Direct contact with bone marrow stromal cells promotes the invasions of SHI-1 leukemia cells.
Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 (CXCR4) and extracellular matrix metalloproteinase inducer (EMMPRIN) had reported to participate in this process. However the roles of bone marrow microenvironment in leukemic infiltration were not well investigated. A co-culture system between SHI-1 cells and bone marrow stromal cells (BMSCs) is used to simulate the interactions of leukemic cells with their microenvironment. The trans-matrigel invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and SHI-1 cells were mixed in a ratio of 1:10 and added to the millicell chamber coated with matrigel. Either the co-culture supernatant or the functional blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT-PCR. The changes of the expression of matrix metalloproteinase-2, 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase 2 (TIMP-2), and CXCR4 mRNA in SHI-1 cells were determined by real-time PCR. The concentration of stromal cell derived factor 1 (SDF-1) in serum free supernatant was measured by ELISA. Both SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the matrigel membrane; the coculture supernatant did not induce the invasion of SHI-1 cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower chamber of millicell were significantly increased. The functional blocking peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a significantly higher level of SDF-1 in the co-cultured serum-free supernatant. The interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.


[Methodology and progress in adjusting time-dependent covariates in clinical prediction models].
Adjusting time-dependent covariates into prediction models may help improve model performance and expand clinical applications. The methodology of handling time-dependent covariates is limited in traditional regression strategies (i.e., landmark model, joint model). For example, the number of predictors and practical situations which can be handled are restricted when using regression models. One new strategy is to use machine learning (i.e., neural networks). This review summarizes the methodology of handling time-dependent covariates in prediction models, such as applicable scenarios, strengths, and limitations, to offer methodological enlightenment for processing time-dependent covariates.


Cognitive Component Structure of a Neuropsychological Battery Administered to Cognitively-Normal Adults in the SIU Longitudinal Cognitive Aging Study.
We used principal component analysis (PCA) to examine the component structure of a neuropsychological test battery administered to 943 cognitively-normal adults enrolled in the Southern Illinois University (SIU) Longitudinal Cognitive Aging Study (LCAS). Four components explaining the most variance (63.9%) in the dataset were identified: speed/cognitive flexibility, visuospatial skills, word-list learning/memory, and story memory. Regression analyses confirmed that increased age was associated with decreased component scores after controlling for gender and education. Our identified components differ slightly from previous studies using PCA on similar test batteries. Factors such as the demographic characteristics of the study sample, the inclusion of mixed patient and control samples, the inclusion of different test measures in previous studies, and the fact that many neuropsychological test measures assess multiple cognitive processes simultaneously, may help to explain these inconsistencies.


Sexting and other risky sexual behaviour among female students in a Nigerian academic institution.
The increase in the use of social media has led to a concurrent rise in the prevalence of sexting, which has, in turn, resulted in risky sexual behaviour. This study aims to investigate the role of sexting in risky sexual behaviour among female students who own smartphones for social and educational purposes. A cross-sectional study was conducted on 200 undergraduate students of the Niger Delta University using a pre-tested and validated structured questionnaire. Data for the study were analysed using descriptive statistics to describe the socio-demographic characteristics and trends in sexting and risky sexual behaviour. In addition, inferential statistics (logistic regression) was used in testing the association between the dependent and independent variables. IBM SPSS version 21.0 was used for data analysis. The results from the study indicated that those who had ever-sent nude pictures to their partners (OR = 2.504, p < 0.05) and the use of android phones were found to be significantly related to risky sexual behaviour of students (OR = 16.139, p < 0.05). Moreover, age (OR = 83.962, p < 0.01), ethnic group (OR = 130.612, p < 0.05), and monthly allowances (OR = 83.962, p < 0.05) were also associated with risky sexual behaviour. This study confirmed the string influence of sexting on high-risk sexual behaviour caused by sexting. In light of this, academic institutions are advised to discourage the licentious use of smartphones.


