Trocar site hernia after gastric sleeve.
Laparoscopy is common in abdominal surgery. Trocar site hernia (TSH) is a most likely underestimated complication. Among risk factors, obesity, the use of larger trocars and the umbilical trocar site has been described. In a previous study, CT scan in the prone position was found to be a reliable method for the detection of TSH following gastric bypass (LRYGB). In the present study, our aim was to examine the incidence of TSH after gastric sleeve, and further to investigate the proportion of symptomatic trocar site hernias. Seventy-nine patients subjected to laparoscopic gastric sleeve in 2011-2016 were examined using CT in the prone position upon a ring. Symptoms of TSH were assessed using a digital survey. The incidence of trocar site hernia was 17 out of 79 (21.5%), all at the umbilical trocar site. The mean follow-up time was 37 months. There was no significant correlation between patient symptoms and a TSH. The incidence of TSH is high after laparoscopic gastric sleeve, a finding in line with several recent studies as well as with our first trial on trocar site hernia after LRYGB. Up to follow-up, none of the patients had been subjected to hernia repair. Although the consequence of a trocar site hernia can be serious, the proportion of symptomatic TSH needs to be more clarified.


Tight association of CpcL with photosystem I in Anabaena sp. PCC 7120 grown under iron-deficient conditions.
Phycobilisomes (PBSs), which are huge pigment-protein complexes displaying distinctive color variations, bind to photosystem cores for excitation-energy transfer. It is known that isolation of supercomplexes consisting of PBSs and photosystem I (PSI) or PBSs and photosystem II is challenging due to weak interactions between PBSs and the photosystem cores. In this study, we succeeded in purifying PSI-monomer-PBS and PSI-dimer-PBS supercomplexes from the cyanobacterium Anabaena sp. PCC 7120 grown under iron-deficient conditions by anion-exchange chromatography, followed by trehalose density gradient centrifugation. The absorption spectra of the two types of supercomplexes showed apparent bands originating from PBSs, and their fluorescence-emission spectra exhibited characteristic peaks of PBSs. Two-dimensional blue-native (BN)/SDS-PAGE of the two samples showed a band of CpcL, which is a linker protein of PBS, in addition to PsaA/B. Since interactions of PBSs with PSI are easily dissociated during BN-PAGE using thylakoids from this cyanobacterium grown under iron-replete conditions, it is suggested that iron deficiency for Anabaena induces tight association of CpcL with PSI, resulting in the formation of PSI-monomer-PBS and PSI-dimer-PBS supercomplexes. Based on these findings, we discuss interactions of PBSs with PSI in Anabaena.


Use of the Zung Self-Rating Depression Scale in cancer patients: feasibility as a screening tool.
The feasibility, utility and reliability of the Zung Self-Rating Depression Scale (ZSDS) was examined in a large sample of ambulatory cancer patients. This tool and a brief 11-item version of the ZSDS (excluding nine items concerning somatic symptoms), which was developed during the course of the survey, were used to estimate the prevalence of self-reported depressive symptoms. Patient characteristics that may be associated with an increased risk of clinically significant depressive symptoms were also explored. Twenty-five ambulatory oncology clinics affiliated with Community Cancer Care, Inc. enrolled and surveyed 1109 subjects. The alpha coefficients for the ZSDS (0.84) and the Brief ZSDS (0.84) indicated high levels of internal consistency. The overall prevalence of clinically significant depressive symptoms as defined by the ZSDS was 35.9% and by the Brief ZSDS was 31.1%. The ZSDS and the Brief ZSDS were highly correlated (r = 0.92). The medical and demographic variables most associated with clinically significant depressive symptoms were more advanced stage of disease at time of diagnosis, lung cancer as primary tumor type, higher ECOG rating (greater degree of physical disability), and having been prescribed antidepressant medications. The high prevalence of depressive symptoms observed in this study is consistent with rates found in other studies of self-report depression instruments in cancer patients. The initial indicators of internal consistency and validity suggest that the Zung SDS or the brief version may be useful screening tools to identify depressive symptoms in oncology patients.


Electron spin resonance studies on photosensitized formation of hydroxyl radical by C-phycocyanin from Spirulina platensis.
Visible light (>470 nm) irradiation of an oxygen-saturated solution of C-phycocyanin (C-PC) in the presence of the spin trap 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) gave an ESR spectrum characteristic of the DMPO-hydroxyl radical spin adduct DMPO-OH. The signal intensities of DMPO-OH adduct were enhanced by superoxide dismutase (SOD) and partly inhibited by catalase. It was partly responsible for the production of DMPO-OH that superoxide anion radical (O.-2) dismutated to generate hydrogen peroxide (H2O2) which decomposed ultimately to generate the highly reactive .OH. In addition, it can be concluded that singlet oxygen (1O2) was an important intermediate according to the strong inhibitory action of 1,4-diazabicyclo[2.2.2]octane (DABCO) and histidine on DMPO-OH formation. The experimental results suggest that photodynamic action of C-PC proceed via both type I and type II mechanisms. Furthermore, the decay kinetics of DMPO-OH adduct, the effects of DMPO and C-PC concentrations as well as irradiation time on DMPO-OH adduct formation were also discussed. Concentration of C-PC should be an important factor to influence the ESR signal intensities of DMPO-OH. Therefore, it may be concluded that reasonably lower concentration of C-PC might prolong the duration of photosensitized formation of .OH and might strengthen the photodynamic action.


Asthma morbidity during pregnancy can be predicted by severity classification.
The 1993 National Asthma Education Program Working Group on Asthma and Pregnancy defined asthma severity as mild, moderate, or severe on the basis of symptoms and spirometry, but no studies have evaluated the relationship between this classification system and subsequent asthma morbidity during pregnancy. The objective of this study was to evaluate the relationship between asthma severity classification during pregnancy and gestational asthma exacerbations. Asthma severity was defined according to the 1993 classification, adjusted to include medication requirements, in a volunteer sample of 1739 pregnant asthmatic patients who were less than 26 weeks' gestation. Initial asthma classification (mild, moderate, or severe) was significantly related to subsequent asthma morbidity during pregnancy (hospitalizations, unscheduled visits, corticosteroid requirements, and asthma symptoms during labor and delivery). Exacerbations during pregnancy occurred in 12.6% of patients initially classified as mild, 25.7% of patients classified as moderate, and 51.9% of patients classified as severe (P <.001). Asthma morbidity was similar, whether patients were classified as moderate or severe by symptoms and spirometry or by medication requirement. Thirty percent of initially mild patients were reclassified as moderate-severe during pregnancy, and 23% of the initially moderate-severe patients were reclassified as mild later in pregnancy; asthma morbidity in these patients changed accordingly. The National Asthma Education Program Working Group on Asthma and Pregnancy classification of asthma severity, adapted to include medication use, predicts subsequent asthma morbidity during pregnancy.


Comparison of the Xpert Carba-R and NG-Test CARBA5 for the detection of carbapenemases in an IMP-type carbapenemase endemic region in Japan.
The real-time PCR assay Xpert Carba-R and the lateral flow immunoassay NG-Test CARBA5 were developed to detect 5 types of carbapenemase genes (blaIMP, blaKPC, blaVIM, blaOXA-48, and blaNDM). We compared the diagnostic performance, turn-around time, and cost of these assays. Carbapenemase genes were defined using the Carba NP test, modified Carbapenem Inactivation Methods (mCIM), multiplex PCR, and whole-genome sequencing. We included clinical Enterobacterales isolates (n = 36) and nonfermenting gram-negative bacilli isolates (n = 17) collected from 16 acute-care hospitals in the Kinki region of Japan. Twenty-six of these 53 isolates were positive according to both of the Carba NP test and mCIM and, contained the following carbapenemase genes: blaIMP-1 (n = 3), blaIMP-6 (n = 1), blaIMP-19 (n = 12), blaIMP-26 (n = 1), blaIMP-41 (n = 2), blaIMP-66 (n = 2), blaNDM-1 (n = 3), and blaVIM-2 (n = 2). All of the remaining 27 isolates were negative according to the Carba NP test, mCIM, and multiplex PCR. The specificities of both assays were 100%. The sensitivity of the Xpert Carba-R assay was as low as 53.8% and that of the NG-Test CARBA5 was 92.3% because the former failed to detect all isolates with blaIMP-19 (n = 12) and the latter failed to detect isolates with blaIMP-66 (n = 2). Both assays can easily be performed in less than 5 min. The NG-Test CARBA5 assay was superior with regard to assay time and cost per sample. We propose the use of the NG-Test CARBA5 assay in clinical laboratories where IMP-type carbapenemases are endemic.


Perceptions of Dishonesty: Understanding Parents' Reports of and Influence on Children and Adolescents' Lie-Telling.
Previous studies suggest parents lack knowledge regarding child and adolescent lie-telling; however, no study to date has examined children's and parents' reports of lying within parent-child dyads. The current study examined parents' knowledge of and influence on children's and adolescents' lie-telling. Parent-child dyads (N= 351) completed self-report surveys. Children (8-14 years, 52.3% children female) reported on prosocial and antisocial lie-telling. Parents (Mage = 41.68, 89.5% parents female) reported on their child's lie-telling, as well as their own honesty-targeted parenting strategies and modeling of dishonest behaviors. Parents' reports were unrelated to children's and adolescents' reports of prosocial and antisocial lie-telling. Additionally, parents' honesty-targeted parenting strategies and modeling of dishonesty did not predict children's lie-telling. Parents' behaviors predicted their reports of children's lie-telling, suggesting parents' behaviors bias their reports. Parents' biased perception of adolescents lie-telling may have negative implications for parent-child relationships.


Risk of Esophageal Cancer Following Percutaneous Endoscopic Gastrostomy in Head and Neck Cancer Patients: A Nationwide Population-Based Cohort Study in Taiwan.
Esophageal cancers account for majority of synchronous or metachronous head and neck cancers. This study examined the risk of esophageal cancer following percutaneous endoscopic gastrostomy (PEG) in head and neck cancer patients using the Taiwan National Health Insurance Research Database. From 1997 to 2010, we identified and analyzed 1851 PEG patients and 3702 sex-, age-, and index date-matched controls. After adjusting for esophagitis, esophagus stricture, esophageal reflux, and primary sites, the PEG cohort had a higher adjusted hazard ratio (2.31, 95% confidence interval [CI] = 1.09-4.09) of developing esophageal cancer than the controls. Primary tumors in the oropharynx, hypopharynx, and larynx were associated with higher incidence of esophageal cancer. The adjusted hazard ratios were 1.49 (95% CI = 1.01-1.88), 3.99 (95% CI = 2.76-4.98), and 1.98 (95% CI = 1.11-2.76), respectively. Head and neck cancer patients treated with PEG were associated with a higher risk of developing esophageal cancer, which could be fixed by surgically placed tubes.


