including positive surgical margin rate, biochemical recurrence, and need for adjuvant or salvage treatments. The time to urinary continence and immediate continence rate was superior in the rsRARP group. The Retzius-sparing approach can be safely adopted by surgeons experienced in sRARP without compromising early oncologic outcomes and with the benefit of improved early continence recovery.


Qualitative and quantitative observations of bone tissue reactions to anodised implants.
Research projects focusing on biomaterials related factors; the bulk implant material, the macro-design of the implant and the microsurface roughness are routinely being conducted at our laboratories. In this study, we have investigated the bone tissue reactions to turned commercially pure (c.p.) titanium implants with various thicknesses of the oxide films after 6 weeks of insertion in rabbit bone. The control c.p. titanium implants had an oxide thickness of 17-200 nm while the test implants revealed an oxide thickness between 600 and 1000 nm. Routine histological investigations of the tissue reactions around the implants and enzyme histochemical detections of alkaline and acid phosphatase activities demonstrated similar findings around both the control and test implants. In general, the histomorphometrical parameters (bone to implant contact and newly formed bone) revealed significant quantitative differences between the control and test implants. The test implants demonstrated a greater bone response histomorphometrically than control implants and the osteoconductivity was more pronounced around the test implant surfaces. The parameters that differed between the implant surfaces, i.e. the oxide thickness, the pore size distribution, the porosity and the crystallinity of the surface oxides may represent factors that have an influence on the histomorphometrical results indicated by a stronger bone tissue response to the test implant surfaces, with an oxide thickness of more than 600 nm.


Identifying barriers and facilitators to seeking care for symptoms of bacterial sepsis: A qualitative study.
Research suggests that early access to quality care is essential to improving bacteraemia outcomes and reducing the risk of developing sepsis because it allows for early intervention. Currently, there are limited data regarding the facilitators and barriers that alter the trajectory of arrival at the hospital when patients in the United States experience symptoms of bacteraemia and sepsis. This study sought to explore and describe the facilitators and barriers to seeking care for suspected bacteraemia and sepsis symptoms. A qualitative descriptive study. Ten men and women were recruited using convenience sampling. The study used audio-recorded semi-structured interviews and the collection of socio-demographic data as the data collection techniques. Thematic analysis was used, including inductive and deductive approaches, to analyse the data. During data analysis, the codes related to barriers and facilitators were collapsed into three themes-symptom recognition, psychosocial support and healthcare planning and coordination. The patients' participation in the study has contributed to our understanding of patients' perspectives and experiences in the pre-hospital phase and provides important insights into what barriers and facilitators are encountered. Study findings highlight the need to develop interventions to improve patient decision time, patient-provider interactions and knowledge of bacteraemia and sepsis through patient and provider education.


[The characteristics of the protein composition of the anomalous needles of spruce (Picea abies) and pine (Pinus silvestris) from the 10-kilometer zone of the Chernobyl Atomic Electric Power Station].
Comparative analysis for different antibodies' binding sites at the proteins samples, which were isolated from control and morphologically abnormal coniferous plants tissues have been investigated. Monoclonal antibodies against cytoskeletal proteins (actin, alpha- and beta tubulin), hsp 70 and against phosphotyrosine were used. It was detected that investigated biochemical features reflect morphological similarities between different plant species. Some differences between cytoskeleton proteins content in control and abnormal tissues have been also indicated. It is assumed that abnormal morphogenesis may be determined by low-level chronic irradiation during plants growth and development.


Relationship between corneal tissue and shape in short-term soft contact lens wear.
To investigate which morphometric and ocular surface tissue parameters are affected by short-term soft contact lens (CL) wear and to assess whether they carry related or independent information. Twenty-two healthy participants wore silicone hydrogel (SiHy; MyDay, CooperVision) soft CLs for 8 h in their left eye. Corneal tomography and corneoscleral topography were captured before and immediately after CL wear. Central corneal thickness (CCT), corneoscleral parameters (limbus position and corneoscleral junction [CSJ] angle) and corneal tissue parameters (corneal transparency and homogeneity) were evaluated. Corneoscleral parameters (limbus position and CSJ angle) were independent of corneal tissue parameters (transparency and homogeneity) at baseline and after CL wear. CCT was independent of all the other parameters examined at baseline, but baseline values of corneal tissue parameters were moderately correlated with CCT change (transparency: r = -0.51; p = 0.007), homogeneity: r = -0.46; p = 0.02). A complete characterisation of ocular surface changes following CL wear should consider corneoscleral topography and corneal densitometry simultaneously, since they carry complementary information.


The new soft intraocular lens implant.
The 29 cases using the Type E soft implant demonstrated that: 1. This implant is acceptable to the eye. 2. Good visual acuity can be obtained from a soft implant. 3. Postoperative course is characterized by minimal reaction. 4. This intraocular implant design is acceptable to the eye and stable within it. As with any new procedure, the actual facts are only known after a number of years of experience. The potential long-term success of the soft implant opens up a new vista in the field of intraocular lens implantation. We hope that our continuing efforts will prove useful in approaching the goal of perfect sight following cataract surgery.


Evidence that AphB, essential for the virulence of Vibrio vulnificus, is a global regulator.
The Vibrio vulnificus aphB mutant was significantly less virulent than the wild type and was impaired in motility and adherence to host cells. Microarray analysis revealed that AphB of V. vulnificus (AphB(Vv)) influences the expression of over 10% of the V. vulnificus genome. The combined results indicated that AphB(Vv) is a global regulator contributing to the pathogenesis of V. vulnificus.


Sequence, map position and genome organization of the RPL17B gene, encoding ribosomal protein L17b in Saccharomyces cerevisiae.
Sequence analysis of the newly defined SSU81 gene revealed an adjacent open reading frame (ORF) encoding a protein whose deduced amino acid sequence is identical to that of ribosomal protein L17. The DNA sequence of this region is different from that of the RPL17A gene and therefore represents a duplicate gene encoding L17. We have designated this gene RPL17B. The RPL17B coding region is split by an intron that occurs in the same position (codons 14/15) as the intron in RPL17A. The RPL17B promoter region includes two TATA boxes, a canonical UASRPG motif, and several pyrimidine-rich tracts. RPL17B was mapped by CHEF and lambda clone grid hybridization blots to the right arm of chromosome V, linked to the TRP2 and RAD51 genes. A partial ORF was identified adjacent to RPL17B and SSU81 that is homologous to an ORF (designated A509) physically linked to RPL17A. This observation, and the identical position of the introns within the RPL17 genes, suggest that one RPL17 locus arose by duplication and translocation of the other.


