Comparing the Metabolic Profiles Associated with Fitness Status between Insulin-Sensitive and Insulin-Resistant Non-Obese Individuals.
(1) Background: Young non-obese insulin-resistant (IR) individuals could be at risk of developing metabolic diseases including type 2 diabetes mellitus. The protective effect of physical activity in this apparently healthy group is expected but not well characterized. In this study, clinically relevant metabolic profiles were determined and compared among active and sedentary insulin-sensitive (IS) and IR young non-obese individuals. (2) Methods: Data obtained from Qatar Biobank for 2110 young (20-30 years old) non-obese (BMI ≤ 30) healthy participants were divided into four groups, insulin-sensitive active (ISA, 30.7%), insulin-sensitive sedentary (ISS, 21.4%), insulin-resistant active (IRA, 20%), and insulin-resistant sedentary (IRS, 23.3%), using the homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires. The effect of physical activity on 66 clinically relevant biochemical tests was compared among the four groups using linear models. (3) Results: Overall, non-obese IR participants had significantly (p ≤ 0.001) worse vital signs, blood sugar profiles, inflammatory markers, liver function, lipid profiles, and vitamin D levels than their IS counterparts. Physical activity was positively associated with left handgrip (p ≤ 0.01) and levels of creatine kinase (p ≤ 0.001) and creatine kinase-2 (p ≤ 0.001) in both IS and IR subjects. Furthermore, physical activity was positively associated with levels of creatinine (p ≤ 0.01) and total vitamin D (p = 0.006) in the IR group and AST (p = 0.001), folate (p = 0.001), and hematocrit (p = 0.007) in the IS group. Conversely, physical inactivity was negatively associated with the white blood cell count (p = 0.001) and an absolute number of lymphocytes (p = 0.003) in the IR subjects and with triglycerides (p = 0.005) and GGT-2 (p ≤ 0.001) in the IS counterparts. (4) Conclusions: An independent effect of moderate physical activity was observed in non-obese apparently healthy individuals a with different HOMA-IR index. The effect was marked by an improved health profile including higher vitamin D and lower inflammatory markers in IRA compared to IRS, and a higher oxygen carrying capacity and lipid profile in ISA compared to the ISS counterparts.


Trisomy-3,4 and triploidy (3A-ZZZW) in chick embryos: autosomal and sex chromosomal nondisjunction in meiosis.
The first known cases of trisomy-3, trisomy-4, and triploidy (3A-ZZZW) in chickens are reported. The trisomic embryos were near death at 4 days of incubation; the triploid embryo appeared normal and probably could have developed further. Although the triploid (3A-ZZZW) was found after sampling more than 2000 embryos, the trisomic-3 and trisomic-4 embryos were discovered in the first sampling of a line of chickens selected for low egg production. These studies suggest that the sex chromosomes (Z and W), as well as the autosomes, can undergo nondisjunction in meiosis of chickens.


Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment.
Invasive pulmonary aspergillosis (IPA) is the most devastating Aspergillus-related lung disease. Voriconazole (VRZ) is the first-line treatment against IPA. Despite availability in oral and parenteral dosage forms, risks of systemic toxicity dictate alternative pulmonary administration. Inspired by natural lung surfactants, dipalmitoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DPPC/DMPG) surface-modified lipid nanoparticles (LNPs) were scrutinized for pulmonary administration. DPPC/DMPG-VRZ-LNPs prepared using ultrasonication/thin film hydration were investigated for colloidal properties over 3-month shelf storage. They were stable with a slight change in entrapment efficiency. They provided a sustained VRZ release over 24 h, with a rapid initial release. In vitro aerosolization indicated higher percentages of VRZ deposited on stages corresponding to secondary bronchi and alveolar ducts. Moreover, intrapulmonary administration maintained high lung VRZ concentration (27 ± 1.14 µg/g) after 6 h. A preclinical study using a cyclophosphamide-induced neutropenic rat model demonstrated a 3-fold reduction in BALF-Galactomannan down to 0.515 ± 0.22 µg/L confirming DPPC/DMPG-VRZ-LNPs potential in hyphal growth inhibition. Histopathological examination of infected/nontreated lung sections exhibited dense fungal load inside alveoli and blood vessels indicating massive tissue and angio-invasiveness. Nevertheless, DPPC/DMPG-VRZ-LNPs-treated animals displayed minimal hyphae with no signs of invasiveness. The developed bioinspired nanoparticles serve as prospective bioactive nanocarrier candidates for pulmonary administration of VRZ in the management of IPA.


A cross sectional serological study of the co-infection of hepatitis B virus, hepatitis C virus and human immunodeficiency virus amongst a cohort of IDUs at Delhi.
A cross-sectional study was undertaken to find out co-prevalence of various infectious markers like Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Syphilis infection amongst a cohort of injecting drug users (IDUs) in the city of Delhi. A total of 246 IDUs were enrolled during the 3 months period of the study. The results revealed a high prevalence of the viral markers studied i.e., HBV-39.59%, HCV-36.45%, HIV-36.99% and Syphilis-6.09%. A single marker infection was detected amongst 9.14% for HBV, 8.37% for HCV, 4.87% for HIV and 0.83% for Syphilis in samples tested for multiple markers. All the four markers could be detected in 1.76%. Amongst 11.16% and 27.9% of these samples, three and two markers respectively could be detected. The study revealed the problem of IV drug use and high prevalence of infectious markers including HIV in certain populations of Delhi and emphasizes the need for relevant interventions in these localised pockets.


Heterogeneity of pemphigus vulgaris antigens.
The immunologic specificity of pemphigus vulgaris (PV) antigens was studied by serologic analysis. Serum samples of 19 patients with PV antibodies were tested for reactivity with seven specimens of normal human skin by indirect immunofluorescence. Some PV antibodies reacted to antigens expressed in all specimens of skin, while others reacted to antigens expressed in only some specimens of skin. This was not due to differences in the titer of PV antibodies among serum samples or to regional variation or individual-to-individual fluctuations in the expression of a single PV antigen. The patterns of cross-reactivity suggest that PV antigens are heterogeneous. Two different groups can be defined serologically: (1) a "major" (PV) antigen expressed in all individuals, antibodies to which are the most common in PV; (2) a family of "minor" PV antigens whose expression varies from individual to individual. Several immunologically distinct PV antigens are expressed concurrently in the same specimen of skin.


Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua.
While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. In this study, we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemocompatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, for example, by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery.


The awareness of patients with non - muscle invasive bladder cancer regarding the importance of smoking cessation and their access to smoking cessation programs.
Smoking is the most important risk factor for bladder cancer and smoking cessation is associated with reduced risk of tumor recurrence and progression. The aim of this study is to assess the awareness of non-muscle invasive bladder cancer (NMIBC) patients regarding the importance of smoking cessation, determine their access to smoking cessation programs and the effects of smoking cessation on recurrence rates of NMIBC. NMIBC patients who were followed with cystoscopy were included in the study. Their demographic properties were recorded, along with their smoking habits, awareness regarding the effects of smoking on bladder cancer and previous attempts for smoking cessation. Moreover, the patients were asked whether they applied for a smoking cessation program. Recurrence of bladder cancer during the follow-up period was also noted. A total of 187 patients were included in the study. The mean age was 64.68±12.05 (range: 15-90) and the male to female ratio was 167/20. At the time of diagnosis, 114 patients (61.0%) were active smokers, 35 patients (18.7%) were ex-smokers and 38 patients (20.3%) had never smoked before. After the diagnosis, 83.3% of the actively smoking patients were advised to quit smoking and 57.9% of them quit smoking. At the time of the study, 46.52% of the NMIBC patients were aware of the link between smoking and bladder cancer, whereas only 4.1% of the smoking patients were referred to smoking cessation programs. After a mean follow-up of 32.28±11.42 months, 84 patients (44.91%) had recurrence; however, current smoking status or awareness of the causative role of smoking on NMIBC did not affect the recurrence. In our study group, the majority of the NMIBC patients were not aware of the association between smoking and bladder cancer. Although most of the physicians advised patients to quit smoking, a significant amount of the patients were still active smokers during follow-up. Only a small proportion of patients were referred to smoking cessation programs. Urologists should take a more active role in the battle against smoking and refer those patients to smoking cessation programs. Larger study populations with longer follow-up periods are needed to better demonstrate the beneficial effects of smoking cessation on recurrence rates.


Intelligent data analysis of instrumented gait data in stroke patients-a systematic review.
Instrumented gait analysis (GA) may be used to analyze the causes of gait deviation in stroke patients but generates a large amount of complex data. The task of transforming this data into a comprehensible report is cumbersome. Intelligent data analysis (IDA) refers to the use of computational methods in order to analyze quantitative data more effectively. The purpose of this review was to identify and appraise the available IDA methods for handling GA data collected from patients with stroke using the standard equipment of a gait lab (3D/2D motion capture, force plates, EMG). Eleven databases were systematically searched and fifteen studies that employed some type of IDA method for the analysis of kinematic and/or kinetic and/or EMG data in populations involving stroke patients were identified. Four categories of IDA methods were employed for the analysis of sensor-acquired data in these fifteen studies: classification methods, dimensionality reduction methods, clustering methods and expert systems. The methodological quality of these studies was critically appraised by examining sample characteristics, measurements and IDA properties. Three overall methodological shortcomings were identified: (1) small sample sizes and underreported patient characteristics, (2) testing of which method is best suited to the analysis was neglected and (3) lack of stringent validation procedures. No IDA method for GA data from stroke patients was identified that can be directly applied to clinical practice. Our findings suggest that the potential provided by IDA methods is not being fully exploited.


