Neuropeptide Y directly inhibits neuronal activity in a subpopulation of gonadotropin-releasing hormone-1 neurons via Y1 receptors.
Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is an orexigenic hormone. GnRH-1 neurons express NPY receptors. This suggests a direct link between metabolic function and reproduction. However, the effect of NPY on GnRH-1 cells has been variable, dependent on metabolic and reproductive status of the animal. This study circumvents these issues by examining the role of NPY on GnRH-1 neuronal activity in an explant model that is based on the extra-central nervous system origin of GnRH-1 neurons. These prenatal GnRH-1 neurons express many receptors found in GnRH-1 neurons in the brain and use similar transduction pathways. In addition, these GnRH-1 cells exhibit spontaneous and ligand-induced oscillations in intracellular calcium as well as pulsatile calcium-controlled GnRH-1 release. Single-cell PCR determined that prenatal GnRH-1 neurons express the G protein-coupled Y1 receptor (Y1R). To address the influence of NPY on GnRH-1 neuronal activity, calcium imaging was used to monitor individual and population dynamics. NPY treatment, mimicked with Y1R agonist, significantly decreased the number of calcium peaks per minute in GnRH-1 neurons and was prevented by a Y1R antagonist. Pertussis toxin blocked the effect of NPY on GnRH-1 neuronal activity, indicating the coupling of Y1R to inhibitory G protein. The NPY-induced inhibition was independent of the adenylate cyclase pathway but mediated by the activation of G protein-coupled inwardly rectifying potassium channels. These results indicate that at an early developmental stage, GnRH-1 neuronal activity can be directly inhibited by NPY via its Y1R.


Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells.
Chronic myeloid leukaemia (CML) arises after transformation of a haemopoietic stem cell (HSC) by the protein-tyrosine kinase BCR-ABL. Direct inhibition of BCR-ABL kinase has revolutionized disease management, but fails to eradicate leukaemic stem cells (LSCs), which maintain CML. LSCs are independent of BCR-ABL for survival, providing a rationale for identifying and targeting kinase-independent pathways. Here we show--using proteomics, transcriptomics and network analyses--that in human LSCs, aberrantly expressed proteins, in both imatinib-responder and non-responder patients, are modulated in concert with p53 (also known as TP53) and c-MYC regulation. Perturbation of both p53 and c-MYC, and not BCR-ABL itself, leads to synergistic cell kill, differentiation, and near elimination of transplantable human LSCs in mice, while sparing normal HSCs. This unbiased systems approach targeting connected nodes exemplifies a novel precision medicine strategy providing evidence that LSCs can be eradicated.


Transition to motherhood in type 1 diabetes: design of the pregnancy and postnatal well-being in transition questionnaires.
Life transitions are associated with high levels of stress affecting health behaviours among people with Type 1 diabetes. Transition to motherhood is a major transition with potential complications accelerated by pregnancy with risks of adverse childbirth outcomes and added anxiety and worries about pregnancy outcomes. Further, preparing and going through pregnancy requires vigilant attention to a diabetes management regimen and detailed planning of everyday activities with added stress on women. Psychological and social well-being during and after pregnancy are integral for good pregnancy outcomes for both mother and baby. The aim of this study is to establish the face and content validity of two novel measures assessing the well-being of women with type 1 diabetes in their transition to motherhood, 1) during pregnancy and 2) during the postnatal period. The approach to the development of the Pregnancy and Postnatal Well-being in T1DM Transition questionnaires was based on a four-stage pre-testing process; systematic overview of literature, items development, piloting testing of questionnaire and refinement of questionnaire. The questionnaire was reviewed at every stage by expert clinicians, researchers and representatives from consumer groups. The cognitive debriefing approach confirmed relevance of issues and identified additional items. The literature review and interviews identified three main areas impacting on the women's postnatal self-management; (1) psychological well-being; (2) social environment, (3) physical (maternal and fetal) well-being. The cognitive debriefing in pilot testing of the questionnaire identified that immediate postnatal period was difficult, particularly when the women were breastfeeding and felt depressed. The questionnaires fill an important gap by systematically assessing the psychosocial needs of women with type 1 diabetes during pregnancy and in the immediate postnatal period. The questionnaires can be used in larger data collection to establish psychometric properties. The questionnaires potentially play a key role in prospective research to determine the self-management and psychological needs of women with type 1 diabetes transitioning to motherhood and to evaluate health education interventions.


Human Regulatory Protein Ki-1/57 Is a Target of SUMOylation and Affects PML Nuclear Body Formation.
Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins and undergoes phosphorylation by PKC and methylation by PRMT1. Previous characterization of its protein interaction profile by yeast two-hybrid screening showed that Ki-1/57 interacts with proteins of the SUMOylation machinery, the SUMO E2 conjugating enzyme UBC9 and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with this process. Here we identified seven potential SUMO target sites (lysine residues) on Ki-1/57 sequence and observed that Ki-1/57 is modified by SUMO proteins in vitro and in vivo. We showed that SUMOylation of Ki-1/57 occurred on lysines 213, 276, and 336. In transfected cells expressing FLAG-Ki-1/57 wild-type, its paralog FLAG-CGI-55 wild-type, or their non-SUMOylated triple mutants, the number of PML-nuclear bodies (PML-NBs) is reduced compared with the control cells not expressing the constructs. More interestingly, after treating cells with arsenic trioxide (As2O3), the number of PML-NBs is no longer reduced when the non-SUMOylated triple mutant Ki-1/57 is expressed, suggesting that the SUMOylation of Ki-1/57 has a role in the control of As2O3-induced PML-NB formation. A proteome-wide analysis of Ki-1/57 partners in the presence of either SUMO-1 or SUMO-2 suggests that the involvement of Ki-1/57 with the regulation of gene expression is independent of the presence of either SUMO-1 or SUMO-2; however, the presence of SUMO-1 strongly influences the interaction of Ki-1/57 with proteins associated with cellular metabolism, maintenance, and cell cycle.


Effects of salinity and light on organic carbon and nitrogen uptake in a hypersaline microbial mat.
Utilization of dissolved organic matter (DOM) is thought to be the purview of heterotrophic microorganisms, but photoautotrophs can take up dissolved organic nitrogen (DON) and dissolved organic carbon (DOC). This study investigated DOC and DON uptake in a laminated cyanobacterial mat community from hypersaline Salt Pond (San Salvador, Bahamas). The total community uptake of (3)H-labeled substrates was measured in the light and in the dark and under conditions of high and low salinity. Salinity was the primary control of DOM uptake, with increased uptake occurring under low-salinity, 'freshened' conditions. DOC uptake was also enhanced in the light as compared with the dark and in samples incubated with the photosystem II inhibitor 3(3,4-dichlorophenyl)-1, 1-dimethylurea, suggesting a positive association between photosynthetic activity and DOC uptake. Microautoradiography revealed that some DOM uptake was attributed to cyanobacteria. Cyanobacteria DOM uptake was negatively correlated with that of smaller filamentous microorganisms, and DOM uptake by individual coccoid cells was negatively correlated with uptake by colonial coccoids. These patterns of activity suggest that Salt Pond microorganisms are engaged in resource partitioning, and DOM utilization may provide a metabolic boost to both heterotrophs and photoautrophs during periods of lowered salinity.


Thermally-efficient reconfigurable narrowband RF-photonic filter.
We present the design and fabrication of thermally-efficient tuning structures integrated into a narrowband reconfigurable radio-frequency (RF)-photonics filter using silicon-on-insulator waveguide optical delay lines. By introducing thermal isolation trenching, we are able to achieve IIR, FIR or arbitrary mixed response with less than 120 mW average tuning power in a single RF-photonic unit cell filter.


Relationship between domain-specific physical activity and different body composition measures in a working population.
With respect to the overweight epidemic, this study aimed to investigate the association between domain-specific physical activity and body composition measures in Swiss male employees. A total of 192 healthy male adults in full-time employment were investigated. Height, weight, and waist circumference were measured and body mass index was calculated. Relative fat mass and relative muscle mass were determined by bioelectric impedance analysis. Physical activity was assessed by the validated International Physical Activity Questionnaire. In multiple linear regressions, leisure-time activity showed an inverse association with waist circumference and relative fat mass and a positive correlation with relative muscle mass. Work activity was positively related to waist circumference and body mass index. This study shows that leisure-time activity may be the most effective physical activity domain for body composition. Work activity does not seem to be protective against overweight.


Biomarkers of manganese exposure in a population living close to a mine and mineral processing plant in Mexico.
Manganese (Mn) is considered an essential metal; nevertheless, excessive Mn exposure in humans is known to affect central nervous system. Mn access to its toxic target, the brain, is a complex phenomenon subject to physiological and physiopathological processes; in which, among others, the route of exposure plays an important role. Mn airborne exposure has gained interest both in occupational and environmental studies in order to understand the effects of low-level, long-term exposure. The objective of the present study was to describe the relationship between blood Mn and prolactin as marker of effect exposure, as well as other variables from subjects dwelling in a mining district in central Mexico environmentally exposed to the metal. This study was conducted on 230 volunteers; blood samples were obtained from cubital vein and hemoglobin, prolactin, lead (Pb), and Mn levels were measured. Non-parametrical Spearman's correlation showed statistical associations between blood and Mn levels and prolactin (rho=0.197), hemoglobin (rho= -0.213), age (rho= -0.186), and blood lead (rho= -0.167). Multiple regression analysis showed that blood Mn levels as an important factor to determine serum prolactin levels (beta=0.111, p=0.029) in a model corrected by gender and age. Results suggest that assessment of Mn exposure by biomarkers on general population is complex due to the variability and characteristics of the metal; however, specific subpopulations such as iron-deficient individuals are suspected to accumulate Mn in blood and thus they may be susceptible to the neurotoxic effects of Mn.


Nanoparticles-induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models.
Nanoparticles (NPs) have become one of the most popular objects of scientific study during the past decades. However, despite wealth of study reports, still there is a gap, particularly in health toxicology studies, underlying mechanisms, and related evaluation models to deeply understanding the NPs risk effects. In this review, we first present a comprehensive landscape of the applications of NPs on health, especially addressing the role of NPs in medical diagnosis, therapy. Then, the toxicity of NPs on health systems is introduced. We describe in detail the effects of NPs on various systems, including respiratory, nervous, endocrine, immune, and reproductive systems, and the carcinogenicity of NPs. Furthermore, we unravels the underlying mechanisms of NPs including ROS accumulation, mitochondrial damage, inflammatory reaction, apoptosis, DNA damage, cell cycle, and epigenetic regulation. In addition, the classical study models such as cell lines and mice and the emerging models such as 3D organoids used for evaluating the toxicity or scientific study are both introduced. Overall, this review presents a critical summary and evaluation of the state of understanding of NPs, giving readers more better understanding of the NPs toxicology to remedy key gaps in knowledge and techniques.