Receptor tyrosine kinase inhibitors block proliferation of TGEV mainly through p38 mitogen-activated protein kinase pathways.
Emerging coronaviruses (CoVs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, and no approved therapeutics are currently available. Here, A9, a receptor tyrosine kinase inhibitor (RTKI) of the tyrphostin class, is identified as a robust inhibitor of transmissible gastroenteritis virus (TGEV) infection in cell-based assays. Moreover, A9 exhibited potent antiviral activity against the replication of various CoVs, including murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV). We further performed a comparative phosphoproteomic analysis to investigate the mechanism of action of A9 against TGEV infection in vitro. We specifically identified p38 and JNK1, which are the downstream molecules of receptor tyrosine kinases (RTKs) required for efficient TGEV replication, as A9 targets through plaque assays, qRT-PCR and Western blotting assays. p38 and JNK1 inhibitors and RNA interference further showed that the inhibitory activity of A9 against TGEV infection was mainly mediated by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. All these findings indicated that the RTKI A9 directly inhibits TGEV replication and that its inhibitory activity against TGEV replication mainly occurs by targeting p38, which provides vital clues to the design of novel drugs against CoVs.


Therapeutic drug monitoring of disease-modifying antirheumatic drugs in circulating leukocytes in immune-mediated inflammatory diseases.
The treatment of immune-mediated inflammatory diseases (IMIDs) is one of the main challenges of modern medicine. Although a number of disease-modifying antirheumatic drugs (DMARDs) are available, there is wide variability in clinical response to treatment among individuals. Therapeutic drug monitoring (TDM) has been proposed to optimize treatment; however, some patients still experience unsatisfactory outcomes, although the blood concentrations of drugs in these patients remain in the therapeutic range. One possible reason for this is that the conventional samples (e.g., whole blood or plasma) used in TDM may not accurately reflect drug concentrations or concentrations of their metabolites at the target site. Hence, more refined TDM approaches to guide clinical decisions related to dose optimization are necessary. Circulating leukocytes or white blood cells have a critical role in driving the inflammatory process. They are recruited to the site of injury, infection and inflammation, and the main target of small molecule DMARDs is within immune cells. Given this, assaying drug concentrations in leukocytes has been proposed to be of possible relevance to the interpretation of outcomes. This review focuses on the clinical implications and challenges of drug monitoring of DMARDs in peripheral blood leukocytes from therapeutic or toxicological perspectives in IMIDs.


Environmental pathways affecting gene expression (E.PAGE) as an R package to predict gene-environment associations.
The purpose of this study is to manually and semi-automatically curate a database and develop an R package that will act as a comprehensive resource to understand how biological processes are dysregulated due to interactions with environmental factors. The initial database search run on the Gene Expression Omnibus and the Molecular Signature Database retrieved a total of 90,018 articles. After title and abstract screening against pre-set criteria, a total of 237 datasets were selected and 522 gene modules were manually annotated. We then curated a database containing four environmental factors, cigarette smoking, diet, infections and toxic chemicals, along with a total of 25,789 genes that had an association with one or more of gene modules. The database and statistical analysis package was then tested with the differentially expressed genes obtained from the published literature related to type 1 diabetes, rheumatoid arthritis, small cell lung cancer, COVID-19, cobalt exposure and smoking. On testing, we uncovered statistically enriched biological processes, which revealed pathways associated with environmental factors and the genes. The curated database and enrichment tool are available as R packages at https://github.com/AhmedMehdiLab/E.PATH and https://github.com/AhmedMehdiLab/E.PAGE respectively.


The variable subdomain of Escherichia coli SecA functions to regulate SecA ATPase activity and ADP release.
Bacterial SecA proteins can be categorized by the presence or absence of a variable subdomain (VAR) located within nucleotide-binding domain II of the SecA DEAD motor. Here we show that VAR is dispensable for SecA function, since the VAR deletion mutant secAΔ519-547 displayed a wild-type rate of cellular growth and protein export. Loss or gain of VAR is extremely rare in the history of bacterial evolution, indicating that it appears to contribute to secA function within the relevant species in their natural environments. VAR removal also results in additional secA phenotypes: azide resistance (Azi(r)) and suppression of signal sequence defects (PrlD). The SecAΔ(519-547) protein was found to be modestly hyperactive for SecA ATPase activities and displayed an accelerated rate of ADP release, consistent with the biochemical basis of azide resistance. Based on our findings, we discuss models whereby VAR allosterically regulates SecA DEAD motor function at SecYEG.


(4-Benzyl-1-methyl-1,2,4-triazol-5-yl-idene)[(1,2,5,6-η)-cyclo-octa-1,5-diene](tri-phenyl-phosphane-κP)iridium(I) tetra-fluorido-borate.
A new triazole-based N-heterocyclic carbene iridium(I) cationic complex with a tetra-fluorido-borate counter-anion, [Ir(C10H11N3)(C8H12)(C18H15P)]BF4, has been synthesized and structurally characterized. The cationic complex exhibits a distorted square-planar environment around the IrI ion. One significant non-standard hydrogen-bonding inter-action exists between a hydrogen atom on the N-heterocyclic carbene ligand and a fluorine atom from the counter-ion, BF4 -. In the crystal, π-π stacking inter-actions are observed between one of the phenyl rings and the triazole ring. Both inter-molecular and intra-molecular C-H⋯π(ring) inter-actions are also observed.