On- Versus Off-Hours Presentation and Mortality of ST-Segment Elevation Myocardial Infarction Patients Treated With Primary Percutaneous Coronary Intervention.
The authors sought to assess the association between admission time with patient's care, procedure characteristics, and clinical outcomes within a contemporary ST-segment elevation myocardial infarction (STEMI) network of patients referred for primary percutaneous coronary intervention (PCI). The effect of admission time on STEMI patient's outcomes remains controversial when primary PCI is the preferred reperfusion strategy. Characteristics and clinical outcomes of 2,167 consecutive STEMI patients admitted in a tertiary PCI-capable center were collected. On-hours were defined as admission from Monday through Friday between 8 am and 6 pm and off-hours as admission during night shift, weekend, and nonworking holidays. In-hospital and 1-year all-cause mortality were assessed as well as key time delays. A total of 1,048 patients (48.3%) were admitted during on-hours, and 1,119 patients (51.7%) during off-hours. Characteristics were well-balanced between the 2 groups, including rates of cardiac arrest (7.9% vs. 8.8%; p = 0.55) and cardiogenic shock (12.3% vs. 14.7%; p = 0.16). Median symptom-to-first medical contact time and median first medical contact-to-sheath insertion time did not differ according to on- versus off-hours admission (120 min vs. 126 min; p = 0.25 and 90 min vs. 93 min; p = 0.58, respectively), as well as the rate of radial access for catheterization (85.6% vs. 87.5%; p = 0.27). There was no association between on- versus off-hours groups and in-hospital (8.1% vs. 7.0%; p = 0.49) or 1-year mortality (11.0% vs. 11.1%; p = 0.89), respectively. In a contemporary organized STEMI network, patients admitted in a high-volume tertiary primary PCI center during on-hours or off-hours had similar management and 1-year outcomes.


Survival after cytoreductive surgery for peritoneal metastases in colorectal cancer patients: Does a history of resected liver metastases worsen the prognosis?
Nowadays, resection of two (liver and peritoneum) concomitant colorectal cancer metastatic sites is no longer contraindicated. However, the oncologic outcomes of resecting peritoneal metastases (PM) occurring more than six months after resection of liver metastases (LM) are unknown. The aim of this study was to compare patients with complete cytoreductive surgery (CRS) with or without a history of previous liver resection (LR). Analysis from a prospective database of 74 patients with metachronous PM treated with CRS between 2010 and 2020. All patients had PM metachronous to primary, 64 patients underwent CRS alone (CRSa) and 10 CRS more than six months after LR (LR-CRS). There was no statistical difference between the groups for clinical or therapeutic characteristics. There were more signet ring cell/mucinous adenocarcinomas in the CRSa group than in the LR-CRS group (19% vs. 0%, p = 0.049). The median peritoneal cancer index (PCI) was 4 and 6 (p = 0.749) in the LR-CRS and CRSa groups, respectively. Median overall survival (OS) and disease-free survival (DFS) were not statistically different between the two groups with 43.6 and 13 months for the CRSa group and 31.1 months and 9.4 months for LR-CRS. Advanced age was an independent negative prognostic factor for OS and high PCI was limit significant. No prognostic factor for DFS was found. LR before CRS has no major prognostic impact. Resection of iterative liver and peritoneum metastases can achieve long-term survival.


Clinical Aspects of Huntington's Disease.
Huntington's disease (HD) is a devastating inherited neurodegenerative condition characterized by progressive motor, cognitive, and psychiatric symptoms. Symptoms progress over 15-20 years, and there are currently no disease-modifying therapies. The causative genetic mutation is an expanded CAG repeat in the HTT gene encoding the Huntingtin protein, and is inherited in an autosomal dominant manner. In this chapter we discuss the genetics, clinical presentation, and management of this condition, as well as new data from large-scale clinical research studies on the natural history of HD.


Present status and vision for veterinary higher education in the Arab world.
The veterinary profession and veterinary education stand, in the Arab world and worldwide, in the middle of many changes resulting from rapid communication, explosion of large amounts of information, international traffic of people, animals, and animal products, flow of capital, recent political changes, and new threats to global public health. These changes have put more pressure on veterinary leaders and educators to reconsider the different programs, projects, attitudes, and methodologies of thinking in faculties and institutes of veterinary medicine.


Acute toxicity of heavy metals towards freshwater ciliated protists.
The acute toxicity of five heavy metals to four species of freshwater ciliates (Colpidium colpoda, Dexiotricha granulosa, Euplotes aediculatus, and Halteria grandinella) was examined in laboratory tests. After exposing the ciliates to soluble compound of cadmium, copper, chromium, lead, and nickel at several selected concentrations, the mortality rate was registered and the LC50 values (with 95% confidence intervals) were calculated. Large differences appeared in sensitivities of the four species to the metals. H. grandinella showed the highest sensitivity for cadmium (0.07 mg l(-1), LC50) and lead (0.12 mg l(-1), LC50), whilst E. aediculatus showed the highest sensitivity for nickel (0.03 mg l(-1), LC50). The comparison with data obtained with other species indicate that Halteria grandinella and Euplotes aediculatus are excellent and convenient bioindicator for evaluating the toxicity of waters and wastewaters polluted by heavy metals. The short time (24 h) and simplicity of the test procedure enable this test to be used in laboratory studies.


Prognostic factors for patients with small cell lung carcinoma: analysis of a series of 763 patients included in 4 consecutive prospective trials with a minimum follow-up of 5 years.
The purposes of this study were to identify prognostic factors for response to chemotherapy, overall survival, and long term survival of patients with small cell lung carcinoma and to construct a classification of patients on the basis of their expected overall survival. In the 763 patients registered in 4 consecutive clinical trials conducted by the European Lung Cancer Working Party from 1982 to 1993, the impact of 21 pretreatment variables assessable in a routine practice was analyzed for the various outcomes with a minimum follow-up of 5 years. The key prognostic role of disease extent was confirmed for all the outcomes. Additional independent prognostic factors for response to chemotherapy were gender, neutrophil count, and hemoglobin level; for overall survival, these factors were Karnofsky performance status, gender, and neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM) analysis classified patients into 4 groups, taking into consideration disease extent, Karnofsky performance status, age, gender, and neutrophil count. Median survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For long term survival, defined as a minimum survival of 2 years (9% of the patients), Karnofsky performance status was the only independent predictive factor, along with the achievement of a complete response (if this was taken into consideration). Small cell lung carcinoma remained the main cause of death among these patients. Cure was infrequent, with only 14 patients alive and disease free at 5 years (1.8%). In this study the long term prognosis associated with small cell lung carcinoma was poor. The well-known prognostic values of disease extent and Karnofsky performance status were confirmed, but the authors also identified age and gender (which are more controversial) as independent characteristics, in addition to citing the role of complete response in the attainment of long term survival. The independent role of neutrophils observed by the authors. must be validated by further studies.


Diagnosis and treatment of right ventricular dysfunction in patients with COVID-19 on veno-venous extra-corporeal membrane oxygenation.
Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is an effective, but highly resource intensive salvage treatment option in COVID patients with acute respiratory distress syndrome (ARDS). Right ventricular (RV) dysfunction is a known sequelae of COVID-19 induced ARDS, yet there is a paucity of data on the incidence and determinants of RV dysfunction on VV ECMO. We retrospectively examined the determining factors leading to RV failure and means of early identification of this phenomenon in patients on VV ECMO. The data was extracted from March 2020 to March 2021 from the regional University of Washington Extracorporeal Life Support database. The inclusion criteria included patients > 18 years of age with diagnosis of COVID-19. All had already been intubated and mechanically ventilated prior to VV ECMO deployment. Univariate analysis was performed to identify risk factors and surrogate markers for RV dysfunction. In addition, we compared outcomes between those with and without RV dysfunction. Of the 33 patients that met inclusion criteria, 14 (42%) had echocardiographic evidence of RV dysfunction, 3 of whom were placed on right ventricular assist device support. Chronic lung disease was an independent risk factor for RV dysfunction (p = 0.0002). RV dysfunction was associated with a six-fold increase in troponin I (0.07 ng/ml vs. 0.44 ng/ml, p = 0.039) and four-fold increase in brain natriuretic peptide (BNP) (158 pg/ml vs. 662 pg/ml, p = 0.037). Deep vein thrombosis (DVT, 21% vs. 43%, p = 0.005) and pulmonary embolism (PE, 11% vs. 21%, p = 0.045) were found to be nearly twice as common in the RV dysfunction group. Total survival rate to hospital discharge was 39%. Data trended towards shorter duration of hospital stay (47 vs. 65.6 days, p = 0.15), shorter duration of ECMO support (21 days vs. 36 days, p = 0.06) and improved survival rate to hospital discharge (42.1% vs. 35.7%, p = 0.47) for those with intact RV function compared to the RV dysfunction group. RV dysfunction in critically ill patients with COVID-19 pneumonia in common. Trends of troponin I and BNP may be important surrogates for monitoring RV function in patients on VV ECMO. We recommend echocardiographic assessment of the RV on such patients.


[Use of the flow-guided catheter to check the course of congenital heart-disease in children (author's transl)].
Since 1968 a flow-guided-catheter (Pulmocath) was used in 326 examinations of 217 children. This is an excellent method to control the course of congenital heart disease. The findings of children with pulmonary stenosis and with ventricular septal defect are discussed.


Effects of post-ovulatory aging on centromeric cohesin protection in murine MII oocytes.
Post-ovulatory aging causes a high frequency of aneuploidy during meiosis II in mouse oocytes, irrespective of maternal age. In this study, we evaluated the effects of post-ovulatory oocyte aging on the protection of chromosomal cohesion involved in aneuploidy and verified the relationship between PP2A or SGO2 expression and the phosphorylation level of REC8 in oocytes. Murine ovulated oocytes were incubated for 6 or 12 h in vitro after collection and denoted as the aged group. The oocytes examined immediately after collection were used as the control group. Immunofluorescent staining was used to detect the localization of PP2A, SGO2, BUB1, AURORA B, and MAD2 in the chromosomal centromere. Immunoblotting was used to quantify the expression of proteins describe above and REC8 in the oocytes. PP2A expression involved in the de-phosphorylation of REC8 decreased over time in oocytes, suggesting a deficiency in PP2A in centromeres. This indicated an increase in the level of phosphorylated REC8, which destabilizes centromeric cohesion in oocytes. In contrast, SGO2 expression was significantly high in aged oocytes. The findings show that post-ovulatory aging destabilizes the centromeric cohesin protection in oocytes and can cause aneuploidy, which is often observed in aged oocytes during meiosis II.