The interaction of mast cells with membranes from lung cancer cells induces the release of extracellular vesicles with a unique miRNA signature.
Mast cells (MCs) are immune cells that play roles in both normal and abnormal processes. They have been linked to tumor progression in several types of cancer, including non-small cell lung cancer (NSCLC). However, the exact role of MCs in NSCLC is still unclear. Some studies have shown that the presence of a large number of MCs is associated with poor prognosis, while others have suggested that MCs have protective effects. To better understand the role of MCs in NSCLC, we aimed to identify the initial mechanisms underlying the communication between MCs and lung cancer cells. Here, we recapitulated cell-to-cell contact by exposing MCs to membranes derived from lung cancer cells and confirming their activation, as evidenced by increased phosphorylation of the ERK and AKT kinases. Profiling of the microRNAs that were selectively enriched in the extracellular vesicles (EVs) released by the lung cancer-activated MCs revealed that they contained significantly increased amounts of miR-100-5p and miR-125b, two protumorigenic miRNAs. We explored the pathways regulated by these miRNAs via enrichment analysis using the KEGG database, demonstrating that these two miRNAs regulate p53 signaling, cancer pathways, and pathways associated with apoptosis and the cell cycle.


Local generation of sulfidopeptide leukotrienes upon nasal provocation with cold, dry air.
In order to assess whether sulfidopeptide leukotrienes are generated following nonimmunologic stimulation of inflammatory cells in vivo, 11 subjects complaining of symptoms of rhinitis when exposed to cold and dry environments were challenged by nasal breathing, first with warm, moist air and then with cold, dry air. Nasal lavages with normal saline were performed before and after each exposure. Immunoreactive leukotriene in the lavage fluids was significantly increased following cold, dry air exposure (2.6 ng/ml) compared with that after warm, moist air exposure (0.7 ng/ml) or at baseline (0.4 ng/ml) (p less than 0.01 in both instances). Six more subjects, denying cold-air sensitivity, were subjected to the same protocol and had no mediator and symptom score changes after cold, dry air challenge. Leukotriene changes after cold, dry air were highly concordant with increments in histamine, prostaglandin D2,N-alpha-tosyl-L-arginine methyl ester (TAME) esterase(s) activity and symptom scores (p less than 0.001). Separation of leukotrienes by high performance liquid chromatography in the nasal washes of 3 subjects showed variable amounts of LTC4, D4, and E4, suggesting metabolism of the former to the latter 2. To our knowledge, this is the first in vivo demonstration of leukotriene production in response to a physical stimulus, and it suggests a possible role of these and other inflammatory mediators in pathologic conditions, such as exercise-induced asthma, that involve physical causative factors.


Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence.
Poxviruses are known to contain a large number of open reading frames, particularly near the termini of the viral genome, that are not required for growth in tissue culture. However, many of these gene products are believed to play important roles in determining the virulence of the virus by modulating the host immune response to the infection. Recently it has been shown that Shope fibroma virus encodes, within the terminal inverted repeats, a protein (T2) related to the cellular tumor necrosis factor receptor (TNFR) and which specifically binds both TNF alpha and TNF beta. We have sequenced the terminal regions of two other Leporipoxviruses (myxoma virus and malignant rabbit fibroma virus) that are extremely invasive and capable of inducing extensive immunosuppression in rabbits and demonstrate that they also encode a closely related T2 homolog with all the structural motifs predicted for a secreted TNF binding protein. To investigate the biological role of the T2 protein, we have inactivated the myxoma virus T2 gene within each copy of the viral TIR by the insertion of a dominant selectable marker (Escherichia coli guanosine phosphoribosyltransferase) and selection of the recombinant virus in the presence of mycophenolic acid. The success of the inactivation of both copies of T2 was confirmed by the loss a broad protein band (52-56 kDa) of the predicted size for T2 from the profile of proteins secreted from mutant virus-infected BGMK cells at early times after infection. Although the T2-minus recombinant myxoma virus grew normally in tissue culture, upon infection of susceptible rabbits the viral disease was observed to be significantly attenuated. The majority of infected rabbits were able to mount an effective immune response to the infection and completely recovered. These survivor rabbits became immune to subsequent challenge with wild type myxoma virus. We conclude that the T2 viral protein is an important secreted virulence factor and that it in all likelihood functions by compromising the antiviral effects of TNF. We propose the term "viroceptor" to describe viral-encoded homologs of cellular lymphokine receptors whose function is to intercept the activity of the cognate lymphokine in order to short circuit the host immune response to the viral infection.


Bioavailability of iron, zinc, folic acid, and vitamin A from fortified maize.
Several strategies appear suitable to improve iron and zinc bioavailability from fortified maize, and fortification per se will increase the intake of bioavailable iron and zinc. Corn masa flour or whole maize should be fortified with sodium iron ethylenediaminetetraacetate (NaFeEDTA), ferrous fumarate, or ferrous sulfate, and degermed corn flour should be fortified with ferrous sulfate or ferrous fumarate. The choice of zinc fortificant appears to have a limited impact on zinc bioavailability. Phytic acid is a major inhibitor of both iron and zinc absorption. Degermination at the mill will reduce phytic acid content, and degermed maize appears to be a suitable vehicle for iron and zinc fortification. Enzymatic phytate degradation may be a suitable home-based technique to enhance the bioavailability of iron and zinc from fortified maize. Bioavailability experiments with low phytic acid-containing maize varieties have suggested an improved zinc bioavailability compared to wild-type counterparts. The bioavailability of folic acid from maize porridge was reported to be slightly higher than from baked wheat bread. The bioavailability of vitamin A provided as encapsulated retinyl esters is generally high and is typically not strongly influenced by the food matrix, but has not been fully investigated in maize.


Mechanisms of persistent NF-kappaB activation by HTLV-I tax.
Human T cell leukemia virus type I (HTLV-I) is the causative agent of a fatal malignancy known as adult T cell leukemia (ATL). The HTLV-I Tax protein is thought to play a significant role in the initiation and pathogenesis of HTLV-I-mediated disease. Tax is a potent oncogene that deregulates cellular gene expression by persistently activating signaling pathways such as NF-kappaB. Tax activation of NF-kappaB is critical for the immortalization and survival of HTLV-I-infected T cells. In this review, we describe recent insights into the mechanisms employed by Tax to activate the canonical and noncanonical NF-kappaB signaling pathways. The adaptor function of Tax appears to be a common and important mechanism for the pathological activation of both NF-kappaB pathways.


Addition of nintedanib or placebo to neoadjuvant gemcitabine and cisplatin in locally advanced muscle-invasive bladder cancer (NEOBLADE): a double-blind, randomised, phase 2 trial.
Recurrence is common after neoadjuvant chemotherapy and radical treatment for muscle-invasive bladder cancer. We investigated the effect of adding nintedanib to neoadjuvant chemotherapy on response and survival in muscle-invasive bladder cancer. NEOBLADE was a parallel-arm, double-blind, randomised, placebo-controlled, phase 2 trial of neoadjuvant gemcitabine and cisplatin chemotherapy with nintedanib or placebo in locally advanced muscle-invasive bladder cancer. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 15 hospitals in the UK. Patients were randomly assigned (1:1) to nintedanib or placebo using permuted blocks with random block sizes of two or four, stratified by centre and glomerular filtration rate. Treatments were allocated using an interactive web-based system, and patients and investigators were masked to treatment allocation throughout the study. Patients received oral nintedanib (150 mg or 200 mg twice daily for 12 weeks) or placebo, in addition to usual neoadjuvant chemotherapy with intravenous gemcitabine 1000 mg/m2 on days 1 and 8 and intravenous cisplatin 70 mg/m2 on day 1 of a 3-weekly cycle. The primary endpoint was pathological complete response rate, assessed at cystectomy or at day 8 of cyclde 3 (plus or minus 7 days) if cystectomy did not occur. Primary analyses were done in the intention-to-treat population. The trial is registered with EudraCT, 2012-004895-01, and ISRCTN, 56349930, and has completed planned recruitment. Between Dec 4, 2014, and Sept 3, 2018, 120 patients were recruited and were randomly allocated to receive nintedanib (n=57) or placebo (n=63). The median follow-up for the study was 33·5 months (IQR 14·0-44·0). Pathological complete response in the intention-to-treat population was reached in 21 (37%) of 57 patients in the nintedanib group and 20 (32%) of 63 in the placebo group (odds ratio [OR] 1·25, 70% CI 0·84-1·87; p=0·28). Grade 3 or worse toxicities were observed in 53 (93%) of 57 participants who received nintedanib and 50 (79%) of 63 patients in the placebo group (OR 1·65, 95% CI 0·74-3·65; p=0·24). The most common grade 3 or worse adverse events were thromboembolic events (17 [30%] of 57 patients in the nintedanib group vs 13 [21%] of 63 patients in the placebo group [OR 1·63, 95% CI 0·71-3·76; p=0·29]) and decreased neutrophil count (22 [39%] in the nintedanib group vs seven [11%] in the placebo group [5·03, 1·95-13·00; p=0·0006]). 45 treatment-related serious adverse events occurred in the nintedanib group and 43 occurred in the placebo group. One treatment-related death occurred in the placebo group, which was due to myocardial infarction. The addition of nintedanib to chemotherapy was safe but did not improve the rate of pathological complete response in muscle-invasive bladder cancer. Boehringer Ingelheim.


Crystallization of the oxygen-evolving reaction centre of photosystem II in nine different detergent mixtures.
Oxygen-evolving photosystem II reaction centres (RCII) isolated from both spinach and pea have been crystallized. A single crystal form grew from RCII monomers in the presence of nine different three-component mixtures of non-ionic detergents and heptane-1,2, 3-triol. The crystals grew as hexagonal rods with dimensions of up to 1 x 0.3 x 0.3 mm. The crystals diffracted to a maximum resolution of 6.5 A and belong to a hexagonal space group with unit-cell parameters a = 495, b = 495, c = 115 A, alpha = beta = 90, gamma = 120 degrees. The growth of a single crystal form in the presence of such a large variety of detergents suggests a very limited range of crystal lattice formation sites in the RCII complex.


Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research.
The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.