Therapeutic strategies against epilepsy in Mediterranean countries: a report from an international collaborative survey.
A collaborative survey was performed to compare prescribing strategies for the treatment of epilepsy in Mediterranean countries, based on analysis of 500 questionnaires compiled by physicians in 14 different countries. For partial seizures, carbamazepine was the drug of choice in most countries, whereas the second choice of drug differed widely. For primarily generalized tonic-clonic seizures, valproic acid was usually preferred, but other drugs used widely in some countries included phenobarbital, phenytoin and carbamazepine. Lamotrigine was the most popular second-line drug for primarily generalized tonic-clonic seizures in the European countries. In patients where the initial drug failed, switching to an alternative monotherapy was usually the preferred strategy, but advocates of early use of combination therapy exceeded 30% in the respondents of seven countries. Most respondents, in all countries except Turkey, did not prescribe drugs to prevent recurrence of febrile seizures; however, intermittent prophylaxis with a benzodiazepine was advocated by a considerable number of physicians, and continuous prophylaxis was prescribed by a significant minority of respondents in France, Syria and Tunisia. New drugs were rarely used as first-line treatment due to high cost and inadequate experience. Overall, this survey indicates that there is a wide variability in therapeutic practices between and within countries. This information may be useful for the implementation of national educational activities and for the design of pragmatic trials aimed at comparing different therapeutic strategies.


Assessment of population-based input functions for Patlak imaging of whole body dynamic 18F-FDG PET.
Arterial blood sampling is the gold standard method to obtain the arterial input function (AIF) for quantification of whole body (WB) dynamic 18F-FDG PET imaging. However, this procedure is invasive and not typically available in clinical environments. As an alternative, we compared AIFs to population-based input functions (PBIFs) using two normalization methods: area under the curve (AUC) and extrapolated initial plasma concentration (CP*(0)). To scale the PBIFs, we tested two methods: (1) the AUC of the image-derived input function (IDIF) and (2) the estimated CP*(0). The aim of this study was to validate IDIF and PBIF for FDG oncological WB PET studies by comparing to the gold standard arterial blood sampling. The Feng 18F-FDG plasma concentration model was applied to estimate AIF parameters (n = 23). AIF normalization used either AUC(0-60 min) or CP*(0), estimated from an exponential fit. CP*(0) is also described as the ratio of the injected dose (ID) to initial distribution volume (iDV). iDV was modeled using the subject height and weight, with coefficients that were estimated in 23 subjects. In 12 oncological patients, we computed IDIF (from the aorta) and PBIFs with scaling by the AUC of the IDIF from 4 time windows (15-45, 30-60, 45-75, 60-90 min) (PBIFAUC) and estimated CP*(0) (PBIFiDV). The IDIF and PBIFs were compared with the gold standard AIF, using AUC values and Patlak Ki values. The IDIF underestimated the AIF at early times and overestimated it at later times. Thus, based on the AUC and Ki comparison, 30-60 min was the most accurate time window for PBIFAUC; later time windows for scaling underestimated Ki (- 6 ± 8 to - 13 ± 9%). Correlations of AUC between AIF and IDIF, PBIFAUC(30-60), and PBIFiDV were 0.91, 0.94, and 0.90, respectively. The bias of Ki was - 9 ± 10%, - 1 ± 8%, and 3 ± 9%, respectively. Both PBIF scaling methods provided good mean performance with moderate variation. Improved performance can be obtained by refining IDIF methods and by evaluating PBIFs with test-retest data.


TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation.
Secondary lymphedema is a common complication of cancer treatment, and previous studies have shown that the expression of transforming growth factor-beta 1 (TGF-β1), a pro-fibrotic and anti-lymphangiogenic growth factor, is increased in this disease. Inhibition of TGF-β1 decreases the severity of the disease in mouse models; however, the mechanisms that regulate this improvement remain unknown. Expression of TGF-β1 and extracellular matrix molecules (ECM) was assessed in biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL). The effects of TGF-β1 inhibition using neutralizing antibodies or a topical formulation of pirfenidone (PFD) were analyzed in mouse models of lymphedema. We also assessed the direct effects of TGF-β1 on lymphatic endothelial cells (LECs) using transgenic mice that expressed a dominant-negative TGF-β receptor selectively on LECs (LECDN-RII ). The expression of TGF-β1 and ECM molecules is significantly increased in BCRL skin biopsies. Inhibition of TGF-β1 in mouse models of lymphedema using neutralizing antibodies or with topical PFD decreased ECM deposition, increased the formation of collateral lymphatics, and inhibited infiltration of T cells. In vitro studies showed that TGF-β1 in lymphedematous tissues increases fibroblast, lymphatic endothelial cell (LEC), and lymphatic smooth muscle cell stiffness. Knockdown of TGF-β1 responsiveness in LECDN-RII resulted in increased lymphangiogenesis and collateral lymphatic formation; however, ECM deposition and fibrosis persisted, and the severity of lymphedema was indistinguishable from controls. Our results show that TGF-β1 is an essential regulator of ECM deposition in secondary lymphedema and that inhibition of this response is a promising means of treating lymphedema.


Clinical characteristics and functional outcome of stroke patients 75 years old and older.
To examine the demographic and clinical characteristics of stroke patients 75 years old and older admitted for rehabilitation, to study medical complications that occurred during rehabilitation, and to document functional outcome and possible factors influencing outcome. A case series of 59 consecutive inpatients admitted to a rehabilitation facility with confirmed strokes over a 2-year period. Patients were selected by rehabilitation physicians for admission into the rehabilitation program. Measures for outcome include the Modified Barthel Index (MBI) and the patient's discharge disposition. The mean age of this cohort was 80.4+/-3.2 years, and mean lengths of stay in the acute and rehabilitation facilities were 15.2 and 37.4 days. Twelve patients had three or more medical illnesses; hypertension and diabetes were the most common. Cognitive impairment, urinary incontinence, and dysphagia requiring tube feeding were present in 45.1%, 33.9%, and 11.9% of patients, respectively. Nineteen patients (32.2%) developed medical complications, and urinary tract infection was the most common. Improvements in functional status, motor power, continence, and dysphagia were noted after rehabilitation. Fifty-three patients (89.8%) were successfully discharged home, 28.8% of whom employed domestic maids as caregivers. The discharge MBI score was strongly predicted by the admission MBI and cognition scores. Despite their age, significant functional improvements were documented in this cohort of aged stroke patients, and the majority were discharged home. Admission MBI and cognition scores strongly predicted functional outcome.