Optimum wavelet based masking for the contrast enhancement of medical images using enhanced cuckoo search algorithm.
Unsharp masking techniques are a prominent approach in contrast enhancement. Generalized masking formulation has static scale value selection, which limits the gain of contrast. In this paper, we propose an Optimum Wavelet Based Masking (OWBM) using Enhanced Cuckoo Search Algorithm (ECSA) for the contrast improvement of medical images. The ECSA can automatically adjust the ratio of nest rebuilding, using genetic operators such as adaptive crossover and mutation. First, the proposed contrast enhancement approach is validated quantitatively using Brain Web and MIAS database images. Later, the conventional nest rebuilding of cuckoo search optimization is modified using Adaptive Rebuilding of Worst Nests (ARWN). Experimental results are analyzed using various performance matrices, and our OWBM shows improved results as compared with other reported literature.


Behavioral and neurological characteristics of a hydranencephalic infant.
A modified Prechtl neurological examination and the Brazelton Neonatal Assessment Scale were serially administered to a hydranencephalic infant over the first eight weeks of life. Clinical, roentgenographic, neurological and behavioral findings are reported. In contrast to earlier reports, visual tracking of a moving field and auditory and visual habituation were observed. Further, in addition to previously reported reflex automatisms, the infant also possessed what are termed "socially relevant behavioral automatisms". The implications of these findings are discussed.


The polysaccharide fraction of Propionibacterium acnes modulates the development of experimental focal segmental glomerulosclerosis.
The pathogenesis of focal segmental glomerulosclerosis (FSGS) appears to be associated with type-2 cytokines and podocyte dysfunction. In this study, we tested the hypothesis that immunization with the polysaccharide fraction of Propionibacterium acnes (PS), a pro-Th1 agonist, may subvert the type-2 profile and protect podocytes from adriamycin-induced glomerulosclerosis. Adriamycin injection resulted in albuminuria and increased serum creatinine in association with loss of glomerular podocin and podoplanin expression, which is consistent with podocyte dysfunction. Renal tissue analysis revealed the expression of transcripts for GATA3 and fibrogenic-related proteins, such as TGF-β, tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase 9 (MMP9). In association with the expression of fibrogenic transcripts, we observed peri-glomerular expression of α-smooth muscle actin (α-SMA), indicating epithelial-to-mesenchymal transition, and increased expression of proliferating cell nuclear antigen (PCNA) in tubular cells, suggesting intense proliferative activity. Previous immunization with PS inhibited albuminuria and serum creatinine in association with the preservation of podocyte proteins and inhibition of fibrogenic transcripts and the expression of α-SMA and PCNA proteins. Tissue analysis also revealed that PS treatment induced expression of mRNA for GD3 synthase, which is a glycosiltransferase related to the synthesis of GD3, a ganglioside associated with podocyte physiology. In addition, PS treatment inhibited the influx of inflammatory CD8(pos) and CD11b(pos) cells to kidney tissue. Finally, PS treatment on day 4 post-ADM, a period when proteinuria was already established, was able to improve renal function. Thus, we demonstrate that the PS fraction of P. acnes can inhibit FSGS pathogenesis, suggesting that immunomodulation can represent an alternative approach for disease management.


Benefit of a staged in-hospital revascularization strategy in hemodynamically stable patients with ST-segment elevation myocardial infarction and multivessel disease: Analyses by risk stratification.
The proper timing and indication of revascularization for a non-culprit artery in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) without cardiogenic shock remains controversial. This multicenter study included patients with STEMI and MVD without cardiogenic shock. Data were analyzed at 3 years according to the percutaneous coronary intervention (PCI) strategy: immediate multivessel revascularization (MVR) (n = 351), stepwise MVR (n = 510), and culprit-only PCI (n = 1,142). The primary outcome was all-cause mortality. The stepwise MVR group had a lower risk of all-cause death. The results were consistent after multivariate regression, propensity-score matching, inverse probability weighting, and Bayesian proportional hazards modeling. In subgroup analyses stratified by the Global Registry of Acute Coronary Events score, stepwise MVR also lowered the risk of all-cause death compared to culprit-only PCI and immediate MVR in high risk patients but not in patients at low to intermediate risk. In patients with STEMI and MVD without cardiogenic shock, in-hospital stepwise MVR was associated with a lower risk of all-cause death than culprit-only PCI or immediate MVR, particularly in the high-risk subgroup.


Anal sphincter repair for fecal incontinence: effect on symptom severity, quality of life, and anal sphincter squeeze pressures.
The objective of this study was to determine the effect of external anal sphincter repair on fecal incontinence symptoms, quality of life, and anal sphincter squeeze pressures. The fecal incontinence symptoms and impact on quality of life, patient satisfaction, and anorectal manometry were assessed pre- and post-operatively. One hundred four women were eligible and 74/104 (71%) returned post-operative questionnaires. Fifty-four of 74 (73%) had pre- and post-operative questionnaires. Twenty-five of 74 (34%) had pre- and post-operative anorectal manometry measures. Mean length of follow-up for participants (n = 54) was 32 ± 19 months. Modified Manchester Health Questionnaire scores decreased from 47.3 ± 21.9 to 28.4 ± 24.3 (p < 0.01) and Fecal Incontinence Severity Index scores from 30.6 ± 13.0 to 21.6 ± 15.5 (p < 0.01). Seventy-seven percent of the participants was satisfied. Sphincter squeeze pressures increased from 53.4 ± 25.0 to 71.8 ± 29.1 mmHg (p < 0.01). External anal sphincter repair resulted in sustained improvements in fecal incontinence severity and quality of life along with improved anal sphincter squeeze pressures.


Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study).
We investigated the efficacy and safety of fulvestrant plus goserelin (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin (G) alone in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), tamoxifen-pretreated metastatic breast cancer (MBC). In this multicentre, open-label, randomised phase II study, premenopausal women aged ≥18 years with HR+, HER2-, tamoxifen-pretreated MBC were randomly assigned (1:1:1) to F + G, A + G or G alone. The primary end-point was time to progression (TTP). Secondary end-points included overall survival, overall response rate, clinical benefit rate and toxicity. Of 138 eligible patients, 44 were randomly assigned to receive F + G, 47 to A + G and 47 to G alone. The median follow-up duration was 32.2 months (interquartile range: 23.69-40.86) and the median age was 43.0 years (range 23.0-55.0). The median TTP was 16.3 months (95% confidence interval [CI] 7.5-25.1) for F + G, 14.5 months (95% CI 11.0-18.0) for A + G and 13.5 months (95% CI 10.3-16.8) for G alone. Compared with G alone, the hazard ratios were 0.608 for F + G (95% CI, 0.370-0.998; p = 0.049) and 0.982 for A + G (95% CI, 0.624-1.546; p = 0.937). In terms of visceral metastasis, a stratification factor, there were no TTP differences according to treatment arm. Grade III or IV toxicities were rarely observed. Of the common adverse events, grade I arthralgia and joint stiffness were more frequently observed in the F + G than in the A + G or G-alone groups (p < 0.05, respectively). F + G provides a promising new option for the treatment of premenopausal women with HR+, HER2-, tamoxifen-pretreated MBC. ClinicalTrials.gov number NCT01266213 and Korean Cancer Study Group (KCSG) Breast cancer protocol number BR10-04.


Mitochondrial-targeting antioxidant MitoQ modulates angiogenesis and promotes functional recovery after spinal cord injury.
In traumatic spinal cord injury (SCI), secondary injuries, including cellular death, mitochondrial dysfunction, and vascular injury, have been considered as important causes of impaired functional recovery after SCI. Postinjury angiogenesis has been considered to be a potential strategy for SCI treatment. New-born vessels may play a key role in nerve regeneration, which indicates the importance of angiogenesis in nerve regeneration. Recent studies have revealed the crosstalk between reactive oxygen species (ROS) and angiogenesis. As the main source of cellular ROS, mitochondria have been proven to be essential to the angiogenesis process. SCI was established in a T10 clip-compression animal model. Then, the animals received an intraperitoneal injection of MitoQ (5 mg/kg/d) on Days 0, 1, and 2 after surgery. The Basso Mouse Scale (BMS) score and footprint analysis (CatWalk analysis) were performed to evaluate functional recovery after SCI. Immunofluorescence and fluorescence assays (LEL-FITC/CD31/Iba-1/Neurofilament) were performed to evaluate angiogenesis, microglia activation and neural regeneration. RT-qPCR (VEGFR-1, VEGFR-2 and VEGFA) was performed to evaluate angiogenesis-related factor in injured spinal cord. ATP production assay and western-blotting assay (Mfn-1 and Drp-1) were performed to evaluate mitochondrial function in the injured spinal cord. BV2 cells were used as in vitro cell model. After receiving TBHP or TBHP-MitoQ treatment, ELISA and immunofluorescence assays were used to evaluate the level of VEGFA secretion from BV2 cells. A coculture system of HUVECs and BV2 cells was established. Tube formation assays and immunofluorescence assays (CD31) were performed on HUVECs in a coculture system to evaluate angiogenesis promotion. ATP production assays were performed to evaluate mitochondrial function in BV2 cells. MitoSOX Red and DCFH-DA staining were performed to evaluate mitochondrial and cellular ROS. In vitro MitoQ promoted the secretion of VEGFA from BV2 cells, which was verified through ELISA and immunofluorescence assays. The angiogenic promotion of MitoQ-treated BV2 cells was evaluated by tube formation and immunofluorescence assays (CD31) in a coculture system of BV2 cells and HUVECs. MitoQ inhibited cellular and mitochondrial-derived ROS in TBHP-treated BV2 cells. ATP production was increased in MitoQ-treated BV2 cells. To verify MitoQ's effect in vivo, a T10 clip-compression animal model was established successfully. MitoQ significantly promoted functional recovery, as shown by the BMS assay and gait analysis. The promotion of neural regeneration was identified through immunofluorescence assay of neurofilament. Immunofluorescence and fluorescence assays (LEL-FITC/CD31/Iba-1) and RT-qPCR (VEGFR-1, VEGFR-2 and VEGFA) indicated that MitoQ could promote angiogenesis and inhibit macrophage/microglia activation in lesion-site after SCI. Enhanced ATP production and increased Mfn-1 with decreased Drp-1 protein expression showed MitoQ could promote mitochondrial function in SCI. The mitochondrial-specific antioxidant MitoQ promotes functional recovery and tissue preservation through the enhancement of angiogenesis with the modification of mitochondrial function after SCI.