Genetics of hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM), the most common inherited cardiac disorder, exhibits remarkable genetic and clinical heterogeneity. This manuscript reviews recent discoveries of disease-causing genes and their clinical consequences, and provides an overview of research that aims to elucidate how HCM ensues from a single-nucleotide mutation. The spectrum of genes that are mutated in HCM has expanded. In combination with newly developed sequencing technologies, there are now robust strategies for gene-based diagnosis in HCM. Understanding the molecular pathophysiology of HCM has emerged from the study of genetically engineered animal models of disease, and new data indicate important roles for altered intracellular Ca²⁺ regulation and oxidative stress. Pharmacologic strategies to normalize these processes show promise in attenuating HCM in experimental models. The current repertoire of HCM genes allows effective gene-based diagnosis, information that enables accurate assessment of disease risk in family members, and provides some insight into clinical course. From mechanistic insights gleaned from fundamental investigations of experimental HCM models, novel therapeutic targets that may provide new benefits for HCM patients have surfaced.


Tendon transfers for irreparable rotator cuff tears.
Tendon transfer is one treatment option for patients with massive irreparable rotator cuff tears. Although surgical indications are not clearly defined, the traditional thought is that the ideal candidate is young and lacks significant glenohumeral arthritis. The proposed benefits of tendon transfers are pain relief and potential increase in strength. The biomechanical rationale for the procedure is to restore the glenohumeral joint force couple and possibly to restore normal shoulder kinematics. The selection of donor tendon depends on the location of the rotator cuff deficiency. Transfers of latissimus dorsi and pectoralis major tendons have been shown to consistently improve pain; however, functional benefits are unpredictable. Trapezius tendon transfer may be an alternative in patients with massive posterosuperior rotator cuff tears, although longer-term follow-up is required.


Polyethylene glycol-induced calcium appetite.
Polyethylene glycol (PEG) has been used to investigate the physiological basis of sodium intake because it sequesters sodium from the extracellular fluid (ECF) and causes rats to drink concentrated NaCl solutions. To test the hypothesis that PEG also depletes ECF calcium and thus activates calcium intake, male Sprague-Dawley rats received two-bottle tests with a choice between a taste solution and water. Relative to intakes after control injections, rats injected with PEG (5 ml of 30% wt/wt sc) drank significantly greater volumes of several calcium solutions (0.1, 1, 10, or 32 mM CaCl2 or 10 or 100 mM calcium lactate). They also drank more 10 mM SrCl2, 300 mM NaCl, and 100 mM KHCO3, drank less 10 mM sodium saccharin, and did not alter intakes of 10 or 100 mM KCl, 32 mM NH4Cl, 10 mM AlCl3, 10 mM FeCl2, 100 mM CaCl2, or 1,000 mM NaCl. Thus PEG treatment produced an appetite that was specific to low and moderate concentrations of calcium, sodium, and perhaps bicarbonate. The physiological basis for this appetite was explored. At 24 h after PEG injection, plasma total calcium concentrations were either unaltered or increased, but plasma ionized calcium concentrations were reduced. Concentrations of parathyroid hormone and calcitonin but not 1 alpha, 25-dihydroxyvitamin D3 were elevated. Perhaps one or more of these changes in calcium homeostasis is responsible for the increased calcium intake. Whatever the mechanism, it is clear that PEG treatment induces an appetite for calcium in addition to the well-known appetite for sodium.


What constitutes a 'successful' recovery? Patient perceptions of the recovery process after a traumatic injury.
As the number of patients surviving traumatic injuries has grown, understanding the factors that shape the recovery process has become increasingly important. However, the psychosocial factors affecting recovery from trauma have received limited attention. We conducted an exploratory qualitative study to better understand how patients view recovery after traumatic injury. This qualitative, descriptive study was conducted at a Level One university trauma center. Participants 1-3 years postinjury were purposefully sampled to include common blunt-force mechanisms of injuries and a range of ages, socioeconomic backgrounds and injury severities. Semi-structured interviews explored participants' perceptions of self and the recovery process after traumatic injury. Interviews were transcribed verbatim; the data were inductively coded and thematically analyzed. We conducted 15 interviews, 13 of which were with male participants (87%); average hospital length of stay was 8.9 days and mean injury severity score was 18.3. An essential aspect of the patient experience centered around the recovery of both the body and the 'self', a composite of one's roles, values, identities and beliefs. The process of regaining a sound sense of self was essential to achieving favorable subjective outcomes. Participants expressed varying levels of engagement in their recovery process, with those on the high end of the engagement spectrum tending to speak more positively about their outcomes. Participants described their own subjective interpretations of their recovery as most important, which was primarily influenced by their engagement in the recovery process and ability to recover their sense of self. Patients who are able to maintain or regain a cohesive sense of self after injury and who are highly engaged in the recovery process have more positive assessments of their outcomes. Our findings offer a novel framework for healthcare providers and researchers to use as they approach the issue of recovery after injury with patients. III-descriptive, exploratory study.


Three subsequent single doses of gadolinium chelate for brain MR imaging in multiple sclerosis.
A triple-dose (TD) of gadolinium chelate is highly sensitive approach for detecting lesion activity in multiple sclerosis (MS). However, individual TD injections do not provide data on the severity of the pathologic process in a population of lesions, and its clinical use is limited by the cost-benefit considerations. Our aim was to determine whether the use of three subsequent single doses (SD) of a gadolinium chelate in brain MR imaging is useful in detecting MS lesions with different patterns of enhancement. In 10 patients, T1-weighted spin-echo images were acquired before and after three intravenous administrations of 0.1 mmol/kg of gadodiamide. In all patients, SD images showed six enhancing lesions; double-dose (DD) images, 13; and TD images, 22. Differences between SD and TD and between DD and TD were significant (P <.018). Six lesions (27%) enhanced with all the three doses; seven (32%), with both DD and TD; and nine (41%), with only TD. Proportions of patients with at least one enhancing lesion were, for SD, four of 10; DD, seven of 10; and TD, nine of 10. In defining active disease in these nine patients, we needed only 19 SDs versus the 30 SDs that would have been needed if individual TD injections were used. With three subsequent SD injections, the number of enhancing lesions progressively increases. This approach allows the distinction of three levels of enhancement, and it reduces the amount of contrast agent needed to distinguish patients with active MS from those with nonactive MS.


Magnetic resonance imagination of the peroneus longus tendon after anterior cruciate ligament reconstruction.
Several studies report that tendons can regenerate after harvesting. These studies have been performed especially in patellar and hamstring tendons. At our institution, 10 cm length of full thickness peroneus longus tendon has been harvested to reconstruct torn anterior cruciate ligament since 1997 as a different graft source. The aim of this study was to investigate whether the peroneus longus tendon used the anterior cruciate ligament reconstruction has a regeneration potential or not. Twelve patients, who had originally undergone harvesting of the peroneus longus tendon for the primary surgery of the anterior cruciate ligament reconstruction, underwent magnetic resonance imaging (MRI). Images of both legs were acquired simultaneously with the use of the scanner's extremity coil, as we aimed to compare harvested peroneus longus tendon with the other leg's peroneus longus tendon (healthy side) for evaluation of the regeneration potential. The average age of the patients was 31 years. There were eight right and four left legs. The average time interval was 52 months between ligament surgery and MRI. In all patients, a varying amount of the regeneration of the peroneus longus tendon was seen on the MRI images. Although the extent of PLT regeneration in proximal sections seemed better than in mid- and distal sections, there was no statistical difference between sections (P = 0.130). These data show that the peroneus longus tendon has a regeneration potential after harvesting for anterior cruciate ligament reconstruction.


Clinical determinants of survival from postoperative renal failure.
In a series of 114 consecutive patients with acute renal failure, the over-all mortality rate was 60 per cent; 62 per cent of the patients had a documented episode of hypotension just prior to the development of acute renal failure. In 11 patients, a second episode of renal failure developed following recovery from the initial episode of acute renal failure; all of these patients died. The urine output rate during the course of acute renal failure was inversely related to the mortality rate in the series as a whole. The mean duration of acute renal failure in survivors of the present series was 11.0 plus or minus 1.4 days. Complications of renal failure in the order of their frequency included hemorrhagic hypotension, sepsis, sepsis with hypotension and consumption coagulopathies; only 12 per cent had no complications. Only six of 51 patients whose clinical course was complicated by sepsis with or without an episode of hypotension survived. By contrast, 30 of 53 patients who had hemorrhagic hypotension without sepsis survived. The date suggest that although acute renal failure has a high mortality rate, it is a benign disease that is potentially reversible. Regardless of age and sex, renal functional recovery will take place if the patient is maintained in good physiologic condition long enough without a continued stress, such as sepsis, hypotension or hypovolemia, all of which prolong renal ischemia. During the course of renal failure, extreme care is essential to maintain adequate circulating volume without extracellular fluid overload; a second hemodynamic insult may result in serious damage to the regenerating renal tubules. We conclude that early recognition of acute renal failure, aggressive management of sepsis, careful titration of fluid and electrolyte therapy, meticulous monitoring, maintenance of the circulation and judicious utilization of dialysis will aid in reduction of mortality in these critically ill patients.


Ectomycorrhizal fungal diversity in orchards of cultivated pecan (Carya illinoinensis; Juglandaceae).
Carya illinoinensis (pecan) belongs to the Juglandaceae (walnut family) and is a major economic nut crop in the southern USA. Although evidence suggests that some species in the Juglandaceae are ectomycorrhizal, investigations on their ectomycorrhizal fungal symbionts are quite limited. Here we assessed the ectomycorrhizal fungal diversity in cultivated orchards of C. illinoinensis. Five pecan orchards in southern Georgia, USA, were studied, three of which were known to fruit the native edible truffle species Tuber lyonii. We sequenced rDNA from single ectomycorrhizal root tips sampled from a total of 50 individual trees. Mycorrhizae were identified by ITS and LSU rDNA sequence-based methods. Forty-four distinct ectomycorrhizal taxa were detected. Sequestrate taxa including Tuber and Scleroderma were particularly abundant. The two most abundant sequence types belonged to T. lyonii (17%) and an undescribed Tuber species (~20%). Because of our interest in the ecology of T. lyonii, we also conducted greenhouse studies to determine whether this species would colonize and form ectomycorrhizae on roots of pecan, oak, or pine species endemic to the region. T. lyonii ectomycorrhizae were formed on pecan and oak seedlings, but not pine, when these were inoculated with spores. That oak and pecan seedling roots were receptive to truffle spores indicates that spore slurry inoculation could be a suitable method for commercial use and that, ecologically, T. lyonii may function as a pioneer ectomycorrhizal species for these hosts.