Measuring clinical outcomes in neuro-oncology. A battery to evaluate low-grade gliomas (LGG).
We describe how a neuropsychological evaluation in patients with brain tumors should be performed, specifically in the case of low-grade gliomas. Neuropsychological examination is crucial before starting any treatment as well as during the follow-up, since it can improve neurosurgery techniques and reveal potential cognitive effects of chemotherapy and radiotherapy, besides planning rehabilitation. We underline that sensitive and wide-ranging tests are required; specific tasks based on the lesion site should be added. Moreover, some tests can provide additional information about the evolution of the tumor. A careful, thorough examination improves quality of life.


Tracheal cancer: a rare and deadly but potentially curable disease that also affects younger people.
The incidence of tracheal cancer is low, few clinicians get much experience and the awareness may be low. Recent data on the treatment and outcome are limited. The aim of the present study was to present updated, national data on the incidence, characteristics, treatment and outcome for patients with tracheal cancer. All tracheal cancers registered at the Cancer Registry of Norway in 2000-2020 were extracted. The patient and tumour characteristics age, sex, stage, histology and treatment modality (surgery and radiotherapy) were examined. Overall, median and relative survival were estimated. Cox regression models were used to identify independent prognostic factors. The 77 patients diagnosed with tracheal cancer equals a crude incidence rate and an age-standardized incidence rate of 0.075 and 0.046 per 100,000 per year respectively. The mean age was 63.8 years (range: 26-94). The numerical preponderance of men (n = 41) is not statistically significant. Eighteen patients (23.4%) were diagnosed in the localized stage. The 5-year overall survival was 31.7% [95% confidence interval (CI): 21.0-42.9], and in those treated with surgical resection or curative radiotherapy, it was 53.7% (95% CI: 26.1-75.0) and 37.8% (95% CI: 18.8-56.7), respectively. Age, histological type and treatment modality were identified as independent prognostic factors. Despite improved survival, the prognosis for patients with tracheal cancer is still poor. Few are diagnosed in the early stage and thus most are not eligible for curative treatment, mainly surgery. An increased awareness and diagnosis in the earlier stage is crucial.


Depot naltrexone: long-lasting antagonism of the effects of heroin in humans.
Naltrexone, an opioid antagonist, is currently approved as a treatment for heroin dependence. However, naltrexone is generally not well accepted by patients, and medication non-compliance is a difficult obstacle to treatment. A sustained-release form of naltrexone may improve compliance. The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex). Twelve heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, six participants received 192 mg naltrexone base and six participants received 384 mg naltrexone base. For safety, the low dose of depot naltrexone was tested before the high dose. The effects of heroin (0, 6.25, 12.5, 18.75, 25 mg, i.v.) were evaluated for the next 6 weeks. One dose of heroin was tested per day on Mondays through Fridays, and the entire dose range was tested each week. Active heroin doses were administered in ascending order during the week, while placebo could be administered on any day. Subjective, performance, and physiological effects were measured both before and after heroin administration. The hypotheses were that depot naltrexone would antagonize the effects of heroin, and that the high dose of depot naltrexone would produce a more effective and longer-lasting antagonism than the low dose. The low and high doses of depot naltrexone antagonized heroin-induced subjective ratings for 3 and 5 weeks, respectively. Plasma levels of naltrexone remained above 1 ng/ml for approximately 3 and 4 weeks after administration of 192 mg and 384 mg naltrexone. Other than the initial discomfort associated with the injection of depot naltrexone, there were no untoward side-effects. These results suggest that this depot formulation of naltrexone provides a safe, effective, long-lasting antagonism of the effects of heroin.


The inactive X chromosome accumulates widespread epigenetic variability with age.
Loss of epigenetic control is a hallmark of aging. Among the most prominent roles of epigenetic mechanisms is the inactivation of one of two copies of the X chromosome in females through DNA methylation. Hence, age-related disruption of X-chromosome inactivation (XCI) may contribute to the aging process in women. We analyzed 9,777 CpGs on the X chromosome in whole blood samples from 2343 females and 1688 males (Illumina 450k methylation array) and replicated findings in duplicate using one whole blood and one purified monocyte data set (in total, 991/924 females/males). We used double generalized linear models to detect age-related differentially methylated CpGs (aDMCs), whose mean methylation level differs with age, and age-related variably methylated CpGs (aVMCs), whose methylation level becomes more variable with age. In females, aDMCs were relatively uncommon (n = 33) and preferentially occurred in regions known to escape XCI. In contrast, many CpGs (n = 987) were found to display an increased variance with age (aVMCs). Of note, the replication rate of aVMCs was also high in purified monocytes (94%), indicating an independence of cell composition. aVMCs accumulated in CpG islands and regions subject to XCI suggesting that they stemmed from the inactive X. In males, carrying an active copy of the X chromosome only, aDMCs (n = 316) were primarily driven by cell composition, while aVMCs replicated well (95%) but were infrequent (n = 37). Our results imply that age-related DNA methylation differences at the inactive X chromosome are dominated by the accumulation of variability.


Comorbidities and mortality rate in COVID-19 patients with hematological malignancies: A systematic review and meta-analysis.
The global pandemic of coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It seems that there is an association between blood cancer and an increased risk of severe COVID-19. This study aimed to review the literature reporting the COVID-19 outcomes in patients with hematological malignancies. In this systematic review and meta-analysis, Pubmed, Embase, and Web of Science databases were searched using the following keywords: COVID-19, SARS-CoV-2, blood cancer, myeloma, lymphoma, and leukemia. All the published articles in English from January 1, 2019, until March 10, 2021 were collected and evaluated. In total, 53 studies with 2395 patients were included based on inclusion criteria. Most of these studies took place in Spain (14.81%), followed by the USA (11.11%), China (9.26%), and the UK (9.26%). More than half of COVID-19 patients with hematological malignancy were male (56.73%). Oxygen therapy played an important role in COVID-19 treatment. Moreover, anticoagulant therapies such as enoxaparin and heparin were two great assists for these patients. Fever (74.24%), cough (67.64%), and fatigue (53.19%) were the most reported clinical manifestations. In addition, hypertension and dyslipidemia were the most common comorbidities. The mortality rate due to COVID-19 in patients with hematological malignancies was 21.34%. This study demonstrated that hematologic cancer patients were more susceptible to a severe COVID-19 than patients without blood cancer. Thus, the management of COVID-19 in these patients requires much more attention, and their screening should perform regularly.


