Long non-coding RNA PSMB8-AS1 regulates influenza virus replication.
Long non-coding RNAs (lncRNAs) are a new arm of gene regulatory mechanism as discovered by sequencing techniques and follow-up functional studies. There are only few studies on lncRNAs as related to gene expression regulation and anti-viral activity during influenza virus infection. We sought to identify and characterize lncRNAs involved in influenza virus replication. Using RNA sequencing analysis, we found that 1,912 lncRNAs were significantly changed in human lung epithelial A549 cells infected with influenza A/Puerto Rico/8/34. Gene ontology analysis on neighboring genes of these lncRNAs revealed that the genes involved in type I interferon signaling and cellular response were highly enriched. Seven selected up-regulated lncRNAs (AC015849.2, RP-1-7H24.1, PSMB8-AS1, CTD-2639E6.9, PSOR1C3, AC007283.5 and RP11-670E13.5) were verified by real-time PCR. These lncRNAs were also induced by other two influenza H1N1 virus strains (A/WSN/1933 and A/Oklahoma/3052/09) and interferon β1. Repression of PSMB8 antisense RNA 1 (PSMB8-AS1) using CRISPR interference reduced viral mRNA and protein levels as well as the release of progeny influenza virus particles. Our study suggests that lncRNA PSMB8-AS1 could be a new host factor target for developing antiviral therapy against influenza virus infection.


Sexual functioning in women after surgical treatment for endometrial cancer: a prospective controlled study.
Endometrial cancer (EC) can affect sexual functioning based on anatomical, physiological, psychological, and relational mechanisms. The aim of this study was to prospectively investigate sexual adjustment of women with EC during a follow-up period of 2 years after surgical treatment and to compare the results with women who underwent a hysterectomy for a benign gynecological condition and healthy control women. In this prospective controlled study, participants completed the Short Sexual Functioning Scale, Specific Sexual Problems Questionnaire, Beck Depression Inventory Scale, World Health Organization-5 Well-being Scale, and Dyadic Adjustment Scale to assess various aspects of sexual and psychosocial functioning before undergoing a hysterectomy and 6 months, 1 year, and 2 years after surgery. Eighty-four women with EC, 84 women with a benign gynecological condition, and 84 healthy controls completed the survey. In EC survivors, no differences were found in sexual functioning during prospective analyses. In comparison with women with a benign gynecological condition, significantly more EC patients reported entry dyspareunia 1 year after surgical treatment. Moreover, compared with healthy women, pre- and postoperatively, significantly more EC patients reported sexual dysfunctions, including sexual desire dysfunction, arousal dysfunction, entry dyspareunia, and a reduced intensity of orgasm. Furthermore, compared with healthy controls, EC patients reported significantly lower overall well-being 1 year after surgical treatment. Nevertheless, consensus in the partner relationship was significantly higher in EC patients compared with healthy controls. Moreover, before treatment, quality of partner relationship was negatively associated with sexual arousal dysfunction and orgasm dysfunction. In EC patients, no differences were found in sexual functioning when prospectively comparing the situation before surgery with the situation after surgery. However, when compared with healthy controls, EC patients are at high risk for sexual dysfunctions, both before and after surgical treatment.


Adsorption and thermal evolution of [C1C1Im][Tf2N] on Pt(111).
In the context of ionic liquid (IL)-assisted catalysis, we have investigated the adsorption and thermal evolution of the IL 1,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide ([C1C1Im][Tf2N]) on Pt(111) between 100 and 800 K by angle-resolved X-ray photoelectron spectroscopy and scanning tunneling microscopy. Defined amounts of IL in the coverage range of a complete first wetting layer were deposited at low temperature (100-200 K), and subsequently heated to 300 K, or directly at 300 K. At 100 K, the IL adsorbs as an intact disordered layer. Upon heating to 200 K, the IL stays intact, but forms an ordered and well-oriented structure. Upon heating to 250 K, the surface order increases, but at the same time STM and XPS indicate the onset of decomposition. Upon heating to 300 K, decomposition progresses, such that 50-60% of the IL is decomposed. The anion-related reaction products desorb instantaneously, and the cation-related products remain on the surface. Thereby, the surface is partly passivated, enabling the remaining IL to still be adsorbed intact at 300 K. For IL deposition directly at 300 K, a fraction of the IL instantaneously decomposes, with the anion-related products desorbing, opening free space for further deposition of IL. Hence, cation-related species accumulate at the expense of anions, until one fully closed wetting layer is formed. As a consequence, a higher dose is required to reach this coverage at 300 K, compared to 100-200 K.


Increased rate of arterial stiffening with obesity in adolescents: a five-year follow-up study.
We prospectively and longitudinally determined the effects of childhood obesity on arterial stiffening and vascular wall changes. Changes in arterial stiffness measured as pulse wave velocity (PWV) and vascular morphology of the radial (RA) and dorsal pedal arteries (DPA) were examined in obese adolescents compared to lean subjects in a 5-year follow-up study. A total of 28 obese subjects and 14 lean controls participated in both baseline (14 years old) and follow-up studies. PWV was measured by tonometer (SphygmoCor®) and recorded at RA and carotid artery, respectively. Intima thickness (IT), intima-media thickness (IMT) and RA and DPA diameters were measured using high-resolution ultrasound (Vevo 770™). Over the course of 5 years, PWV increased by 25% in the obese subjects as compared to 3% in the controls (p = 0.01). Diastolic blood pressure (DBP) increased by 23% in the obese subjects as opposed to 6% in controls (p = 0.009). BMI increased similarly in both groups, as did the IT and IMT. The change in PWV was strongly associated to the baseline BMI z -score (r = 0.51, p<0.001), as was the change in DBP (r = 0.50, p = 0.001). During the transition from early to late adolescence, there was a general increase in arterial stiffness, which was aggravated by childhood obesity. The increase in arterial stiffness and DBP after 5 years was closely correlated to the baseline BMI z -score, indicating that childhood obesity has an adverse impact on vascular adaptation.


Construction and characterization of a site-directed CC-1065-N3-adenine adduct within a 117 base pair DNA restriction fragment.
The design, construction, and characterization of a site-directed CC-1065-N3-adenine adduct in a 117 base pair segment of M13mpI DNA are described. CC-1065 is an extremely potent antitumor antibiotic produced by Streptomyces zelensis. Previous studies have demonstrated that the cyclopropyl ring of CC-1065 reacts quite specifically with N3 of adenine in double-stranded DNA to form a CC-1065-DNA adduct. Following alkylation, the drug molecule lies snugly within the minor groove of DNA, overlapping with five base pairs for which a marked sequence preference exists [Hurley, L. H., Reynolds, V. R., Swenson, D. H., Petzold, G. L., & Scahill, T. A. (1984) Science (Washington, D.C.) 226, 843-844]. On the basis of the unique characteristics of the reaction of CC-1065 with DNA and the structure of the resulting DNA adduct, we have designed a general strategy to construct a site-directed CC-1065-DNA adduct in a restriction fragment. The presence of unique AluI and HaeIII restriction enzymes sites on each side of a high-affinity CC-1065 binding sequence (5'-GATTA) permitted the preparation of a partial duplex DNA molecule containing the CC-1065 binding sequence in the duplex DNA region. Since CC-1065 only binds to duplex DNA, potential CC-1065 binding sequences in the long single-stranded regions were protected from drug binding during the construction process.(ABSTRACT TRUNCATED AT 250 WORDS)


[Women's expectations towards gynaecological examination ].
It is commonly known that gynaecologi- cal examinations cause a lot of negative emotions in the majority of women. The aim of my work was: 1. Getting to know women's views on the nature of a pelvic examination and their expectations regarding gynaecologists. 2. To determine the correlation between the examined views and independent variables such as the age of the respondents, residence, and place of examination. The research material consisted of 1200 women living in the region of Western Pomerania and in Lódź. The measurement tool was a survey of my own authorship. 1. In the opinion of most women, gynaecological examination is embarrassing and stressful. It has not been proven that this opinion was related to age, residence or place of examination. 2. According to women, the most embarrassing moment of a visit to the gynaecologist is lying down on the gynaecological chair, and the gynecological examination. The most unpleasant aspect is palpation through the vagina and rectum. These feelings differ depending on age, residence and place of taking the examination. 3. The choice of the gynaecologist's gender is dependent on women's age. 4. The frequency of reporting for the gynaecological examination decreases with women's age, and is dependent on their place of residence. 5. A sense of safety and mental comfort during the gynaecological examination is provided by the lack of third parties, except for the presence of a midwife. It is also dependent on the patient's age, her place of residence, as well as the examination site. 6. Women's expectations of a gynaecologist are focused mainly on maintaining a sense of intimacy and safety, getting information about the procedures, as well as a pleasant and individual approach.


AB0 blood subgroup allele frequencies in the Turkish population.
We determined the AB0 blood group system with a PCR based technique termed APLP (Amplified Product Length Polymorphism) in the Turkish population. The method includes ten different allele specific primers and permits identification of the major AB0 genotypes and its suballeles (A1-A2-B-0A-02-0G-AG). The suballeles were amplified in a single tube reaction. We have determined AB0 phenotypes in 129 Turkish individuals. No significant deviation from the Hardy-Weinberg equilibrium was observed.


Consumer-Centered, Collaborative, and Comprehensive Care: The Core Essentials of Recovery-Oriented System of Care.
Recovery from substance abuse and mental health disorders represents a journey through which individuals move beyond treatment of provider-identified problems toward a path of achieving wellness and productive lives. Overcoming obstacles and barriers encountered along the recovery process, individuals reveal their own strengths and resilience necessary to cope, survive, and thrive in the face of adversity. Recovery-oriented system of care (ROSC) is a framework designed to address the multidimensional nature of recovery by creating a system for coordinating multiple systems, services, and supports that are person centered and build on the strengths and resiliencies of individuals, families, and communities. As is common knowledge among substance abuse and mental health providers, consumers often present with high rates of comorbidity, which complicates care. In addition, behavioral health consumers engage in risky health behaviors (e.g., smoking) at a disproportionate rate, which places them at increased risk for developing noncommunicable diseases. ROSCs are ideal for addressing the complicated and varied needs of consumers as they progress toward wellness. The challenges of creating an ROSC framework that is effective, efficient, and acceptable to consumers is formidable. It requires change on the part of agencies, organizations, providers, and consumers. The importance of comprehensive, integrated screening is highlighted as a critical component of ROSC. Key suggestions for initiating ROSC are offered.