Rhodococcus sp. Q5, a novel agarolytic bacterium isolated from printing and dyeing wastewater.
An agar-degrading bacterium, Rhodococcus sp. Q5, was isolated from printing and dyeing wastewater using a mineral salts agar plate containing agar as the sole carbon source. The bacterium grew from pH 4.0 to 9.0, from 15 to 35°C, and in NaCl concentrations of 0-5 %; optimal values were pH 6.0, 30°C, and 1 % NaCl. Maximal agarase production was observed at pH 6.0 and 30°C. The bacterium did not require NaCl for growth or agarase production. The agarase secreted by Q5 was inducible by agar and was repressed by all simple sugars tested except lactose. Strain Q5 could hydrolyze starch but not cellulose or carboxymethyl cellulose. Agarase activity could also be detected in the medium when lactose or starch was the sole source of carbon and energy. Strain Q5 could grow in nitrogen-free mineral media; an organic nitrogen source was more effective than inorganic carbon sources for growth and agarase production. Addition of more organic nitrogen (peptone) to the medium corresponded with reduced agarase activity.


Toxicity of 8-methoxypsoralen, 5-methoxypsoralen, 3-carbethoxypsoralen, or 5-methylisopsoralen with ultraviolet radiation in the hairless (HRA/Skh) mouse.
An experimental design to simulate PUVA therapy (oral 8-methoxypsoralen followed by uv radiation) has been tested in a 13-week subchronic study to determine the relative toxicities of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 5-methylisopsoralen (5-MIP), and 3-carbethoxypsoralen (3-CEP) in inbred hairless mice (HRA/Skh). Drug was administered by 1-hr pulse feedings three times a week after mice were fasted overnight; individually housed animals were then exposed to uv radiation (320-400 nm; less than 2% output less than 320 nm). 8-MOP or 5-MOP administered orally (at doses of approximately 240 or 480 mg/m2 body surface area per week) followed one-half hour later with uv radiation of 2 J/cm2 for 13 weeks were found to cause skin toxicity including inflammation, hyperplasia, ulceration, and cellular atypia. Dose-related toxicity was not seen in other organ systems. Corresponding levels of 5-MIP or 3-CEP with uv radiation did not produce skin toxicity. These studies show that the psoralens with two potential DNA-binding sites (8-MOP and 5-MOP) were more toxic than psoralens with only one photoreactive site (5-MIP and 3-CEP).


Hip fractures and Parkinson's disease: A case series.
There are no specific guidelines for treating Parkinson's disease patients who present with a hip fracture. Here we present a large cohort of patients with Parkinson's disease who suffered hip fractures. Our aim was to assess for differences between a Parkinson's disease population and a non-Parkinson's disease population with hip fractures and make recommendations on management guidelines. We performed a comprehensive analysis of prospectively collected data on all patients with hip fracture who were admitted into our department over a period of 29 years. In total 9225 patients with hip fractures were included in this study, 452 (4.9%) patients had Parkinson's disease. The mobility scores were worse pre- and post-operatively in the Parkinson's group as were mini-mental scores and ASA grade. Post-operative complications were similar between the two groups, with no difference in dislocation rate or wound complications. However, other outcomes including mobility and mortality rate at 1year were worse in the Parkinson's group. These patients also had a longer hospital stay and were more likely to be immobile and discharged to an institution. We recommend that Parkinson's disease patients should be assessed more thoroughly in the peri-operative period and arrangement for rehab and discharge planning should commence as soon as possible following admission. The consent process should reflect longer hospital stays, worse mobility, higher mortality and increased likelihood of discharge to institution but concern over increased complications, specifically dislocation was not evident in our data.


Induction of lymphokine-activated killer cells from nude mouse spleen cells by interleukin-4.
The induction of lymphokine-activated killer (LAK) cells from natural killer (NK) lineage cells by interleukin-4 (IL-4) was studied in vitro. Activation of nude mouse spleen cells by IL-4 generated cytotoxic cells, capable of killing NK-sensitive as well as NK-resistant tumor cells. The induction of peak lytic activity was demonstrated after 3 days of culture with IL-4. Surface marker analysis indicated that the majority of precursor cells were aGM1+, Thy1-, and the majority of effector cells were aGM1+, Thy1+, suggesting that IL-4 induced LAK cells from nude mouse spleen cells were similar to those from normal mouse spleen cells. The induction of nude mouse LAK cells by IL-4 was partially inhibited by anti-IL-4 or anti-interferon (IFN)-alpha,beta antibody, and it was further inhibited by the combination of two antibodies, suggesting that IFN-alpha,beta production was associated with LAK induction of NK lineage cells by IL-4.


Mycobacterium bovis BCG killed by extended freeze-drying induces an immunoregulatory profile and protects against atherosclerosis.
Atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. Regulatory T cells (Tregs) and IL-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. We have previously shown that Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) decreases lung and colon inflammation by recruiting IL-10-producing Tregs. Therefore, the aim of this study was to investigate the effect of EFD BCG on the development of atherosclerosis. We used two strains of atherosclerosis-prone mice: Ldlr(-/-) (four or six EFD BCG injections) and Apoe(-/-) (six injections). In both models, EFD BCG significantly reduced the size of atherosclerotic lesions, increased IL-10 production and reduced the serum levels of pro-inflammatory cytokines (IL-6, IL-13, KC and tumour necrosis factor-α). Shortly after treatment with EFD BCG, the number of plasmacytoid dendritic cells (pDCs) and Foxp3(+) Tregs in the draining lymph nodes increased. EFD BCG also led to accumulation of Tregs, but not of pDCs in the spleen, and reduced activity of NF-κB and increased activity of PPAR-γ in both the spleen and vascular tissue of treated mice. EFD BCG has atheroprotective effects through IL-10 production and Treg expansion. These findings support a novel approach to the prevention and treatment of atherosclerosis.


Standardized pelvic floor exercises improve stress urinary incontinence in women with intrinsic sphincter deficiency.
Pelvic floor rehabilitation is the conservative therapy of choice for women with stress urinary incontinence (SUI). The success rate of surgical procedures in SUI patients with intrinsic sphincter deficiency (ISD) is low. The aim of this study was to analyse the effect of a standardized physiotherapy on patients with SUI and normotonic urethra and ISD. In this study, 64 patients with ISD and 69 patients with normotonic urethra were enrolled. Maximum urethral pressure (MUCP) >20 cm H2 O was considered as normotonic urethral pressure. Before and after physiotherapy MUCP was measured and cough testing was performed. Additionally, patient reported outcome was assessed using the King's Health Questionnaire (KHQ). For statistical analyses Excel 2010 (Microsoft Inc; Redmond, Washington) and SPSS 20 (SPSS Inc; Chicago, Illinois) for Windows were used. Power calculation was based on the primary endpoint incontinence impact and general health. For power calculation, GraphPad Statmate version 2.00 for Windows was used. Sixty-four patients with ISD and 69 patients with normotonic urethra were included in the study. In SUI patients with normotonic and hypotonic urethra KHQ-scores regarding the primary endpoins "general health" and "incontinence impact" significantly improved following standardized physiotherapy. In both groups MUCP increased after physiotherapy. In SUI patients with ISD standardized physiotherapy resulted in a decreased incidence of a positive cough test. Standardized physiotherapy should be offered to patients with SUI and ISD. Long-term results are subject to future studies. Neurourol. Urodynam. 35:711-716, 2016. © 2015 Wiley Periodicals, Inc.


Village chicken production in Turkey: Tokat province example.
The aim of this work was to reveal the current form of village chicken production in Tokat province of Turkey. A survey was applied to 153 randomly selected farmers of 5 subdistricts in Tokat province. The ratios of domestic fowls in the survey region were as follows: hen 98.83%, goose 0.65%, turkey 0.29% and duck 0.16% (P < 0.01). Feather colours of laying hens were white (2.76%), brown (8.63%) and mixed color (88.60%). The hen farms in this region consisted of native breeds (91.42%), commercial breeds (5.71%) and their crosses (2.85%). The mean egg weight of the village hens was between 30 and 40 g. Wheat (65.73%) and mixed (wheat, barley, maize and kitchen refuse) feed (34.22%) were used to supplement the hens (P < 0.01). For producing natural chicks, the hens were brooded between 1.10 and 1.46 times/year, 1.31 on average. For each brooding, the number of placed eggs under the broody hens was between 11.39 and 12.42 (P < 0.05).


Cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome in the setting of opioid and phencyclidine use.
Cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome is a constellation of specific imaging findings characterized by cytotoxic edema in the bilateral hippocampi, cerebellar cortices, and basal ganglia in patients presenting with altered mental status in the setting of substance intoxication. Previous case reports have demonstrated a strong correlation between CHANTER syndrome and polysubstance abuse, particularly with opioid intoxication. The patient we present in this case was found unresponsive following opioid use and demonstrated a constellation of findings on initial and follow-up imaging, consistent with CHANTER syndrome. While cases of irreversible brain damage or death during hospitalization have been reported in the literature, our patient demonstrated near-full recovery a few days after admission to the hospital. We aim to highlight the presentation and progression of CHANTER syndrome and alert clinicians and radiologists to include this entity in their diagnostic checklist for patients with polysubstance abuse and altered mental status.


Ga3+ inhibits parathyroid hormone release without interacting with the Ca2+ receptor of the parathyroid cell.
Gallium nitrate is an antihypercalcemic agent with established actions on bone. The effects of Ga(NO3)3 on parathyroid hormone (PTH) release, cytoplasmic Ca2+ concentration ([Ca2+]i) and cAMP production of enzymatically dispersed parathyroid cells from bovine as well as normal and pathological human parathyroid glands have now been studied. Ga3+ at 200 microM inhibited PTH release whereas 600 microM NO3- had no effect. The inhibition was additive to that obtained by elevating extracellular Ca2+. Unlike Ca2+, Ga3+ failed to increase [Ca2+]i or reduce cAMP formation. The results indicate that Ga3+ inhibits PTH release by a mechanism other than activation of the cation receptor of the parathyroid cells. This mechanism may contribute also to inhibition by other cations.


Development and Validation of Tawakkul Scale for Muslim Adults in Pakistan.
As a fundamental value in the Islamic belief system, tawakkul is defined as the belief in the sufficiency of God that involves positive efforts to achieve one's goals while accepting the outcomes unconditionally. The present research intended to develop a psychometrically sound measure of tawakkul and it comprised two studies. In study I, an initial item pool of 60 items was developed based on the content analyses of Quranic verses with the root word 'w-k-l' and the findings of two focus group discussions with psychologists, Islamic scholars, and common Muslim adults. This item pool was reviewed by a committee of experts resulting in a 40-item initial draft of the Tawakkul Scale, which was administered on a purposive sample of (N = 300) Pakistani Muslim adults. The findings of the exploratory factor analysis revealed a four-factor structure (loadings ranged from .56 to .96) of the Tawakkul Scale that cumulatively explained 76.67% variance. The factors included belief in the sufficiency of God (11 items), unconditional acceptance of God's will (6 items), efforts (4 items), and annihilation of one's own will (3 items). All factors were moderately related to each other with good values of Cronbach's alpha (α ≥ .83). Study II replicated the factorial structure of the Tawakkul Scale through confirmatory factor analysis and established its construct validity in an independent sample of (N = 350) Pakistani Muslim adults. Tawakkul had a positive relationship with secure attachment to God and a negative relationship with insecure attachment to God that affirmed its construct validity. Overall, the findings indicated that the Tawakkul Scale is a psychometrically sound measure that needs to be further studied in Muslim populations across the globe.