Cyclophosphamide leads to persistent deficits in physical performance and in vivo mitochondria function in a mouse model of chemotherapy late effects.
Fatigue is the symptom most commonly reported by long-term cancer survivors and is increasingly recognized as related to skeletal muscle dysfunction. Traditional chemotherapeutic agents can cause acute toxicities including cardiac and skeletal myopathies. To investigate the mechanism by which chemotherapy may lead to persistent skeletal muscle dysfunction, mature adult mice were injected with a single cyclophosphamide dose and evaluated for 6 weeks. We found that exposed mice developed a persistent decrease in treadmill running time compared to baseline (25.7±10.6 vs. 49.0±16.8 min, P = 0.0012). Further, 6 weeks after drug exposure, in vivo parameters of mitochondrial function remained below baseline including maximum ATP production (482.1 ± 48.6 vs. 696.2 ± 76.6, P = 0.029) and phosphocreatine to ATP ratio (3.243 ± 0.1 vs. 3.878 ± 0.1, P = 0.004). Immunoblotting of homogenized muscles from treated animals demonstrated a transient increase in HNE adducts 1 week after exposure that resolved by 6 weeks. However, there was no evidence of an oxidative stress response as measured by quantitation of SOD1, SOD2, and catalase protein levels. Examination of mtDNA demonstrated that the mutation frequency remained comparable between control and treated groups. Interestingly, there was evidence of a transient increase in NF-ĸB p65 protein 1 day after drug exposure as compared to saline controls (0.091±0.017 vs. 0.053±0.022, P = 0.033). These data suggest that continued impairment in muscle and mitochondria function in cyclophosphamide-treated animals is not linked to persistent oxidative stress and that alternative mechanisms need to be considered.


Leiomyoblastomas and their relationship to other smooth-muscle tumors of the gastrointestinal tract. An electron-microscopic study.
Twelve cases of gastrointestinal leiomyoblastoma were studied by electron microscopy, and the findings were compared with those in 12 cases of leiomyoma and nine cases of leiomyosarcoma of the gastrointestinal tract. All of the "classic" ultrastructural features of smooth-muscle tumors, including subplasmalemmal dense patches, pinocytotic vesicles, cytoplasmic microfilaments and dense bodies, and focal basement membrane formation, were present in the leiomyoblastomas ; however, extensive sampling was commonly necessary to demonstrate such findings. In contrast, these features were more prominent in leiomyomas and leiomyosarcomas.


Use of ultrasound in horses for diagnosis of left dorsal displacement of the large colon and monitoring its nonsurgical correction.
During a 28 month period, 82 horses with clinical signs of abdominal pain were examined for left dorsal displacement of the large colon (LDDLC) using percutaneous ultrasound. Left dorsal displacement of the large colon was diagnosed when a gas echo dorsal to the spleen obliterated the dorsal splenic border, or when the colon was observed lateral to the spleen. In 42 horses, ultrasound confirmed a diagnosis of LDDLC and 40 horses had no evidence of LDDLC. There were five false negative results and no false positives. In four horses with LDDLC, the colon was displaced between the spleen and body wall; three of these colic episodes resolved with medical therapy and the fourth required a celiotomy to relieve a sand impaction. The remaining 38 horses had a renosplenic entrapment; surgical correction was elected in 4 horses, 21 horses were corrected by a nonsurgical rolling procedure, 12 were corrected at surgery after an unsuccessful rolling attempt, and one was corrected by rolling but required surgery later because of an additional lesion. Percutaneous abdominal ultrasound was a valuable aid in the diagnosis of LDDLC and in confirming correction of the displacement after a nonsurgical rolling procedure.


Impact of Hepatic Encephalopathy on Clinical Characteristics and Adverse Outcomes in Prospective and Multicenter Cohorts of Patients With Acute-on-Chronic Liver Diseases.
Importance: Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear. Objective: We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases. Design: We conducted a cohort study of two multicenter prospective cohorts. Setting: China. Participants: Acute-on-chronic liver disease patients with various etiologies. Exposure: The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale. Main Outcome Measure: The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients. Results: A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1-4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1-2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures. Conclusions and Relevance: Hepatic encephalopathy grades 3-4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.


Good prognostic value of the intraoperative tissue Doppler-derived index E/e' after non-cardiac surgery.
The index E/e' derived from tissue Doppler imaging and pulsed Doppler is the ratio of the early transmitral flow velocity and the early mitral annular velocity and it correlates with left ventricular filling pressure. The purpose of this study was to investigate the relationship between intraoperative E/e' and postoperative cardiovascular complications and length of ICU and hospital stays after a non cardiac surgery. This observational study investigated a total of 82 patients with cardiac disease undergoing non cardiac surgery. Diastolic function was evaluated by conventional echocardiographic pulsed-wave Doppler and TDI. The early peak (E) as well as the late peak (A) filling velocity of the left ventricle (LV) were measured at the mid-esophageal four-chamber at the mitral leaflet tips. Early Peak diastolic filling velocity (e'), Late peak diastolic filling velocity (a') and systolic velocity (s') were obtained from the mid-esophageal four-chamber view placed in the septal and lateral mitral annular sites. Patients were divided into three groups: E/e'<8 (normal LV filling pressure= 24 patients), E/e' 8-15 (moderately increased =35 patients) and E/e'>15 (severely increased = 23 patients). An elevated E/e' ratio was significantly associated with increased postoperative cardiovascular events, pulmonary congestion (P<0.05) arrhythmias (P<0.05) and with longer ICU and hospital stays (P<0.05). This data suggests that the tissue Doppler index E/e' may be a useful indicator for predicting morbid events after non-cardiac surgery. Furthermore, patients with an elevated intraoperative E/e' may need more careful postoperative management.


Linear and Nonlinear Intersubband Optical Properties of Direct Band Gap GeSn Quantum Dots.
Intersubband optical transitions, refractive index changes, and absorption coefficients are numerically driven for direct bandgap strained GeSn/Ge quantum dots. The linear, third-order nonlinear and total, absorption coefficients and refractive index changes are evaluated over useful dot sizes' range ensuring p-like Γ-electron energy state to be lower than s-like L-electron energy state. The results show strong dependence of the total absorption coefficient and refractive index changes on the quantum dot sizes. The third order nonlinear contribution is found to be sensitive to the incident light intensity affecting both total absorption coefficient and refractive index changes, especially for larger dot sizes.


Bundles of fluid fibers formed by bent-core molecules.
The internal structures, stability, and elastic properties of free-standing filament bundles of bent-core smectic liquid crystals are studied using polarizing microscopy, scanning electron microscopy, and a customized cantilever containing, temperature controlled heat stage for force measurements. We find that in bundles, the individual filaments fuse together to form semiseparable filaments with radii approximately two and three times larger than the individual fibers. We also find that the effective surface tension of wide bundles is about 10% smaller than a single filament. Finally, we describe the metastable coexistences of single fibers within the bundles that lead to bending of the bundles. All of these observations were explained with simple macroscopic models.


Driving policy after seizures and unexplained syncope: a practice guide for RI physicians.
Physicians in Rhode Island sometimes find it difficult to advise patients about returning to driving after they present with a seizure or syncopal episode due to lack of statutory or professional guidance on the issue. We provide an overview of the medical literature on public policies and recommendations regarding driving after seizures or syncope. We also present the laws in Rhode Island regarding physician notification of the medical advisory board of the Department of Motor Vehicles, legal obligations, and immunity from prosecution for those who report. Finally, we present the results of a survey of current practice by Rhode Island neurologists when they advise patients who have had a recent seizure or unexplained syncopal event. Based upon this information, we hope local practitioners are empowered in their decision making on driving restrictions and we hope this data informs future public policy efforts.


Steady-State Human Pharmacokinetics of Monobutyl Phthalate Predicted by Physiologically Based Pharmacokinetic Modeling Using Single-Dose Data from Humanized-Liver Mice Orally Administered with Dibutyl Phthalate.
Dibutyl phthalate (DBP) was widely used as a plasticizer but it has been recently replaced with other kinds of phthalates such as di(2-ethylhexyl)phthalate and diisononyl phthalate because of its toxicity. To evaluate the human risk of DBP, forward and reverse dosimetry was conducted using in silico simplified physiologically based pharmacokinetic (PBPK) modeling based on in vivo experimental pharmacokinetic data in humanized-liver mice (HL-mice) obtained after an oral dose of 100 mg/kg. Absorbed DBP was converted to monobutyl phthalate (MBP) and its glucuronide extensively in vivo. HL-mice had higher concentrations of MBP glucuronide in plasma than did the control mice. Concentrations of MBP glucuronide in 0-7 h accumulated urine samples from HL-mice were significantly higher than those in control mice. Similarly, in vitro MBP glucuronidation rates mediated by pooled microsomes from rat or mouse livers were lower than those mediated by human liver microsomes. Liver damage by MBP to humanized liver was detected by measuring human albumin mRNA in HL-mouse plasma. By simple PBPK modeling, in silico concentration curves in plasma, liver, or urine following virtual oral administration of DBP were created for rats, control mice, and HL-mice. A human PBPK model for MBP was established based on the HL-mouse PBPK model using allometric scaling without consideration of interspecies factors in terms of liver metabolism. Human PBPK models were used to estimate urinary and plasma concentrations of MBP and its glucuronide throughout 14 days of oral DBP administration (1.2 and 13 μg/kg/day). Reverse dosimetry PBPK modeling found that reported 50th and 95th percentile MBP urine and plasma concentrations of the general population could potentially imply exposures similar to or exceeding tolerable daily intake levels (5-10 μg/kg/day) recommended by the European and Japanese authorities. Further in-depth assessment of DBP is needed to assess the validity of assumptions made based on human biomonitoring data.