Laparoscopic surgery for subfertility related to endometriosis: a meta-analysis.
Endometriosis is the presence of an endometrial gland or stroma in sites other than the uterine cavity and it is frequently diagnosed in infertile women. It has not been well established whether laparoscopic surgery improves fertility. The objective of this study was to assess the effectiveness of laparoscopic surgery for subfertility related to endometriosis. Main electronic databases were searched for randomized and nonrandomized controlled trials. Trials were included if they were randomized or nonrandomized controlled trials that compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment methods or diagnostic laparoscopy only. Six studies were included in this meta-analysis. Outcomes analyzed included live birth rate, pregnancy rate, fetal losses, and surgical complications. An overall advantage of laparoscopic surgery was demonstrated when analyzing live birth rate [relative risk (RR) 1.52, 95% confidence interval (CI) 1.26-1.84, p < 0.01]. An increase in pregnancy rate after laparoscopic surgery was seen (RR of 1.44, 95% CI 1.24-1.68, p < 0.01). No significant difference in foetal losses. The use of laparoscopic surgery in the treatment of subfertility related to minimal endometriosis may increase the chances of future pregnancy and live birth.


Long-Term Follow-up Consultation After Childhood Cancer in the Rhône-Alpes Region of France: Feedback From Adult Survivors and Their General Practitioners.
We evaluated the satisfaction of adult survivors of childhood cancers and their general practitioners (GP) after a long-term consultation. The first Long-term Follow-up Study in Oncology (SALTO1) is a prospective cohort study of survivors of childhood cancers (except leukemia) diagnosed between 1987 and 1992 in the Rhône-Alpes and Auvergne regions of France. Of the 481 patients eligible for the study, 150 participated in a long-term consultation with a pediatric oncologist and an internist, after which survivors and their GPs received long-term plans and recommendations based on consultation findings. A year after the consultation, survivors and their GPs assessed their satisfaction with the process. Of the 150 survivor participants in the long-term follow-up, 120 (80%) completed the satisfaction form, with 107 (89%) reporting satisfaction. Forty-eight (32%) expressed strengthening their follow-up as a consequence of the consultation. Of the 79 survivors sent recommendations, 76 (96%) reported reading them, most (n = 68; 86%) found them useful, and 56 (71%) followed recommendations. Of the 107 GPs of the survivors, 82 (77%) conceded having been poorly informed about long-term complications for their patients after chemotherapy, and 93 (88%) appreciated having a hospital contact available for these patients. The long-term consultations ultimately enhanced medical follow-up of survivor participants, improving knowledge of both patients and family physicians regarding the patients' early disease, its treatments, and possible concerns, and offering consultative resources of medical specialists. The levels of participation of survivors and their physicians and reported satisfaction encourage the adoption of such consultations throughout France.


Strain differences in the response of the mouse to diethylstilbestrol.
BALB/c StCrlfC3Hf/Nctr, C57BL/6/, C57BL/6 X BALB/c F1 hybrid (B6CF1), and monohybrid-cross offspring from the breeding of B6CF1 mice were examined with respect to uterine, vaginal, and thymus responses to diethylstilbestrol (DES). About 400 mice of each genetic population were used. Weanling mice were fed DES at dietary concentrations of 2.5 to 1,000 ppb (microgram/kg feed) for 6 days and were killed by cervical dislocation about 20 hr after removal of the feed. C57BL/6, B6CF1, and the monohybrid-cross offspring did not differ in the uterine-weight response to DES, but the slope of the dose-response line was shallower for the BALB/c than for the other strains. Dietary DES concentrations of 250 ppb or more inhibited the uterotrophic response in all populations. Vaginal cornification occurred at lower concentrations of DES in the C57BL/6 strain than in the B6CF1 animals. BALB/c and monohybrid-cross offspring were indistinguishable from each other in their vaginal response to Des and were less sensitive to DES than the other mouse populations. The use of ethanol or corn oil as the solvent for mixing DES into the diet had no apparent effect on the uterine weight or vaginal response in any of the mice. DES depressed thymus weight in a dose-related fashion at dietary concentrations of 100 ppb and above in all genetic populations.


Noninvasive and Local Delivery of Adenoviral-Mediated Herpes Simplex Virus Thymidine Kinase to Treat Glioma Through Focused Ultrasound-Induced Blood-Brain Barrier Opening in Rats.
Adenoviral-mediated gene therapy has been shown great prospects for tumor treatment. However, it is still a great challenge for its application in the glioma. A main cause is the blood-brain barrier (BBB) limits the delivery of adenoviral vectors, greatly compromising their efficacy. Here, we used focused ultrasound (FUS) induced microbubble cavitation to locally and reversibly open BBB for enhancing gene delivery. In this study, Ad-CMV-TK-IRES-EGFP (Ad-HSV-TK-EGFP) carrying the herpes simplex virus thymidine kinase (HSV-TK) and EGFP transgenes was chose as gendicine and Ad-CMV-IRES-EGFP (Ad-EGFP) as the control. The in vitro experiments showed that Ad-HSV-TK-EGFP had a high infection efficiency for C6 glioma cells, producing good tumor cell killing effects when these cells were exposed to more than 10 μg/ml ganciclovir (GCV). Taking advantage of FUS-induced BBB opening, Ad-HSV-TK-EGFP could be effectively delivered into the brain tumors, getting the overexpression of HSV-TK gene in the tumor cells. After exposure to GCV, the significantly stronger anti-tumor efficacy and longer survival time were observed in tumor-bearing mice treated with Ad-HSV-TK-EGFP + FUS than those treated with Ad-EGFP + FUS or only Ad-HSV-TK-EGFP. Histological examination indicated that the reduced expression level of Ki67 proteins and the increased apoptotic tumor cells in tumor xenografts, causing the inhibition of tumor growth. In conclusion, our study provided a new strategy to efficiently and locally deliver recombinant adenoviral vector-mediated HSV-TK gene into the brain to treat glioma.


Retrograde labeling of mouse spinal descending tracts by a recombinant adenovirus.
The present study tested whether a gene-transfer based upon the retrograde axonal transport of the lacZ adenovirus is effective in the spinal descending tracts of the adult mouse. A small volume of a replication-defective recombinant adenovirus encoding E. coli beta-galactosidase was injected into the upper lumbar cord, and, seven days later, the mice were transcardially perfused by a fixative solution. X-gal staining of coronal or sagittal sections of the spinal cord and the brain revealed that many sites of origin for rubrospinal, vestibulospinal, and reticulospinal tracts were retrogradely labeled, whereas few of the corticospinal tract neurons were retrogradely labeled. Ependymal cells surrounding the central canal of the spinal cord, which were located far from the injection site, showed a high expression of beta-galactosidase activity. Motoneurons around the injection site were strongly stained by X-gal staining, and their axons in the ventral root were anterogradely labeled. Afferent fibers in the dorsal root were labeled by the transganglionic transport of beta-galactosidase. To examine the efficacy of the uptake and retrograde transport of HRP and adenovirus, we injected a mixed solution of 10% HRP and recombinant adenovirus. The number of HRP-labeled corticospinal neurons overwhelmed the number of X-gal stained ones, while the numbers of HRP-labeled rubrospinal and subcoeruleus-spinal neurons were smaller in comparison with the numbers of beta-galactosidase-positive counterparts. The present study revealed that the origins for the spinal descending tracts except for corticospinal neurons could be efficiently gene-transferred by the retrograde infection of a recombinant adenovirus. Such a difference in efficacy of retrograde infection among the spinal descending tracts is practically important when an adenovirus-mediated gene transfer is designed to treat certain neurological diseases affecting the spinal descending tracts.


THERAPEUTIC AGENTS IN ACNE VULGARIS. I. TETRACYCLINE.
A total of 120 consecutive patients with pustular and cystic acne vulgaris were selected for study. Patients were assigned a placebo and a tetracycline medication in a random method. Of the 53 patients who were given tetracycline, 45 showed some response, which was fair in 19 and excellent in 26. Of the 55 patients who received placebo, 24 showed no response while 31 showed some improvement. No side effects were reported. The difference in response between the two groups is statistically significant. It is concluded that administration of 250 mg. tetracycline four times daily, even for periods as short as two weeks, enhances the likelihood of improvement of cystic or pustular acne vulgaris.


Withanolides from Jaborosa laciniata.
Six new trechonolide type withanolides (compounds 1- 6), together with trechonolide A, jaborotetrol, and 12- O-methyl jaborosotetrol, were isolated from the aerial parts of Jaborosa laciniata. The structures were elucidated on the basis of spectroscopic methods (1D and 2D NMR, MS).


Carcinoma of an unknown primary: are EGF receptor, Her-2/neu, and c-Kit tyrosine kinases potential targets for therapy?
Carcinomas of an unknown primary site (CUP) are heterogeneous tumours with a median survival of only 8 months. Tyrosine kinase inhibitors are promising new drugs. The aim of this study was to determine the expression of EGF-receptor, Her-2/neu, and c-Kit tyrosine kinases in CUP. Paraffin-embedded specimens were obtained from 54 patients with a CUP who were included in the GEFCAPI 01 randomised phase II trial. Immunohistochemistry was performed using the Dako autostainer with antibodies directed against HER-2/neu protein, EGFR protein, and c-Kit protein (CD117). EGFR expression was found in 36 out of 54 samples (66%). In contrast, Her-2/neu overexpression and c-Kit positivity were only detected in 4 and 10% of patients, respectively. No significant association was found between the expression of the tyrosine kinase receptors and prognosis. EGFR expression was significantly associated with response to cisplatin-based chemotherapy: the response rates were 50 and 22% in patients with EGFR-positive tumours and EGFR-negative tumours, respectively (P<0.05). This study shows that EGFR is frequently expressed in CUP. This finding may prompt clinical trials investigating EGFR inhibitors in this setting. In contrast, c-Kit expression and Her-2/neu overexpression occur infrequently in CUP. EGFR expression was correlated to tumour chemosensitivity.