Evidence of kinesin motors involved in stable kinetochore assembly during early meiosis.
During mitosis, the budding yeast, kinetochores remain attached to microtubules, except for a brief period during S phase. Sister-kinetochores separate into two clusters (bilobed organization) upon stable end-on attachment to microtubules emanating from opposite spindle poles. However, in meiosis, the outer kinetochore protein (Ndc80) reassembles at the centromeres much later after prophase I, establishing new kinetochore-microtubule attachments. Perhaps due to this, despite homolog bi-orientation, we observed that the Ndc80 are linearly dispersed between spindle poles during metaphase I of meiosis. The presence of end-on attachment marker Dam1 as a cluster near each pole suggests one of the other possibilities that the pole-proximal and pole-distal kinetochores are attached end-on and laterally to the microtubules, respectively. Colocalization studies of kinetochores and kinesin motors suggest that budding yeast kinesin 5, Cin8, and Kip1 perhaps localize to the end-on attached kinetochores while kinesin 8 and Kip3 resides at all the kinetochores. Our findings, including kinesin 5 and Ndc80 coappearance after prophase I and reduced Ndc80 levels in cin8 null mutant, suggest that kinesin motors are crucial for kinetochore reassembly and stability during early meiosis. Thus, this work reports yet another meiosis specific function of kinesin motors.


Melatonin Alleviates the Oxygen-Glucose Deprivation/Reperfusion-Induced Pyroptosis of HEI-OC1 Cells and Cochlear Hair Cells via MT-1,2/Nrf2 (NFE2L2)/ROS/NLRP3 Pathway.
Substantial evidence suggests that pyroptosis is involved in renal, cerebral, and myocardial ischemia-reperfusion injury. However, whether pyroptosis is involved in ischemia-reperfusion injury of cochlear hair cells has not been explored. In this study, we examined the effects of melatonin on the oxygen-glucose deprivation/reperfusion (OGD/R) of hair cell-like House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear hair cells in vitro to mimic cochlear ischemia-reperfusion injury in vivo. We found that melatonin treatment protected the HEI-OC1 and cochlear hair cells against OGD/R-induced cell pyroptosis and reduced the expression level of ROS in these cells. However, these effects were completely abolished by the application of luzindole (a non-selective melatonin receptor blocker) and largely offset by the use of ML385 (an nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor). These findings suggest that melatonin alleviates OGD/R-induced pyroptosis of the hair cell-like HEI-OC1 cells and cochlear hair cells via the melatonin receptor 1A (MT-1) and melatonin receptor 1B (MT-2)/Nrf2 (NFE2L2)/ROS/NLRP3 pathway, which may provide credible evidence for melatonin being used as a potential drug for the treatment of idiopathic sudden sensorineural hearing loss in the future.


Research on natal and neonatal teeth in Africa: A systematic scoping review of empirical evidence.
In Africa, natal and neonatal teeth is a culture-bound phenomenon which is associated with several sociocultural connotations which might affect child survival. Different empirical studies have been conducted in Africa on natal and neonatal teeth; however, no known scoping review has been conducted to map the empirical evidence. This systematic scoping review (SSR) aims to document the available empirical evidence, research gaps, and hotspots on neonatal and natal teeth in Africa. The methodology of this SSR was informed by the Joanna Brigg's Institute guidelines for SSRs, and it was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Eleven research databases were systematically searched to scooped out all literatures relevant to the scoping review question, after which they were screened for eligibility based on the review's selection criteria. Only the eligible literatures were included in the review. Data were extracted from the included literatures, after which the extracted data were collated, summarized, and presented as results. This review included only three journal articles. All the reviewed articles revealed knowledge gaps about natal/neonatal teeth. These articles also found misconceptions around natal/neonatal teeth; for example, nurses' and traditional birth attendants' beliefs about these teeth are contrary to scientifically known facts. Multiple myths associated with natal/neonatal teeth, as indicated in the reviewed studies, point to a poor understanding of the condition. Neonates and infants are highly vulnerable persons; they require care and safeguarding from dental myths that could threaten their survival. Educative information concerning natal/neonatal teeth should be included in public health education programs to address the observed knowledge gaps among African populations and correct wrong beliefs on neonatal and natal teeth.


MWASTools: an R/bioconductor package for metabolome-wide association studies.
MWASTools is an R package designed to provide an integrated pipeline to analyse metabonomic data in large-scale epidemiological studies. Key functionalities of our package include: quality control analysis; metabolome-wide association analysis using various models (partial correlations, generalized linear models); visualization of statistical outcomes; metabolite assignment using statistical total correlation spectroscopy (STOCSY); and biological interpretation of metabolome-wide association studies results. The MWASTools R package is implemented in R (version > =3.4) and is available from Bioconductor: https://bioconductor.org/packages/MWASTools/. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Cutaneous tumor of northern pike, Esox lucius L. II. Expression of surface and cytoplasmic immunoglobulins and alpha-naphthyl acetate esterase by mononuclear cells from lymphoid tissues and tumor.
Rabbit anti-pike IgM antibodies showed that up to 95% of mononuclear (MN) cells isolated on Ficoll-Isopaque gradients from peripheral blood, spleen, and head kidney of northern pikes carrying cutaneous tumors were surface (SIg) and cytoplasmic (CIg) immunoglobulin positive by indirect immunofluorescence. On the contrary, rabbit anti-winter flounder IgM antibodies gave totally negative results. Monoclonal anti-carp IgM antibodies stained approximately 40-56% of peripheral blood, splenic, and head kidney MN cells in assays for SIg and CIg. Monoclonal anti-rainbow trout IgM antibodies, however, did not cross-react with pike Ig. A maximum of 5% of MN cells from the tumor were SIg and CIg positive by anti-pike IgM as well as 6% by anti-carp IgM antibodies, and were negative by the other two antibodies even at low dilutions. A majority of cells in the tumor exhibited an intense diffuse staining pattern for alpha-naphthyl acetate esterase (ANAE) which was inhibited by sodium fluoride and was reminiscent of that noted in human monocytes. These findings show that the Aland pike neoplasm is not a B cell tumor or plasmacytoma, but more representative markers are needed to demonstrate whether it is of T lymphocytic or monocytic origin.