Diagnosing and treating renal disease in cirrhotic patients.
Renal dysfunction in cirrhosis is mostly related to the development of acute kidney injury (AKI), precipitated by either an acute disturbance of hemodynamics, or acute structural damage to the kidneys. The incidence of chronic renal failure is rising, due to increasing prevalence of conditions such as diabetes, viral hepatitis, which can be associated with renal damage. AKI is defined as a rise in serum creatinine of 0.3 mg/dL in <48 hours or by 50% from baseline within the past 3 months without setting a threshold for the final serum creatinine. Stages 1, 2, and 3 of AKI are defined as 150%, 200% and 300% of baseline serum creatinine respectively, which allows for assessment of AKI progression. Chronic kidney disease (CKD) is defined as an estimated glomerular filtration rate of <60 mL/min for >3 months. Treatment of AKI consists of removal of precipitating factors and replenishment of the intravascular volume using colloids such as albumin. Frequently, AKI can be reversed using these measures alone. Non-responders to removal of precipitating factors and volume challenge can receive vasoconstrictors such as terlipressin or norepinephrine together with albumin. Midodrine is inferior in efficacy as a vasoconstrictor when compared to terlipressin. Liver transplantation is the definitive treatment for type 1 hepatorenal syndrome with liver failure. Delay in receiving a liver transplant can result in non-recovery of renal function post transplant. Treatment of CKD in cirrhosis is unsatisfactory, mostly aimed at optimizing management of comorbid conditions, or treating the underlying refractory ascites in patients with type 2 hepatorenal syndrome.


Indirect costs associated with deaths of children aged 0-14 years from measles in a weak health system and conflict and fragile zone: the case of Somalia.
This study recognises periodic outbreaks of measles continue to affect conflict and fragile zones in the least developed countries. This study set out to provide evidence for the indirect costs or economic loss associated with measles-related deaths among children aged 0-14 years in Somalia. Using epidemiologic and economic data, the indirect cost was calculated based on the framework of the World Health Organisation guide of identifying the economic consequences of disease and injury. The baseline indirect cost was computed as the product of discounted future productive years of life lost (PYLL), non-health gross domestic product per capita (NHGDPPC) and the estimated total measles deaths (ETMD). The model was adjusted for conflict and fragility conditions and further extension considered a finite and stable upper limit growth of the instability-adjusted NHGDPPC. To discount future costs, a rate of 3% was applied. Using a ±20% variability assumption of the epidemiologic and economic factor inputs, a sensitivity analysis was conducted to account for uncertainty. In 2015 values, the ETMD of 3723 measles deaths of children aged 0-14 years could decrease non-health GDP of the country by $23.46 million, a potential loss of $6303 per death over the discounted PYLL. The loss would increase by 5.3% when adjusted for conflict and fragility conditions. Assuming growth, the future adjusted loss is expected to be $35.91 million in 2015 values. Girl-child deaths accounted for 51.2% of the burden. Results are robust to the variations in the model inputs, although sensitivity analyses suggest the proportion of total measles deaths and the discount rate accounted for greater uncertainty of the loss than do the proportion of growth and instability assumption. Conflict and fragility accounted for the least uncertainty, perhaps confirming their relative perpetuity in Somalia. Results show significant indirect cost related to measles deaths of children, exacerbated by conflict and fragility. This is an economic burden, but one which the health system, policy-makers, government and other stakeholders should be prepared to colossally discount by collectively taking measles surveillance and security measures now to reduce further deaths in the future.


Regulatory T cells in ankylosing spondylitis and the response after adalimumab treatment.
The aim of this study was to investigate the role of regulatory T cells (Tregs) in ankylosing spondylitis (AS). We included 69 AS patients (15 of them received anti-tumor necrosis factor-apha agent-adalimumab) in the study and used a questionnaire to record the demographic data, disease activity index, functional index, human leukocyte antigen-B27, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Thirty healthy subjects were used as controls. The peripheral blood mononuclear cells (PMBCs) were stained with anti-CD4, anti-CD25 and anti-Forkhead/winged helix transcription factor P3 (anti-FoxP3) antibodies and flow-cytometry was used to determine cell populations. The percentages of Tregs in PMBCs were significantly higher in AS patients than in healthy controls. In AS patients who had poor disease functional index with higher levels of ESR and CRP were positively and significantly correlated with Tregs percentages in PMBCs. After adalimumab treatment in 15 patients, the percentages of Tregs, the ESR/CRP levels and the Bath Ankylosing Spondylitis Disease Activity Index/Bath Ankylosing Spondylitis Functional Index were significantly and gradually decreased over time. The high expression of FoxP3 and CD25 on CD4(+) T cells in PBMCs in AS patients was noted, and could be reversed by adalimumab therapy. These findings suggest that Tregs may play a role in modulating the inflammatory process in AS. Whether Tregs can be taken as a predictor for disease activity or treatment outcome is unclear and requires further study.


Evaluation of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels, and their relations with disease type and activity in inflammatory bowel diseases
Inflammatory bowel disease (IBD) mainly encompass two entities called ulcerative colitis (UC) and Crohn's disease (CD), both of which are chronic, progressive and, inflammatory conditions of the gastrointestinal tract. Various indicators and non-invasive markers have been sought and used in IBD patients to help assessing disease activity and treatment effectiveness although none of them are proven to yield definite results in full correlation with the clinical, endoscopic, and histopathological examinations. The aim of the current study was to investigate the relationship of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels with disease type and activity and to assess their potential use in establishing diagnosis and activity status of IBD, namely UC and CD. A total of 111 IBD patients with determined active and inactive disease periods and 70 matched controls were recruited. Serum NGAL levels of the patients and the control group were measured using commercially available ELISA kits. ADMA and SMDA levels were measured by high performance liquid chromatography. The IBD group had significantly higher serum levels of NGAL (p = 0.001), ADMA (p = 0.0001), and SDMA (p = 0.0001) in comparison to the control group. Likewise, serum NGAL, ADMA, and SDMA levels were significantly higher in the active IBD group compared to the inactive IBD group (p = 0.0001). Active UC and active CD patients similarly had significantly higher levels of serum NGAL, ADMA, and SDMA than the respective levels in inactive UK and inactive CD patients (p = 0.0001). Serum NGAL, ADMA and SMDA levels are increased in patients with IBD, and serum NGAL, ADMA and SMDA concentrations are significantly higher in active IBD patients than inactive IBD patients. Our results suggest these biomarkers may serve in estimating IBD activity and severity.


The prevalence and impact of psychiatric symptoms in an undiagnosed diseases clinical program.
In 2008, the NIH launched an undiagnosed diseases program to investigate difficult to diagnose, and typically, multi-system diseases. The objective of this study was to evaluate the presence of psychiatric symptoms or psychiatric diagnoses in a cohort of patients seeking care at the Emory Special Diagnostic Service clinic. We hypothesized that psychiatric symptoms would be prevalent and associated with trauma exposure, and a decreased quality of life and functioning. This is a cross-sectional, retrospective analysis of 247 patients seen between February 7, 2014 and May 31, 2017. The sources for data included the Emory Health History Questionnaire (HHQ) that had the work and social adjustment and quality of life enjoyment and satisfaction questionnaire-short form (QLSQ) embedded in it; medical records, and the comprehensive standardized special diagnostic clinic forms. Primary outcomes were presence of any psychiatric symptom, based on report of the symptom on the HHQ or medical record, or presence of a confirmed preexisting psychiatric disorder. Seventy-two percent of patients had at least one psychiatric symptom while 24.3% of patients had a pre-existing psychiatric diagnosis. Patients with any psychiatric symptom had significantly diminished Q-LES-Q scores (45.27 ± 18.63) versus patients with no psychiatric symptoms (62.01 ± 21.57, t = 5.60, df = 225, p<0.0001) and they had significantly greater functional disability. Patients with a psychiatric disorder also had significantly diminished Q-LES-Q scores (45.16 ± 17.28) versus those without a psychiatric diagnosis (51.85 ± 21.54, t = 2.11, df = 225, p = 0.036) but did not have significantly increased functional impairment. Both patients with psychiatric symptoms and ones with psychiatric disorders had an increased prevalence of trauma. Psychiatric symptoms are prevalent in patients evaluated for undiagnosed disorders. The presence of any psychiatric symptom, with or without a formal psychiatric diagnosis, significantly decreases quality of life and functioning. This suggests that assessment for psychiatric symptoms should be part of the evaluation of individuals with undiagnosed disorders and may have important diagnostic and treatment implications.