Cyproheptadine for prevention of neuropsychiatric adverse effects of efavirenz: a randomized clinical trial.
Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean±SD ages of 36±9 years) in a cyproheptadine group, and 26 patients (17 males and 9 females with mean±SD ages of 34±7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients' neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients' follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz.


Social support moderates caregiver life satisfaction following traumatic brain injury.
Social support is an important determinant of adjustment following traumatic brain injury (TBI) sustained by a family member. The present study examined the extent to which social support moderates the influence of characteristics of the person with injury on caregiver subjective well-being. Sixty pairs of individuals who had sustained a moderate to severe TBI and their caregivers (N=120) participated. Years postinjury ranged from 0.3 to 9.9 ( M=4.8, SD=2.6). Cognitive, functional, and neurobehavioral functioning of participants with TBI were assessed using neuropsychological tests and rating scales. Caregiver life satisfaction and perceived social support were assessed using self-report questionnaires. Results indicated that time since injury was unrelated to life satisfaction. Neurobehavioral disturbances showed an inverse relation with life satisfaction. Social support emerged as an important moderator of life satisfaction. Only among caregivers with low social support was cognitive dysfunction adversely related to life satisfaction. Similarly, a trend suggested that patient unawareness of deficit was associated with caregiver life dissatisfaction only among caregivers with low social support. In contrast, these characteristics were unrelated to life satisfaction among caregivers with adequate social support.


PrimerDesign-M: a multiple-alignment based multiple-primer design tool for walking across variable genomes.
Analyses of entire viral genomes or mtDNA requires comprehensive design of many primers across their genomes. Furthermore, simultaneous optimization of several DNA primer design criteria may improve overall experimental efficiency and downstream bioinformatic processing. To achieve these goals, we developed PrimerDesign-M. It includes several options for multiple-primer design, allowing researchers to efficiently design walking primers that cover long DNA targets, such as entire HIV-1 genomes, and that optimizes primers simultaneously informed by genetic diversity in multiple alignments and experimental design constraints given by the user. PrimerDesign-M can also design primers that include DNA barcodes and minimize primer dimerization. PrimerDesign-M finds optimal primers for highly variable DNA targets and facilitates design flexibility by suggesting alternative designs to adapt to experimental conditions. PrimerDesign-M is available as a webtool at http://www.hiv.lanl.gov/content/sequence/PRIMER_DESIGN/primer_design.html firstname.lastname@example.com or email@example.com.


Cisplatin pasting for radiotherapy of penile cancer.
A case of penile cancer (Jackson's stage II) was treated with cisplatin pasta along with radiotherapy. The cancerous masses dissolved by the time of 27 Gy (913 ret) of radiotherapy, and the initial plan of penile amputation was abandoned. This cisplatin pasting would probably be a useful technique in radiotherapy of penile cancer, preserving the function of the organ.


Congenital erythrocytosis with increased erythropoietin level.
The term "absolute erythrocytosis" denotes a heterogeneous group of disorders characterized by an increased red blood cell mass. The authors describe a 20-month-old girl with absolute erythrocytosis. Erythropoietin levels were found to be extremely increased, although extensive evaluation failed to reveal a cause for such an inappropriate increase. Of interest is also the documentation of spontaneous erythroid colony formation in the patient's bone marrow cultures. Although such a finding is considered typical of polycythemia vera, the diagnostic criteria of this myeloproliferative disorder were not met.


Astrocytes are more resistant than cerebral endothelial cells toward geno- and cytotoxicity mediated by short-term oxidative stress.
Evidence is accumulating that capillary endothelial cells (cEC) and astrocytes play a pivotal role in neuroprotection, in particular with respect to counteract oxidative injury. Furthermore, differences among both cell types in response to oxidative stress have been shown and astrocytes seem to be more tolerant in terms of cytotoxicity, however, no reports exist on oxidative stress mediated genotoxicity in astrocytes. We investigated genotoxic and cytotoxic effects of oxidative stress in astrocytes and cECs induced by hypoxia/reoxygenation or by the redox cycling quinone DMNQ. Additionally, the dependence of these effects on glucose availabilty was also studied. On exposure to Hy/Re or 10 muM DMNQ for 24 hr, the frequency of micronucleated and apoptotic cells was significantly increasing, however, astrocytes proved to be more resistant to apoptosis induction, in particular on use of DMNQ. In astrocytes, the low background rates of necrotic cells were not affected and a significant necrosis induction was only detectable in cECs exposed to DMNQ for 24 hr. Short-term exposure to DMNQ (1 hr) had no effect in astrocytes but exerted significant geno- and cytotoxicity in cECs. Increasing the glucose concentration markedly reduced oxidative stress mediated geno- and cytotoxicity in astrocytes. Surprisingly, glucose deprivation (aglycemia) suppressed DMNQ induced micronucleus formation in astrocytes without affecting the frequency of apoptotic cells. Our results indicate that astrocytes are more resistant to oxidative stress than cECs, in particular regarding the potential to counteract genotoxicity as well as apoptosis induction mediated by a short term oxidative insult.


Palliative Treatment of Bowel Obstruction With Colostomy Under Local Anesthesia in Frail Patients: A Single-Site Experience.
Attendance of patients to the emergency department due to acute large bowel obstruction is a common phenomenon. Most of these patients are elderly, critically ill, and with high comorbidity. The literature suggests that more than 50% of these cases are due to colon cancer. Since this condition is considered to be an emergency, immediate intervention and response is imperative. The aim of the present study is to present our surgical technique of colostomy formation under local anesthesia in selected critically ill patients, with increased perioperative risk and acute large bowel obstruction. This is a retrospective study of 24 patients, with obstipation, who underwent emergency colostomy under local anesthesia, during the period from 2014 to 2021. The mean age of the patients was 77 years. The vast majority of patients had an American Society of Anesthesiologists (ASA) score of ≥3 and a Charlson score of ≥7. The most common colostomy was transverse colostomy (21/24 patients). The patients' hospitalization ranged from four to 42 days. Only one patient died. All colostomies functioned properly in the immediate postoperative period. Only one patient required postoperative admission to the ICU. Colostomy under local anesthesia in critically ill, elderly patients is an alternative option for the treatment of ileus.


[Cronkhite-Canada syndrome is a rare polyposis syndrome].
Cronkhite-Canada syndrome (CCS) is rare and associated with diarrhoea, gastrointestinal polyps, malnutrition, weight loss, alopecia, skin- and nail changes. The patient was hospitalized with dehydration, diarrhoea and weight loss. Objectively emaciated, skin changes, poor nail status and alopecia. Biochemistry compatible with malnutrition. Gastroscopy showed polyps. Treatment of symptomatic replacement therapy and prednisolone resulted in remission. It is a diagnosis with a 55% 5-year mortality. Early treatment leads to better prognosis.


Pelvic reconstruction following resection of malignant bone tumours using a stemmed acetabular pedestal cup.
Pelvic reconstruction after the resection of a tumour around the acetabulum is a challenging procedure due to the complex anatomy and biomechanics. Several pelvic endoprostheses have been introduced, but the rates of complication remain high. Our aim was to review the use of a stemmed acetabular pedestal cup in the management of these patients. The study involved 48 patients who underwent periacetabular reconstruction using a stemmed pedestal cup (Schoellner cup; Zimmer Biomet Inc., Warsaw, Indiana) between 2000 and 2013. The indications for treatment included a primary bone tumour in 27 patients and metastatic disease in 21 patients. The mean age of the patients at the time of surgery was 52 years (16 to 83). At a median follow-up of 6.6 years (95% confidence interval 4.6 to 8.2), local control was achieved in all patients; 19 patients had died (16 of disease). Complications occurred in 19 patients (40%), of which deep infection was the most common, affecting eight patients (17%). Seven patients (15%) had a dislocation of the hip. Aseptic loosening was found in three patients (6%). Two (4%) underwent hindquarter amputation for non-oncological reasons. The risk of revision, with death being treated as a competing event, was 28% at one year, 39% at five years and 48% at ten years post-operatively. The mean Musculoskeletal Tumour Society Score at final follow-up was 71% (27% to 93%). This type of reconstruction is a satisfactory option for the treatment of patients with a periacetabular tumour. There remains, however, a high rate of complication, which may be reduced by future modifications of the device such as silver coating and tripolar articulation. Cite this article: Bone Joint J 2017;99-B:841-8.


[The tolerance of hydroxypropylmethylcellulose in implantation of posterior chamber lenses].
In 65 patients, the safety of a 2% solution of hydroxypropylmethylcellulose (HPMC) was investigated by comparing HPMC with a balanced salt solution during posterior chamber lens implantation. The controlled open randomized trial consisted of two groups of patients: 1) in 37 patients the surface of the implant was coated with HPMC and the inner wound sealed prior to insertion; 2) in the control group with 28 patients the lens was dipped in the balanced salt solution. There were no statistically significant differences between the two groups as regards any of the characteristics investigated, such as visual acuity, intraocular pressure, corneal thickness, endothelial cell loss, and postoperative irritation within the anterior chamber. There was no rise in mean intraocular pressure in the HPMC group on the first postoperative day, and a rise of 1 mm Hg in the control group. The increase in corneal thickness on the first postoperative day in the HPMC group was 0.07 and in the control group 0.04 mm. At re-examination (50th postoperative day) the mean thickness in both groups was identical to the initial values. The mean endothelial cell loss at re-examination was 18% (+/- 16%). No serious side effects were observed. HPMC may be regarded as a well-tolerated viscoelastic substance.