Neurovascular morbidity from the lithotomy position.
The lithotomy position is used in pediatric surgery when it is necessary to have simultaneous access to the abdomen and perineum. At the authors' institution, after a prolonged period in the lithotomy position, significant lower limb complications developed in four patients. Two patients with Hirschsprung's disease underwent a redo Duhamel procedure, one had an anorectal leiomyoma excised, and one had an ileoanal anastomosis for ulcerative colitis. Sciatic nerve injury developed in two patients and deep venous thrombosis and bilateral compartment syndrome resulting in myonecrosis developed in one each. There is an association between operations that require prolonged lithotomy position and the development of postoperative neurovascular complications. By placing the child in the lithotomy position only when access to the perineum is required, these significant injuries may be avoided.


Preliminary study of lithium tetraborate doped with Cu and in for external dosimetry.
A potentially tissue-equivalent dosimeter based on lithium tetraborate co-doped with Cu and In was successfully synthesized in two steps melting process. Basic material properties were characterized using Differential scanning calorimetry, X-ray diffraction, and Fourier Transform Infrared Spectroscopy, the dosimetric properties using Thermoluminescence. The highest sensitivity was observed for dopant concentrations of 0.1% Cu and 0.5% In. Tmax-Tstop analysis revealed the existence of eight individual peaks in the composite TL glow curve, which was confirmed by computerized glow curve deconvolution. A linear dose-response was seen up to about 30 Gy, for higher doses saturation effects occurred. The minimum detectable dose was estimated at about 670 μGy. TL peaks, with peak temperature above 150 °C faded to values between 3.3 and 14.9% of the respective of initial values after 70 days storage.


Pregnancy rates and gravid uterine parameters in single, twin and triplet pregnancies in naturally bred ewes and ewes after transfer of in vitro produced embryos.
The objectives of this study were to: (1) evaluate the pregnancy rates after transfer of embryos produced in the presence or absence of epidermal growth factor (EGF) during in vitro maturation, and (2) compare several variables of the gravid uterus on day 140 after fertilization in single, twin and triplet pregnancies in ewes (n = 12) bred naturally and in ewes (n = 18) after transfer of embryos produced in vitro. Oocytes collected from FSH-treated ewes (n = 18) were collected from all visible follicles and cultured in maturation medium with or without EGF. Oocytes were then fertilized in vitro by frozen-thawed semen. On day 5 after fertilization, embryos with > or = 16 cells were transferred to recipient ewes (n = 39). In addition 12 ewes were bred naturally. Pregnancy was verified by real-time ultrasonography on day 45 or later after embryo transfer (ET) or breeding. On day 140 of pregnancy, the reproductive tract was collected from all ewes and the following parameters were determined: the number, sex, weight and crown to rump length (CRL) of fetuses, weights of gravid uterus and fetal membranes, and weight and number of placentomes. Presence of EGF in maturation medium increased (P < 0.04) cleavage rates (78% versus 59%) and percentage of > or = 16 cell embryos on day 5 after fertilization (62% versus 40%). Pregnancy rates tended to be greater (P < 0.1) after transfer of embryos matured in the presence of EGF (52%) than in the absence of EGF (39%). EGF presence in maturation medium did not affect any variables of gravid uterus or fetal weight. For single pregnancies in naturally bred ewes and ewes after ET all uterine variables were similar. For twin pregnancies, weight of gravid uterus, weight of uterus plus fetal membranes, total weight of placentomes/ewe, mean weight of individual placentome, mean weight of fetus, total fetal weight/ewe and CRL were greater (P < 0.0001-0.04) for ewes after ET than for ewes bred naturally. The weights of gravid uterus, fluid, uterus plus fetal membranes, fetal membranes, total placentomes/ewe, mean weight of individual placentome and total fetal weight/ewe were greater (P < 0.0001-0.08) for triplet pregnancies in ewes after ET than single and twin pregnancies in ewes naturally bred or after ET. The number of placentomes/fetus was greatest (P < 0.0001-0.06) in single pregnancies in ewes bred naturally and after ET fewer in twin pregnancies in ewes bred naturally and after ET and fewest in triplet pregnancies in ewes after ET. The total number of placentomes/ewe was greatest (P < 0.0001-0.06) for twin pregnancies in ewes naturally bred, fewer in single pregnancies in ewes naturally bred and twin and triplet pregnancies after ET, and fewest in single pregnancies in ewes after ET. The mean weight of fetus was greater (P < 0.0001-0.07) in single pregnancies in ewes naturally bred or after ET than in twin or triplet pregnancies in ewes naturally bred or after ET. The CRL was the lowest (P < 0.01) in twin pregnancies in ewes bred naturally. For pregnancies after natural breeding and after ET, the number of fetuses/ewe was negatively correlated (P < 0.03-0.0001) with the weight of placentomes/fetus, the number of placentomes/fetus, the mean weight of the fetus and CRL, and was positively correlated (P < 0.0001-0.05) with weight of gravid uterus, the total number of placentomes/ewe and total fetal weight/ewe. These data demonstrate that the presence of EGF in maturation medium increases the rates of cleavage and early embryonic development, and has a tendency to enhance rates of pregnancy but does not affect variables of the gravid uteri in ewes after transfer of in vitro produced embryos. Transfer of embryos produced in vitro affected some uterine variables in twin but not single pregnancies to compare with pregnancies after natural breeding. In addition, culture conditions in the present experiment did not create large offspring syndrome. The low number of placentomes/fetus seen in triple pregnancies appears to be compensated for by the increase in the weight of each individual placentome.