Electrochemical Reversible Reforming between Ethylamine and Acetonitrile on Heterostructured Pd-Ni(OH)2 Nanosheets.
Rational design of electrocatalysts is essential to achieve desirable performance of electrochemical synthesis process. Heterostructured catalysts have thus attracted widespread attention due to their multifunctional intrinsic properties, and diverse catalytic applications with corresponding outstanding activities. Here, we report an in situ restoration strategy for the synthesis of ultrathin Pd-Ni(OH)2 nanosheets. Such Pd-Ni(OH)2 nanosheets exhibit excellent activity and selectivity towards reversible electrochemical reforming of ethylamine and acetonitrile. In the acetonitrile reduction process, Pd acts as reaction center, while Ni(OH)2 provide proton hydrogen through promoting the dissociation of water. Also ethylamine oxidation process can be achieved on the surface of the heterostructured nanosheets with abundant Ni(II) defects. More importantly, an electrolytic cell driven by solar cells was successfully constructed to realize ethylamine-acetonitrile reversible reforming. This work demonstrates the importance of heterostructure engineering in the rational synthesis of multifunctional catalysts towards electrochemical synthesis of fine chemicals.


SWORD '93. Surveillance of work-related and occupational respiratory disease in the UK.
Some 3500 new cases of occupational respiratory disease are estimated to have been seen annually by SWORD participants in 1992 and 1993 with little important difference between the two years. As the number of new cases recognized and reported by chest physicians is close to complete, the estimated incidence is essentially correct. The pattern of disease which clearly emerges shows that at least half is attributable to asbestos exposure, despite the fact that lung cancer from this cause may be under-reported. Benign pleural disease comprises a large proportion of the cases, the long-term implications of which are unknown. Almost 40% of the cases reported are of occupational asthma or inhalation accidents, both due to a very large number of different agents and affecting many and varied occupations. These cases are preventable providing their occupational aetiology is recognized and appropriate measures of control are intensified.


Brief Report: Deficiency of Complement 1r Subcomponent in Early-Onset Systemic Lupus Erythematosus: The Role of Disease-Modifying Alleles in a Monogenic Disease.
To identify a genetic cause of early-onset systemic lupus erythematosus (SLE) in a large consanguineous family from Turkey and to study the mechanisms of the disease. We performed whole-exome sequencing and single-nucleotide polymorphism array genotyping in family members with and without SLE. Protein and gene expression, cytokine profile, neutrophil extracellular trap (NET) formation, and presence of low-density granulocytes were evaluated in patient primary cells and serum samples. We identified a novel, homozygous, loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. Using the Sanger method of DNA sequencing in 14 family members, we confirmed the presence of the mutation in 4 patients with SLE and in an asymptomatic 9-year-old girl. Complement levels were low in sera from patients with truncated C1r protein. Two siblings with SLE who were available for detailed evaluation exhibited strong type I interferon (IFN) inflammatory signatures despite their disease being clinically inactive at the time of sampling. The type I IFN transcriptional signature in the patients' blood correlated with disease expressivity, whereas the neutrophil signature in peripheral blood mononuclear cells was likely associated with disease severity. The female patient with SLE with the most severe phenotype presented with a stronger neutrophil signature, defined by enhanced NET formation and the presence of low-density granulocytes. Analysis of exome data for modifying alleles suggested enrichment of common SLE-associated variants in the more severely affected patients. Lupus-associated HLA alleles or HLA haplotypes were not shared among the 4 affected subjects. Our findings revealed a novel high-penetrance mutation in C1R as the cause of monogenic SLE. Disease expressivity in this family appears to be influenced by additional common and rare genetic variants.


Targeting Angiotensinogen With N-Acetylgalactosamine-Conjugated Small Interfering RNA to Reduce Blood Pressure.
Blood pressure management involves antihypertensive therapies blocking the renin-angiotensin system (RAS). Yet, it might be inadequate due to poor patient adherence or the so-called RAS escape phenomenon, elicited by the compensatory renin elevation upon RAS blockade. Recently, evidence points toward targeting hepatic AGT (angiotensinogen) as a novel approach to block the RAS pathway that could circumvent the RAS escape phenomenon. Removing AGT, from which all angiotensins originate, should prevent further angiotensin generation, even when renin rises. Furthermore, by making use of a trivalent N-acetylgalactosamine ligand-conjugated small interfering RNA that specifically targets the degradation of hepatocyte-produced mRNAs in a highly potent and specific manner, it may be possible in the future to manage hypertension with therapy that is administered 1 to 2× per year, thereby supporting medication adherence. This review summarizes all current findings on AGT small interfering RNA in preclinical models, making a comparison versus classical RAS blockade with either ACE (angiotensin-converting enzyme) inhibitors or AT1 (angiotensin II type 1) receptor antagonists and AGT suppression with antisense oligonucleotides. It ends with discussing the first-in-human study with AGT small interfering RNA.


[First aid education - a questionnaire survey].
Introduction: The ability to provide first aid, especially cardiopulmonary resuscitation (CPR) in accordance with the guidelines of the European Resuscitation Council (ERC) is a key element in helping and rescuing people with pre-hospital cardiac arrest. As recommended by the ERC 2015 guidelines, one of the most important steps to be taken to increase the rate of CPR appraisal by participants or cardiac arrest witnesses is to teach these skills to all children in schools. Numerous studies have shown that school-age children are positive about learning resuscitation, and moreover, they are important multipliers of knowledge because they are happy to transmit the information they receive to family members and the closest surroundings. The aim: To get to know the opinions of young people about the need for first aid education and the period in which it is best to start learning in this area. Materials and methods: The study was attended by 498 people, students of various types of universities, the research method was an online diagnostic survey, a self-help questionnaire tool. Results: The study involved 309 women (62%) and 189 (38%) men. The respondents are young people between 18-30. Almost all respondents (97.2%) are of the opinion that learning first aid should be compulsory in the course of school education. The majority of respondents (76.7%) expressed the opinion that the knowledge regarding first aid should be updated, 16.3% had no opinion on this subject, while only 7.0% of respondents believed that there was no need to do so. Almost half of respondents (48.3%) are of the opinion that learning first aid should take place from the elementary school, while 30.3% of respondents think that they should be educated at pre-school age. Conclusions: The vast majority of respondents consider first aid education to be significant and needed during education. Young people are aware of the need to practice skills and to repeat and update information on first aid. The majority of respondents are of the opinion that education in this area should be started very early, even in the pre-school period.


Risk factors of potentially inappropriate medications among older patients visiting the community health center in rural Taiwan.
The adverse drug reactions caused by potentially inappropriate medications (PIMs) are closely related to emergency department visits and acute hospital admissions in the elderly population. It has been reported that 11.5-14% of community-dwelling elderly patients were prescribed for at least one PIM, but little is known regarding to it in rural Taiwan. The purpose of this study was to evaluate the prevalence and risk factors of PIMs among older patients visiting the outpatient clinic of a community health center in rural Taiwan. In August of 2008, all elderly patients attended the outpatient clinic of a community health center in I-Lan County were enrolled for study. PIMs are evaluated by Beers' criteria. In total, 327 patients (mean age: 74.8 ± 5.3 years old, 49.5% males) were enrolled, and 27.5% (90/327) of them were prescribed for at least one PIM. The most common PIMs were antihistamines (50.9%) and muscle relaxants (39.0%). In particular, 87.6% of these PIMs were having a high severity potential. Patients had PIMs were significantly older (76.2 ± 6.9 vs. 74.2 ± 6.1 years, p = 0.011), being prescribed for more drugs (3.7 ± 1.4 vs. 2.4 ± 1.7 items, p<0.001), and more commonly to visit due to acute diseases (64.4% vs. 24.9%, p < 0.001) than those had no PIM. Multiple logistic regression showed that older age (OR = 1.05, 95% CI = 1.00-1.09, p = 0.046), higher number of prescribed medications (OR = 1.66, 95% CI = 1.39-1.98, p < 0.001), and diagnosis of acute diseases (OR = 8.98, 95% CI = 4.71-17.10, p < 0.001) are all independent risk factors for PIMs. In conclusion, the prevalence of PIMs in the outpatient clinic of the community health care center in rural Taiwan was 27.5%. Older age, higher number of prescribed medications and diagnosis of acute diseases are independent risk factors for PIMs in rural Taiwan.


Femtosecond snapshot imaging of propagating light itself.
An ultrafast imaging technique has been developed to visualize directly a light pulse that is propagating in a medium. The method, called femtosecond time-resolved optical polarigraphy (FTOP), senses instantaneous changes in the birefringence within the medium that are induced by the propagation of an intense light. A snapshot sequence composed of each femtosecond probing the pulse delay enables ultrafast propagation dynamics of the intense femtosecond laser pulse in the medium, such as gases and liquids, to be visualized directly. Other examples include the filamentation dynamics in CS2 liquid and the propagation dynamics in air related to the interaction with laser breakdown plasma. FTOP can also be used to extract information on the optical Kerr constant and its decay time in media. This method is useful in the monitoring of the intensity distribution in the nonlinear propagation of intense light pulses, which is a frequently studied subject in the field of physics regarding nonlinear optics and laser processing.


Immunophenotype of lymphocytes in pericardial fluid from patients with different forms of heart disease.
Cytofluorometric analysis was performed to characterize the immunophenotype of lymphocytes of the pericardial fluid (PF) from 127 patients undergoing open cardiac operation (heart valve disease, congenital heart defects, chronic ischemic heart disease). Macrophages and T cells represented the dominant cell types. Similar to T cells of body fluids other than peripheral blood, a high percentage of PF T cells expressed CD45RO and activation-associated molecules such as HLA-DR, CD69, CD54 and CD26. Surprisingly, we could demonstrate a very high proportion of CD11b+ T cells in PF. Furthermore, a significant proportion of PFT cells expressed aminopeptidase N/CD13. PF was further analyzed for the presence of IL-6, TGF-beta as well as TNF-alpha. IL-6 levels were low (undetectable to 4,500 U/ml), TGF-beta levels ranged from < 3 ng/ml up to 80 ng/ml, and TNF-alpha levels from < 3 pg/ml to 233 pg/ml. These findings show evidence of the presence of activated lymphocytes with a special immunophenotype as well as multiple cytokines in PF of patients with different forms of heart disease.