Transmission Dynamics of Rhodesian Sleeping Sickness at the Interface of Wildlife and Livestock Areas.
Many wilderness areas of East and Southern Africa are foci for Rhodesian sleeping sickness, a fatal zoonotic disease caused by trypanosomes transmitted by tsetse flies. Although transmission in these foci is traditionally driven by wildlife reservoirs, rising human and livestock populations may increase the role of livestock in transmission cycles. Deciphering transmission dynamics at wildlife and livestock interface areas is key to developing appropriate control. Data are lacking for key parameters, including host distributions, tsetse density, and mortality rates, and the relative roles of livestock and wildlife as hosts in fragmented habitats, limiting the development of meaningful models to assist in the assessment and implementation of control strategies.


Emotional adjustment to cardiac transplantation.
Emotional adjustment to cardiac transplantation is a phasic process. Each step is associated with a milestone in the transplantation protocol. The adjustment process is divided into seven distinct stages: 1) transplant proposal, 2) evaluation, 3) awaiting a donor organ, 4) perioperative period, 5) inhospital convalescence, 6) discharge, and 7) post-discharge adaptation. Patient adjustment to transplantation is influenced by the adaptive task of each stage in the procedure, personality factors, previous experience with illness, and social support. Patients need time to adjust to each stage. Do not pressure them into premature acceptance of transplantation. Verbalization of feelings should be encouraged, and adequate support ensured. Contact with already transplanted patients is helpful to surgical candidates. Psychiatric assistance can greatly aid in patient management and emotional adjustment.


Differential effects of anti-allergic compounds on peritoneal mast cells of the rat, mouse and hamster.
The effects of various inhibitors and anti-allergic drugs on histamine secretion from peritoneal mast cells of the rat, mouse and hamster have been compared. Phosphodiesterase inhibitors, cAMP analogues and beta-adrenoceptor agonists variously blocked release of the amine from all three cell types. The mouse cells were rather less sensitive to the former agents than those of the rat and hamster. Disodium cromoglycate inhibited histamine secretion from rat peritoneal mast cells, was less active against the hamster cells and completely ineffective against those of the mouse. Other chromones showed varied patterns of differential reactivity but phloretin and the flavonoid quercetin were essentially equiactive against all three cell types. The tetrazoles AH 9679 and doxantrazole prevented histamine release in each case but were significantly less active against the mouse cells. These results further emphasize the functional heterogeneity of mast cells from different sources.


Spruce budworm elastase precipitates Bacillus thuringiensis delta-endotoxin by specifically recognizing the C-terminal region.
A gut juice protein from Choristoneura fumiferana (spruce budworm) larvae that precipitates certain delta-endotoxins shows a unique specificity for the C-terminal amino acid sequence. Using homolog scanning mutants, we have identified a contiguous region of the Cry1Aa toxin which interacts with the 75-kDa toxin precipitating protein (TPP-75)' resulting in precipitation. The contiguous region from Cry1Aa can be transferred to Cry1Ac and results in an identical precipitation reaction. The precipitation reaction occurs rapidly and is unique in that the ratio of precipitating protein to toxin is low (estimated at 0.01), unlike antibody-antigen reactions which exhibit mole ratios close to 1. TPP-75 has been characterized as an elastase-like serine protease. We have taken advantage of this serine protease character and incorporated a radiolabel using an irreversible inhibitor. The radiolabel has allowed us to show the coincidence of the catalytically-inhibited TPP-75 with the toxin in a blotting assay and to follow the degradation of TPP-75 during storage. TPP-75 represents the first evidence that gut juice proteins may selectively attenuate the activity of delta-endotoxins, prior to binding to putative receptors on susceptible cells. TPP-75 should be evaluated as a possible resistance mechanism for those larvae that do not exhibit a receptor-based resistance.


Sister chromatid exchanges induced by cyclophosphamide in V79 cells cultured in diffusion chambers in mice.
Chinese hamster cells V79 were cultured in diffusion chambers (DC) and implanted into mice. An exponential growth was observed from the 2nd to 4th day after implantation. The maximum growth was reached on the 6th day. After that, cell growth and viable cell counts decreased. Three days after implantation of DC with V79 cells, the hosts received 6 hourly injections of 0.2 ml of 5-bromodeoxyuridine (BUdR) solution at concentrations of 0.125 to 1.0 x 10(-2) M. DC were removed for chromosome and sister-chromatid exchanges (SCE) analyses 24 h after the first BUdR injection. The frequency of metaphases with differentially stained chromatids, with aberrations, and the number of SCE per cell increased with BUdR dose. The frequency of metaphases with differentially stained chromatids was also positively correlated with the duration of BUdR exposure or the number of hourly injections of BUdR-solution. The effects of cyclophosphamide (CY) in V79 cells in DC in mice were studied. Injections of CY at 2.5, 5, 10 and 15 microgram per gram of body weight to the hosts caused an increase in the number of SCE per cell in a linear manner. The results from this study indicate that V79 cells cultured in DC in mice may provide a potential test system for mutagenicity.


Comparative study of two arginine ester hydrolases, E-I and E-II from the venom of Crotalus ruber ruber (red rattlesnake).
1. Two arginine ester hydrolases, E-I and E-II from the venom of Crotalus ruber ruber were isolated and characterized. 2. E-I and E-II have molecular weights of 32,000 and 33,000, and isoelectric points of 5.2 and 4.6, respectively. 3. E-I and E-II are active upon the glandular kallikrein substrate, but neither enzyme was shown to have plasma kallikrein substrate hydrolytic activity. 4. E-I has minimal fibrinogen-clotting activity. It was found to induce clotting by catalyzing the hydrolysis of only the A fibrinopeptide from the A alpha-chain of fibrinogen.


Molecular mechanism of the smart attack of pathogenic bacteria on nematodes.
Nematode-bacterial associations are far-reaching subjects in view of their impact on ecosystems, economies, agriculture and human health. There is still no conclusion regarding which pathogenic bacteria sense nematodes. Here, we found that the pathogenic bacterium Bacillus nematocida B16 was sensitive to C. elegans and could launch smart attacks to kill the nematodes. Further analysis revealed that the spores of B. nematocida B16 are essential virulence factors. Once gaseous molecules (morpholine) produced from C. elegans were sensed, the sporulation of B16 was greatly accelerated. Then, B16 showed maximum attraction to C. elegans during the spore-forming process but had no attraction until all the spores were formed. The disruption of either the spore formation gene spo0A or the germination gene gerD impaired colonization and attenuated infection in B16. In contrast, complementation with the intact genes restored most of the above-mentioned deficient phenotypes, which indicated that the spo0A gene was a key factor in the smart attack of B16 on C. elegans. Further, transcriptome, molecular simulations and quantitative PCR analysis showed that morpholine from C. elegans could promote sporulation and initiate infection by increasing the transcription of the spo0A gene by decreasing the transcription of the rapA and spo0E genes. The overexpression of rapA or spo0E decreased the induced sporulation effect, and morpholine directly reduced the level of phosphorylation of purified recombinant RapA and Spo0E compared to that of Spo0A. Collectively, these findings further support a 'Trojan horse-like' infection model. The significance of our paper is that we showed that the soil-dwelling bacterium B. nematocida B16 has the ability to actively detect, attract and attack their host C. elegans. These studies are the first report on the behaviours, signalling molecules and mechanism of the smart attack of B16 on nematodes and also reveal new insights into microbe-host interactions.


Effects of changing health care financial policy on very low birthweight neonatal outcomes.
Our objective was to determine whether perinatal referral patterns and clinical outcomes for very low birthweight infants changed in relation to changing Medicaid financial policies in coastal South Carolina. Referral patterns and outcome indicators for very low birthweight infants were compared during two periods in a cohort design. A total of 520 infants were identified over two funding periods. A decrease in the proportion of nonwhite very low birthweight infants was identified. There was an increase in very low birthweight infants with Medicaid funding born outside our level III center. Changes in financial public policy have been successful in the movement of low risk pregnancies into the private sector. However, an increased proportion of deliveries of very low birthweight infants occurred outside the level III center.


Contact with the N termini in the central E domain enhances the reactivities of the distal D domains of fibrin to factor XIIIa.
The reaction of Factor XIIIa with fibrin is the last enzyme-catalyzed step on the coagulation cascade, leading to the formation of a normal blood clot. The finding that fibrin is preferred by the cross-linking enzyme about 10-fold over the circulating fibrinogen suggests the operation of a unique substrate-level control for the orderly functioning of the physiological process in the forward direction. An important task is to elucidate the molecular mechanism for the transmission of the signal generated by the thrombin-catalyzed cleavage in the central E domain of fibrin to the distant Factor XIIIa-reactive glutamine residues. By focusing on the substrate sites present in gamma chain remnants of D type domains of fibrinogen and by employing the approach of fragment complementation with the regulatory E domain, which represents the thrombin-modified portion of fibrin, we have now succeeded in reconstructing in solution the phenomenon of kinetic enhancement for the reaction with Factor XIIIa. Two D type preparations (truncated fibrinogen, approximately 250 kDa and D', approximately 105 kDa) were obtained by digestion of human fibrinogen with endo Lys-C. Neither product could be cross-linked by Factor XIIIa, but as shown by the incorporation of dansylcadaverine, both were acceptor substrates for the enzyme. The plasmin-derived D (approximately 105-kDa) product, however, could be cross-linked into DD dimers. In all cases, the admixture of E fragments exerted a remarkable boosting effect on the reactions with Factor XIIIa. Even with native fibrinogen as substrate, cross-linking of gamma chains was enhanced in the presence of E. Nondenaturing electrophoresis was used to demonstrate the complex forming potential of E fragments with fibrinogen, truncated fibrinogen, D', or D. The GPRP tetrapeptide mimic of the GPRV N-terminal sequence of the alpha chains in the E fragments, abolished both complex formation and the kinetic boosting effect of E on the reactions of substrates with Factor XIIIa. Thus, the N-terminal alpha chain sequences seem to act as organizing templates for spatially orienting the D domains, probably during the protofibrillar assembly of the fibrin units, for favorable reaction with Factor XIIIa.