The constraints on day-case total knee arthroplasty: the fastest fast track.
Total knee arthroplasty (TKA) is a major orthopaedic intervention. The length of a patient's stay has been progressively reduced with the introduction of enhanced recovery protocols: day-case surgery has become the ultimate challenge. This narrative review shows the potential limitations of day-case TKA. These constraints may be social, linked to patient's comorbidities, or due to surgery-related adverse events (e.g. pain, post-operative nausea and vomiting, etc.). Using patient stratification, tailored surgical techniques and multimodal opioid-sparing analgesia, day-case TKA might be achievable in a limited group of patients. The younger, male patient without comorbidities and with an excellent social network around him might be a candidate. Demographic changes, effective recovery programmes and less invasive surgical techniques such as unicondylar knee arthroplasty, may increase the size of the group of potential day-case patients. The cost reduction achieved by day-case TKA needs to be balanced against any increase in morbidity and mortality and the cost of advanced follow-up at a distance with new technology. These factors need to be evaluated before adopting this ultimate 'fast-track' approach.


Cytotoxicity of an anti-cancer lysophospholipid through selective modification of lipid raft composition.
Edelfosine is a prototypical member of the alkylphosphocholine class of antitumor drugs. Saccharomyces cerevisiae was used to screen for genes that modulate edelfosine cytotoxicity and identified sterol and sphingolipid pathways as relevant regulators. Edelfosine addition to yeast resulted in the selective partitioning of the essential plasma membrane protein Pma1p out of lipid rafts. Microscopic analysis revealed that Pma1p moved from the plasma membrane to intracellular punctate regions and finally localized to the vacuole. Consistent with altered sterol and sphingolipid synthesis resulting in increased edelfosine sensitivity, mislocalization of Pma1p was preceded by the movement of sterols out of the plasma membrane. Cells with enfeebled endocytosis and vacuolar protease activities prevented edelfosine-mediated (i) mobilization of sterols, (ii) loss of Pma1p from lipid rafts, and (iii) cell death. The activities of proteins and signaling processes are meaningfully altered by changes in lipid raft biophysical properties. This study points to a novel mode of action for an anti-cancer drug through modification of plasma membrane lipid composition resulting in the displacement of an essential protein from lipid rafts.


How we manage iron overload in sickle cell patients.
Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging.


The Relationship Between Physical Activity and Emotional Intelligence in College Students: The Mediating Role of Self-Efficacy.
College students are an inexhaustible driving force for social development, and college students with good physical and psychological qualities can better adapt to changes in the external environment. The purpose of this study was to explore the intrinsic relationship of physical activity and emotional intelligence among college students and to determine the primary role of self-efficacy in their relationships. Eight hundred thirty-five college students from two comprehensive universities in Southwest China, whose average age was 20.13 ± 1.06 years old, were investigated using the Physical Activity Rating Scale (PARS-3), Chinese Emotional Intelligence Scale (EIS), General Self-Efficacy Scale (GSES), and other measuring tools. SPSS 22.0 software was used to analyze and process the data with Independent sample t-test, One-way ANOVA, Pearson correlation analysis, and regression analysis, and Amos 21.0 software was used to build the structural equation model. (1) In terms of physical activity amount, self-efficacy, and emotional intelligence, male college students scored higher than female students. Furthermore, college students in humanities and social sciences had lower self-efficacy. In contrast, senior students had the lowest levels of physical activity and self-efficacy, and there was no discipline or grade distribution difference in emotional intelligence. (2) Physical activity amount was positively correlated with emotional intelligence (r = 0.24, P < 0.001) and with self-efficacy (r = 0.26, P < 0.001), and self-efficacy was positively correlated with emotional intelligence in college students (r = 0.18, P < 0.001). (3) Self-efficacy played a partial mediating role between physical activity and emotional intelligence in college students (ES = 0.06). Regular physical activity can improve the self-efficacy and emotional intelligence of college students, and effectively promote the physical and mental development of students.


Catalytic sol-gel co-polycondensation of para-substituted phenylsilanes and bis(silyl)phenylene to robust organosilicas using colloidal nickel nanoparticles.
The dry sol-gel co-polycondensation at toluene in ambient air atmosphere of p-X-C6H4SiH3 (X = H, CH3, CH3O, F, Cl) and p-H3Si-C6H4SiH3 (9:1 mole ratio) to co-silicas (p-X-C6H4SiO1.5)9(p-O1.5Si-C6H4SiO1.5)1 in high yield, catalyzed by colloidal nickel nanoparticles in-situ generated from nickelocene(II) is described. The co-gels (p-X-C6H4SiO1.5)9(p-O1.5Si-C6H4SiO1.5)1 with higher molecular weights and TGA residue yield were obtained when compared to the homogels p-X-C6H4SiO1.5 Some degree of unreacted Si-H bonds still remained in the gel matrix because of steric bulkiness. All the insoluble gels adopt an amorphous structure with a smooth surface. A plausible mechanism for the dry sol-gel reaction was provided.


Gender-associated differential expression of cytokines in specific areas of the brain during helminth infection.
Intraperitoneal infection with Taenia crassiceps cysticerci in mice alters several behaviors, including sexual, aggressive, and cognitive function. Cytokines and their receptors are produced in the central nervous system (CNS) by specific neural cell lineages under physiological and pathological conditions, regulating such processes as neurotransmission. This study is aimed to determine the expression patterns of cytokines in various areas of the brain in normal and T. crassiceps-infected mice in both genders and correlate them with the pathology of the CNS and parasite counts. IL-4, IFN-γ, and TNF-α levels in the hippocampus and olfactory bulb increased significantly in infected male mice, but IL-6 was downregulated in these regions in female mice. IL-1β expression in the hippocampus was unaffected by infection in either gender. Our novel findings demonstrate a clear gender-associated pattern of cytokine expression in specific areas of the brain in mammals that parasitic infection can alter. Thus, we hypothesize that intraperitoneal infection is sensed by the CNS of the host, wherein cytokines are important messengers in the host-parasite neuroimmunoendocrine network.


Use of daptomycin in the treatment of vancomycin-resistant enterococcal urinary tract infections: a short case series.
Vancomycin-resistant enterococci are a leading cause of hospital-acquired urinary tract infection and a growing concern for the clinician. The aim of this study was to evaluate the effectiveness of daptomycin in the treatment of patients with vancomycin-resistant enterococcal urinary tract infection treated in our 200-bed community-based institution. Patients with confirmed symptomatic vancomycin-resistant enterococcal urinary tract infection identified by infectious disease consultation between January 1, 2007, and December 8, 2009, vancomycin-resistant enterococci-positive urine culture, and urinary symptoms and/or pyuria on urinalysis, and treated with daptomycin, were included in this case series. Daptomycin was generally administered at a planned dosage regimen of ≥ 5 mg/kg every 24 hours in patients with normal to moderately impaired kidney function or every 48 hours in patients with severe kidney disease. Microbiologic cure was defined as eradication of vancomycin-resistant enterococci in urine cultures taken after the completion of daptomycin treatment. Clinical cure was defined by symptom resolution, as assessed by the infectious disease clinician caring for the patient. Included in this case series are 10 patients who received daptomycin for confirmed vancomycin-resistant enterococcal urinary tract infection. Patients had a history of extensive hospital stays. Chart review revealed that all levels of kidney function (3, 2, 3, and 2 patients with kidney disease classified as normal, mild, moderate, and severe/kidney failure, respectively) were represented in the sample and that patients with (n = 5) or without (n = 5) previous urinary tract infection and with (n = 3) or without (n = 7) Foley catheters were included. Treatment with daptomycin achieved clinical cure and vancomycin-resistant enterococcal eradication in all cases in this series. Treatment with daptomycin was well tolerated and effective in all patients in this series, regardless of renal function, history of urinary tract infection, or Foley catheter use. This study adds to emerging clinical evidence that daptomycin is a valuable treatment for vancomycin-resistant enterococcal urinary tract infection.


Effects of different etching strategies on the microtensile repair bond strength of beautifil II giomer material.
Considering the differences in the filler particles between giomer and conventional composite resins and the importance of these fillers in the repair bond strength, the aim was to evaluate the effects of different etching strategies with phosphoric acid (PA) and hydrofluoric acid (HF) on the microtensile repair bond strength (µTRBS) of giomer. Ten giomer blocks were randomly assigned into 10: 1) control; 2) 37%PA-20s; 3) 3%HF-20s; 4) 3%HF-120s; 5) 9.6%HF-20s; 6) 9.6%HF-120s; 7) 37%PA-20s + 3%HF-120s; 8) 37%PA-20s + 9.6%HF-120s; 9) 3%HF-120s + 37%PA-20s; 10) 9.6%HF-120s + 37%PA-20s. In all groups, the One-Step Plus bonding system was applied and the new giomer block was bonded to the existing giomer. After cross-sectional cutting, 18 samples were prepared from each block and the µTRBS of the samples was measured at a strain rate of 0.5 mm/min. Data were analyzed with one-way ANOVA and post hoc Tukey tests (P<0.05). The µTRBS in groups 4, 5, 6, 7, 8 and 10 were significantly higher than that in the control group (P<0.05). The µTRBS in group 2 was even less than that in the control group (P<0.001). The highest µTRBS was recorded in group 10, which was significantly different from those in groups 3, 4 and 9 (P<0.05). In addition, the differences between group 9 and groups 6, 7 and 8 were significantly different (P<0.05). Etching with PA resulted in a decrease in µTRBS. Etching with HF, except for 3%HF-20s and HF after etching with PA, resulted in a significant increase in giomer`s µTRBS. An increase in the application time of 3%HF resulted in a significant increase in the µTRBS. Key words:Dental restoration repair, Hydrofluoric acid, Phosphoric acid, etching.


Do injection drug users have more adverse events during procedural sedation and analgesia for incision and drainage of cutaneous abscesses?
Injection drug users (IDUs) often undergo procedural sedation and analgesia (PSA) in the emergency department (ED). We compared adverse events (AEs) for IDUs to those for non-IDUs receiving PSA for incision and drainage of cutaneous abscesses. This was a retrospective analysis of a PSA safety audit. IDU status was prospectively documented among consecutive patients undergoing PSA at two urban EDs. Structured data describing comorbidities, vital signs, sedation regimens, and adverse events were collected. Primary outcome was the proportion of patients in each group experiencing an AE, whereas the secondary outcomes included recovery times. Of 525 consecutive patients receiving PSA for incision and drainage of an abscess, 244 were deemed IDUs and 281 non-IDUs. IDUs received higher doses of sedatives and analgesics, and 14 experienced AEs (5.7%), whereas 10 non-IDUs had AEs (3.6%), for a risk difference of 2.1% (95% CI -1.8, 6.5). Median recovery times were 18 minutes (interquartile range [IQR] 10-36) for IDUs and 12 minutes (IQR 7-19) for non-IDUs, for a difference of 6 minutes (95% CI 2-9 minutes). Median sedation times were also longer in IDUs, for a difference of 6 minutes (95% CI 5-10 minutes). Of 20 IDU patients and 1 non-IDU patient admitted to hospital, none had experienced an AE related to PSA. For ED patients requiring PSA for incision and drainage, IDUs had an AE rate similar to that of non-IDUs but longer sedation and recovery times. In experienced hands, PSA may be as safe in IDUs as in patients who do not use injection drugs.