Full Solar-Spectrum-Driven Antibacterial Therapy over Hierarchical Sn3 O4 /PDINH with Enhanced Photocatalytic Activity.
Antibacterial photocatalytic therapy (APCT) is considered to be a potential treatment for administrating antibiotic-resistant bacteria. However, due to the low photocatalytic efficiency and weak ability to capture bacteria, it is not practically applied. In this work, an organic-metal oxide hybrid semiconductor heterostructure is fabricated for the photocatalytic generation of reactive oxygen species (ROS) to kill the drug-resistant bacteria. The organic semiconductor, perylene diimide (PDI), can self-assemble on Sn3 O4 nanosheets to form a "hook-and-loop" sticky surface that can capture bacteria, via large numbers of hydrogen bonding and π-π stacking interactions, which are not possible in inorganic semiconductors. This easy-to-fabricate hybrid semiconductor also possesses improved photocatalytic activity, which is owing to the formation of heterostructure that achieves full-spectrum absorption, and the reduction of the photocarrier recombination rate to produce more reactive oxygen species. It has a good promoting effect on the wounds of mice infected by Staphylococcus aureus. This work shows new ideas for fabricating smart full-spectrum inorganic-organic hybrid adhesive heterostructure photocatalysts for antibacterial photocatalytic therapy.


Dreaming during anesthesia and anesthetic depth in elective surgery patients: a prospective cohort study.
Dreaming reported after anesthesia remains a poorly understood phenomenon. Dreaming may be related to light anesthesia and represent near-miss awareness. However, few studies have assessed the relation between dreaming and depth of anesthesia, and their results were inconclusive. Therefore, the authors tested the hypothesis that dreaming during anesthesia is associated with light anesthesia, as evidenced by higher Bispectral Index values during maintenance of anesthesia. With approval, 300 consenting healthy patients, aged 18-50 yr, presenting for elective surgery requiring relaxant general anesthesia with a broad range of agents were studied. Patients were interviewed on emergence and 2-4 h postoperatively. The Bispectral Index was recorded from induction until the first interview. Dream content and form were also assessed. Dreaming was reported by 22% of patients on emergence. There was no difference between dreamers and nondreamers in median Bispectral Index values during maintenance (37 [23-55] vs. 38 [20-59]; P=0.68) or the time at Bispectral Index values greater than 60 (0 [0-7] vs. 0 [0-31] min; P=0.38). Dreamers tended to be younger and male, to have high home dream recall, to receive propofol maintenance or regional anesthesia, and to open their eyes sooner after surgery. Most dreams were similar to dreams of sleep and were pleasant, and the content was unrelated to surgery. Dreaming during anesthesia is unrelated to the depth of anesthesia in almost all cases. Similarities with dreams of sleep suggest that anesthetic dreaming occurs during recovery, when patients are sedated or in a physiologic sleep state.


Medical infrared thermography as hidradenitis suppurativa diagnostic tool: literature review.
Hidradenitis suppurativa (HS) is a rare, chronic, inflammatory skin disease that has a strong impact on the quality of life. Medical infrared thermography (MIT) is a non-invasive imaging method that could be used for evaluation of skin inflammation, which is an important biomarker in HS. We performed a comprehensive review of the literature to verify the possibilities of using MIT for HS. Key words "hidradenitis suppurativa", "acne inversa" and "thermography" were used for PubMed, Embase and Scopus literature analysis and in total four articles fulfilled the inclusion criteria. The inflamed areas have shown the increase in temperature (34.3°C) and after the removal of lesions the temperature has become similar to the healthy skin sites. The margins of the inflammatory lesions identified by MIT were used in the surgical treatment. Also, MIT was used in combination with other imaging tests for inflammation evaluation. Thermography is an advantageous tool to detect inflammation and to secure the success of surgical treatment.


[Ultrasonic and biochemical detection and prenatal treatments of intra-uterine fetal growth retardation (author's transl)].
Efficacy of three ultrasonographic and six biochemical methods for the detection of intrauterine growth retardation were assessed in prospective studies of 40 cases associated with short uterine fundal height less than -1.5 SD and/or small ultrasonographically determined total intrauterine volume (TIUV) less than -1 SD of normal populations. Prenatal treatments, consisting of bed rest, high protein diet, intravenous drip infusion of 10% maltose, 500 ml per day, for more than 12 days, etc., were administered on them. Fifteen cases (37.5%) delivered small-for-date infants, 9 of which complicated by toxemia of pregnancy. At the final determinations, small TIUV were found in all small-for-date cases (100%), short biparietal diameter 80.0%, and short longitudinal intracavital uterine length 53.3% of 15 small-for-date cases. In biochemical parameters, low maternal plasma estriol levels were found in 73.3%, low plasma human placental lactogen levels 66.7%, low urinary estriol excretion 53.3%, abnormal plasma alpha-fetoprotein levels 33.3%, and low plasma progesterone levels 20.0% of 15 small-for-date cases. Nineteen cases (47.5%) demonstrated remarkable increases in TIUV following prenatal treatments, and delivered appropriate-for-date infants. Despite of marked growth in biophysical parameters, abnormal biochemical values were mostly not improved by these treatments.


Parasites of domestic and wild animals in South Africa. LI. Ticks infesting leopard tortoises Stigmochelys pardalis, hingeback tortoises Kinixys zombensis and angulate tortoises Chersina angulata.
The objective of the study was to record the tick species collected from three species of tortoise, each in a different province of South Africa. Ticks were collected from leopard tortoises, Stigmochyles pardalis, in the southern region of the Kruger National Park, Mpumalanga province; from hingeback tortoises, Kinixys zombensis, in the Enseleni Nature Reserve, KwaZulu-Natal province and from angulate tortoises, Chersina angulata, in the West Coast National Park, Western Cape province. Of the 63 leopard tortoises examined, 58 were infested with Amblyomma marmoreum and 49 with Amblyomma hebraeum, and all stages of development of both species were recovered. Amblyomma nuttalli was collected from 25 hingeback tortoises, and all stages of development were present. All 24 angulate tortoises examined were infested with Amblyomma sylvaticum, and large numbers of larvae, nymphs and adults were collected. Three snake species and a sand lizard were also infested with A. sylvaticum. The adults of A. marmoreum, A. nuttalli and A. sylvaticum were identified as specific parasites of the family Testudinidae, whereas all stages of development of A. hebraeum were classified as generalists.


High genetic diversity and novelty in eukaryotic plankton assemblages inhabiting saline lakes in the Qaidam basin.
Saline lakes are intriguing ecosystems harboring extremely productive microbial communities in spite of their extreme environmental conditions. We performed a comprehensive analysis of the genetic diversity (18S rRNA gene) of the planktonic microbial eukaryotes (nano- and picoeukaryotes) in six different inland saline lakes located in the Qaidam Basin. The novelty level are high, with about 11.23% of the whole dataset showing <90% identity to any previously reported sequence in GenBank. At least 4 operational taxonomic units (OTUs) in mesosaline lakes, while up to eighteen OTUs in hypersaline lakes show very low CCM and CEM scores, indicating that these sequences are highly distantly related to any existing sequence. Most of the 18S rRNA gene sequence reads obtained in investigated mesosaline lakes is closely related to Holozoa group (48.13%), whereas Stramenopiles (26.65%) and Alveolates (10.84%) are the next most common groups. Hypersaline lakes in the Qaidam Basin are also dominated by Holozoa group, accounting for 26.65% of the total number of sequence reads. Notably, Chlorophyta group are only found in high abundance in Lake Gasikule (28.00%), whereas less represented in other hypersaline lakes such as Gahai (0.50%) and Xiaochaidan (1.15%). Further analysis show that the compositions of planktonic eukaryotic assemblages are also most variable between different sampling sites in the same lake. Out of the parameters, four show significant correlation to this CCA: altitude, calcium, sodium and potassium concentrations. Overall, this study shows important gaps in the current knowledge about planktonic microbial eukaryotes inhabiting Qaidam Basin (hyper) saline water bodies. The identified diversity and novelty patterns among eukaryotic plankton assemblages in saline lake are of great importance for understanding and interpreting their ecology and evolution.


Three-dimensional systems for in vitro follicular culture: overview of alginate-based matrices.
The in vitro culture of ovarian follicles has provided critical insight into the biology of the follicle and its enclosed oocyte and the physical interaction and communication between the theca and granulosa cells and the oocyte that is necessary to produce meiotically competent oocytes. Various two-dimensional (2D) and three-dimensional (3D) culture systems have been developed to evaluate the effect of growth factors, hormones, extracellular matrix components and culture conditions on follicle development and oocyte growth and maturation. Among these culture systems, 3D systems make it possible to maintain follicle structure and support communication between the various cell compartments within the follicle. In this review article, we will discuss the three main approaches to ovarian follicle culture: 2D attachment systems, 3D floating systems and 3D encapsulated systems. We will specifically emphasise the development of and advances in alginate-based encapsulated systems for in vitro follicle culture.


Template-directed self-assembly of 10-microm-sized hexagonal plates.
This article presents a strategy for the fabrication of ordered microstructures using concepts of design inspired by molecular self-assembly and template-directed synthesis. The self-assembling components are 4-microm-thick hexagonal metal plates having sides 10 microm in length ("hexagons"), and each template consists of a 4-microm-thick circular metal plate surrounding a central cavity, the perimeter of which is complementary in shape to the external edges of a two-dimensional, close-packed array of hexagons. The hexagons and templates (collectively, "pieces") were fabricated via standard procedures and patterned into hydrophobic and hydrophilic regions using self-assembled monolayers (SAMs). Templated self-assembly occurs in water through capillary interactions between thin films of a nonpolar liquid adhesive coating the hydrophobic faces of the pieces. The hexagons tile the cavities enclosed by the templates, and the boundaries of the cavities determine the sizes and shapes of the assemblies. Curing the adhesive with ultraviolet light furnishes mechanically stable arrays having well-defined morphologies. By allowing control over the structures of the resulting aggregates, this work represents a step toward the development of practical methods for microfabrication based on self-assembly.


A Millimeter-Wave 3D Imaging Algorithm for MIMO Synthetic Aperture Radar.
Multiple-input-multiple-output synthetic aperture radar (MIMO-SAR) is being studied and applied in more and more scenarios. However, there is still a certain distance away from real-time imaging using advanced algorithms. The traditional backpropagation algorithm (BPA) multi-accumulation integration is unsuitable for dealing with large-size scanning data, and the wavenumber domain algorithm requires the array to satisfy Nyquist sampling law in azimuth to avoid aliasing in imaging reconstruction. Based on these issues, a novel 3D imaging method is proposed for MIMO-SAR. An appropriate transformation and inverse Fourier transform (FT) is carried out for the frequency domain; thus, accumulation in the wavenumber domain is not required, which is easy to implement. The computational complexity of the algorithm is much lower than BPA and has better generalizability than the wavenumber domain algorithm. Coherence factor (CF) is also introduced to achieve sidelobe suppression. Proof-of-principle experiments were also carried out in the 92.5 GHz band based on the MIMO-SAR prototype system. Both simulation and experimental results of different distributed targets show good performance of imaging and do not lose the quality of image reconstruction.