Human optokinetic afternystagmus. Is the fast component of OKAN decay due to smooth pursuit?
Eye movement after-effects subsequent to pursuit of a single LED target were studied in human subjects to test the hypothesis that constant velocity pursuit activates a velocity storage system in the neuronal pathway. The temporal characteristics of observed after-effects fall within those predicted from the Robinson model of eyeball mechanics, indicating that neuronal integration was not a factor.


Pharmacological and therapeutic potentials of cordycepin in hematological malignancies.
Hematological malignancies(HMs) are highly heterogeneous diseases with globally rising incidence. Despite major improvements in the management of HMs, conventional therapies have limited efficacy, and relapses with high mortality rates are still frequent. Cordycepin, a nucleoside analog extracted from Cordyceps species, represents a wide range of therapeutic effects, including anti-inflammatory, anti-tumor, and anti-metastatic activities. Cordycepin induces apoptosis in different subtypes of HMs by triggering adenosine receptors, death receptors, and several vital signaling pathways such as MAPK, ERK, PI3K, AKT, and GSK-3β/β-catenin. This review article summarizes the impact of utilizing cordycepin on HMs, and highlights its potential as a promising avenue for future cancer research based on evidence from in vitro and in vivo studies, as well as clinical trials.


Protecting effect of vitamin E supplementation on submaximal exercise-induced oxidative stress in sedentary dogs as assessed by erythrocyte membrane fluidity and paraoxonase-1 activity.
The aim of this placebo-controlled study was to investigate the effects of oral vitamin E supplementation for 10 weeks on exercise-induced oxidative damage in untrained dogs. Eight dogs were randomly assigned to a supplementation (n=4) or control (n=4) group and underwent two isolated submaximal exercise sessions, 10 weeks apart. Blood was collected during each session to measure erythrocyte membrane fluidity (EMF), paraoxonase-1 (PON1) activity, plasma malondialdehyde (MDA) and vitamin E concentrations. These biomarkers were measured in venous blood samples collected before (t(0)), just after (t, EMF only) and 1d (t+1d) and 7d (t+7d) after the dogs ran on a treadmill. Prior to vitamin E supplementation, exercise induced a significant decrease in PON1 activity, EMF, vitamin E concentration and a significant increase in MDA concentration at t+1d. After a 10 week vitamin E supplementation period, these exercise-induced changes in PON1 activity, EMF and MDA concentration were still significant in the control group, but not in the supplemented group. These results suggested that vitamin E supplementation had a protective effect on submaximal exercise-induced oxidative damage in sedentary dogs.


Tumor-mediated immunosuppression: prevention by inhibitors of prostaglandin synthesis.
The addition of MC16 tumor cells (a prostaglandin E2-producing cell line induced in C57BL/6J mice by methylcholanthrene) to cultures of cells to sheep red blood cells. This inhibition can be blocked by adding to the cultures prostaglandin synthetase inhibitors, such as indomethacin, flufenamic acid and aspirin. These MC16 tumor cells are also immunosuppressive in vivo. Mice bearing the syngeneic MC16 tumor become unresponsive to sheep red blood cells as the tumor grows. As in the in vitro test system, inhibitors of prostaglandin synthetases seem to block the immunosuppressive activity of MC16 cells in vivo since tumor-bearing mice, treated therapeutically with indomethacin, responded normally in their production of antibody to sheep red blood cells.


Phyllodes Tumor of the Breast in Pregnancy and Lactation.
Phyllodes tumor constitutes around 1% of all and 2.5% of fibroepithelial breast lumps. Three types including benign, borderline, and malignant tumors have been described. The benign variant is the most common, is close to fibroadenoma, but is usually larger and recurs more frequently. The rare malignant type is aggressive. Standard treatment consists of lumpectomy with appropriate margins for benign phyllodes tumor, while the borderline and malignant variants must be treated by wide resection or mastectomy. Phyllodes tumor is a rare tumor in pregnancy and lactation, and the effect of gestational alterations in hormone levels on this tumor have not been discussed in the literature, except for several case reports. In summary and alluding to our recent literature review, large size, fast growth, bilaterality, and probably malignancy are more commonly expected in gestational phyllodes tumors.


High-performance liquid chromatographic determination of indoleamines, dopamine, and norepinephrine in rat brain with fluorometric detection.
A high-performance liquid chromatography-fluorescence procedure for the determination of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tryptophan, dopamine, and norepinephrine has been developed. The method uses an ion-pairing system on an Ultrasphere ODS (5-microns) column with detector wavelength settings of excitation at 290 nm and emission at 330 nm. The procedure has been used to quantitate these indoleamines and catecholamines in rat brain tissue after homogenization in a perchloric acid solution; an aliquot of this solution is injected directly onto the HPLC column. Column sensitivities range from 6.1 pmol for tryptophan to 1.1 pmol for 5-hydroxytryptamine.


Ultrasound examination of peripheral nerves in the forearm.
We examined in a volunteer population whether nerves in the forearm could be seen consistently using ultrasound imaging and whether this new information could have implications for the way we perform regional anesthesia of the median, radial, and ulnar nerves. Eleven volunteers underwent ultrasound examination of both forearms. The median, ulnar, and radial nerves were followed and images were obtained at the elbow, proximal forearm, mid forearm, distal forearm and wrist levels. In addition the radial nerve was followed proximally to a point 5 cm above the elbow. Images were compared for consistency of location of the nerves and depth from skin and width was calculated for each nerve at each level. Anatomy of each nerve was consistent except for one forearm where the median nerve was lateral to the brachial artery at the elbow and one forearm where a superficial ulnar artery only joined the ulnar nerve at the wrist. A convenient location for blockade of both median and ulnar nerves is the midforearm combining ease of visualization, ability to block all terminal branches and minimal potential for vascular injury. The radial nerve is seen most easily at the elbow although blockade of the superficial radial nerve may spare radial motor function. Nerves in the forearm are consistently located using ultrasound. Further confirmation in clinical practice is required.


Enhancement of xylitol production in Candida tropicalis by co-expression of two genes involved in pentose phosphate pathway.
The yeast Candida tropicalis produces xylitol, a natural, low-calorie sweetener whose metabolism does not require insulin, by catalytic activity of NADPH-dependent xylose reductase. The oxidative pentose phosphate pathway (PPP) is a major basis for NADPH biosynthesis in C. tropicalis. In order to increase xylitol production rate, xylitol dehydrogenase gene (XYL2)disrupted C. tropicalis strain BSXDH-3 was engineered to co-express zwf and gnd genes which, respectively encodes glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6-PGDH), under the control of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter. NADPH-dependent xylitol production was higher in the engineered strain, termed "PP", than in BSXDH-3. In fermentation experiments using glycerol as a co-substrate with xylose, strain PP showed volumetric xylitol productivity of 1.25 g l(-1) h(-1), 21% higher than the rate (1.04 g l(-1) h(-1)) in BSXDH-3. This is the first report of increased metabolic flux toward PPP in C. tropicalis for NADPH regeneration and enhanced xylitol production.


[Current practice of empiric antibiotic treatment for spondylodiscitis].
In pyogenic spondylodiscitis, infections with coagulase-negative staphylococci must be given increasing importance. Empirical antibiosis is particularly necessary in patients with severe or progressive neurological deficits or hemodynamic instability, as well as in the case of culture-negative spondylodiscitis. It is unclear whether uniform empirical antibiosis standards adapted to the resistance profiles exist in Germany. A survey on the empirical antibiotic therapy for pyogenic spondylodiscitis was conducted at German university and Berufsgenossenschaft clinics, each in the departments of orthopedics and trauma surgery. The survey results were applied to the resistance profiles of pathogens in 45 spondylodiscitis patients treated in our department between 2013 and 2020. Thus, the potential susceptibility and resistance rates were calculated for the indicated antibiotic therapies. Of the 71 clinics queried, a total of 44 (62.0%) responded. Sixteen different antibiotic therapies were reported as standard regimes. Among these, 14 different combination therapies were reported. The most commonly reported empirical antibiotics, namely amoxicillin/clavulanic acid or ampicillin/sulbactam (29.5%) and cephalosporins (18.2%) showed high potential resistance rates of 20.0% and 35.6%, respectively, in relation to the previously published resistance profile. The highest potential susceptibility rates were achieved with a combination of vancomycin + ampicillin/sulbactam (91.1% sensitive pathogens), vancomycin + piperacillin/tazobactam (91.1% sensitive pathogens), and ampicillin/sulbactam + teicoplanin (95.6% sensitive pathogens). One out of these combinations was reported as standard regime by three clinics (6.8%). The nationwide survey of empiric antibiotic treatment for pyogenic spondylodiscitis revealed a large heterogeneity in the standard of care. A combination of a broad-spectrum-β-lactam antibiotic with an additional glycopeptide antibiotic may be justified.


Surgical Outcomes of Synchronous Multiple Primary Non-Small Cell Lung Cancers.
The prognostic indicators for synchronous multiple primary non-small cell lung cancer (NSCLC) vary across reports. In present study, the prognostic factors for the patients with synchronous multiple primary NSCLC were analyzed in a large cohort. A total of 285 patients with synchronous multiple primary NSCLC who underwent radical surgical resection and with complete follow-up information were included in this study. The Kaplan-Meier method were used for survival analysis, Cox proportional hazards regression models were used for risk factors evaluation. Among them, 94 (33.0%) patients had bilateral tumors and 51 (17.9%) had multiple (≥3) tumors. The 5-year disease-free survival (DFS) and overall survival (OS) rate was 58.7% and 77.6%, respectively. Univariate analysis identified parameters conferring shorter OS including male gender, symptomatic disease, negative family history, large maximal tumor size, not all adenocarcinomas, advanced highest T stage, and lymph node involvement. Multivariate analysis showed that male gender (p = 0.020), symptomatic disease (p = 0.017), and lymph node involvement (p < 0.001) were independent adverse prognosticators. For patients with multiple adenocarcinomas, the 5-year DFS and OS rate was 59.6% and 82.4%, respectively. The subtypes other than lepidic predominant (p < 0.001) and lymph node involvement (p = 0.002) were the independent unfavorable prognosticators. In conclusion, we identified independent prognosticators which will provide the valuable clues for postoperative management of patients with synchronous multiple primary NSCLC.