Periodontal effects of a biobehavioral prevention program.
The present study tested preventive regimens in older subjects using dental services sporadically. 297 persons aged 60-90 (mean age 72.8; 43% ethnic minorities), were randomly assigned to either a control group or four interventions with incrementally more complex preventive strategies; behavioral training (group 2), added weekly chlorhexidine rinse (group 3), added semi-annual fluoride varnish (group 4), and added semi-annual prophylaxis (group 5). The control group received dental care as they preferred, primarily emergency care. All subjects were re-examined annually for 3 years. At baseline, 190 (64%) of the subjects were considered at risk for future periodontal disease progression. At baseline there were no group differences for any clinical parameter studied. Gingival bleeding varied between 19% and 23% over time and with no group differences. After 1 year, the greater decrease in probing depth for group 5 approached significance compared to the control group (p<0.06). Clinical attachment levels (CAL) improved in group 5 compared to the control group (p<0.01 for mesio-buccal, p<0.05 for mid-buccal tooth surfaces). The group differences did not persist at year 3. At year 3 in group 1, 9.2% and in group 5, 4.9% subjects lost > or =2.0 mm CAL. 310 teeth (6.5%) were extracted during the study period. A 21% increased risk for tooth loss was found in group 2, a 15% reduced risk in group 3, a 28% reduced risk in group 4, and a 44% reduced risk in group 5 compared to the control group (Wald-statistics robust p-value 0.12). At year 3, the tooth mortality rate in groups 3, 4 and 5 combined was reduced to 59% and significantly lower than groups 1 and 2 together (p<0.04). Self-efficacy was the best predictor of periodontal disease progression (F=7.02, p<0.01). Thus older persons benefited from a preventive oral health care program.


Adhesins of Enteropathogenic Escherichia coli.
Enteropathogenic Escherichia coli (EPEC) strains induce morphological changes in infected epithelial cells. The resulting attaching and effacing (A/E) lesion is characterized by intimate bacterial adherence to epithelial cells, with microvillus destruction, cytoskeletal rearrangement, and aggregation of host cytoskeletal proteins. This review presents an overview of the adhesion mechanisms used for the colonization of the human gastrointestinal tract by EPEC. The mechanisms underlying EPEC adhesion, prior to and during the formation of the A/E lesion, and the host cytosolic responses to bacterial infection leading to diarrheal disease are discussed.


Stereoselective construction of spiro(butyrolactonepyrrolidines) by highly efficient copper(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar cycloaddition.
Pyrrole into one: The catalytic asymmetric 1,3-dipolar cycloaddition of cyclic aldimino esters has been accomplished for the first time, enabling facile access to spiro(butyrolactonepyrrolidines) containing one spiro quaternary center and three tertiary stereogenic centers (see scheme). The catalytic system performs well with a broad range of substrates, furnishing synthetically useful adducts in high yields, with excellent diastereo- and enantioselectivities under mild conditions.


Genetic Organization of the aprX-lipA2 Operon Affects the Proteolytic Potential of Pseudomonas Species in Milk.
Psychrotolerant Pseudomonas species are a main cause of proteolytic spoilage of ultra-high temperature (UHT) milk products due to the secretion of the heat-resistant metallopeptidase AprX, which is encoded by the first gene of the aprX-lipA2 operon. While the proteolytic property has been characterized for many different Pseudomonas isolates, the underlying aprX-lipA2 gene organization was only described for a few strains so far. In this study, the phylogenomic analysis of 185 Pseudomonas type strains revealed that the presence of aprX is strongly associated to a monophylum composed of 81 species, of which 83% carried the aprX locus. Furthermore, almost all type strains of known milk-relevant species were shown to be members of the three monophyletic groups P. fluorescens, P. gessardii, and P. fragi. In total, 22 different types of aprX-lipA2 genetic organizations were identified in the genus, whereby 31% of the species tested carried the type 1 operon structure consisting of eight genes (aprXIDEF prtAB lipA2). Other genetic structures differed from type 1 mainly in the presence and location of genes coding for two lipases (lipA1 and lipA2) and putative autotransporters (prtA and prtB). The peptidase activity of 129 strains, as determined on skim milk agar and in UHT-milk, correlated largely with different aprX-lipA2 gene compositions. Particularly, isolates harboring the type 1 operon were highly proteolytic, while strains with other operon types, especially ones lacking prtA and prtB, exhibited significantly lower peptidase activities. In conclusion, the phylogenomic position and the aprX-lipA2 gene organization specify the proteolytic potential of Pseudomonas isolates. In addition, however, an interplay of several environmental factors and intrinsic traits influences production and activity of AprX, leading to strain-specific proteolytic phenotypes.