Interpretation and use of the dental admission and aptitude tests.
Despite the fact that all dental school applicants in Canada are required to take the Dental Aptitude Test (DAT) and their counterparts in the United States take the Dental Admission Test (DAT), there is an apparent lack of understanding in the translation and application of the information provided by the test. A review of the literature might assist admissions committee members in interpreting DAT results and in making more sound decisions in selecting students, To put the information into perspective, a brief overview of the history of the DAT, its composition, underlying concepts, and the problems of validation and guidelines for its use are presented.


The effects of Maras powder (smokeless tobacco) on oxidative stress in users.
Maras Powder (MP) is a special kind of smokeless tobacco widely used in the southeast region of Turkey especially in Kahramanmaras and Gaziantep and other southeastern cities. It is obtained from a tobacco species, Nicotiana rustica L and ash of oak or grapevine wood. Tobacco may increase oxidative stress, which is related to the products of the oxygen metabolism taking place in all cells. Cellular antioxidants, e.g. catalase (CAT), superoxide dismutase (SOD) and glucose 6-phosphate dehydrogenase (G6PD) protect the cell against oxidative damage. An imbalance between the ROS and antioxidants in favour of ROS is described as oxidative stress. In this study, we aimed to investigate the effect of MP on antioxidant enzyme levels and lipid peroxidation. We measured malondialdehyde (MDA), CAT, SOD and G6PD levels in blood of 68 MP users and 30 healthy controls who did not use MP. CAT, SOD and G6PD levels were lower in MP users than in the controls. On the other hand, lipid peroxidation levels (MDA), one of the best indicators of cytological damage, was increased in MP users compared with the controls. The present study showed that MP increases oxidative stress, which may cause many systemic disorders, including arteriosclerosis.


Looking past the appearance: a comprehensive description of the clinical contribution of poor-quality blastocysts to increase live birth rates during cycles with aneuploidy testing.
Which are the clinical benefits and risks of including poor-quality blastocysts (PQBs) in the cohort of biopsied embryos during a cycle with preimplantation genetic testing for aneuploidies (PGT-A)? PQBs show a worse prognosis with respect to sibling non-PQBs, but their clinical use allows an overall 2.6% increase in the number of live births (LBs) achievable after PGT-A. PQBs (<BB according to Gardner and Schoolcraft's classification) are generally disregarded for clinical use and/or research purposes. Therefore, limited data exist in literature to estimate the benefits and risks deriving from the transfer of a PQB. In Italy, the law imposes the transfer or cryopreservation of all embryos, unless proven not viable. This regulation has allowed the production of a large amount of data regarding poor-quality embryos. Previous reports outlined a lower chance of euploidy and implantation for PQBs. Yet, a comprehensive picture of their real clinical contribution is missing. This observational cohort study including 2757 oocyte retrievals for PGT-A (mean maternal age, 39.6 ± 3.3 years) conducted at a private IVF centre between April 2013 and May 2018. A total of 1497 PQBs were obtained and their embryological, chromosomal and clinical features were compared to 5250 non-PQBs (≥BB according to Gardner and Schoolcraft's classification) and adjusted for all significant confounders. After defining the overall increase in LBs due to PQBs, we outlined the population of patients who might benefit the most from their clinical use. ICSI cycles, involving ovarian stimulation, blastocyst culture, trophectoderm biopsy, vitrification, comprehensive chromosome testing and vitrified-warmed euploid single embryo transfers (SETs), were conducted. Overall analyses and sub-analyses in populations of patients clustered according to maternal age at retrieval and size of the cohort of sibling non-PQBs were performed. Finally, the risk of miscarriage and the chance of LB per biopsied PQB and non-PQB were estimated. PQBs allowed a 12.4% increase in the cycles where ≥1 blastocyst was biopsied. To date, we report a concurrent 2.6% increase in the cycles resulting in ≥1 LB. On average 0.7 ± 0.9 (range, 0-9) PQBs were obtained per cycle for biopsy, including 0.2 ± 0.4 (range, 0-5) euploid PQBs. Maternal age solely correlates with the prevalence of PQBs from both overall and cycle-based analyses. Indeed, the patients who benefit the most from these embryos (i.e. 18 women achieving their only LBs thanks to PQBs) cluster among women older than 42 years and/or those with no or few sibling non-PQBs (1.1 ± 1.1; range, 0-3). The 1497 PQBs compared to the 5250 non-PQBs showed slower development (Day 5, 10.1% versus 43.9%; Day 6, 60.5% versus 50.8%; Day 7, 29.4% versus 5.2%) and lower euploidy rates (23.5% versus 51%; adjusted OR, 0.36). Among the 195 and 1697 transferred euploid PQBs and non-PQBs, the former involved a lower implantation rate (16.9% versus 52.3%) and a higher miscarriage rate per clinical pregnancy (36.4% versus 13.9%), therefore resulting in a lower LB rate (LBR, 10.8% versus 44.6%; adjusted OR, 0.22). Based on these rates, we estimated an overall 1.5% risk of miscarriage and 2.6% chance of LB after euploid vitrified-warmed SET per each biopsied PQB. The same estimates for non-PQBs were 3.7% and 22.8%. The clinical benefit of PQBs is underestimated since they are the last option for transfer and this analysis entailed only the first LB. The higher miscarriage rate per clinical pregnancy here reported might be the consequence of a population of patients of poorer prognosis undergoing the SET of euploid PQBs, an option that requires further investigation. Finally, a cost-benefit analysis is needed in a prospective non-selection fashion. PQBs show higher aneuploidy rates. If to be included, PGT-A is recommended. When selected against aneuploid-PQBs, euploid ones could still involve a worse prognosis, yet, their LBR is not negligible. Women should be informed that a poor morphology does not define a non-viable embryo per se, although PQBs show a reduced chance of resulting in an LB. No external funding was used for this study. The authors have no conflict of interest related to this study. N/A.


New chromosomal location for structural genes of ribosomal proteins.
An Escherichia coli mutant, ts9, previously reported by Flaks et al. (Cold Spring Harbor Symp. Quant. Biol. 31, 623-631, 1966) to have an electrophoretically altered ribosomal protein, has been further characterized and the altered component has been identified as L7/L12. Although mutant ts9 is temperature sensitive for growth (rts-), the rts and L7/L12 mutations are genetically separable and are both located between argH and rif. The L7/L12 mutation (rpyL) maps very close to relC, mutants of which have a defect in the 50S ribosomal subunit. The gene order is argH-rts-(rpyL,relC)-rif. Protein synthesis directed by bacteriophage lambdacI857S7drifd18 in ultraviolet-irradiated cells indicates that L7/L12, As well as L1, L10, L11, and possibly L8 or L9 are coded by the phage DNA. Our results indicate that rpyL is the structural gene for L7/L12 and that this region of the E. coli chromosome contains a cluster of structural genes for ribosomal proteins.


The risk of healing complications in primary teeth with extrusive or lateral luxation-A retrospective cohort study.
Traumatic dental injuries (TDI) in the primary dentition occur frequently. Long-term complications may potentially cause damage to the permanent successor. The aim of this study was to report the risk of pulp necrosis (PN), pulp canal obliteration (PCO), infection-related resorption (IRR), ankylosis-related resorption (ARR) and premature tooth loss (PTL) in primary teeth following extrusion or lateral luxation and to identify risk factors for PN and PTL. This was a retrospective study of 24 patients with 26 extruded primary teeth and 242 patients with 331 primary teeth with lateral luxation. Laterally luxated teeth were left without treatment. Extruded teeth were repositioned. Follow up included examination after 4 weeks, 8 weeks, 6 months, 1 year and when the patients were 6 years old. The minimum follow up was 1 year or until tooth loss. Kaplan-Meier and Aahlen-Johansson tests were used along with Cox regression analysis. The level of significance was 5%. Risk estimated after 3 years-Extrusion: PCO 39.8% (95% CI: NA), PN 15.6% (95% CI: 1.5-29.7), IRR 3.8% (95% CI: 0-11.2) and PTL 43.3% (95% CI: 25.5-61.2). All cases of PN and PTL occurred within the first year. Lateral luxation: PCO 41.3% (CI: 95% 35.7-46.9), PN 19.8% CI: 95% (15.3-24.2), IRR 7.0% (95% CI: 4.1-9.8), ARR 1.4% (95% CI: 0-3.3) and PTL 24.8% (95% CI: 18.8-30.8). Risk factors for PN: concomitant crown fracture and patient aged 4 years or more. Nearly all teeth (95%) realigned spontaneously within the first year. Nearly all cases of PN and PTL (95.7%) occurred within the first year. The healing potential for laterally luxated teeth was high and more than half of the extruded teeth, which were repositioned after injury, showed long-term survival.


The NIMA protein kinase is hyperphosphorylated and activated downstream of p34cdc2/cyclin B: coordination of two mitosis promoting kinases.
Initiation of mitosis in Aspergillus nidulans requires activation of two protein kinases, p34cdc2/cyclin B and NIMA. Forced expression of NIMA, even when p34cdc2 was inactivated, promoted chromatin condensation. NIMA may therefore directly cause mitotic chromosome condensation. However, the mitosis-promoting function of NIMA is normally under control of p34cdc2/cyclin B as the active G2 form of NIMA is hyperphosphorylated and further activated by p34cdc2/cyclin B when cells initiate mitosis. To see the p34cdc2/cyclin B dependent activation of NIMA, okadaic acid had to be added to isolation buffers to prevent dephosphorylation of NIMA during isolation. Hyperphosphorylated NIMA contained the MPM-2 epitope and, in vitro, phosphorylation of NIMA by p34cdc2/cyclin B generated the MPM-2 epitope, suggesting that NIMA is phosphorylated directly by p34cdc2/cyclin B during mitotic initiation. These two kinases, which are both essential for mitotic initiation, are therefore independently activated as protein kinases during G2. Then, to initiate mitosis, we suggest that each activates the other's mitosis-promoting functions. This ensures that cells coordinately activate p34cdc2/cyclin B and NIMA to initiate mitosis only upon completion of all interphase events. Finally, we show that NIMA is regulated through the cell cycle like cyclin B, as it accumulates during G2 and is degraded only when cells traverse mitosis.