Enriched Environment Increases PCNA and PARP1 Levels in Octopus vulgaris Central Nervous System: First Evidence of Adult Neurogenesis in Lophotrochozoa.
Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, reviled cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis.


Characterization and subcellular localization of ribonuclease H activities from Xenopus laevis oocytes.
Ribonuclease H activities present in fully grown Xenopus oocytes were investigated by using either liquid assays or renaturation gel assays. Whereas the test in solution detected an apparently unique class I ribonuclease H activity, the activity gels did not detect this enzyme but another one with the molecular weight expected for a class II ribonuclease H. The ribonuclease HI was found to be primarily concentrated in the germinal vesicle, but around 5% of this activity was detectged in the cytoplasm and may correspond to the activity involved in antisense oligonucleotide-mediated destruction of messenger RNAs. The concentration of this class I ribonuclease H in oocytes is similar to that in somatic cells. The class II ribonuclease H remained undetectable by the test in solution because its activity was cryptic. On activity gel, a polypeptide with the apparent molecular mass of 32 kDa, expected for a ribonuclease HII, was found to be concentrated in mitochondria although no RNase H activity could be detected by using the liquid assay. Based on sedimentation studies, we hypothesize that the apparent absence of RNase H activity in solution could be the result of the association of this 32-kDa polypeptide with other polypeptides, or possibly nucleic acids, to form a multimer of, until now, unknown function.


Imaging detectors for the ultraviolet.
A review is presented of the available types of efficient middle- and far-UV imaging detectors. These include luminescent phosphors, semitransparent and opaque photocathodes, mesh-based photocathodes, microchannel plates, and solid-state devices. Certain important aspects of their performance and calibration are discussed, and mention is also made of some applications of these systems, particularly in UV astronomy.


Phagocytosis and killing of Listeria by guinea pig macrophages and neutrophils.
The rate of the phagocytosis and intracellular killing of Listeria monocytogenes by guinea pig macrophages and neutrophils in vitro was determined. The anti-bacterial activity of the phagocytes against virulent Listeria monocytogenes was compared with their activity against avirulent strain of Listeria and Proteus mirabilis. It is suggested that the contribution of the macrophages and the neutrophils to anti-bacterial protection can depend on physiological state of bacteria.


Development of Trivia Game for speech understanding in background noise.
Listening in noise is an everyday activity and poses a challenge for many people. To improve the ability to understand speech in noise, a computerized auditory rehabilitation game was developed. In Trivia Game players are challenged to answer trivia questions spoken aloud. As players progress through the game, the level of background noise increases. A study using Trivia Game was conducted as a proof-of-concept investigation in healthy participants. College students with normal hearing were randomly assigned to a control (n = 13) or a treatment (n = 14) group. Treatment participants played Trivia Game 12 times over a 4-week period. All participants completed objective (auditory-only and audiovisual formats) and subjective listening in noise measures at baseline and 4 weeks later. There were no statistical differences between the groups at baseline. At post-test, the treatment group significantly improved their overall speech understanding in noise in the audiovisual condition and reported significant benefits in their functional listening abilities. Playing Trivia Game improved speech understanding in noise in healthy listeners. Significant findings for the audiovisual condition suggest that participants improved face-reading abilities. Trivia Game may be a platform for investigating changes in speech understanding in individuals with sensory, linguistic and cognitive impairments.


Ensuring inter-tester reliability of voluntary muscle and monofilament sensory testing in the INFIR Cohort Study.
To assess the reliability of monofilament (MF) and voluntary muscle strength (VMT) testing carried out by nine physiotherapy staff recruited for the ILEP Nerve Function Impairment & Reaction (INFIR) Cohort Study in India. A multiple pair inter-tester reliability study was carried out in Uttar Pradesh, India. Newly trained testers were paired up with an experienced physiotherapist, whose assessment served as the gold standard. Each pair completed a series of assessments. All testers had undertaken a week of specific VMT and MF training, followed by a month of practice in the hospital setting. Reliability was assessed by calculating weighted Kappa (Kw) statistics, which may be interpreted as the chance-corrected proportion of agreement between testers. Eight newly-trained physiotherapists and one physiotechnician took part in the study. In the early stages of the study some areas of weak agreement were identified and correct assessment technique was reviewed, particularly for the eye. Good to very good reliability (Kw 0.62 to 0.99) was found for all sensory tests and most muscle strength tests. The only lower Kw scores (0-48 to 0-59, suggesting only moderate reliability) were for the VMT of muscles supplied by the median nerve in one of the study's two field centres. Even in this case, testers never varied by more than one grade, but calculation of Kw was negatively influenced by a lack of variation among the subjects. In addition, testers never varied by more than one grade from the gold standard. Even though all testers were professionally trained and received additional specific training and practice in MF and VMT testing, discrepancies in technique required an early review and correction. This fact highlights the need for careful training and formal reliability testing. This should extend to referral centres where staff are involved in assessing the symptoms of reaction and monitoring response to treatment. Reliability testing provides the opportunity to address important discrepancies in technique that may persist even in the presence of protocols and qualified and trained staff. It is therefore a valuable tool as part of a training procedure for situations, where patients may be assessed by different testers. Overall, our results were deemed good enough to proceed with the INFIR study, using VMT and MF testing as a baseline against which to compare more sophisticated methods of nerve function testing.


Transport of matter and energy in a mesoscopic thermo-hydrodynamic approach.
We derive a thermo-hydrodynamic theory for particles and energy flow, based on a nonequilibrium grand-canonical ensemble formalism. The time-dependent kinetic coefficients are explicitly given in terms of microscopic mechanical quantities. The time evolution equations describing the coupled flow of energy and particles are derived. The second-rank tensorial fluxes of current of energy and particles present in the nonequilibrium ensemble are nondiagonal. We obtain a generalized Fick's Law, which presents the effect of the energy flow on the particle diffusion equation.


Native myosin from adult rabbit skeletal muscle: isoenzymes and states of aggregation.
The globular heads of skeletal muscle myosin have been shown to exist as isoenzymes S1 (A1) and S1 (A2), and there are also isoforms of the heavy chains. Using capillary electrophoresis, we found two dominant isoenzymes of the whole native myosin molecule, in agreement with what has previously been found by various techniques for native and nondenatured myosin from adult rabbits. Findings about possible states of aggregation of myosin and its heads are contradictory. By analytical ultracentrifugation, we confirmed the existence of a tail-tail dimer. By laser light scattering, we found a head-head dimer in the presence of MgATP. Capillary electrophoresis coupled with analytical ultracentrifugation and laser light scattering led us to refine these results. We found tail-tail dimers in a conventional buffer. We found tail-tail and head-head dimers in the presence of 0.5 mM MgATP and pure head-head dimers in the presence of 6 mM MgATP. All the dimers were homodimers. Naming the dominant isoenzymes of myosin a and b, we observed tail-tail dimers with isoenzyme a (TaTa) and with isoenzyme b (TbTb) and also head-head dimers with isoenzyme a (HaHa) and with isoenzyme b (HbHb).


Asthma, power, and the therapeutic conversation.
Previous research has indicated that family therapy may be of use when a child has chronic, uncontrolled asthma. The significant power relations were considered to be those between the child and the parents. In this article, I examine the wider contextual relations that the family encounters when asthma is a problem, and suggest that these relations are unable to be understood without more thoroughly theorizing power. Because of power relations, the meanings of therapeutic encounters for families and health care professionals may not be consensual. The effect may be to hamper adequate asthma management. I suggest that when Foucault's work is examined alongside that of Hoffman, and Anderson and Goolishian, then the processes that distort these understandings are more readily understood. These ideas are illustrated with examples from a research project.


Public trust and the COVID-19 vaccination campaign: lessons from the Philippines as it emerges from the Dengvaxia controversy.
While the entire world prepares and begins to roll out COVID-19 vaccines, the Philippines is still reeling from the consequences of the Dengvaxia controversy in 2016. Those highly political events led to the erosion of public trust in leaders and a significant damage to vaccine confidence in the country, now potentially impacting the uptake of COVID-19 vaccines. We discuss how public trust and confidence can be rehabilitated through accountability, transparency, and proper communication from the most trusted sources of the population. We also highlight key lessons for policymakers and leaders on allowing science to take the front seat, and politics behind, for the safety and well-being of the people during this public health crisis.


Reduction in intracellular calcium levels inhibits myoblast differentiation.
In myocytes, calcium plays an important role in intracellular signaling and contraction. However, the ability of calcium to modulate the differentiation of striated muscle cells is poorly understood. To examine this issue we studied C2C12 cells, which is a myoblast cell line that differentiates in vitro. First, we observed that the L-type calcium channel blockers nifedipine and verapamil effectively inhibited electrically induced calcium transients. Next, C2C12 cells were exposed to these agents during conditions that induce myocyte differentiation. In the presence of nifedipine and verapamil, myoblasts failed to form myotubes. Dantrolene and thapsigargin, which decrease intracellular calcium by different mechanisms, also inhibited differentiation. In addition, nifedipine and verapamil inhibited the expression of myosin heavy chain and myogenin, two markers of skeletal myoblast differentiation. In contrast, levels of the transcriptional factor Myf5, which is expressed in undifferentiated myoblasts, did not decline. Calcium channel blockade also prevented the expression of a reporter driven by the skeletal muscle alpha-actin promoter. These data demonstrate that lowering intracellular calcium levels inhibits the differentiation of skeletal myoblasts into mature myotubes.