Rapid learning of a phonemic discrimination in the first hours of life.
Human neonates can discriminate phonemes, but the neural mechanism underlying this ability is poorly understood. Here we show that the neonatal brain can learn to discriminate natural vowels from backward vowels, a contrast unlikely to have been learnt in the womb. Using functional near-infrared spectroscopy, we examined the neuroplastic changes caused by 5 h of postnatal exposure to random sequences of natural and reversed (backward) vowels (T1), and again 2 h later (T2). Neonates in the experimental group were trained with the same stimuli as those used at T1 and T2. Compared with controls, infants in the experimental group showed shorter haemodynamic response latencies for forward vs backward vowels at T1, maximally over the inferior frontal region. At T2, neural activity differentially increased, maximally over superior temporal regions and the left inferior parietal region. Neonates thus exhibit ultra-fast tuning to natural phonemes in the first hours after birth.


Primary abscess of the omentum: report of a case.
We report a case of a primary abscess of the omentum without any obvious etiology. A 62-year-old man was referred to our clinic with lower abdominal pain, and computed tomography showed an intra-abdominal abscess in the left pelvic area. Laparotomy revealed that the abscess adhered to the urinary bladder and abdominal wall, but no perforation of the alimentary tract was identified and there was no foreign body in the abscess cavity. A culture of the abscess fluid grew Clostridium perfringens. The patient was discharged on the 16th hospital day after an uneventful postoperative course without any complications.


[Prescribing neuroleptics to senile dementia patients. On outcome in old age homes after inpatient psychiatric treatment].
Psychopharmacological treatment of all demented patients (n = 49), discharged to nursing homes after gerontopsychiatric hospital treatment in 1992 and 1993, was analyzed. In spite of the higher risk of secondary effects in elderly, demented people are after prescriptions for psychopharmacologic medications, especially neuroleptics. It was shown that the residents in nursing homes receive significantly more neuroleptics than patients who are discharged (P = 0.0001). Prescriptions for benzodiazepines were two times higher, whereas clomethiazole was rarely given. In nursing homes these substances were prescribed as continuous treatment. Most prescriptions resulted from agitation, sleep disturbances or aggressive behavior. Astonishingly, the patients without positive effects from treatment, who worsened regarding behavioral complications of dementia, obtained the highest doses of neuroleptics.


Polycystic ovary syndrome: symptomatology, pathophysiology, and epidemiology.
Women with polycystic ovary syndrome seek health care for 3 major reasons: infertility, menstrual irregularity, and androgen excess. The infertility is associated with anovulation. The menstrual irregularity is typically chronic, beginning with menarche. Although amenorrhea may sometimes occur, the more common presentation is irregular bleeding characteristic of anovulation. Androgen excess may be manifested by varying degrees of hirsutism. Patients may also report acne. The rapid development of virilizing signs, such as deepening of the voice, increased muscle mass, and temporal balding, should prompt a search for a tumor and lead one away from a diagnosis of polycystic ovary syndrome. Typically treatment is directed at alleviating the symptoms: ovulation induction for infertility, oral contraceptives or a progestin for menstrual irregularity, and oral contraceptives or spironolactone for hirsutism. On the basis of recent epidemiologic data suggestive of increased cardiovascular risk among women with polycystic ovary syndrome, such treatment might be complemented by a long-term approach that addresses the underlying pathophysiology of insulin resistance.


Malpractice Liability Risk and Use of Diagnostic Imaging Services: A Systematic Review of the Literature.
A widespread concern among physicians is that fear of medical malpractice liability may affect their decisions for diagnostic imaging orders. The purpose of this article is to synthesize evidence regarding the defensive use of imaging services. A literature search was conducted using a number of databases. The review included peer-reviewed publications that studied the link between physician orders of imaging tests and malpractice liability pressure. We identified 13 peer-reviewed studies conducted in the United States. Five of the studies reported physician assessments of the role of defensive medicine in imaging-order decisions; five assessed the association between physicians' liability risk and imaging ordering, and three assessed the impact of liability risk on imaging ordering at the state level. Although the belief that medical liability risk could influence decisions is highly prevalent among physicians, findings are mixed regarding the impact of liability risk on imaging orders at both the state and physician level. Inconclusive evidence suggests that physician ordering of imaging tests is affected by malpractice liability risk. Further research is needed to disentangle defensive medicine from other reasons for inefficient use of imaging.


Distribution of Met-enkephalyl-Arg-Gly-Leu in rat larynx: partial coexistence with vasoactive intestinal polypeptide, peptide histidine isoleucine and neuropeptide Y.
Using light microscopic (LM) enzyme-immunohistochemistry on deparaffinized adjacent sections Met-enkephalyl-Arg-Gly-Leu (ME-RGL) immunoreactivity was found to partially coexist with immunoreactive neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in intrinsic laryngeal neurons of the rat. Further ME-RGL-immunoreactive (ir) fibres were found around glands in the subepithelium, in connective tissue of striated muscle and in the perichondrium, as well as around arterial and venous blood vessels. They frequently contacted mast cells and macrophages. The presence of ME-RGL indicates pro-enkephalin-related origin of this novel laryngeal opioid system. From the specific target relations and close interrelations of fibres staining for opioids with those staining for the other peptides--which are known to be more or less characteristic of the sympathetic (NPY), parasympathetic (VIP, PHI) and sensory (calcitonin gene-related peptide; CGRP) subdivisions of the peripheral nervous system--we deduce that opioid/non-opioid interactions might co-control various laryngeal functions, e.g. glandular secretion, blood flow, immune and inflammatory responses and/or might be of relevance in trophic mechanisms.