Sucrose metabolism contributes to in vivo fitness of Streptococcus pneumoniae.
We characterized two sucrose-metabolizing systems -sus and scr- and describe their roles in the physiology and virulence of Streptococcus pneumoniae in murine models of carriage and pneumonia. The sus and scr systems are regulated by LacI family repressors SusR and ScrR respectively. SusR regulates an adjacent ABC transporter (susT1/susT2/susX) and sucrose-6-phosphate (S-6-P) hydrolase (susH). ScrR controls an adjacent PTS transporter (scrT), fructokinase (scrK) and second S-6-P hydrolase (scrH). sus and scr play niche-specific roles in virulence. The susH and sus locus mutants are attenuated in the lung, but dispensable in nasopharyngeal carriage. Conversely, the scrH and scr locus mutants, while dispensable in the lung, are attenuated for nasopharyngeal colonization. The scrH/susH double mutant is more attenuated than scrH in the nasopharynx, indicating SusH can substitute in this niche. Both systems are sucrose-inducible, with ScrH being the major in vitro hydrolase. The scrH/susH mutant does not grow on sucrose indicating that sus and scr are the only sucrose-metabolizing systems in S. pneumoniae. We propose a model describing hierarchical regulation of the scr and sus systems by the putative inducer, S-6-P. The transport and metabolism of sucrose or a related disaccharide thus contributes to S. pneumoniae colonization and disease.


[Therapy of hepatitis B].
Worldwide, there are approximately 350 million carriers of hepatitis B virus (HBV), of whom half a million to 1 million die from liver disease. The goal of treatment is to prevent cirrhosis, hepatic failure, and hepatocellular carcinoma. Substantial progress has been made in the treatment for hepatitis B in the past decade. Currently approved therapeutic options include interferon alpha, lamivudine and adefovir. The efficacy ot the respective antivirals is affected by virological and clinical parameters, thus requiring individual treatment strategies that will be discussed in detail.


Association Of Surfactant Protein-D With Obesity.
Obesity is associated with inflammatory diseases and obese individual's poses high risk for infections. Surfactant protein D (SP-D) is an important regulator of immunity and inflammation. Latest studies have suggested that it is also involved in lipid homeostasis and obese subjects have decrease concentration of SP-D as compared to normal weight peoples. The aim of the current study was to elucidate the relationship among serum SP-D and BMI. This cross sectional study was performed at Dow University of health sciences (DUHS), Karachi. We analysed 90 obese and non-obese subjects for serum SP-D concentration. SP-D was estimated by ELISA. Data was analysed by SPSS 16. Mean SP-D level and demographical variables between the groups were compared by t test, Associations of SP-D with BMI investigated by regression analysis. obese subjects have significant lower levels of Serum SP-D than non-obese and negatively associated with BMI in both genders (p=0.000). This study concluded that obese subjects have lower concentration of SP-D as compare to non-obese and there is an inverse association between the SP-D and BMI.


Technology developments in endovascular treatment of intracranial aneurysms.
Advances in the management and endovascular treatment of intracranial aneurysms are progressing at a tremendous rate. Developments in novel imaging technology may improve diagnosis, risk stratification, treatment planning, intraprocedural assessment, and follow-up evaluation. Evolution of devices, including microwires, microcatheters, balloons, stents, and novel scaffolding devices, has greatly expanded the potential to treat difficult aneurysms. Although developments in technology have greatly improved the efficiency and efficacy of treatment of neurovascular disorders, novel devices do not always improve outcomes and may be associated with unique complications. As such, it is paramount to have an in-depth understanding of new devices and the implications of their introduction into clinical practice. This review provides an update on developments in endovascular treatment of intracranial aneurysms.


Dopamine (3-hydroxytyramine) replacement and metabolism in sympathetic nerve and adrenal medullary depletions after prolonged thermal injury.
After severe thermal injury, the adrenal medulla and the sympathetic nerves can be partially or totally depleted of their adrenaline (epinephrine) and noradrenaline (norepinephrine). The purpose of this paper is to elucidate the rate at which dopamine-2-(14)C, a precursor of noradrenaline, is synthesized into noradrenaline and noradrenaline metabolic products, thereby giving some indication as to dopamine's utilization, turnover, and possible use in treating such noradrenaline-adrenaline depletions. Three burned subjects, 3 wk postburn, were infused with 104.6 muc (872 mug) of dopamine-2-(14)C for 4 hr. Urine was collected at various hourly intervals for the 1st day, and thereafter for 4 days, assayed, and compared with the metabolism of dopamine in normal subjects. Methods for separating, identifying, and counting radioactivity of the various metabolic products of dopamine are described. Normally 87.6 +/-3.1% of the total radioactivity is recovered within 24 hr after an infusion of dopamine-2-(14)C, but in the three severely burned patients, this value was increased to 93.1, 97.3, and 97.5% in 24 hr. There was a marked decrease in the percentage of radioactivity recovered as noradrenaline in all collection periods, and in contrast to normal subjects, no radioactive noradrenaline was recovered after 24 hr. Concomitantly, there was an increase in radioactivity recovered as metabolic products of noradrenaline, reflecting a compensatory shift toward noradrenaline synthesis and utilization at the expense of the dopamine metabolic products. The results indicate that in the burned patients the infused dopamine-2-(14)C was rapidly synthesized into noradrenaline and then rapidly released and metabolized. From these results it seems evident that dopamine would be a useful adjunct in the treatment of sympathico-adrenal medullary depletion in burns.


Low body mass index negatively affects muscle mass and intramuscular fat of chronic stroke survivors.
Relationship between secondary changes in skeletal muscle and body weight in chronic stroke survivors has not yet been carefully examined. The objective of this study was to clarify the relationships between muscle mass, intramuscular fat, and body weight in chronic stroke survivors. Seventy-two chronic stroke survivors participated in this study. Transverse ultrasound images were acquired using B-mode ultrasound imaging. Quadriceps muscle mass and intramuscular fat were assessed based on muscle thickness and echo intensity, respectively. We used a stepwise multiple regression analysis to identify the factors that were independently associated with the body mass index. We entered quadriceps thickness and echo intensity of the paretic and non-paretic sides into another stepwise multiple regression model to avoid multicollinearity. Age, sex, type of stroke, time since stroke, thigh length, number of medications, and an updated Charlson comorbidity index were included as the independent variables. The quadriceps thickness and echo intensity of the paretic and non-paretic sides were significantly independently associated with the body mass index: quadriceps thickness of the paretic side, β = 0.52; quadriceps thickness of the non-paretic side, β = 0.55; quadriceps echo intensity of the paretic side, β = -0.35; quadriceps echo intensity of the non-paretic side, β = -0.27). Our results suggest that low body mass index is associated with loss of muscle mass and increased intramuscular fat on both the paretic and non-paretic sides of chronic stroke survivors. Further studies examining whether appropriate weight management, along with targeted rehabilitation programs aimed at increasing muscle mass and decreasing intramuscular fat, achieves good outcomes in chronic stroke survivors are warranted.


Molecular dissection of purinergic P2X receptor channels.
The P2X receptors (P2XRs) are a family of ATP-gated channels expressed in the plasma membrane of numerous excitable and nonexcitable cells and play important roles in control of cellular functions, such as neurotransmission, hormone secretion, transcriptional regulation, and protein synthesis. P2XRs are homomeric or heteromeric proteins, formed by assembly of at least three of seven subunits named P2X(1)-P2X(7). All subunits possess intracellular N- and C-termini, two transmembrane domains, and a relatively large extracellular ligand-binding loop. ATP binds to still an unidentified extracellular domain, leading to a sequence of conformational transitions between closed, open, and desensitized states. Removal of extracellular ATP leads to deactivation and resensitization of receptors. Activated P2XRs generate inward currents caused by Na(+) and Ca(2+) influx through the pore of channels, and thus mediate membrane depolarization and facilitation of voltage-gated calcium entry in excitable cells. No crystal structures are available for P2XRs and these receptors have no obvious similarity to other ion channels or ATP binding proteins, which limits the progress in understanding the relationship between molecular structure and conformational transitions of receptor in the presence of agonist and after its washout. We summarize here the alternative approaches in studies on molecular properties of P2XRs, including heteromerization, chimerization, mutagenesis, and biochemical studies.


Endocannabinoid signaling dynamics probed with optical tools.
Intercellular signaling dynamics critically influence the functional roles that the signals can play. Small lipids are synthesized and released from neurons, acting as intercellular signals in regulating neurotransmitter release, modulating ion channels on target cells, and modifying synaptic plasticity. The repertoire of biological effects of lipids such as endocannabinoids (eCBs) is rapidly expanding, yet lipid signaling dynamics have not been studied. The eCB system constitutes a powerful tool for bioassaying the dynamics of lipid signaling. The eCBs are synthesized in, and released from, postsynaptic somatodendritic domains that are readily accessible to whole-cell patch electrodes. The dramatic effects of these lipid signals are detected electrophysiologically as CB1-dependent alterations in conventional synaptic transmission, which therefore serve as a sensitive reporter of eCB actions. We used electrophysiological recording, photolytic release of caged glutamate and a newly developed caged AEA (anandamide), together with rapid [Ca2+]i measurements, to investigate the dynamics of retrograde eCB signaling between CA1 pyramidal cells and GABAergic synapses in rat hippocampus in vitro. We show that, at 22 degrees C, eCB synthesis and release must occur within 75-190 ms after the initiating stimulus, almost an order of magnitude faster than previously thought. At 37 degrees C, the time could be < 50 ms. Activation of CB1 and downstream processes constitute a significant fraction of the total delay and are identified as major rate-limiting steps in retrograde signaling. Our findings imply that lipid messenger dynamics are comparable with those of metabotropic neurotransmitters and can modulate neuronal interactions on a similarly fast time scale.