[Misdirection of a Catheter for Clean Intermittent Catheterization into the Upper Ureter in a Female Patient with Neurogenic Bladder Due to Myelomeningocele : A Case Report].
We report a case of misdirection of a catheter for clean intermittent catheterization (CIC) into the ureter. A four-year-old girl with neurogenic bladder due to myelomeningocele had been managed with CIC by her parents for several years. From about a month before her visit, macroscopic hematuria appeared intermittently followed by abdominal pain and fever-up for a short time which ceased spontaneously. As cystography demonstrated bilateral vesicoureteral reflux, we performed endoscopic intraureteral injection of Deflux[TM] and during the operation we confirmed influx of bloody urine from the right ureteral orifice but not from the left one. As computed tomography revealed a tubular foreign body located in the upper portion of the right ureter, another endoscopic operation was performed and it was removed successfully. The removed foreign body was identified as a disposable catheter that was used for CIC.


Molecular characterization of KMT2A fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes.
In pediatric acute leukemias, reciprocal chromosomal translocations frequently cause gene fusions involving the lysine (K)-specific methyltransferase 2A gene (KMT2A, also known as MLL). Specific KMT2A fusion partners are associated with the disease phenotype (lymphoblastic vs. myeloid), and the type of KMT2A rearrangement also has prognostic implications. However, the KMT2A partner gene cannot always be identified by banding karyotyping. We sought to identify such partner genes in 13 cases of childhood leukemia with uninformative karyotypes by combining molecular techniques, including multicolor banding FISH, reverse-transcriptase PCR, and long-distance inverse PCR. Of the KMT2A fusion partner genes, MLLT3 was present in five patients, all with acute lymphoblastic leukemia, MLLT1 in two patients, and MLLT10, MLLT4, MLLT11, and AFF1 in one patient each. Reciprocal reading by long-distance inverse PCR also disclosed KMT2A fusions with PITPNA in one patient, with LOC100132273 in another patient, and with DNA sequences not compatible with any gene in three patients. The most common KMT2A breakpoint region was intron/exon 9 (3/8 patients), followed by intron/exon 11 and 10. Finally, multicolor banding revealed breakpoints in other chromosomes whose biological and prognostic implications remain to be determined. We conclude that the combination of molecular techniques used in this study can efficiently identify KMT2A fusion partners in complex pediatric acute leukemia karyotypes. Copyright © 2016 John Wiley & Sons, Ltd.


Vaccination coverage of recommended vaccines and determinants of vaccination in at-risk groups.
Upon exposure to vaccine-preventable diseases, certain individuals are at increased risk for complications due to preexisting diseases, age or immunosuppressive treatment. Vaccination against influenza, pneumococcal disease and hepatitis B (for some groups) is advised in addition to standard vaccination against diphtheria, tetanus and pertussis. We estimated the vaccination coverage and determinants of recommended vaccinations in patients with diabetes mellitus type 1 (n = 173) and type 2 (n = 177), chronic kidney disease (CKD) (n = 138), heart failure (n = 200), chronic obstructive pulmonary disease (COPD) (n = 187), HIV (n = 201) or solid organ transplantation (SOT) (n = 201) in a monocentric study. Vaccination data were retrieved from documents provided by patients and general practitioners, and from the Flemish vaccination register. Less than 10% had received all recommended vaccines. Overall, 29% of subjects were vaccinated against diphtheria-tetanus, 10% against pertussis, 44% against influenza, 32% against pneumococcal disease and 24% of HIV patients and 31% of CKD patients against hepatitis B. Age was positively associated with vaccination against influenza (OR:2.0, p < .01) and pneumococcal disease (OR:2.6, p < .001). Patients with COPD, HIV and SOT were more likely to be vaccinated against influenza (OR:2.8, p < .001, OR:1.8, p < .05; OR:2.0, p < .001, respectively) and pneumococcal disease (OR:2.9, p < .001, OR:25.0, p < .001; OR:2.6, p < .001, respectively) than patients with heart failure. Reason for non-vaccination were concerns about effectiveness, necessity and side effects of influenza vaccines, and not being aware of the recommendation for pneumococcal disease. Initiatives to monitor the vaccination status of vulnerable patients are needed, which is why we advocate systematic vaccination registration and frequent communication about vaccination.


The Optical Fractionator Technique to Estimate Cell Numbers in a Rat Model of Electroconvulsive Therapy.
Stereological methods are designed to describe quantitative parameters without making assumptions about size, shape, orientation and distribution of cells or structures. These methods have been revolutionary for quantitative analysis of the mammalian brain, in which volumetric cell populations are too high to count manually, and stereology is now the technique of choice whenever estimates of three-dimensional quantities need to be extracted from measurements on two-dimensional sections. All stereological methods are in principle unbiased; however, they rely on proper knowledge about the structure of interest and the characteristics of the tissue. Stereology is based on Systematic Uniformly Random Sampling (SURS), with adjustment of sampling to the most efficient level in respect to precision, providing reliable, quantitative information about the whole structure of interest. Here we present the optical fractionator in conjunction with BrdU immunohistochemistry to estimate the production and survival of newly-formed neurons in the granule cell layer (including the sub-granular zone) of the rat hippocampus following electroconvulsive stimulation, which is among the most potent stimulators of neurogenesis. The optical fractionator technique is designed to provide estimates of the total number of cells from thick sections sampled from the full structure. Thick sections provide the opportunity to observe cells in their full 3-D extent and thus, allow for easy and robust cell classification based on morphological criteria. When correctly implemented, the sensitivity and efficiency of the optical fractionator provides accurate estimates with a fixed and predetermined precision.


[Research on WiFi-based wireless microscopy on a mobile phone and its application].
We proposed and realized a new device that acquires microscopic image wirelessly based on mobile phone and WiFi system. The mobile terminals could record, display and store the image from the far end via the wireless LAN. Using this system, a series of conceptual experiments on monitoring the microscopic images of common objects and liver cancer cells were successfully demonstrated. This system is expected to have important value in the experimental investigations on wirelessly monitoring the cell culture, and small insect etc.


A review of human physiological and performance changes associated with desynchronosis of biological rhythms.
This review discusses the effects, in the aerospace environment, of alterations in approximately 24-h periodicities (circadian rhythms) upon physiological and psychological functions and possible therapies for desynchronosis induced by such alterations. The consequences of circadian rhythm alteration resulting from shift work, transmeridian flight, or altered day lengths are known as desynchronosis, dysrhythmia, dyschrony, jet lag, or jet syndrome. Considerable attention is focused on the ability to operate jet aircraft and manned space vehicles. The importance of environmental cues, such as light-dark cycles, which influence physiological and psychological rhythms is discussed. A section on mathematical models is presented to enable selection and verification of appropriate preventive and corrective measures and to better understand the problem of dysrhythmia.


Universal, strong and long-ranged trapping by optical conveyors.
Optical conveyors are active tractor beams that selectively transport illuminated objects either upstream or downstream along their axes. Formed by the coherent superposition of coaxial Bessel beams, an optical conveyor features an axial array of equally spaced intensity maxima that act as optical traps for small objects. We demonstrate through measurements on colloidal spheres and numerical calculations based on the generalized Lorenz-Mie theory that optical conveyors' interferometric structure endows them with trapping characteristics far superior to those of conventional optical tweezers. Optical conveyors form substantially stiffer traps and can transport a wider variety of materials over a much longer axial range.


Frequency and severity of asymptomatic coronary disease in patients with different causes of stroke.
We sought (1) to compare the frequency and severity of asymptomatic coronary artery disease (CAD) in patients with different causes of brain ischemia and (2) to determine profiles of patients with brain ischemia who are at highest risk of asymptomatic CAD. Sixty-nine patients with transient ischemic attack or stroke and without overt CAD underwent a cardiac stress test and a diagnostic evaluation to determine the cause of brain ischemia. The frequency of abnormal cardiac stress tests was compared in patients with large-artery cerebrovascular disease versus other causes of brain ischemia (90% of whom had penetrating artery disease or cryptogenic stroke). Additionally, the frequencies of vascular risk factors, resting electrocardiographic abnormalities, and cause of stroke (large-artery disease versus other causes) were compared in patients with abnormal stress tests versus patients with normal stress tests. The frequency of abnormal stress tests was 50% (15 of 30) in patients with large-artery cerebrovascular disease versus 23% (9 of 39) in patients with other causes of brain ischemia (P = .04). Moreover, 60% of abnormal stress tests (9 of 15) in patients with large-artery cerebrovascular disease suggested severe underlying CAD that was confirmed in 7 of 7 patients who underwent coronary angiography. On the other hand, less than 25% of abnormal stress tests (2 of 9) in patients with other causes of brain ischemia suggested severe underlying CAD. Features that were more common in patients with abnormal stress tests were smoking (P = .006), large-artery cerebrovascular disease (P = .02), veteran status (P = .02), and left ventricular hypertrophy (P = .07). Patients with penetrating artery disease or cryptogenic stroke have a significantly lower frequency of asymptomatic CAD than patients with large-artery cerebrovascular disease. Large-artery cerebrovascular disease, smoking, veteran status, and possibly left ventricular hypertrophy may be useful features for identifying patients with transient ischemic attack or stroke who are at highest risk of harboring asymptomatic CAD.


[Circulating serum STN antigen as a prognostic marker in epithelial ovarian cancer].
Circulating serum sialyl Tn (STN) antigen levels were measured in 89 patients with epithelial ovarian cancer. Survival at 5 years for patients with STN-negative (serum STN levels less than 50 U/ml) versus STN-positive tumors (serum STN levels greater than or equal to 50 U/ml) was 76.9% versus 10.8%, respectively (p less than 0.05). The overall survival probability was worse in patients with STN-positive sera. Percent progression-free survival at 5 years for patients with STN-negative versus STN-positive tumors was 51.9% versus 5.4%, respectively (p less than 0.05). The overall progression-free survival was shorter in patients with STN-positive sera. Multivariate regression analysis revealed that positive STN antigen level in sera is an independent predictor of poor prognosis in epithelial ovarian cancer.