Persistence of uncontrolled cardiovascular risk factors in patients treated with percutaneous interventions for stable coronary artery disease not receiving cardiac rehabilitation.
Cardiac rehabilitation programmes are strongly recommended for all forms of coronary artery disease to reduce recurrent events and mortality. Few patients seem to participate in these programmes after elective percutaneous coronary intervention (PCI). The aim of this study was to assess changes in lifestyle and risk factors after PCI for patients with stable disease and not included in cardiac rehabilitation programmes. We prospectively enrolled 207 consecutive patients with stable disease who underwent a first elective PCI. Follow up was performed at 13.0 ± 3.2 months for 94.7%; 28 patients were excluded due to participation in a cardiac rehabilitation programme. Baseline values from admission sheets were compared to follow up values collected from the treating physician. At follow up, systolic and diastolic blood pressures dropped (p = 0.001) as well as the prevalence of hypertension (p < 0.001). Significant reductions in cholesterol (p < 0.001) and blood glucose (p = 0.004) were also noted. Low-density lipoprotein levels stayed outside target in 47.2% and high-density lipoprotein levels in 75.0% of patients initially presenting with lipid disorders. Obesity prevalence remained high at follow up. Only 45.6% were performing regular physical exercise and 8.3% of smokers quit smoking. Only 13.3% attended any form of dietary advice programme. HADS-A score was 5.1 ± 3.9 and the HADS-D score was 3.8 ± 3.6. SF 36 questionnaire revealed a good quality of life with a mean value of 45.6 for physical and 42.9 for mental wellbeing. A considerable percentage of patients receiving PCI for stable angina do not achieve lifestyle and risk factor goals and therefore remain at increased risk for recurrent events. Efforts should be initiated to better implement guidelines that strongly recommend secondary prevention through cardiac rehabilitation after elective PCI.


Chordoid meningioma: presentation of two case reports, review of the literature, and plea for data standardisation.
Chordoid meningioma is a rare variant of meningioma with histological features resembling those of chordoma. This tumour should have a greater risk of recurrence and aggressive growth (WHO grade II). So far, 92 such tumours have been described in the literature. We report two cases of chordoid meningioma occurring in adult female patients. In our two patients (aged 28 and 60 years with chordoid meningioma of the convexity and left-sided outer sphenoid wing, respectively) we centred on some rarely discussed aspects of the tumour. MRI scans showed no edema in the vicinity of either of the two meningiomas, whereas selective angiography of ACI and ACE revealed a dural type of vascular supply to the two neoplasms. In both cases, the tumour was removed by radical surgery (Simpson grade I resection) with a normal post-operative course. Both women (one 2 years post-surgery and one 4 years post-surgery) are now free from any signs of relapse on MRI and with normal neurological findings. The vascular endothelial growth factor (VEGF) expression was low in either case (5 and 40%, respectively). We regard the factors under consideration in our study (i.e. absence of edema, dural supply, low VEGF expression and radical Simpson grade I resection) as an important contribution to the discussion of the biological behaviour of chordoid meningioma.


Epidemiology and Treatment Patterns of Venous Thromboembolism: an Observational Study of Nationwide Time-Series Trends in Japan.
Previous studies on anticoagulation treatment trends have mostly focused on hospitalized patients. This study aimed to clarify the treatment status of patients with venous thromboembolism (VTE) in Japan from 2011 to 2018, including outpatients, and to assess adherence with current guidelines. Data of inpatients and outpatients who were treated for VTE were extracted from a nationwide claims database (Medical Data Vision Co., Ltd., Tokyo, Japan) and analyzed. The study included 79,330 patients with VTE; half were diagnosed during hospitalization for diseases other than VTE. The proportion of outpatient treatment increased significantly from 2015 to 2018 (Cochran-Armitage trend test, P < 0.0001), while 80% were anticoagulated in hospital after pulmonary embolism (PE) diagnosis. The proportion of patients with VTE treated as outpatients was no lower than the proportion of inpatients, even in the presence of active cancer, and there were no clear differences in anticoagulant choices. Treatment with direct oral anticoagulants (DOACs) did not always include the recommended initial intensification therapy. There was wide variation in the duration of DOAC treatment and the median duration of use was shorter than that recommended in VTE treatment guidelines. While the gradual increase in VTE outpatient treatment appears to be in line with guideline recommendations, PE outpatient treatment could be further facilitated. The large proportion of patients diagnosed with VTE during hospitalization for other conditions suggests the importance of further utilizing in-hospital manuals for thrombosis prevention. The presence or absence of cancer did not appear to affect the basic treatment strategy of anticoagulation for VTE. Future studies are expected to better define the characteristics of patients who can be safely and effectively treated in an outpatient setting, and to examine whether anticoagulation for a shorter treatment period than recommended by the guidelines or DOAC therapy without initial intensification would improve patient outcomes.


Remission induction in a Jehovah's witness patient with acute myeloid leukaemia using gemtuzumab ozogamicin.
A 40-year-old patient, who was a Jehovah's Witness, with acute myeloid leukaemia entered remission using a chemotherapeutic based regime aided by the addition of gemtuzumab ozogamicin without requiring any blood product support. The use of gemtuzumab ozogamicin may have helped avoid fatal pancytopenia. The use of gemtuzumab ozogamicin might be considered in similar situations.


Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides.
Tumor-associated lymphocytes (TAL) isolated from ovarian cancer patients contain cytotoxic T lymphocytes (CTL) capable of recognizing specific HLA/peptide complexes on tumor cells leading to tumor cell lysis. Currently, HER2/neu, overexpressed in only 30% of breast and ovarian cancers, is the only known source of CTL-recognized peptides in epithelial cancers. Therefore, we have investigated peptides derived from folate binding protein (FBP), which is over-expressed in more than 90% of ovarian cancers and in the majority of other epithelial tumors. TAL were isolated from the malignant ascites of four consecutive HLA-A2+ ovarian cancer patients and incubated in IL-2. Initial chromium-release assays were performed within 1 week. T2 cells, incubated with peptide, were used to reconstitute T cell epitopes. The FBP sequence was interrogated for HLA-A2 binding peptides, and five were synthesized (E37-41). Freshly cultured, unstimulated ovarian TAL recognize peptides derived from FBP. These peptides are presented in the context of HLA-A2, and are specifically recognized in a HLA class I-restricted fashion. TAL recognition of these reconstituted T cell epitopes is concentration dependent. Furthermore, the FBP peptides are shown by cold target inhibition studies to be naturally processed and presented antigens. FBP peptides are recognized by freshly isolated TAL from ovarian cancer patients, suggesting in vivo expression and sensitization. Because FBP is over-expressed 20-fold in most adenocarcinomas, these peptides may be used in a widely applicable peptide-based vaccine for epithelial tumors.