Emerging drugs for acromegaly.
Acromegaly is a rare disease that severely impacts patients' health all the while, being a slowly progressing illness. In the past decades, advancements in treatment modalities, especially development of new drugs, as well as focused guidelines has improved management of acromegaly. Still, many patients are considered not sufficiently treated and there remains an ongoing need for further development. This article reviews new medical treatments currently under clinical investigation (such as pasireotide, oral octreotide and somatoprim) and under experimental development (such as octreotide implants, CAM2029 and ATL-1103). As it seems unlikely that one single agent may achieve cure in 100% of cases, there is an urgent need for new agents that help patients where current medication fails. Imperatively, this means we have to improve our understanding of the underlying pathogenetic and molecular mechanisms.


5'-Terminal cap structures of oligo(uridylic acid)-containing messenger ribonucleic acid from HeLa cells: comparison with other ribonucleic acid subpopulations.
The 5'-terminal cap structures of 32P-labeled oligo(uridylic acid)-containing messenger ribonucleic acid [oligo(U+)mRNA] isolated from HeLa cell polyadenylated [poly(A+)] mRNA were analyzed and compared to those of the poly(A+) mRNA. A method employing P1 nuclease, alkaline phosphatase, and adsorption to activated charcoal showed that the types of cap core (m7 GpppXm) in oligo(U+) mRNA were essentially identical with those in poly(A+) mRNA. Analysis of RNase T2 digestion products of oligo(U+) mRNA demonstrated the presence of both cap 1 (m7GpppXmpYp) and cap 2 (m7GpppXmpYmpZp) in this subpopulation, confirming its cytoplasmic location. The base compositions of these two types of caps were different from each other and nonrandom but did not differ significantly between oligo(U+) and poly(A+) m RNA. The only observed difference between the mRNA populations was a higher ratio of cap 1 and cap 2 in the former. Possible implications of these findings for the relationship between oligo(U+) mRNA and poly(A+) mRNA are discussed.


An Improved Inoculation Method to Detect Wheat and Barley Genotypes for Resistance to Fusarium Crown Rot.
Fusarium crown rot (FCR), caused by Fusarium species, is a serious soilborne fungal disease in many wheat growing regions in the world. A reliable FCR assessment method is essential for germplasm screening and host resistance studies. Here, we report a new assay in which we inoculated wheat seedlings grown in a glasshouse for FCR by injecting spore suspensions into the seedling stems. The effects of inoculum concentration and injection time points on disease severity were investigated. Of different treatments, the injection of 107 macroconidia/ml suspension at one leaf and one heart stage gave best results. A collection of 92 emmer-derived hexaploid bread wheats, 43 barley germplasms, and four wheat genotypes with known resistance levels to FCR was used to validate this new method. Repeatability of the two trials in the validation experiments was high (r = 0.97, P < 0.01). Two emmer-derived hexaploid bread wheat and three Chinese barley germplasms showed consistent resistance to FCR in multiple rounds of selection. The short timeframe of this assay for phenotypic screening makes it a valuable tool to eliminate germplasms with undesirable susceptibility to FCR at seedling stage before costly field assays.


Anatomic types of anomalous aortic origin of a coronary artery: A pictorial summary.
Anomalous aortic origin of a coronary artery is a congenital abnormality of the origin or course of a coronary artery that arises from the aorta. As commonly seen in congenital heart disease, a wide spectrum of anatomic variability is seen and hence, it is important for clinicians to document the precise anatomy and course of the anomalous vessel. This article describes coronary artery nomenclature using computerized tomography angiography and virtual angioscopy. These details are important for decision making, useful for surgical planning, and may have prognostic implications.


Quantifying Cell Confluency by Plasmonic Nanodot Arrays to Achieve Cultivating Consistency.
The determination of cell confluency and subculture timing for cell culture consistency is crucial in the field of cell-based research, but there is no universal standard concerning optimal confluence. In this study, gold nanodot arrays on glass substrates were used as culture substrates, and their spectral shifts of localized surface plasmon resonance (LSPR) were employed to monitor cell growth and quantify cell confluency. Experiments including cell counting, metabolic activity, focal adhesion, and cell cycle were also performed to confirm the cell growth monitoring accuracy of the LSPR signals. The LSPR signal exhibited the same trends like the increase of cell numbers and cell metabolic activity and reached the maximum as the cell growth achieved confluency, suggesting its great capability as an effective indicator to predict suitable subculture timing. The proposed sensing approach is a noninterventional, nondestructive, real-time, and useful tool to help biologists quantify the optimal subculture timing, achieve cell culture consistency, and obtain reproducible experimental results efficiently.


Development and Assessment of Early Utilization of the Standardized Letter of Recommendation for Use in the Radiology Residency Match.
Letters of recommendation are essential for residency applications. Traditionally, narrative letters have been used. Standardized letters of recommendation (SLOR) have been developed and have benefits to the writer and reader. The goal was to develop an informative, meaningful, and efficient SLOR for the radiology residency Match and to assess its early use. An Association of University Radiologists (AUR) Research and Education Venture Fund Grant was awarded for the development of a SLOR for use in the radiology residency Match. Grant recipients developed the letter and modifications were based on feedback from the Alliance of Medical Student Educators in Radiology (AMSER) SLOR task force and a larger task force including additional AUR and Association of Program Directors in Radiology (APDR) members. AUR and APDR members were surveyed in 2020 to assess the radiology SLOR. The radiology SLOR became available for use in September 2018. It highlights the top six traits or abilities deemed most valued in a resident candidate and guides the writer to develop a concrete narrative. Top perceived benefits of the Radiology SLOR are ease of reading and interpretation. Top perceived drawbacks are an impersonal format and concerns regarding program directors' perceptions of the new SLOR. SLOR utilization increased in the second year of availability. The radiology SLOR was developed and first used in 2018. Its use increased over two years and will likely continue to increase given the perceived benefits and increasing awareness of the SLOR.


[Drug agents for the treatment of systemic connective tissue diseases].
Besides the steroids and the cytostatics used in the treatment of systemic connective tissue diseases, there are other drugs which could be also used in the treatment of these diseases. Of the so-called nonsteroidal anti-inflammatory and slow-acting antirheumatic drugs importance of the quinoline antimalarial drugs is pointed out. The action of the pyrazolone and indole derivatives is weaker. The action of some enzymic drugs in sclerodermia is pointed out as a novelty. The use of direct and indirect anticoagulants and of calcium antagonists is relatively limited but very important in the treatment of systemic vasculitis and lupus nephropathies.


A comparison of goodness-of-fit tests for the logistic regression model.
Recent work has shown that there may be disadvantages in the use of the chi-square-like goodness-of-fit tests for the logistic regression model proposed by Hosmer and Lemeshow that use fixed groups of the estimated probabilities. A particular concern with these grouping strategies based on estimated probabilities, fitted values, is that groups may contain subjects with widely different values of the covariates. It is possible to demonstrate situations where one set of fixed groups shows the model fits while the test rejects fit using a different set of fixed groups. We compare the performance by simulation of these tests to tests based on smoothed residuals proposed by le Cessie and Van Houwelingen and Royston, a score test for an extended logistic regression model proposed by Stukel, the Pearson chi-square and the unweighted residual sum-of-squares. These simulations demonstrate that all but one of Royston's tests have the correct size. An examination of the performance of the tests when the correct model has a quadratic term but a model containing only the linear term has been fit shows that the Pearson chi-square, the unweighted sum-of-squares, the Hosmer-Lemeshow decile of risk, the smoothed residual sum-of-squares and Stukel's score test, have power exceeding 50 per cent to detect moderate departures from linearity when the sample size is 100 and have power over 90 per cent for these same alternatives for samples of size 500. All tests had no power when the correct model had an interaction between a dichotomous and continuous covariate but only the continuous covariate model was fit. Power to detect an incorrectly specified link was poor for samples of size 100. For samples of size 500 Stukel's score test had the best power but it only exceeded 50 per cent to detect an asymmetric link function. The power of the unweighted sum-of-squares test to detect an incorrectly specified link function was slightly less than Stukel's score test. We illustrate the tests within the context of a model for factors associated with low birth weight.


Rhodium-Catalyzed C-H/C-H Cross Coupling of Benzylthioethers or Benzylamines with Thiophenes Enabled by Flexible Directing Groups.
Reported herein is an efficient synthetic protocol to ortho-functionalized 2-aryl thiophenes via Rh(III)-catalyzed C-H/C-H cross coupling of benzylthioethers or benzylamines with thiophenes. Both ortho- and meta-substituted benzylthioethers give monoheteroarylated products, while ortho-unhindered substrates mainly provide diheteroarylated benzylthioethers. The C-H/C-H cross coupling of benzylamines with thiophenes exclusively generates diheteroarylated benzaldehydes. Mechanistic investigation discloses a three-step tandem process involving the ortho-C-H diheteroarylation of benzylamine, the oxidation of benzylamine to imine, and the hydrolysis of imine to aldehyde.


Effectiveness of antimicrobial food packaging materials.
Antimicrobial additives have been used successfully for many years as direct food additives. The literature provides evidence that some of these additives may be effective as indirect food additives incorporated into food packaging materials. Antimicrobial food packaging is directed toward the reduction of surface contamination of processed, prepared foods such as sliced meats and Frankfurter sausages (hot dogs). The use of such packaging materials is not meant to be a substitute for good sanitation practices, but it should enhance the safety of food as an additional hurdle for the growth of pathogenic and/or spoilage microorganisms. Studies have focused on establishing methods for coating low-density polyethylene film or barrier films with methyl cellulose as a carrier for nisin. These films have significantly reduced the presence of Listeria monocytogenes in solutions and in vacuum packaged hot dogs. Other research has focused on the use of chitosan to inhibit L. monocytogenes and chlorine dioxide sachets for the reduction of Salmonella on modified atmosphere-packaged fresh chicken breasts. Overall, antimicrobial packaging shows promise as an effective method for the inhibition of certain bacteria in foods, but barriers to their commercial implementation continue to exist.


Coincidence of genetic loci for plasma cholesterol levels and obesity in a multifactorial mouse model.
We have examined backcross progeny derived from a cross of Mus spretus with C57BL/6J, that range from 1 to 50% carcass lipid (n = 215), and from 22 to 130 mg/dl plasma total cholesterol (n = 238). Statistical analysis revealed that distal mouse chromosome 7 exhibits significant linkage both to plasma total cholesterol (likelihood of the odds [LOD] 5.8) and to carcass lipid (LOD 3.8). A locus on chromosome 6 also shows significant linkage to plasma total cholesterol (LOD 5.6), but no linkage to carcass lipid. Neither chromosomal region contains any previously mapped genes likely to influence lipoprotein metabolism, indicating that novel genetic factors contributing to plasma lipoprotein levels have been identified.