The future of UK/Irish surgery: A European solution.
The United Kingdom (UK) and Republic of Ireland (ROI) hospital systems are dependent on junior doctors for their functionality however it is increasingly difficult to recruit UK/ROI trained doctors to fill these posts. Directive 2005/36/EC, which came into force in 2007, is the principal European legislation on the recognition of equivalence of professional qualifications across Europe. European trained doctors are therefore attractive candidates for junior doctor posts. However, although their training is recognised as equivalent by the Irish Medical Council (IMC) and General Medical Council (GMC) they are not being appointed to equivalent posts by the Health Service Executive (HSE) or National Health Service (NHS). With the influence of European Union (EU) centralisation, modification of UK/ROI consultant grade is imminent, possibly to pyramidal structure of the Continental European model with clearer lines of corporate responsibility.


Enantiospecific deoxyfluorination of cyclic α-OH-β-ketoesters.
We herein report the deoxyfluorination of cyclic α-hydroxy-β-ketoesters using diethylaminosulfur trifluoride (DAST). The reaction proceeds with excellent levels of stereospecificity, giving the configurationally inverted α-fluoro-β-ketoesters in high yields under operationally simple conditions.


Development of the Gambling Disorder Identification Test: Results from an international Delphi and consensus process.
Diverse instruments are used to measure problem gambling and Gambling Disorder intervention outcomes. The 2004 Banff consensus agreement proposed necessary features for reporting gambling treatment efficacy. To address the challenge of including these features in a single instrument, a process was initiated to develop the Gambling Disorder Identification Test (GDIT), as an instrument analogous to the Alcohol Use Disorders Identification Test and the Drug Use Disorders Identification Test. Gambling experts from 10 countries participated in an international two-round Delphi (n = 61; n = 30), rating 30 items proposed for inclusion in the GDIT. Gambling researchers and clinicians from several countries participated in three consensus meetings (n = 10; n = 4; n = 3). User feedback was obtained from individuals with experience of problem gambling (n = 12) and from treatment-seekers with Gambling Disorder (n = 8). Ten items fulfilled Delphi consensus criteria for inclusion in the GDIT (M ≥ 7 on a scale of 1-9 in the second round). Item-related issues were addressed, and four more items were added to conform to the Banff agreement recommendations, yielding a final draft version of the GDIT with 14 items in three domains: gambling behavior, gambling symptoms and negative consequences. This study established preliminary construct and face validity for the GDIT.


Emergency Medical Technicians' Experiences of the Challenges of Prehospital Care Delivery During the COVID-19 Pandemic: A Qualitative Study.
Exploring emergency medical technicians' (EMTs) experiences of COVID-19 epidemic, help to identify the challenges they face in their daily work and develop strategies that address these challenges. This study aimed to explore EMTs' experiences of the challenges of prehospital care delivery during the COVID-19 pandemic. This qualitative study was conducted in March-July 2020 using conventional content analysis approach. Fifteen EMTs were purposively selected from the Emergency Medical Services (EMS) Center in Qom, Iran. For data collection, semi-structured interviews were conducted until data saturation was reached. EMTs' experiences of the challenges of prehospital care delivery during the COVID-19 pandemic were classified into three main categories including "restless society", "difficult care delivery conditions", and "unprepared organization". The emergent subcategories were "need for information", "limited perception of the COVID-19 risk", "obsessive use of disinfectants", "fear over the transmission of COVID-19 to self and others", "burnout due to heavy workload", "altered communication with hospital staff", "ethical conflicts", "lack of a definite treatment plan", "lack of protective equipment", "staff shortage due to the affliction of EMTs by COVID-19", and "inadequate support by authorities". During COVID-19 pandemics, EMTs face many challenges including emotional and occupational stress, social strains, risk of affliction by infections, heavy workload, and ethical conflicts and hence, experience difficulties in quality care delivery. Developing appropriate strategies, guidelines, and policies are needed to effectively manage these challenges and improve the quality of prehospital care delivery in COVID-19 epidemic.


Effect of Timing of Second-Stage Pushing on Pelvic Floor Morbidity After Birth.
The author describes a recent trial on the effect of the timing of pushing during the second stage of labor on postpartum pelvic floor morbidity.


Effects of acoustic insonation parameters on ultrasound contrast agent destruction.
Ultrasound contrast agents (UCAs) are used to enhance the acoustic backscattered intensity of blood and thereby assist the assessment of blood perfusion. Characterization of UCA destruction provides important information for the design of contrast-assisted perfusion imaging. High-speed optical observation of single microbubble destruction during acoustic insonation has been performed in previous studies. The results identified that pressure, center frequency and transmission phase have significant effects on the fragmentation threshold. We proposed an acoustic-based experiment method to demonstrate the relationship between different acoustic exposure conditions and the degree of UCA destruction. The method also provides a simple and convenient way to determine the microbubble destruction threshold. The experiments introduced three insonation parameters, including acoustic pressure (0 to 1 MPa), pulse frequency (1, 2.25, 5 and 7.5 MHz) and pulse length (1 to 10 cycles). The term of surviving percentage (SP) was proposed to represent the ratio of UCA backscattered power with and without acoustic insonation. The results showed that the SP decreased with decreasing pulse frequency, but with increasing transmission acoustic pressure and pulse length. In addition, there was an exponential relationship between SP and acoustic pressure, and thus the UCA destruction pressure threshold could be predicted from the fitted exponential curve. The results also show that the degree of UCA destruction was not related to mechanical index (MI). Potential applications of this method include UCA high-resolution destruction/replenishment imaging model, microbubble cavitation, sonoporation in drug delivery and gene therapy.


Insulin-stimulated mitochondrial adenosine triphosphate synthesis is blunted in skeletal muscles of high-fat-fed rats.
Physiologic elevation of insulin levels induces a significant increase in muscle adenosine triphosphate (ATP) synthesis rate in normal individuals, indicative of an appropriate acceleration in mitochondrial activity. However, the stimulatory effect of insulin is diminished in insulin-resistant patients. In the absence of similar data from preclinical models, the present study investigated the inhibitory effects of increased dietary fat intake on insulin-stimulated ATP synthesis rates in rats. After being placed on a high-fat diet for 8 weeks (n = 10), diet-induced obese male Sprague-Dawley rats were tested against age-matched control rats (n = 9) on a normal chow diet. Muscle ATP synthase flux rates were measured under anesthesia by in vivo (31)P saturation transfer both before and during a euglycemic-hyperinsulinemic clamp. The glucose infusion rates observed during the clamp revealed impaired peripheral insulin sensitivity in the high-fat-fed rats when compared with the age-matched control rats. Under baseline conditions (ie, low insulin), the muscle ATP synthesis rates of high-fat-fed rats were approximately 30% lower (P < .05) than those in chow-fed rats. Moreover, chow-fed animals showed a significant increase (25%, P < .05 vs basal) in muscle ATP synthesis activity upon insulin stimulation, whereas high-fat-fed animals displayed no substantial change. These data demonstrated for the first time in a preclinical model that the insulin challenge not only facilitates an improvement in the dynamic range of ATP turnover measurement by (31)P saturation transfer between normal and insulin-resistant rats, but also mimics challenge that is relevant for pharmacologic studies on antidiabetic drugs aimed at improving mitochondrial function.


Characteristics influencing location of death for children with life-limiting illness.
To determine whether demographic and diagnostic characteristics were associated with location of death in a series of children with life-limiting illnesses. A population-level case series was carried out by reviewing mortality records. Sociodemographic characteristics, diagnosis and referral to paediatric palliative care (PPC) were analysed for association with location of death. New Zealand Children and young people aged 28 days-18 years who died from a life-limiting illness between 2006 and 2009 inclusive. Location of death-home, hospital, other. Of 494 deaths, 53.6% (256/494) died in hospital and 41.9% (203/494) died at home. Asian (OR=2.66, 95% CI 1.17 to 6.04) and Pacific children (OR=2.22, 95% CI 1.15 to 4.29) had an increased risk of death in hospital compared with European children, while children with cancer (adjusted OR=0.48, 95% CI 0.3 to 0.75) and children referred to the PPC service (adjusted OR=0.60, 95% CI 0.38 to 0.96) had a decreased risk. Population-attributable risk for referral to the PPC service was 28.2% (95% CI 11.25 to 47.75). Most children in New Zealand with a life-limiting illness die in hospital with a significant influence resulting from ethnic background, diagnosis and referral to the PPC service. These findings have implications for resourcing PPC services and end-of-life care.


Effects of input data on the performance of a neural network in distinguishing normal and glaucomatous visual fields.
To compare the performance of neural networks for perimetric glaucoma diagnosis when using different types of data inputs: numerical threshold sensitivities, Statpac Total Deviation and Pattern Deviation, and probability scores based on Total and Pattern Deviation probability maps (Carl Zeiss Meditec, Inc., Dublin, CA). The results of SITA Standard visual field tests in 213 healthy subjects, 127 patients with glaucoma, 68 patients with concomitant glaucoma and cataract, and 41 patients with cataract only were included. The five different types of input data were entered into five identically designed artificial neural networks. Network thresholds were adjusted for each network. Receiver operating characteristic (ROC) curves were constructed to display the combinations of sensitivity and specificity. Input data in the form of Pattern Deviation probability scores gave the best results, with an area of 0.988 under the ROC curve, and were significantly better (P < 0.001) than threshold sensitivities and numerical Total Deviations and Total Deviation probability scores. The second best result was obtained with numerical Pattern Deviations with an area of 0.980. The choice of type of data input had important effects on the performance of the neural networks in glaucoma diagnosis. Refined input data, based on Pattern Deviations, resulted in higher sensitivity and specificity than did raw threshold values. Neural networks may have high potential in the production of useful clinical tools for the classification of visual field tests.


Correction: Highly-sensitive detection of Salmonella typhi in clinical blood samples by magnetic nanoparticle-based enrichment and in-situ measurement of isothermal amplification of nucleic acids.
[This corrects the article DOI: 10.1371/journal.pone.0194817.].


Diagnosis of the subtype and affected ear of benign paroxysmal positional vertigo using a questionnaire.
The prediction of subtype and the affected ear of benign paroxysmal positional vertigo (BPPV) derived from the answers to our questionnaire can support the definitive diagnosis of BPPV. We examined to what extent the diagnosis of subtype and the affected ear of BPPV judged from answers to a questionnaire agreed with the diagnosis decided by the results of the positional nystagmus test. We asked the following questions: 'What kind of head movements induce vertigo?' and 'How long does the vertigo continue?'. As for the affected ear, we asked which ear was lower during stronger vertigo when induced in a supine position or during sleep. The percentages of correct diagnosis speculated by the combined answers were 69% in posterior canal-type BPPV, 48% in BPPV with geotropic nystagmus, and 39% in BPPV with apogeotropic nystagmus. The percentage of correct diagnoses of the affected ear was more than 80%.