Changes in the Relative Balance of Approach and Avoidance Inclinations to Use Alcohol Following Cue Exposure Vary in Low and High Risk Drinkers.
According to the ambivalence model of craving, alcohol craving involves the dynamic interplay of separate approach and avoidance inclinations. Cue-elicited increases in approach inclinations are posited to be more likely to result in alcohol consumption and risky drinking behaviors only if unimpeded by restraint inclinations. Current study aims were (1) to test if changes in the net balance between approach and avoidance inclinations following alcohol cue exposure differentiate between low and high risk drinkers, and (2) if this balance is associated with alcohol consumption on a subsequent taste test. In two experiments (N = 60; N = 79), low and high risk social drinkers were exposed to alcohol cues, and pre- and post- approach and avoidance inclinations measured. An ad libitum alcohol consumption paradigm and a non-alcohol exposure condition were also included in Study 2. Cue-elicited craving was characterized by a predominant approach inclination only in the high risk drinkers. Conversely, approach inclinations were adaptively balanced by equally strong avoidance inclinations when cue-elicited craving was induced in low risk drinkers. For these low risk drinkers with the balanced craving profile, neither approach or avoidance inclinations predicted subsequent alcohol consumption levels during the taste test. Conversely, for high risk drinkers, where the approach inclination predominated, each inclination synergistically predicted subsequent drinking levels during the taste test. In conclusion, results support the importance of assessing both approach and avoidance inclinations, and their relative balance following alcohol cue exposure. Specifically, this more comprehensive assessment reveals changes in craving profiles that are not apparent from examining changes in approach inclinations alone, and it is this shift in the net balance that distinguishes high from low risk drinkers.


Artificial intelligence in emergency medicine: A scoping review.
Despite the growing investment in and adoption of artificial intelligence (AI) in medicine, the applications of AI in an emergency setting remain unclear. This scoping review seeks to identify available literature regarding the applications of AI in emergency medicine. The scoping review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews using Medline-OVID, EMBASE, CINAHL, and IEEE, with a double screening and extraction process. The search included articles published until February 28, 2020. Articles were excluded if they did not self-classify as studying an AI intervention, were not relevant to the emergency department (ED), or did not report outcomes or evaluation. Of the 1483 original database citations, 395 were eligible for full-text evaluation. Of these articles, a total of 150 were included in the scoping review. The majority of included studies were retrospective in nature (n = 124, 82.7%), with only 3 (2.0%) prospective controlled trials. We found 37 (24.7%) interventions aimed at improving diagnosis within the ED. Among the 150 studies, 19 (12.7%) focused on diagnostic imaging within the ED. A total of 16 (10.7%) studies were conducted in the out-of-hospital environment (eg, emergency medical services, paramedics) with the remainder occurring either in the ED or the trauma bay. Of the 24 (16%) studies that had human comparators, there were 12 (8%) studies in which AI interventions outperformed clinicians in at least 1 measured outcome. AI-related research is rapidly increasing in emergency medicine. There are several promising AI interventions that can improve emergency care, particularly for acute radiographic imaging and prediction-based diagnoses. Higher quality evidence is needed to further assess both short- and long-term clinical outcomes.


Evaporation induced nanoparticle - binder interaction in electrode film formation.
Processing induced nanoparticle agglomeration and binder distribution affect the electrode microstructure formation and corresponding electrochemical performance in lithium-ion batteries. In the present study, stochastic dynamics computations based on a morphologically detailed mesoscale model are performed to illustrate the microstructural variability of electrode films affected by the evaporation condition (drying temperature) and the binder length (molecular weight). Micropores are observed at the surface of the electrode film when dried at a lower temperature. The pore formation depth tends to increase as the binder length increases. The solvent chemical potential also affects the surface topography of the electrode film. The solvent with higher volatility (more negative chemical potential) tends to produce more micropores. A lower drying temperature is beneficial for improving the electronic conductivity of the porous electrode film due to the better distribution of the conductive additive nanoparticles on and around the active particles, thereby facilitating the electron transport network formation. Agglomeration between active material nanoparticles can also be mitigated at a lower drying temperature. Additionally, better adhesion of the porous electrode film can be achieved due to preferential localization of the binder on the substrate at relatively low-temperature evaporation.


Antimicrobial and synergistic activity of essential oils of Aloysia triphylla and Lippia alba against Aeromonas spp.
The objective of this study was to identify and quantify the chemical constituents, as well as the antimicrobial, antibiofilm and synergistic activity with florfenicol of essential oils of Aloysia triphylla (EOAT) and Lippia alba (EOLA) against Aeromonas spp. The antimicrobial activity of EOAT and EOLA was verified by the minimum bactericidal concentration (MBC) and the action against biofilm forming and consolidated biofilm. The synergistic activity of EOAT and EOLA with florfenicol was performed by the checkerboard technique. The main components of EOAT were α-citral (39.91%), E-carveol (25.36%) and limonene (21.52%), while that of EOLA was linalool (81.64%). Aeromonas spp. isolates showed sensitivity to both essential oils with MBC between 195.3 and 3125.0 μL/mL. Two isolates were classified as non-producing, three as moderate and 16 as weak biofilm producers. The EOAT and EOLA interfered in the biofilm formation, from moderate to weak producers, but did not cause any interference in the consolidated biofilm. The EOAT and EOLA combined with florfenicol showed synergistic effect and reduced MBC. The EOAT and EOLA have potential for application as antimicrobial agents, as they interfere in the initial formation of biofilm and when combined with florfenicol, present a synergic effect with a reduction in the minimum dose of the antibiotic.


[The factors affecting visual outcome in open globe injuries].
To evaluate the factors affecting visual acuity in cases subjected to surgical repair due to open globe injury. The records of the patients who have been subjected to emergency surgical repair due to open globe injury were examined retrospectively. From a total of 195 cases, 119 eyes of 119 cases who fulfilled the inclusion criteria were included into the study. Cases were examined in terms of age, gender, trauma type, localization, preoperative examination findings, the presence of additional surgical interventions and the findings in the last examination. Chi-square test and logistic regression analysis were used in statistical analysis. Original visual acuity (p=0.042), zone (p=0.001), trauma type (p=0.003), preoperative anterior chamber loss (p=0.005), existence of hyphema (p=0.001), vitreous prolapse (p=0.000) and posterior segment pathology development (p=0.000) influenced the visual outcome. In cases with grade 4 or grade 5 resulting visual acuity, statistically significant factors were determined as "existence of pathology in the posterior segment" (p=0.000, Odds ratio=12.397) and "total anterior chamber loss" (p=0.015, Odds ratio=4.661). Changes occurring at the posterior segment pathology and anterior chamber loss are determinant in terms of resulting visual acuity. For this reason, ophthalmoscopy and ultrasonography that should not be omitted in the follow-up period for cases with a transparent media and with media opacity, respectively.


Engaging people with chronic kidney disease in their own care an integrative review.
The treatment of chronic kidney disease (CKD) places a major burden on patients and their families. Interventions such as nutritional management, medication regimen, and renal replacement therapies require active patient participation. An integrative literature review was carried out to identify articles on the engagement and participation of people with CKD in their care. The Medical Subject Headings (MeSH) "Kidney Failure, Chronic", "Self Care", and "Patient Participation" were used to conduct a search on the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), the U.S. National Library of Medicine® (Medline/PubMed), Biblioteca Virtual em Saúde (Bireme). A total of 21 articles published between 2012 and 2016 were selected. The most commonly used data collection and analysis techniques were semi-structured interviews and phenomenological thematic analysis, respectively. The articles were categorized into the following thematic groups: illness management and treatment; involvement in the decision-making process; advanced care plan; and home peritoneal dialysis. We found that there is a lack of qualitative research in certain areas, namely kidney transplant recipients and people with initial stages of CKD. People with CKD should be encouraged to actively engage in their own care, which in turn requires the knowledge, motivation and support of health professionals.


Schilder's disease. A study of the cerebral cortex with Golgi's method.
The cerebral cortex of a patient with Schilder's disease was studied with the Golgi method. The number of synaptic spines, basal dendrites, branching points, and dendritic intersection points of 5th layer pyramids are similar to those of controls, in spite of almost complete loss of extrinsic fibers. These data illustrate the probable remodeling of intrinsic cortical circuits and neuronal plasticity in the human cerebral cortex.


Safety and efficacy of video DLT (VDLT) for lung isolation during the COVID-19 pandemic.
One lung ventilation (OLV) with collapse of the ipsilateral lung is a prerequisite for most thoracic surgical procedures. Double-lumen tube (DLT) is still the preferred method to isolate the lungs and fiberoptic bronchoscopy (FOB) is the gold standard for the confirmation of correct placement of the DLT. However, both these procedures are considered as a high-aerosol-generating procedures and are hazardous to the health workers, particularly at this time of the COVID-19 pandemic. We did nine thoracic surgery cases categorized as essential, requiring OLV during the ongoing period of the COVID-19 between April 2020 and May 2020 where we used Full view DLT for lung isolation. We present our case series which shows that the Full view VDLT can minimize or circumvent the use of FOB during OLV, and reduce the time taken to isolate the lungs thus reducing aerosol in the theater. None of the nine patients required FOB for confirmation of initial positioning nor for diagnosis of intraoperative malposition. The time taken to isolate the lungs was significantly less and the surgical positioning was done under real-time monitoring by visualizing the blue cuff distal to carina at all times. The real-time monitoring by the Full view VDLT offers the additional advantage of detecting any malposition even before it results in loss of isolation or desaturation. We conclude that the Full view VDLT is an efficient and safe alternative for lung isolation at this time of the COVID-19 pandemic.


Integrative proteomic and cytological analysis of the effects of extracellular Ca(2+) influx on Pinus bungeana pollen tube development.
Ca (2+) is an essential ion in the control of pollen germination and tube growth. However, the control of pollen tube development by Ca (2+) signaling and its interactions with cytoskeletal components, energy-providing pathways, and cell-expansion machinery remain elusive. Here, we used nifedipine (Nif) to study Ca (2+) functions in differential protein expression and other cellular processes in Pinus bungeana pollen tube growth. Proteomics analysis indicated that 50 proteins showed differential expression with varying doses of Nif. Thirty-four of these were homologous to previously reported proteins and were classified into different functional categories closely related to tip-growth machinery. Blocking the L-type Ca (2+) channel with Nif in the pollen tube membrane induced several early alterations within a short time, including a reduction of extracellular Ca (2+) influx and a subsequently dramatic decrease in cytosolic free Ca (2+) concentration ([Ca (2+)] c), concomitant with ultrastructural abnormalities and changes in the abundance of proteins involved in energy production and signaling. Secondary alterations included actin filament depolymerization, disrupted patterns of endocytosis/exocytosis, and cell wall remodeling, along with changes in the proteins involved in these processes. These results suggested that extracellular Ca (2+) influx was necessary for the maintenance of the typical tip-focused [Ca (2+)] c gradient in the P. bungeana pollen tube, and that reduced adenosine triphosphate production (ATP), depolymerization of the cytoskeleton, and abnormal endocytosis/exocytosis, together with enhanced rigidity of cell walls, were responsible for the growth arrest observed in pollen tubes treated with Nif.