Production of lipolytic enzymes by bacteria isolated from biological effluent treatment systems.
This work aimed to evaluate the production of lipolytic complexes, produced by microorganisms isolated from a biological treatment system of effluents from a hotel. To select the best lipolytic microorganism for use in biotechnological processes, we tested 45 bacterial isolates recovered from the raw effluent of the hotel's restaurant waste tank. Lipase production was assayed in culture medium supplemented with olive oil and rhodamine B, incubated at 25 °C and 30 °C for 24 h - 48 h. Results showed 22 isolates lipase producers. All isolates were inoculated on medium without yeast extract to select the ones with highest enzyme yields. Out of these, nine isolates showed high lipase activity. The strain with the larger halo was assayed in submerged culture using an orbital shaker and a bioreactor, with three different substrates (olive oil, grape seed oil, and canola oil). Isolate G40 identified as Acinetobacter baylyi was selected to run the production assays because it showed the best result in the solid medium. In the bioreactor, maximum lipase production was obtained after 12 h of culture with the three substrates evaluated: 0,358 U/mL.min-1 in olive oil, 0,352 U/mL.min-1 with grapeseed oil, and 0,348 U/mL.min-1 with canola oil.


Supervised promoter recognition: a benchmark framework.
Deep learning has become a prevalent method in identifying genomic regulatory sequences such as promoters. In a number of recent papers, the performance of deep learning models has continually been reported as an improvement over alternatives for sequence-based promoter recognition. However, the performance improvements in these models do not account for the different datasets that models are evaluated on. The lack of a consensus dataset and procedure for benchmarking purposes has made the comparison of each model's true performance difficult to assess. We present a framework called Supervised Promoter Recognition Framework ('SUPR REF') capable of streamlining the complete process of training, validating, testing, and comparing promoter recognition models in a systematic manner. SUPR REF includes the creation of biologically relevant benchmark datasets to be used in the evaluation process of deep learning promoter recognition models. We showcase this framework by comparing the models' performances on alternative datasets, and properly evaluate previously published models on new benchmark datasets. Our results show that the reliability of deep learning ab initio promoter recognition models on eukaryotic genomic sequences is still not at a sufficient level, as overall performance is still low. These results originate from a subset of promoters, the well-known RNA Polymerase II core promoters. Furthermore, given the observational nature of these data, cross-validation results from small promoter datasets need to be interpreted with caution.


Activated charcoal and syrup of ipecac in prevention of cimetidine and pindolol absorption in man after administration of metoclopramide as an antiemetic agent.
The effects of activated charcoal and ipecac syrup by mouth on cimetidine and pindolol absorption were studied in seven subjects, who had ingested 20 mg metoclopramide 1 h earlier, and compared with the adsorption capacity of charcoal in vitro. Activated charcoal, 50 g, given 5 min after 400 mg cimetidine + 10 mg pindolol, reduced their absorption by 99% or more, based on AUC0-48h and the 48-h urinary excretion of the drugs. Syrup of ipecac caused emesis on each occasion. On the average, ipecac reduced the absorption of cimetidine and pindolol by 75% and 60%, respectively. Based on studies in vitro it seems probable that the adsorbing capacity of charcoal for cimetidine but not for pindolol will be saturated if 50 g charcoal is given after an overdose of about 100 fold the therapeutic dose. Because the use of ipecac allowed an absorption of the drugs at least 30 fold that allowed by charcoal, the immediate administration of activated charcoal, without preceding lavage or emesis, should be considered in such poisonings where the adsorption capacity of high charcoal doses will not be saturated.


Characteristics suggestive of focal Fatty sparing from liver malignancy on ultrasound in liver screening.
The objective of this study was to determine whether there are ultrasound characteristics that can be used to differentiate focal fatty sparing (FFS) from hepatocellular carcinoma and other liver malignancies in liver screening. Data of patients with FFS found at ultrasound were reviewed, 136 patients with FFS were included, and 112 patients with hepatocellular carcinoma and 65 patients with liver metastatic tumor (173 tumors) were selected as control group. Ultrasound and color Doppler characteristics of FFS and liver malignancies were studied. Some characteristics drawn from this study were used as reference to validate the liver malignancies and FFS, and sensitivity, specificity, and positive and negative predictive values were calculated. Hyperechogenicity, isoechogenicity, heterogeneous echotexture, posterior acoustic shadowing, halo, hypervasculature presented exclusively in liver malignancies, posterior acoustic enhancement presented predominantly in liver malignancies, irregularly shaped morphology presented exclusively in FFS, arterial velocity, and maximal size of liver malignancies were significantly higher than those of FFS (P < 0.001). Halo presented in 109 of 285 liver malignancies (38.2%), but was absent in FFS (P < 0.001). The overall sensitivity, specificity, and positive and negative predictive values were 94.38%, 90.44%, and 95.39% and 88.49%, respectively. Combination of hyperechogenicity, isoechogenicity, heterogeneous echotexture, posterior acoustic shadowing, posterior acoustic enhancement, halo appearance, and hypervascularity with high-speed artery has high sensitivity, specificity, and positive and negative predictive values for distinguishing liver malignancy and FFS.


[Radix isatidis and infectious diseases caused by viruses].
Radix Isatidis (Banlangen in Chinese), used to clearing away heat and toxic material, is a traditional Chinese medicinal (TCM) herb. It is frequently used for preventing and treating infectious diseases caused by viruses. To provide scientific basis for the effect of Radix Isatidis on infectious diseases, the traditional effect and new research development on pharmacological activities are summarized in the review. According to the existed problems in the clinical application, the weak links and shortages of quality research and industrialized production of Radix Isatidis are discussed. It could present the new ideas for improving the technology of Radix Isatidis preparation, and promoting the rational use of the preparation in the clinical treatment.


First report of Culicoides caucoliberensis in Spain: Exploring molecular phylogeny, host-feeding behaviour and avian haemosporidian parasites.
Culicoides biting midges (Diptera: Ceratopogonidae) are vectors of pathogens that affect wildlife and livestock. Understanding the composition and distribution of vector species is crucial for implementing control strategies and preventing the spread of infectious diseases. This study provides a morphological and molecular characterisation of Culicoides caucoliberensis, which represents the first record for Spain, increasing the number of Culicoides species in the country to 85. A total of 213 specimens were collected using Onderstepoort-ultraviolet down-draught light traps on a rocky coastline in the Balearic Islands during two sampling periods in 2022. Phylogenetic analysis showed that C. caucoliberensis forms a monophyletic cluster within the Maritimus group. Host preferences were determined for the first time and showed propensity to feed on the European shag (Phalacrocorax aristotelis). The vector role of C. caucoliberensis for haemosporidian transmission remains unclear since molecular detection of Haemosporidians (Haemoproteus and Plasmodium) was negative for all the pools of parous and engorged females analysed. This study emphasises the importance of conducting entomofauna studies in lesser-known Mediterranean islet landscapes and highlights the need for research on vectors within the One Health framework.


Anomalous Glide Plane in Platinum Nano- and Microcrystals.
At the nanoscale, the properties of materials depend critically on the presence of crystal defects. However, imaging and characterizing the structure of defects in three dimensions inside a crystal remain a challenge. Here, by using Bragg coherent diffraction imaging, we observe an unexpected anomalous {110} glide plane in two Pt submicrometer crystals grown by very different processes and having very different morphologies. The structure of the defects (type, associated glide plane, and lattice displacement) is imaged in these faceted Pt crystals. Using this noninvasive technique, both plasticity and unusual defect behavior can be probed at the nanoscale.


The trans-Golgi SNARE syntaxin 10 is required for optimal development of Chlamydia trachomatis.
Chlamydia trachomatis, an obligate intracellular pathogen, grows inside of a vacuole, termed the inclusion. Within the inclusion, the organisms differentiate from the infectious elementary body (EB) into the reticulate body (RB). The RB communicates with the host cell through the inclusion membrane to obtain the nutrients necessary to divide, thus expanding the chlamydial population. At late time points within the developmental cycle, the RBs respond to unknown molecular signals to redifferentiate into infectious EBs to perpetuate the infection cycle. One strategy for Chlamydia to obtain necessary nutrients and metabolites from the host is to intercept host vesicular trafficking pathways. In this study we demonstrate that a trans-Golgi soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE), syntaxin 10, and/or syntaxin 10-associated Golgi elements colocalize with the chlamydial inclusion. We hypothesized that Chlamydia utilizes the molecular machinery of syntaxin 10 at the inclusion membrane to intercept specific vesicular trafficking pathways in order to create and maintain an optimal intra-inclusion environment. To test this hypothesis, we used siRNA knockdown of syntaxin 10 to examine the impact of the loss of syntaxin 10 on chlamydial growth and development. Our results demonstrate that loss of syntaxin 10 leads to defects in normal chlamydial maturation including: variable inclusion size with fewer chlamydial organisms per inclusion, fewer infectious progeny, and delayed or halted RB-EB differentiation. These defects in chlamydial development correlate with an overabundance of NBD-lipid retained by inclusions cultured in syntaxin 10 knockdown cells. Overall, loss of syntaxin 10 at the inclusion membrane negatively affects Chlamydia. Understanding host machinery involved in maintaining an optimal inclusion environment to support chlamydial growth and development is critical toward understanding the molecular signals involved in successful progression through the chlamydial developmental cycle.


Analysis of operational comfort in manual tasks using human force manipulability measure.
This paper proposes a scheme for human force manipulability (HFM) based on the use of isometric joint torque properties to simulate the spatial characteristics of human operation forces at an end-point of a limb with feasible magnitudes for a specified limb posture. This is also applied to the evaluation/prediction of operational comfort (OC) when manually operating a human-machine interface. The effectiveness of HFM is investigated through two experiments and computer simulations of humans generating forces by using their upper extremities. Operation force generation with maximum isometric effort can be roughly estimated with an HFM measure computed from information on the arm posture during a maintained posture. The layout of a human-machine interface is then discussed based on the results of operational experiments using an electric gear-shifting system originally developed for robotic devices. The results indicate a strong relationship between the spatial characteristics of the HFM and OC levels when shifting, and the OC is predicted by using a multiple regression model with HFM measures.