[Serous fluid cytopathology : International system: Ancillary studies for serous fluids and special considerations for peritoneal washings].
The International System for serous fluids cytopathology is a cytologic classification which purpose is to establish a consensus on diagnostic terminology. The exponential discovery of prognostic and theranostic molecular alterations in many cancers, particularly in advanced stages, led the authors to describe the indications and the feasibility of these new markers on cytological samples from serous effusions. The various immunocytochemistry techniques, FISH and those testing DNA and RNA are reported in regard to their ability to identify the main targets currently explored in routine practice. The vast majority of these crucial markers can be reliably tested on effusion fluids. The International System for serous effusion fluids also includes a chapter dedicated to peritoneal washings and the application of the classification to this particular type of sample. The objective is to "wash" the peritoneal cavity with a saline solution to unfix cells from the cavity's wall and collect those that have previously naturally detached. This procedure, performed before surgery of tumors and before any manipulation, allows a cytological analysis that specifies the staging of gynecological and non-gynecological tumors and excludes occult malignant cells in the presence of tumors appearing benign.


Rheumatic diseases: a general practitioner's view.
Patients with rheumatic complaints are the subject of some 10% of the general practitioner's work. Approximately half of this work is related to the hitherto relatively neglected group of varied soft-tissue conditions, most of which are self-limiting and of a minor nature. Against a background of such diagnostic 'noise', the general practitioner has to remain alert for the fainter 'signal' of serious disease--rheumatic and non-rheumatic--at an early stage. Continuity of care calls on special qualities, behaviours and abilities in the doctor to boost and maintain morale, to coordinate management and to participate in team care. In addition to more traditional therapeutic measures, including analgesics, NSAIDs, disease-modifying drugs and physiotherapy, joint replacement is seen as a significant contribution. There is room for improvement in the structure process and outcomes of delivery of care as it may relate to rheumatic diseases. A simple illustration, based on a general practice audit of gout, is suggested as a possible model by which quality of care could be enhanced at the level of individual patients. While there is not a great deal of scope afforded to the general practitioner in the exercise of primary prevention of the rheumatic diseases, early diagnosis and timely support for carers of patients suffering from chronic rheumatic diseases are areas worth attention. Promotion of self-help is seen as a worthwhile activity in humanitarian and economic terms, though it calls for an appropriate balance to be struck.


The luxS gene functions in the pathogenesis of avian pathogenic Escherichia coli.
Avian pathogenic Escherichia coli (APEC) causes avian colibacillosis, the most significant infectious bacterial disease of poultry worldwide. LuxS, the product of the luxS gene, mediates the quorum sensing (QS) mechanism. This involves the production of autoinducer-2 (AI-2), which regulates important physiological traits and a variety of adaptive processes in different bacteria. In this study, a luxS gene deleted APEC mutant strain, ΔDE17, was constructed using strain DE17. Analysis of bioluminescence indicated that deletion of the luxS gene abolished the production of the QS signal AI-2 in the bacteria. Further studies showed that deletion of the luxS gene in DE17 reduced the bacterial virulence by 31.5-fold in ducklings, based on the measurement of the 50% lethal dose. The mutant strain reduced significantly the abilities of adherence and invasion, by 50.0% and 40.7% respectively, compared with the wild strain DE17. The mutant strain also showed reduced survival in vivo: the bacterial loads of the mutant strain in infected liver, spleen and blood were 46.4-fold, 5.2-fold, and 3.7-fold reduced, respectively, compared with the wild-type strain DE17. Real-time polymerase chain reaction (PCR) demonstrated further that the mRNA levels of the virulence-related genes iucD, fyuA, vat, ompA, iss, fimC and tsh were significantly decreased in the mutant strain ΔDE17, when compared with DE17 (p < 0.05). In addition, the deletion of the luxS gene reduced the motility of the bacterium. This study suggests that the luxS gene functions in the pathogenesis of diseases caused by avian pathogenic E. coli.


Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A.
Hepatitis C virus (HCV) uses components of the very-low-density lipoprotein (VLDL) pathway for assembly/release. We previously reported that hepatocyte nuclear factor 4α (HNF4α) participates in HCV assembly/release through downstream factors those participate in VLDL assembly/secretion. Cell-death-inducing DFFA-like effector B (CIDEB) is an important regulator of the VLDL pathway. CIDEB is required for entry of HCV particles from cell culture (HCVcc), but the effects of CIDEB on the post-entry steps of the HCV lifecycle are unclear. In the present study, we determined that CIDEB is required for HCV assembly in addition to HCVcc entry. Furthermore, CIDEB interacts with the HCV NS5A protein, and the N terminus of CIDEB and the domain I of NS5A are involved in this interaction. Moreover, CIDEB silencing impairs the association of apolipoprotein E (ApoE) with HCV particles. Interestingly, CIDEB is also required for the post-entry stages of the dengue virus (DENV) life cycle. Collectively, these results indicate that CIDEB is a new host factor that is involved in HCV assembly, presumably by interacting with viral protein, providing new insight into the exploitation of the VLDL regulator CIDEB by HCV.


[Neurological manifestations of dengue].
An epidemic of type 4 dengue was raging in the Pacific from 2008 to 2010. During this period, several patients were hospitalized at the Hospital Centre of Tahiti for neurological disorders occurring during a dengue fever. These events are not the typical picture, which is represented by a flu-like syndrome and sometimes, in severe cases, a haemorrhagic syndrome or shock. We have established a review of the literature reporting the cases of dengue fever associated with neurological disorders with the terms "dengue" and "neurology". Despite the retrospective nature and incomplete data, we attempted to establish the epidemiological characteristics of these events, to give an order of frequency of these symptoms and the pathophysiological mechanisms involved. Among patients with neurological disorders occurring during a dengue fever, disorders of central nervous system are the most common. Among disorders of central nervous system, encephalopathy is by far the most encountered. None of observed neurologic disorders presenting with specific manifestation, discussion of dengue as etiology in endemic areas or in return from endemic area is well-founded.


Abraham Jacobi, MD: father of American pediatrics and advocate for children's health.
Dr. Abraham Jacobi, often called the "father of American pediatrics," rose from humble beginnings in Germany to the highest positions in pediatrics and medicine in the United States. Most of the history of American pediatrics during the second half of the 19th century is reflected in Jacobi's writings and work. This article presents a brief overview of his life and character, focusing on the important roles he played in establishing the field of pediatrics as a distinct specialty and in advocating for children's health issues.


[Eating better to improve resistance to sars-Cov-2].
Eating habits are evolving. In a public health context, guidelines are regularly updated according to the nutritional status and health of the French population, but some of these recommendations go unheeded. In the context of the current epidemic, nutritional care must be provided to high risk populations as well as to patients presenting, or having presented, COVID-19, in order to favour immunity and recovery.


Microbial degradation of 7-ketocholesterol.
7-Ketocholesterol (7KC) is an oxidized derivative of cholesterol suspected to be involved in the pathogenesis of atherosclerosis and possibly Alzheimer's disease. While some oxysterols are important biological mediators, 7KC is generally cytotoxic and interferes with cellular homeostasis. Despite recent interest in preventing the accumulation of 7KC in a variety of matrices to avoid adverse biological effects, its microbial degradation has not been previously addressed in the peer-reviewed literature. Thus, the rate and extent of biodegradation of this oxysterol was investigated to bridge this gap. A wide variety of bacteria isolated from soil or activated sludge, including Proteobacterium Y-134, Sphingomonas sp. JEM-1, Nocardia nova, Rhodococcus sp. RHA1, and Pseduomonas aeruginosa, utilized 7KC as a sole carbon and energy source, resulting in its mineralization. Nocardia nova, which is known to produce biosurfactants, was the fastest degrader. This study supports the notion that microbial catabolic enzymes could be exploited to control 7KC levels in potential biotechnological applications for agricultural, environmental, or medical use.


Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2).
This article is focused on platelet-activating factor acetylhydrolase (PAF-AH), a lipoprotein bound, calcium-independent phospholipase A(2) activity also referred to as lipoprotein-associated phospholipase A(2) or PLA(2)G7. PAF-AH catalyzes the removal of the acyl group at the sn-2 position of PAF and truncated phospholipids generated in settings of inflammation and oxidant stress. Here, I discuss current knowledge related to the structural features of this enzyme, including the molecular basis for association with lipoproteins and susceptibility to oxidative inactivation. The circulating form of PAF-AH is constitutively active and its expression is upregulated by mediators of inflammation at the transcriptional level. This mechanism is likely responsible for the observed up-regulation of PAF-AH during atherosclerosis and suggests that increased expression of this enzyme is a physiological response to inflammatory stimuli. Administration of recombinant forms of PAF-AH attenuate inflammation in a variety of experimental models. Conversely, genetic deficiency of PAF-AH in defined human populations increases the severity of atherosclerosis and other syndromes. Recent advances pointing to an interplay among oxidized phospholipid substrates, Lp(a), and PAF-AH could hold the key to a number of unanswered questions.


Targeting and killing of prostate cancer cells using lentiviral constructs containing a sequence recognized by translation factor eIF4E and a prostate-specific promoter.
To develop a gene therapy that would selectively kill prostate cancer cells while sparing normal cells, we have constructed lentiviral vectors that contain a therapeutic gene with a short DNA sequence in the 5'-untranslated region (UTR) that is recognized by the translation initiation factor, eIF4E, which is often overexpressed in malignant cells. Infection of cancer (LNCaP, PC-3M, DU145, and MCF-7 cells) and noncancer cell lines (BPH-1, 267-B1, Plat-E, and Huvec-c cells) with lentivirus having a CMV-promoter and EGFP reporter resulted in high levels of EGFP expression in all cells, whereas, inclusion of the eIF4E UTR recognition sequence restricted high expression to cancer cells and Plat-E cells, which also express substantial levels of eIF4E. Infection of the cells with lentiviral vectors having this UTR in front of the HSV thymidine kinase suicide gene resulted in differential sensitivity to the killing effects of ganciclovir, with at least 100-fold more drug required to kill noncancer cells than cancer cells. Furthermore, in experiments where the CMV promoter was replaced by the prostate-specific ARR(2)PB promoter, the killing effects of ganciclovir were restricted to prostate cancer cells and not seen in nonprostate cancer cells. Our results indicate that combined translational regulation, by incorporation of an eIF4E-UTR recognition sequence into a therapeutic gene, together with transcriptional regulation with a prostate-specific promoter, may provide a means to selectively destroy prostate cancer cells while sparing normal prostate cells.


Slowing Down Aging.
The hypothalamus plays a key role in coordinating the physiological changes that underlie mammalian aging. In a recent issue of Nature, Cai and colleagues (2017) shed new light on the mechanism of this effect by providing evidence that hypothalamic stem cells may regulate aging through the release of microRNAs in exosomes.