Data fusion for driver behaviour analysis.
A driver behaviour analysis tool is presented. The proposal offers a novel contribution based on low-cost hardware and advanced software capabilities based on data fusion. The device takes advantage of the information provided by the in-vehicle sensors using Controller Area Network Bus (CAN-BUS), an Inertial Measurement Unit (IMU) and a GPS. By fusing this information, the system can infer the behaviour of the driver, providing aggressive behaviour detection. By means of accurate GPS-based localization, the system is able to add context information, such as digital map information, speed limits, etc. Several parameters and signals are taken into account, both in the temporal and frequency domains, to provide real time behaviour detection. The system was tested in urban, interurban and highways scenarios.


Subunit structure and purification of opioid receptors.
Considerable evidence indicates the existence of multiple types of opioid receptors. The three major types have been named mu, delta and kappa. The earlier evidence was based on pharmacological as well as membrane binding experiments. This paper will emphasize more recent studies using solubilized opioid binding sites. Several laboratories, including our own, have succeeded in separating kappa receptors from other types. A similar separation of mu from delta receptors has not yet been achieved. By crosslinking experiments with 125I- human beta-endorphin we have been able to provide strong evidence for differences in molecular size between the major binding components of mu (65K) and delta (53K) receptors. It is not yet established whether the difference resides in the protein or carbohydrate portion of these glycoproteins. These results suggest that the three major types of opioid receptors represent distinct molecular entities. An active opioid binding protein solubilized from bovine striatal membranes has been purified to apparent homogeneity. The major purification steps involve affinity chromatography and lectin chromatography on immobilized wheat germ agglutinin. The purified material gave a single band of molecular weight 65K Da on SDS-PAGE. Its specific activity for opioid binding was ca. 13,000 pmol/mg protein and its properties are those of a component of the mu receptor.


Absolute spectral radiance responsivity calibration of sun photometers.
Sun photometers are designed to measure direct solar irradiance and diffused sky radiance for the purpose of atmospheric parameters characterization. A sun photometer is usually calibrated by using a lamp-illuminated integrating sphere source for its band-averaged radiance responsivity, which normally has an uncertainty of 3%-5% at present. Considering the calibration coefficients may also change with time, a regular high precision calibration is important to maintain data quality. In this paper, a tunable-laser-based facility for spectral radiance responsivity calibration has been developed at the Key Laboratory of Optical Calibration and Characterization, Chinese Academy of Sciences. A reference standard radiance radiometer, calibrated against cryogenic radiometer, is used to determine the radiance from a laser-illuminated integrating sphere source. Spectral radiance responsivity of CIMEL CE318-2 sun photometer is calibrated using this new calibration system with a combined standard uncertainty of about 0.8%. As a validation, the derived band-averaged radiance responsivity are compared to that from a Goddard Space Flight Center lamp-based sphere calibration and good agreements (difference <1.4%) are found from 675 to 1020 nm bands.


Interactions between the anterior cingulate-insula network and the fronto-parietal network during perceptual decision-making.
Information processing in the human brain during cognitively demanding goal-directed tasks is thought to involve several large-scale brain networks, including the anterior cingulate-insula network (aCIN) and the fronto-parietal network (FPN). Recent functional MRI (fMRI) studies have provided clues that the aCIN initiates activity changes in the FPN. However, when and how often these networks interact remains largely unknown to date. Here, we systematically examined the oscillatory interactions between the aCIN and the FPN by using the spectral Granger causality analysis of reconstructed brain source signals from the scalp electroencephalography (EEG) recorded from human participants performing a face-house perceptual categorization task. We investigated how the aCIN and the FPN interact, what the temporal sequence of events in these nodes is, and what frequency bands of information flow bind these nodes in networks. We found that beta band (13-30Hz) and gamma (30-100Hz) bands of interactions are involved between the aCIN and the FPN during decision-making tasks. In gamma band, the aCIN initiated the Granger causal control over the FPN in 25-225 ms timeframe. In beta band, the FPN achieved a control over the aCIN in 225-425 ms timeframe. These band-specific time-dependent Granger causal controls of the aCIN and the FPN were retained for behaviorally harder decision-making tasks. These findings of times and frequencies of oscillatory interactions in the aCIN and FPN provide us new insights into the general neural mechanisms for sensory information-guided, goal-directed behaviors, including perceptual decision-making processes.


Muscle fiber-type selective propensity to pathology in the nmd mouse model of SMARD1.
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive disease that causes distal limb muscle atrophy, due to motor neuron degeneration. Similar to other motor neuron diseases, SMARD1 shows differential vulnerability to denervation in various muscle groups, which is recapitulated in the nmd mouse, a model of SMARD1. In multiple neurodegenerative disease models, transcriptomic analysis has identified differentially expressed genes between vulnerable motor neuron populations, but the mechanism leading to susceptibility is largely unknown. To investigate if denervation vulnerability is linked to intrinsic muscle properties, we analyzed muscle fiber-type composition in muscles from motor units that show different degrees of denervation in nmd mice: gastrocnemius, tibialis anterior (TA), and extensor digitorum longus (EDL). Our results revealed that denervation vulnerability correlated with atrophy and loss of MyHC-IIb and MyHC-IIx muscle fiber types. Interestingly, increased vulnerability also correlated with an increased abundance of MyHC-I and MyHC-IIa muscle fibers. These results indicated that MyHC-IIx muscle fibers are the most vulnerable to denervation, followed by MyHC-IIb muscle fibers. Moreover, our data indicate that type MyHC-IIa and MyHC-IIb muscle fibers show resistance to denervation and compensate for the loss of MyHC-IIx and MyHC-IIb muscle fibers in the most vulnerable muscles. Taken together these results provide a basis for the selective vulnerability to denervation of specific muscles in nmd mice and identifies new targets for potential therapeutic intervention.


Sativex Associated With Behavioral-Relapse Prevention Strategy as Treatment for Cannabis Dependence: A Case Series.
Cannabis is the most commonly used illicit drug; a substantial minority of users develop dependence. The current lack of pharmacological treatments for cannabis dependence warrants the use of novel approaches and further investigation of promising pharmacotherapy. In this case series, we assessed the use of self-titrated dosages of Sativex (1:1, Δ-tetrahydrocannabinol [THC]/cannabidiol [CBD] combination) and motivational enhancement therapy and cognitive behavioral therapy (MET/CBT) for the treatment of cannabis dependence among 5 treatment-seeking community-recruited cannabis-dependent subjects. Participants underwent a 3-month open-label self-titration phase with Sativex (up to 113.4 of THC/105 mg of CBD) and weekly MET/CBT, with a 3-month follow-up. Sativex was well-tolerated by all participants (average dosage 77.5 THC/71.7 mg CBD). The combination of Sativex and MET/CBT reduced the amount of cannabis use and progressively reduced craving and withdrawal scores. THC/CBD metabolite concentration indicated reduced cannabis use and compliance with medication. In summary, this pilot study found that with Sativex in combination with MET/CBT reduced cannabis use while preventing increases in craving and withdrawal in the 4 participants completing the study. Further systematic exploration of Sativex as a pharmacological treatment option for cannabis dependence should be performed.


Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase.
Methylation of CpG dinucleotides is the major epigenetic modification of mammalian genomes, critical for regulating chromatin structure and gene activity. The mixed-lineage leukaemia (MLL) CXXC domain selectively binds nonmethyl-CpG DNA, and is required for transformation by MLL fusion proteins that commonly arise from recurrent chromosomal translocations in infant and secondary treatment-related acute leukaemias. To elucidate the molecular basis of nonmethyl-CpG DNA recognition, we determined the structure of the human MLL CXXC domain by multidimensional NMR spectroscopy. The CXXC domain has a novel fold in which two zinc ions are each coordinated tetrahedrally by four conserved cysteine ligands provided by two CGXCXXC motifs and two distal cysteine residues. We have identified the CXXC domain DNA binding interface by means of chemical shift perturbation analysis, cross-saturation transfer and site-directed mutagenesis. In particular, we have shown that residues in an extended surface loop are in close contact with the DNA. These data provide a template for the design of specifically targeted therapeutics for poor prognosis MLL-associated leukaemias.


Observation of clinical efficacy of application of enhanced recovery after surgery in perioperative period on esophageal carcinoma patients.
To observe the clinical efficacy of the application of enhanced recovery after surgery (ERAS) in the perioperative period of esophageal carcinoma patients. A total of 114 patients who were admitted to Affiliated Hospital of Jining Medical University for surgical treatment of esophageal carcinoma between June 2012 and June 2016 were enrolled and randomly divided into the intervention group and the regular group according to the difference of management procedures during the perioperative period. ERAS was carried out in 57 patients in the intervention group, while conventional management procedures were applied in 57 patients in the regular group. Thereafter, compared were the fluctuations in nutritional indicators and immunological indicators, postoperative complications, time to recovery of gastrointestinal function, length of stay (LOS) in hospital and cost of patients between the two groups. Seven days post-operation in the intervention group, the evaluation indexes of nutrition status, including total protein (TP), albumin (ALB), prealbumin (PA) and transferrin (TF), and of immunological functions, including immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM) and total blood lymphocyte count (TLC), were significantly higher than those in the regular group. As for postoperative complications, the incidence rate of the intervention group was remarkably lower than that of the regular group; the recovery time of gastrointestinal function in the intervention group was shorter than that in the regular group; the LOS in the intervention group was also shorter than that in the regular group; the in-hospital cost in the intervention group was also lower than that in the regular group. All differences above were statistically significant (p<0.05). During the perioperative period of esophageal carcinoma patients, ERAS should be fully applied to sustain the good status, and promote the recovery of immunological functions and gastrointestinal functions; at the same time, ERAS also reduces the incidence rate of postoperative complications, LOS and in-hospital cost, and we maintain that ERAS should be performed in clinical practice.