Larval carry-over effects from ocean acidification persist in the natural environment.
An extensive body of work suggests that altered marine carbonate chemistry can negatively influence marine invertebrates, but few studies have examined how effects are moderated and persist in the natural environment. A particularly important question is whether impacts initiated in early life might be exacerbated or attenuated over time in the presence or absence of other stressors in the field. We reared Olympia oyster (Ostrea lurida) larvae in laboratory cultures under control and elevated seawater pCO2 concentrations, quantified settlement success and size at metamorphosis, then outplanted juveniles to Tomales Bay, California, in the mid intertidal zone where emersion and temperature stress were higher, and in the low intertidal zone where conditions were more benign. We tracked survival and growth of outplanted juveniles for 4 months, halfway to reproductive age. Survival to metamorphosis in the laboratory was strongly affected by larval exposure to elevated pCO2 conditions. Survival of juvenile outplants was reduced dramatically at mid shore compared to low shore levels regardless of the pCO2 level that oysters experienced as larvae. However, juveniles that were exposed to elevated pCO2 as larvae grew less than control individuals, representing a larval carry-over effect. Although juveniles grew less at mid shore than low shore levels, there was no evidence of an interaction between the larval carry-over effect and shore level, suggesting little modulation of acidification impacts by emersion or temperature stress. Importantly, the carry-over effects of larval exposure to ocean acidification remained unabated 4 months later with no evidence of compensatory growth, even under benign conditions. This latter result points to the potential for extended consequences of brief exposures to altered seawater chemistry with potential consequences for population dynamics.


Implication of neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function in diabetic gastroparesis.
Recently, diabetic gastroparesis (DGP) has received much attention as its prevalence is increasing in a dramatic fashion and management of patients with DGP represents a challenge in the clinical practice due to the limited therapeutic options. DGP highlights an interrelationship between the gastric emptying and pancreatic secretory function that regulate a wide range of digestive and metabolic functions, respectively. It well documented that both gastric emptying and pancreatic secretion are under delicate control by multiple neurohormonal mechanisms including extrinsic parasympathetic pathways and gastrointestinal (GI) hormones. Interestingly, the latter released in response to various determinants that related to the rate and quality of gastric emptying. Others and we have provided strong evidence that the central autonomic nuclei send a dual output (excitatory and inhibitory) to the stomach and the pancreas in response to a variety of hormonal signals from the abdominal viscera. Most of these hormones released upon gastric emptying to provide feedback, and control this process and simultaneously regulate pancreatic secretion and postprandial glycemia. These findings emphasize an important link between gastric emptying and pancreatic secretion and its role in maintaining homeostatic processes within the GI tract. The present review deals with the neurohormonal-coupled mechanisms of gastric emptying and pancreatic secretory function that implicated in DGP and this provides new insights in our understanding of the pathophysiology of DGP. This also enhances the process of identifying potential therapeutic targets to treat DGP and limit the complications of current management practices.


Cardiovascular calcification and subcortical bone demineralization in hypertension.
The present study investigated cardiovascular calcification, peripheral bone mineral density (BMD), and lab indices in hypertensive patients aged 55-74 years without severe kidney dysfunction. Cardiovascular calcification was investigated by ultrasound examinations at eight sites: aortic valve, left and right common carotid artery, left and right carotid artery bifurcation, left and right internal carotid artery, and abdominal aorta. The presence/absence of calcification at each site was coded as 1/0, respectively, for the calculation of a cumulative score. Peripheral bone mineral density was assessed by forearm quantitative computed tomography (pQCT) and was defined as low if the T-score was <-1. Lab work-up included plasma creatinine, calcium, phosphorus, parathyroid hormone and 25-(OH) vitamin D measurements. Ninety-one patients were studied. The range was 2-8 for the calcification score and 229-492 mg cm-3 for bone mineral density. The prevalence of low bone densitometry was 83.5%. The calcification score and bone densitometry were inversely correlated in a non-adjusted analysis (R=-0.297, P=0.004) and in multivariable regression (beta=-0.335, P=0.003). The association was significant for subcortical bone (beta=-0.302, P=0.007) but not for cortical bone or trabecular bone (P⩾0.194 in both cases). The calcification score was associated with a low prevalence of bone densitometry in the non-adjusted analysis (odds ratio=2.53, 95% CI=1.41/4.54, P=0.002) and in the multivariable logistic regression (odds ratio=2.46, 95% CI=1.25/4.81, P=0.009). Cardiovascular calcification was independently associated with peripheral bone densitometry in hypertensive patients. The data support the hypothesis that vascular calcification and low bone densitometry share some determinants in hypertensive patients.


Micro-flowcell conductometric sweat analysis for cystic fibrosis diagnosis.
This paper describes a device specifically designed to facilitate neonatal sweat testing. The components are sized appropriately for attachment to the limbs of newborns. Iontophoretic electrodes, with pilocarpine gel inserts, are latched into small holders attached by straps to the limb. The holder at the anodic site remains in place to receive and align the sensor cell, which uses a conical collecting surface to channel the sweat directly and anaerobically from the sweat ducts to the continuous flow-through conductivity cell within its body. A crib-side analysis unit incorporates an iontophoretic power supply and displays a continuous readout of sweat electrical conductivity. The average conductivity during a specific time interval and the initial sweating rate are automatically displayed. The method, which simplifies sweat tests, is currently being assessed in three neonatal clinical trials to test its ability to reduce test failures in the newborn due to insufficient sweat.


Quality and rural-urban comparison of tuberculosis care in Rivers State, Nigeria.
Nigeria ranks among countries with the highest burden of tuberculosis. Yet evidence continues to indicate poor treatment outcomes which have been attributed to poor quality of care. This study aims to identify some of the systemic problems in order to inform policy decisions for improved quality of services and treatment outcomes in Nigeria. A comparative assessment of the quality of TB care in rural and urban health facilities was carried out between May and June 2013, employing the Donabedian model of quality assessment. Data was analysed using the SPSS software package version 20.0. The level of significance was set at p < 0.05. Health facility infrastructures were more constrained in the urban than rural settings. Both the urban and rural facilities lacked adequate facilities for infection control such as, running water, air filter respirators, hand gloves and extractor fans. Health education and HIV counselling and testing (HCT) were limited in rural facilities compared to urban facilities. Although anti-TB drugs were generally available in both settings, the DOTS strategy in patient care was completely ignored. Finally, laboratory support for diagnosis and patient monitoring was limited in the rural facilities. The study highlights suboptimal quality of TB care in Rivers State with limitations in health education and HCT of patients for HIV as well as laboratory support for TB care in rural health facilities. We, therefore, recommend that adequate infection control measures, strict observance of the DOTS strategy and sufficient laboratory support be provided to TB clinics in the State.


Zolpidem related persistent genital arousal disorder: An interesting case.
The present paper is describing a case of persistent genital arousal disorder that developed to a 55-year-old woman, shortly after the initiation of zolpidem. Persistent genital arousal disorder (PGAD) is a clinical entity that appears with a relatively low frequency in women, and is characterized by persistent or recurrent, unwanted and bothersome feelings of genital arousal, which often do not resolve with orgasm and are not associated with sexual desire (sexual interest, thoughts or fantasies). Women who experience PGAD often have feelings of shame, guilt and distress. Although its exact etiology remains unclear, various etiological factors have been proposed, central or peripheral, which may be psychological, vascular, dietary, pharmacological or neurological. Additionally, its presence has been associated to restless legs syndrome and overactive bladder syndrome. Likewise, multiple therapeutic interventions have been proposed and tried in patients with PGAD, either pharmacological (SSRIs, SNRIs, antiandrogens, benzodiazepines, antipsychotics, anticonvulsive agents) or other (ECT, physiotherapy, psychotherapy, nerve stimulation). Zolpidem is a nonbenzodiazepine indirect GABA A receptor agonist, which has lately been used as a therapeutic agent for PGAD in some cases. Nevertheless, in our patient, receiving zolpidem for insomnia seemed to be timely connected to the onset of PGAD symptomatology. The aim of the present paper is to highlight the need for more research into the possible factors that may contribute to PGAD.


Controversies in perioperative medicine.
Coexisting medical problems are common in surgical patients. Due to the lack of convincing studies, however, the optimal strategies for perioperative management of many medical problems remain unclear. Thus, practices are often based on inconclusive clinical studies or extrapolated from current understanding of pathophysiology. This article reviews guidelines and practices for endocarditis prophylaxis, perioperative anticoagulation in patients with mechanical heart valves, glucose control in diabetic patients undergoing surgery, and the use of beta-blockers to prevent postoperative cardiac complications. In addition, the strength of the evidence supporting these practices is evaluated.