An integrated approach to demonstrating the ANR pathway of proanthocyanidin biosynthesis in plants.
Proanthocyanidins (PAs) are oligomers or polymers of plant flavan-3-ols and are important to plant adaptation in extreme environmental conditions. The characterization of anthocyanidin reductase (ANR) and leucoanthocyanidin reductase (LAR) has demonstrated the different biogenesis of four stereo-configurations of flavan-3-ols. It is important to understand whether ANR and the ANR pathway widely occur in the plant kingdom. Here, we report an integrated approach to demonstrate the ANR pathway in plants. This includes different methods to extract native ANR from different tissues of eight angiosperm plants (Lotus corniculatus, Desmodium uncinatum, Medicago sativa, Hordeum vulgare, Vitis vinifera, Vitis bellula, Parthenocissus heterophylla, and Cerasus serrulata) and one fern plant (Dryopteris pycnopteroides), a general enzymatic analysis approach to demonstrate the ANR activity, high-performance liquid chromatography-based fingerprinting to demonstrate (-)-epicatechin and other flavan-3-ol molecules, and phytochemical analysis of PAs. Results demonstrate that in addition to leaves of M. sativa, tissues of other eight plants contain an active ANR pathway. Particularly, the leaves, flowers and pods of D. uncinatum, which is a model plant to study LAR and the LAR pathways, are demonstrated to express an active ANR pathway. This finding suggests that the ANR pathway involves PA biosynthesis in D. uncinatum. In addition, a sequence BLAST analysis reveals that ANR homologs have been sequenced in plants from both gymnosperms and angiosperms. These data show that the ANR pathway to PA biosynthesis occurs in both seed and seedless vascular plants.


An integrated approach with new strategies for QSAR models and lead optimization.
Computational drug design approaches are important for shortening the time and reducing the cost for drug discovery and development. Among these methods, molecular docking and quantitative structure activity relationship (QSAR) play key roles for lead discovery and optimization. Here, we propose an integrated approach with core strategies to identify the protein-ligand hot spots for QSAR models and lead optimization. These core strategies are: 1) to generate both residue-based and atom-based interactions as the features; 2) to identify compound common and specific skeletons; and 3) to infer consensus features for QSAR models. We evaluated our methods and new strategies on building QSAR models of human acetylcholinesterase (huAChE). The leave-one-out cross validation values q 2 and r 2 of our huAChE QSAR model are 0.82 and 0.78, respectively. The experimental results show that the selected features (resides/atoms) are important for enzymatic functions and stabling the protein structure by forming key interactions (e.g., stack forces and hydrogen bonds) between huAChE and its inhibitors. Finally, we applied our methods to arthrobacter globiformis histamine oxidase (AGHO) which is correlated to heart failure and diabetic. Based on our AGHO QSAR model, we identified a new substrate verified by bioassay experiments for AGHO. These results show that our methods and new strategies can yield stable and high accuracy QSAR models. We believe that our methods and strategies are useful for discovering new leads and guiding lead optimization in drug discovery.


Nitrogen regulation of synthesis of the high affinity methylammonium transport system of Escherichia coli.
Uptake of 14CH3NH+3 (methylammonium) was measured as a probe of NH+4 transport in intact Escherichia coli cells and derivatives impaired in the Ntr regulatory system. The results suggest that expression of the high affinity 14CH3NH+3 transport system (a) requires de novo polypeptide synthesis, (b) is activated by the glnG and glnF regulatory products under nitrogen limitation, and (c) is repressed under nitrogen excess by the glnL product. Cells deficient in glutamate synthase activity by virtue of their harbouring the gltB31 mutation were unable to activate synthesis of 14CH3NH+3 transport. This could explain the inability of cells carrying gltB mutations to grow on low concentrations of NH+4.


[FORCE-FEEDING OR LIFE-SAVING? - DEALING WITH HUNGER STRIKES IN ISRAEL].
Although the management of quality of care by the health funds has contributed to its improvement, medical teams criticize the way it is performed. Many call for renewed values-driven thinking and to leave the concern for quality in the hands of the medical teams, relying on "self control and enforcement", based on values, compassion, concern for others, patient service, discipline and personal responsibility. This article aims to present an economic perspective on the measurement of quality of care. It places the development of "measuring the quality of care and its management" within the development of the organization of care, health insurance and payment arrangements for medical teams. The conclusion is that there is no "first best" method to improve the quality of care. Each method - including the quantitative-functional measurement-based method used in many systems and the value-driven, self enforced method proposed by many - has advantages and disadvantages. The choice of a method should be based on these two sides, discussed jointly by medical teams, the health funds, hospitals and the Health Ministry.


Diagnostic Management of Pregnant Women With Suspected Pulmonary Embolism.
Pulmonary embolism (PE) is one of the most common causes of severe morbidity and mortality during pregnancy. PE diagnosis during pregnancy remains a true challenge for all physicians, as many of the symptoms and signs associated with PE are often reported during physiological pregnancy. The fear of missing a PE during pregnancy leads a low threshold of suspicion, hence to a low prevalence of confirmed PE among pregnant women with suspected PE. This means that most pregnant women with suspected PE do not have the disease. Until recently, international guidelines suggested thoracic imaging in all pregnant women with suspected PE. Two recent prospective management outcome studies based on clinical probability assessment, D-dimer measurement, venous compression ultrasonography of the lower limbs (CUS) and computed tomography pulmonary angiography (CTPA) proved the safety of such strategies, with a very low failure rate. For the first time, these studies also demonstrated that the association of a clinical prediction rule and D-dimer measurement allowed a safe exclusion of PE in a significant proportion of pregnant women, without the need for radiating imaging tests. These two prospective studies pave the way to further improvements in the diagnostic strategies. Indeed, both specific clinical prediction rules and possibly D-dimer cutoffs adapted to pregnant women could help to further reduce the proportion of patients needing thoracic imaging. As an imaging test will still ultimately be necessary in a significant proportion of women, further technical advances in CT scans protocols could reduce the radiation dose to both the fetus and the mother, an important step to reassure clinicians. Finally, educational efforts should be encouraged in the future to pass the challenge of implementing these validated diagnostic strategies in everyday clinical practice.


Mediation analysis of health-related quality of life among people living with HIV infection in China.
The effects of stigma, social support, and depressive symptoms on health-related quality of life are well documented in the literature, but how these psychological factors interact with each other, and the combined effects when taken together on the health-related quality of life for people living with HIV, remain unclear. This cross-sectional study investigated 114 people living with HIV who were taking antiretroviral medication using the HIV/AIDS-related Stigma Scale (Chinese version), the Social Support Rating Scale, the Center for Epidemiological Studies Depression Scale, and the Medical Outcomes Study-HIV health survey. Multiple linear regression analyses were used to examine the mediation effect of the psychosocial factors on health-related quality of life. Results showed that stigma and social support did not have direct effects, but indirect effects on health-related quality of life through a full mediation effect of depressive symptoms. The results indicate that interventions targeting depression might be the most effective approach to improving health-related quality of life among people living with HIV who are taking antiretroviral medication in China.


Characterization and optical transition in tb-doped 12CaO x 7Al2O3 powders.
Tb-doped 12CaO x 7Al2O3 (C12A7:Tb3+) powders with strong green emission were prepared using the sol-gel method. X-ray diffraction, micro-Raman spectra, scanning electron microscopy and absorption spectra showed that C12A7:Tb3+ powders with grain size of 200-300 nm were synthesized. Porous powders could be formed as the concentration of Tb3+ was 5 at%. The absorption band around 209 nm was attributed to the host lattice absorption, and the bands around 255 nm and 274 nm were related to the 4f-5d transitions of Tb3+. The absorption intensity of the visible region was enhanced due to the presence of one 100 nm-diameter hole in every grain of C12A7:Tb3+ powders. The emission spectra showed noticeable influence of Tb-Tb cross relaxation, which favored the green photoluminescence (PL) over the blue PL. The study on the concentration quenching indicated that the energy transfers depopulating the 5D3 and 5D4 levels were assigned to the mechanisms of electric dipole-dipole and exchange interaction, respectively.


Cultivating hope through creative resistance: Puerto Rican undergraduates surviving the disasters of climate and colonization.
This article details what occurred during a youth participatory action research (YPAR) project involving Puerto Rican undergraduates who at first focused their analysis on how their experiences with Hurricane María could be framed as resiliency and then eventually adopted a framework of resistance to further capture their actions, stances, and practices in response to government neglect. The YPAR generative process facilitated this emergence of resistance by beginning with the presentation of a cultural artifact and then helping students to use creative and artistic means to critically reflect on their experiences and the ways that not just resiliency, but also resistance captured their analysis of the actions of the people and government actors both immediately after the hurricane and in the long recovery that followed.


Inhibition of murine osteogenic sarcomas by treatment with type I or type II interferon.
Interferon was used to treat C57BL/6 female mice inoculated with a continuous line of murine osteogenic sarcoma cells. A short 7-day course of 30,000--60,000 U/day of tpe I interferon either completely inhibited or delayed the appearance of tumors in experimental animals. The therapeutic efficacy of type I interferon was compared with murine serum that contained type II interferon as well as other lymphokine activity. Tumor development was strikingly inhibited in animals treated for 7 days with serum containing only 600 U of type II interferon. Inhibition of tumor development was thus achieved with 100-fold less interferon than that required with type I preparation.


Hypoxia-inducible factor-1α promotes cell survival during ammonia stress response in ovarian cancer stem-like cells.
Ammonia is a toxic by-product of metabolism that causes cellular stresses. Although a number of proteins are involved in adaptive stress response, specific factors that counteract ammonia-induced cellular stress and regulate cell metabolism to survive against its toxicity have yet to be identified. We demonstrated that the hypoxia-inducible factor-1α (HIF-1α) is stabilized and activated by ammonia stress. HIF-1α activated by ammonium chloride compromises ammonia-induced apoptosis. Furthermore, we identified glutamine synthetase (GS) as a key driver of cancer cell proliferation under ammonia stress and glutamine-dependent metabolism in ovarian cancer stem-like cells expressing CD90. Interestingly, activated HIF-1α counteracts glutamine synthetase function in glutamine metabolism by facilitating glycolysis and elevating glucose dependency. Our studies reveal the hitherto unknown functions of HIF-1α in a biphasic ammonia stress management in the cancer stem-like cells where GS facilitates cell proliferation and HIF-1α contributes to the metabolic remodeling in energy fuel usage resulting in attenuated proliferation but conversely promoting cell survival.