D-tagatose protects against oleic acid-induced acute respiratory distress syndrome in rats by activating PTEN/PI3K/AKT pathway.
Acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier, resulting in severe alveolar edema and inflammation. D-tagatose (TAG) is a low-calorie fructose isomer with diverse biological activities whose role in ARDS has never been explored. We found that TAG protects lung tissues from injury in the oleic acid-induced rat model of ARDS. Seventeen male Sprague-Dawley rats were randomly assigned to 3 groups: Sham (n = 5), ARDS (n = 6), and TAG + ARDS (n = 6). The treatment groups were injected with oleic acid to induce ARDS, and the TAG + ARDS group was given TAG 3 days before the induction. After the treatments, the effect of TAG was evaluated by blood gas analysis and observing the gross and histological structure of the lung. The results showed that TAG significantly improved the oxygenation function, reduced the respiratory acidosis and the inflammatory response. TAG also improved the vascular permeability in ARDS rats and promoted the differentiation of alveolar type II cells, maintaining the stability of the alveolar structure. This protective effect of TAG on the lung may be achieved by activating the PTEN/PI3K/AKT pathway. Thus, TAG protects against oleic acid-induced ARDS in rats, suggesting a new clinical strategy for treating the condition.


Genetic Basis of Aerobically Supported Voluntary Exercise: Results from a Selection Experiment with House Mice.
The biological basis of exercise behavior is increasingly relevant for maintaining healthy lifestyles. Various quantitative genetic studies and selection experiments have conclusively demonstrated substantial heritability for exercise behavior in both humans and laboratory rodents. In the "High Runner" selection experiment, four replicate lines of Mus domesticus were bred for high voluntary wheel running (HR), along with four nonselected control (C) lines. After 61 generations, the genomes of 79 mice (9-10 from each line) were fully sequenced and single nucleotide polymorphisms (SNPs) were identified. We used nested ANOVA with MIVQUE estimation and other approaches to compare allele frequencies between the HR and C lines for both SNPs and haplotypes. Approximately 61 genomic regions, across all somatic chromosomes, showed evidence of differentiation; 12 of these regions were differentiated by all methods of analysis. Gene function was inferred largely using Panther gene ontology terms and KO phenotypes associated with genes of interest. Some of the differentiated genes are known to be associated with behavior/motivational systems and/or athletic ability, including Sorl1, Dach1, and Cdh10 Sorl1 is a sorting protein associated with cholinergic neuron morphology, vascular wound healing, and metabolism. Dach1 is associated with limb bud development and neural differentiation. Cdh10 is a calcium ion binding protein associated with phrenic neurons. Overall, these results indicate that selective breeding for high voluntary exercise has resulted in changes in allele frequencies for multiple genes associated with both motivation and ability for endurance exercise, providing candidate genes that may explain phenotypic changes observed in previous studies.


Enhanced Neutral Exciton Diffusion in Monolayer WS2 by Exciton-Exciton Annihilation.
Dominant recombination pathways in monolayer transition metal dichalcogenides (TMDCs) depend primarily on background carrier concentration, generation rate, and applied strain. Charged excitons formed in the presence of background carriers mainly recombine nonradiatively. Neutral excitons recombine completely radiatively at low generation rates, but experience nonradiative exciton-exciton annihilation (EEA) at high generation rates. Strain can suppress EEA, resulting in near-unity photoluminescence quantum yield (PL QY) at all exciton densities. Although exciton diffusion is the primary channel of energy transport in excitonic materials and a critical optoelectronic design consideration, the combined effects of these factors on exciton diffusion are not clearly understood. In this work, we decouple the diffusion of neutral and charged excitons with chemical counterdoping and explore the effect of strain and generation rate on exciton diffusion. According to the standard semiconductor paradigm, a shorter carrier recombination lifetime should lead to a smaller diffusion length. Surprisingly, we find that increasing generation rate shortens the exciton lifetime but increases the diffusion length in unstrained monolayers of TMDCs. When we suppress EEA by strain, both lifetime and diffusion length become independent of generation rate. During EEA one exciton nonradiatively recombines and kinetically energizes another exciton, which then diffuses fast. Our results probe concentration-dependent diffusion of pure neutral excitons by counterdoping and elucidate how strain controls exciton transport and many-body interactions in TMDC monolayers.


Broadening of cortical inhibition mediates developmental sharpening of orientation selectivity.
Orientation selectivity (OS) of visual cortical neurons is progressively sharpened during development. However, synaptic circuit mechanisms underlying the OS sharpening remain unclear. In the current study, in vivo whole-cell voltage-clamp recordings from layer 4 excitatory neurons in the developing mouse primary visual cortex revealed changes of orientation tuning profiles of their excitatory and inhibitory inputs during a post-eye-opening period when OS of their spiking responses becomes sharpened. In addition to a parallel strengthening of excitation and inhibition during this developmental period, the orientation tuning of excitatory inputs keeps relatively constant, whereas the tuning of inhibitory inputs is broadened, and becomes significantly broader than that of excitatory inputs. Neuron modeling and dynamic-clamp recording demonstrated that this developmental broadening of the inhibitory tuning is sufficient for sharpening OS. Depriving visual experience by dark rearing impedes the normal developmental strengthening of excitation, but a similar broadening of inhibitory tuning, likely caused by a nonselective strengthening of inhibitory connections, results in the apparently normal OS sharpening in excitatory neurons. Our results thus provide the first demonstration that an inhibitory synaptic mechanism can primarily mediate the functional refinement of cortical neurons.


Implants of an adhesive resin, a calcium hydroxide, and a glass-ionomer cement cause reactional fibrosis with mast cells involvement in rats.
To evaluate the tissue reaction of some pulpar protecting materials. Standardized implants of calcium hydroxide (CH), glass-ionomer cement (GIC), and light-cured dentin adhesive (LDA), surgically introduced into the dorsal connective tissue of Wistar rats, were left for 15 and 30 days. For each of the 2 experimental times, a respective sham group (S) was studied. After experimentation, animals were sacrificed, and the material from implant sites was removed and studied with light microscopy and stereology (volume density of interstitial fibrosis, Vv[f], and numerical density of mast cells per area, NA[mast cell]). The implants and the surfaces of the fibrous capsule were analyzed with scanning electronic microscopy (SEM) adapted with microanalysis. The CH group had the smallest value of Vv[f] and the LDA group the greatest. At day 30, the Vv[f] of the LDA group showed an increase of 30% and was different from that of the CH group in the same period (P <.05). The NA[mast cell] was smaller in both the CH and the S group than in the LDA group (P <.05). The GIC group had intermediate values for Vv[f] and NA[mast cell] between CH and LDA values. There was light fibrosis in the surgical area with few mast cells associated to vessels in the S group. SEM detected presence of silica fragments in the fibrous capsule of the LDA group and calcium in the fibrous capsule of the CH group. All tested materials allowed healing of the implanted area; tissue reaction was smallest in the CH group.


Detecting, grouping, and structure inference for invariant repetitive patterns in images.
The efficient and robust extraction of invariant patterns from an image is a long-standing problem in computer vision. Invariant structures are often related to repetitive or near-repetitive patterns. The perception of repetitive patterns in an image is strongly linked to the visual interpretation and composition of textures. Repetitive patterns are products of both repetitive structures as well as repetitive reflections or color patterns. In other words, patterns that exhibit near-stationary behavior provide rich information about objects, their shapes, and their texture in an image. In this paper, we propose a new algorithm for repetitive pattern detection and grouping. The algorithm follows the classical region growing image segmentation scheme. It utilizes a mean-shift-like dynamic to group local image patches into clusters. It exploits a continuous joint alignment to: 1) match similar patches, and 2) refine the subspace grouping. We also propose an algorithm for inferring the composition structure of the repetitive patterns. The inference algorithm constructs a data-driven structural completion field, which merges the detected repetitive patterns into specific global geometric structures. The result of higher level grouping for image patterns can be used to infer the geometry of objects and estimate the general layout of a crowded scene.


Transmembrane action potentials from smooth muscle in turtle arteries and veins.
Transmembrane potential and active tension were measured in isolated segments of turtle aorta and inferior vena cava. Changes in tension were associated with action potentials, but the potentials had a different pattern in the two tissues. When the frequency of the action potentials increased, the contractions summated, resulting in a steadily maintained contraction.


BGRT: biologically guided radiation therapy-the future is fast approaching!
Rapid advances in functional and biological imaging, predictive assays, and our understanding of the molecular and cellular responses underpinning treatment outcomes herald the coming of the long-sought goal of implementing patient-specific biologically guided radiation therapy (BGRT) in the clinic. Biological imaging and predictive assays have the potential to provide patient-specific, three-dimensional information to characterize the radiation response characteristics of tumor and normal structures. Within the next decade, it will be possible to combine such information with advanced delivery technologies to design and deliver biologically conformed, individualized therapies in the clinic. The full implementation of BGRT in the clinic will require new technologies and additional research. However, even the partial implementation of BGRT treatment planning may have the potential to substantially impact clinical outcomes.


Lipid formation by aqueous Fischer-Tropsch-type synthesis over a temperature range of 100 to 400 degrees C.
The formation of lipid compounds during an aqueous Fischer-Tropsch-type reaction was studied with solutions of oxalic acid as the carbon and hydrogen source. The reactions were conducted in stainless steel vessels by heating the oxalic acid solution at discrete temperatures from 100 to 400 degrees C, at intervals of 50 degrees C for two days each. The maximum lipid yield, especially for oxygenated compounds, is in the window of 150-250 degrees C. At a temperature of 100 degrees C only a trace amount of lipids was detected. At temperatures above 150 degrees C the lipid components ranged from C12 to > C33 and included n-alkanols, n-alkanoic acids, n-alkyl formates, n-alkanals, n-alkanones, n-alkanes, and n-alkenes, all with essentially no carbon number preference. The n-alkanes increased in concentration over the oxygenated compounds at temperatures of 200 degrees C and above, with a slight reduction in their carbon number ranges due to cracking. It was also noted that the n-alkanoic acids increased while n-alkanols decreased with increasing temperature above 200 degrees C. At temperatures above 300 degrees C synthesis competes with cracking and reforming reactions. At 400 degrees C significant cracking was observed and polynuclear aromatic hydrocarbons and their alkylated homologs were detected. The results of this work suggest that the formation of lipid compounds by aqueous FTT reactions proceeds by insertion of a CO group at the terminal end of a carboxylic acid functionality to form n-oxoalkanoic acids, followed by reduction to n-alkanoic acids, to n-alkanals, then to n-alkanols. The n-alkenes are intermediate homologs for n-alkan-2-ones and n-alkanes. This proposed mechanism for aqueous FTT synthesis differs from the surface-catalyzed stepwise FT process (i.e., gaseous) of polymerization of methylene reported in the literature.


A novel assay for the detection of anthelmintic activity mediated by cuticular damage to nematodes: validation on Caenorhabditis elegans exposed to cysteine proteinases.
Plant cysteine proteinases (CPs) from Carica papaya kill parasitic and free-living nematodes in vitro by hydrolysis of the worm cuticle, a mechanism that is different to all commercially available synthetic anthelmintics. We have developed a cheap and effective, rapid-throughput Caenorhabditis elegans-based assay for screening plant CP extracts for anthelmintic activity targeting cuticular integrity. The assay exploits colorimetric methodology for assessment of cuticular damage, and is based on the ability of viable cells to incorporate and bind Neutral red dye within lysosomes and to release the dye when damaged. Living worms are pre-stained with the dye, exposed to CPs and then leakage of the dye through the damaged cuticle is quantified by spectrophotometry. In contrast to motility assays and semi-subjective interpretation of microscopical images, this colorimetric assay is independent of observer bias. Our assay was applied to a series of C. elegans bus mutant strains with leaky cuticles and to cystatin knockout mutants. At ambient temperature and over 0.5-24 h, both bus mutants and the cystatin knockouts were highly susceptible to CPs, whereas wild-type Bristol N2 worms were essentially unstained by Neutral red and unaffected by CPs, providing validation for the utility of this assay.


Clustered Regularly Interspaced Short Palindromic Repeats and Clustered Regularly Interspaced Short Palindromic Repeats-Associated Protein 9 System: Factors Affecting Precision Gene Editing Efficiency and Optimization Strategies.
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) system is a powerful genomic DNA editing tool. The increased applications of gene editing tools, including the CRISPR-Cas system, have contributed to recent advances in biological fields, such as genetic disease therapy, disease-associated gene screening and detection, and cancer therapy. However, the major limiting factor for the wide application of gene editing tools is gene editing efficiency. This review summarizes the recent advances in factors affecting the gene editing efficiency of the CRISPR-Cas9 system and the CRISPR-Cas9 system optimization strategies. The homology-directed repair efficiency-related signal pathways and the form and delivery method of the CRISPR-Cas9 system are the major factors that influence the repair efficiency of gene editing tools. Based on these influencing factors, several strategies have been developed to improve the repair efficiency of gene editing tools. This review provides novel insights for improving the repair efficiency of the CRISPR-Cas9 gene editing system, which may enable the development and improvement of gene editing tools.


[Subcutaneous fat tissue drainage in obese pregnant women after caesarean section].
The authors have analyzed the outcome of cesarean section celiotomy in obese pregnant women. The occurrence of postoperative wound infections, eventually dehiscence, in 2015 pregnant women who underwent caesarean section in a 3-year interval at the Craiova 1st Clinic of Obstetrics was studied. The analysis revealed the relation between postoperative wound infection and its topography, the type of fat tissue drainage (if done), and skin suture. The authors present a very effective method of subcutaneous drainage in obese pregnant women after cesarean section.


On the Power of Gradual Network Alignment Using Dual-Perception Similarities.
Network alignment (NA) is the task of finding the correspondence of nodes between two networks based on the network structure and node attributes. Our study is motivated by the fact that, since most of existing NA methods have attempted to discover all node pairs at once, they do not harness information enriched through interim discovery of node correspondences to more accurately find the next correspondences during the node matching. To tackle this challenge, we propose [Formula: see text], a new NA method that gradually discovers node pairs by making full use of node pairs exhibiting strong consistency, which are easy to be discovered in the early stage of gradual matching. Specifically, [Formula: see text] first generates node embeddings of the two networks based on graph neural networks along with our layer-wise reconstruction loss, a loss built upon capturing the first-order and higher-order neighborhood structures. Then, nodes are gradually aligned by computing dual-perception similarity measures including the multi-layer embedding similarity as well as the Tversky similarity, an asymmetric set similarity using the Tversky index applicable to networks with different scales. Additionally, we incorporate an edge augmentation module into [Formula: see text] to reinforce the structural consistency. Through comprehensive experiments using real-world and synthetic datasets, we empirically demonstrate that [Formula: see text] consistently outperforms state-of-the-art NA methods.


An orthogonal multi-objective evolutionary algorithm for multi-objective optimization problems with constraints.
In this paper, an orthogonal multi-objective evolutionary algorithm (OMOEA) is proposed for multi-objective optimization problems (MOPs) with constraints. Firstly, these constraints are taken into account when determining Pareto dominance. As a result, a strict partial-ordered relation is obtained, and feasibility is not considered later in the selection process. Then, the orthogonal design and the statistical optimal method are generalized to MOPs, and a new type of multi-objective evolutionary algorithm (MOEA) is constructed. In this framework, an original niche evolves first, and splits into a group of sub-niches. Then every sub-niche repeats the above process. Due to the uniformity of the search, the optimality of the statistics, and the exponential increase of the splitting frequency of the niches, OMOEA uses a deterministic search without blindness or stochasticity. It can soon yield a large set of solutions which converges to the Pareto-optimal set with high precision and uniform distribution. We take six test problems designed by Deb, Zitzler et al., and an engineering problem (W) with constraints provided by Ray et al. to test the new technique. The numerical experiments show that our algorithm is superior to other MOGAS and MOEAs, such as FFGA, NSGAII, SPEA2, and so on, in terms of the precision, quantity and distribution of solutions. Notably, for the engineering problem W, it finds the Pareto-optimal set, which was previously unknown.


Development of an openEHR Template for COVID-19 Based on Clinical Guidelines.
The coronavirus disease (COVID-19) was discovered in China in December 2019. It has developed into a threatening international public health emergency. With the exception of China, the number of cases continues to increase worldwide. A number of studies about disease diagnosis and treatment have been carried out, and many clinically proven effective results have been achieved. Although information technology can improve the transferring of such knowledge to clinical practice rapidly, data interoperability is still a challenge due to the heterogeneous nature of hospital information systems. This issue becomes even more serious if the knowledge for diagnosis and treatment is updated rapidly as is the case for COVID-19. An open, semantic-sharing, and collaborative-information modeling framework is needed to rapidly develop a shared data model for exchanging data among systems. openEHR is such a framework and is supported by many open software packages that help to promote information sharing and interoperability. This study aims to develop a shared data model based on the openEHR modeling approach to improve the interoperability among systems for the diagnosis and treatment of COVID-19. The latest Guideline of COVID-19 Diagnosis and Treatment in China was selected as the knowledge source for modeling. First, the guideline was analyzed and the data items used for diagnosis and treatment, and management were extracted. Second, the data items were classified and further organized into domain concepts with a mind map. Third, searching was executed in the international openEHR Clinical Knowledge Manager (CKM) to find the existing archetypes that could represent the concepts. New archetypes were developed for those concepts that could not be found. Fourth, these archetypes were further organized into a template using Ocean Template Editor. Fifth, a test case of data exchanging between the clinical data repository and clinical decision support system based on the template was conducted to verify the feasibility of the study. A total of 203 data items were extracted from the guideline in China, and 16 domain concepts (16 leaf nodes in the mind map) were organized. There were 22 archetypes used to develop the template for all data items extracted from the guideline. All of them could be found in the CKM and reused directly. The archetypes and templates were reviewed and finally released in a public project within the CKM. The test case showed that the template can facilitate the data exchange and meet the requirements of decision support. This study has developed the openEHR template for COVID-19 based on the latest guideline from China using openEHR modeling methodology. It represented the capability of the methodology for rapidly modeling and sharing knowledge through reusing the existing archetypes, which is especially useful in a new and fast-changing area such as with COVID-19.


De novo enantioselective syntheses of galacto-sugars and deoxy sugars via the iterative dihydroxylation of dienoate.
An efficient route to various sugar lactones has been developed. Key to the overall transformation is the sequential osmium-catalyzed dihydroxylation of 2,4-dienoates. The simplest (one-step/racemic) example of this reaction occurs when the dihydroxylation is performed with aqueous NMO in MeOH. When the first dihydroxylation is performed using the AD-mix procedure, an enantioselective variant results. When a matched AD-mix procedure is used for the second dihydroxylation, an exceedingly diastereo- and enantioselective synthesis of galacto-1,4-lactone results. [Reaction: see text]


Impact of the RNA chaperone Hfq on the fitness and virulence potential of uropathogenic Escherichia coli.
Hfq is a bacterial RNA chaperone involved in the posttranscriptional regulation of many stress-inducible genes via small noncoding RNAs. Here, we show that Hfq is critical for the uropathogenic Escherichia coli (UPEC) isolate UTI89 to effectively colonize the bladder and kidneys in a murine urinary tract infection model system. The disruption of hfq did not affect bacterial adherence to or invasion of host cells but did limit the development of intracellular microcolonies by UTI89 within the terminally differentiated epithelial cells that line the lumen of the bladder. In vitro, the hfq mutant was significantly impaired in its abilities to handle the antibacterial cationic peptide polymyxin B and reactive nitrogen and oxygen radicals and to grow in acidic medium (pH 5.0). Relative to the wild-type strain, the hfq mutant also had a substantially reduced migration rate on motility agar and was less prone to form biofilms. Hfq activities are known to impact the regulation of both the stationary-phase sigma factor RpoS (sigma(S)) and the envelope stress response sigma factor RpoE (sigma(E)). Although we saw similarities among hfq, rpoS, and rpoE deletion mutants in our assays, the rpoE and hfq mutants were phenotypically the most alike. Cumulatively, our data indicate that Hfq likely affects UPEC virulence-related phenotypes primarily by modulating membrane homeostasis and envelope stress response pathways.