Effects of perineural invasion on biochemical recurrence and prostate cancer-specific survival in patients treated with definitive external beam radiotherapy.
Perineural invasion (PNI) has not yet gained universal acceptance as an independent predictor of adverse outcomes for prostate cancer treated with external beam radiotherapy (EBRT). We analyzed the prognostic influence of PNI for a large institutional cohort of prostate cancer patients who underwent EBRT with and without androgen deprivation therapy (ADT). We, retrospectively, reviewed prostate cancer patients treated with EBRT from 1993 to 2007 at our institution. The primary endpoint was biochemical failure-free survival (BFFS), with secondary endpoints of metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Univariate and multivariable Cox proportional hazards models were constructed for all survival endpoints. Hazard ratios for PNI were analyzed for the entire cohort and for subsets defined by NCCN risk level. Additionally, Kaplan-Meier survival curves were generated for all survival endpoints after stratification by PNI status, with significant differences computed using the log-rank test. Of 888 men included for analysis, PNI was present on biopsy specimens in 187 (21.1%). PNI was associated with clinical stage, pretreatment PSA level, biopsy Gleason score, and use of ADT (all P<0.01). Men with PNI experienced significantly inferior 10-year BFFS (40.0% vs. 57.8%, P = 0.002), 10-year MFS (79.7% vs. 89.0%, P = 0.001), and 10-year PCSS (90.9% vs. 95.9%, P = 0.009), but not 10-year OS (67.5% vs. 77.5%, P = 0.07). On multivariate analysis, PNI was independently associated with inferior BFFS (P<0.001), but not MFS, PCSS, or OS. In subset analysis, PNI was associated with inferior BFFS (P = 0.04) for high-risk patients and with both inferior BFFS (P = 0.01) and PCSS (P = 0.05) for low-risk patients. Biochemical failure occurred in 33% of low-risk men with PNI who did not receive ADT compared to 8% for low-risk men with PNI treated with ADT (P = 0.01). PNI was an independently significant predictor of adverse survival outcomes in this large institutional cohort, particularly for patients with NCCN low-risk disease. PNI should be carefully considered along with other standard prognostic factors when treating these patients with EBRT. Supplementing EBRT with ADT may be beneficial for select low-risk patients with PNI though independent validation with prospective studies is recommended.


Exposure to diesel exhaust emissions on board locomotives.
Measurements of diesel exhaust emissions (DEEs) were taken in the cabs of leading and trailing locomotives on 48 runs, under winter and summer conditions, on 9 different routes. The cab windows were kept open during the summer runs and closed during the winter runs. The average measurement duration was 9.5 hours. There was virtually no exposure to DEEs in the lead locomotives during winter or summer and very little in the trailing locomotives during winter. The average elemental carbon (EC) concentration in the trailing units of the summer trials was greater than or equal to the proposed American Conference of Governmental Industrial Hygienists' threshold limit value/time-weighted average of 20 microg/m(3) on 26% of the runs, and was greater than or equal to 10 microg/m(3) on 63%. The concentrations of the gaseous components (nitric oxide, nitrogen dioxide, and carbon monoxide) were from 10 to 20 times below their respective threshold limit values. Mean EC concentration was 2.9 microg/m(3) (detection limit 2 microg/m(3)) during the winter runs and 17.1 microg/m(3) during summer. DEEs appeared to be fairly uniformly distributed in the trailing cabs. Configuration of the locomotives had a major impact on EC concentration, with the mean concentration being nearly three times higher in the forward-backward mode than in the forward-forward mode. Descriptive statistics such as means, medians, standard deviations, and so forth, are provided. Various types of statistical comparisons are reported. Recommendations for controlling exposure are made.


Whipple's disease can mimic chronic AIDS enteropathy.
Previous case reports have demonstrated that the intestinal pathology of Mycobacterium avium-intracellulare (MAI) infection in the acquired immune deficiency syndrome (AIDS) has a light microscopic appearance similar to Whipple's disease. This case report describes a 52-yr-old male patient with a clinical picture suggestive of AIDS, including diarrhea, weight loss, oral thrush, and intestinal cryptosporidiosis. The intestinal biopsy showed light microscopic features compatible with either MAI or Whipple's disease, but electron microscopy confirmed the presence of the Whipple bacillus. Markers of human immunodeficiency virus (HIV) infection were absent. Although immune abnormalities have been reported in Whipple's disease, this is the first report of opportunistic infections complicating this condition. A useful clinical pearl emerges from this and other cases: AIDS can mimic Whipple's disease; Whipple's disease can mimic AIDS.


[Stability of the two-stage SBR system treating dyeing wastewater during a long-term operation].
The stability of the two-stage SBR system treating dyeing wastewater was investigated during a 120-cycle continuous operation. The system was fed with influent of low dye concentration and high dye concentration. The results showed that the two-stage SBR system was adaptable to the change of influent quality and operation conditions during the long-term operation. It could efficiently remove the pollutants in the wastewater, the average dyestuff and COD removal rates were 81% to 92.5% and 89.4% to 93.1% respectively for low and high influent loading, and could produce continuous good quality effluent. In the two-stage SBR system, the anaerobic sludge had the characteristics of high activity and strong pollutant degradation ability, and the aerobic sludge existed in the form of aggregate structure, which helped stabilize the effluent quality.


Risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) by trauma patients in the intensive care unit.
In a previous study in the intensive care unit (ICU) of the Alfred Hospital, Melbourne, Australia, it was demonstrated that trauma patients were at particular risk of becoming colonized by methicillin-resistant Staphylococcus aureus (MRSA). We examined risk factors for MRSA acquisition in these patients using a cohort study comparing the 31 patients who acquired MRSA with 65 who did not. Data collected included ICU length of stay (LOS), mechanism of trauma, site of injury, type of surgery, trauma severity and antibiotic usage. Odds ratios (OR) were determined and adjusted for LOS. LOS in the ICU was a significant univariate predictor of MRSA acquisition (OR 13.7). When adjusted for LOS, mechanism of trauma (OR 10.4), laparotomy (OR 6.3) and administration of ticarcillin/clavulanic acid (OR 4.5) or glycopeptides (OR 5.9) remained significant. We confirmed our previous finding that LOS was associated with MRSA acquisition. Receipt of antibiotics correlated with reported literature. Novel associations were road trauma as a mechanism and laparotomy.


Free calcium concentration in platelets closely relates to blood pressure in normal and essentially hypertensive subjects.
Calcium has been implicated in smooth muscle contraction, arterial resistance, and the pathophysiology of essential hypertension. Using the intracellularly trapped fluorescent dye quin2 , the free calcium concentration in platelets was found to be elevated in patients with borderline (n = 8, p less than 0.01) and established essential hypertension (n = 23, p less than 0.001) when compared with normotensive subjects (n = 30). There was a close correlation between intracellular free calcium and systolic blood pressure (n = 61, r = 0.882, p less than 0.001) as well as diastolic blood pressure (n = 61, r = 0.950, p less than 0.001). The slopes of the regression lines did not differ between the groups.


The modified BODE index: validation with mortality in COPD.
Peak oxygen uptake (V'(O(2))) remains the gold standard measurement of exercise capacity and has been associated with survival. A modified BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index replacing the 6-min walk distance (6MWD) with V'(O(2)) as % predicted (mBODE%) has been developed and found to have excellent correlation with the conventional BODE index. The objectives of the present study were to compare the ability of the conventional BODE and the mBODE% to predict mortality in 444 patients with chronic obstructive pulmonary disease (COPD) followed for a mean+/-SD period of 71+/-34 months. Anthropometrics, spirometry, lung volumes, comorbidity, cardiopulmonary cyclo-ergometry test and 6MWD were determined at entry. The mean BODE indices for the cohort were: BODE 4.1+/-2 and mBODE% 5.5+/-2. Both indices were significantly correlated with mortality. Logistic regression analysis with COPD survival as the dependent variable identified the BODE index, Charlson's and exercise capacity (in W) as variables associated with this outcome. In conclusion, the conventional BODE index, which uses the 6-min walk distance, predicts mortality in chronic obstructive pulmonary disease as well as the modified index using peak oxygen uptake. The results support the use of the simpler index, which includes the 6-min walk distance in the comprehensive evaluation of patients with chronic obstructive pulmonary disease.


Safe administration of iron dextran to a patient who reacted to the test dose.
Parenteral iron therapy is infrequently required but generally well tolerated. We present a case in which intravenous iron dextran was successfully given to a patient who had an anaphylactoid reaction to the test dose. After pretreatment with methylprednisolone, diphenhydramine, ephedrine, and dextran 1, 2 g of iron dextran were safely given over several days; pretreatment was administered only on day 1. In the rare cases in which an anaphylactic agent must be given to a patient with a history of a life-threatening reaction to the agent, pretreatment along with slow escalation of dose may allow safe administration of the offending drug.


Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells.
Human mammary epithelial cells (HMECs) exhibit an increase in phosphocholine (PC) and total choline-containing compounds, as well as a switch from high glycerophosphocholine (GPC)/low PC to low GPC/high PC, with progression to malignant phenotype. The treatment of human breast cancer cells with a nonsteroidal anti-inflammatory agent, indomethacin, reverted the high PC/low GPC pattern to a low PC/high GPC pattern indicative of a less malignant phenotype, supported by decreased invasion. Here, we have characterized mechanisms underlying indomethacin-induced alterations in choline membrane metabolism in malignant breast cancer cells and nonmalignant HMECs labeled with [1,2-13C]choline using 1H and 13C magnetic resonance spectroscopy. Microarray gene expression analysis was performed to understand the molecular mechanisms underlying these changes. In breast cancer cells, indomethacin treatment activated phospholipases that, combined with an increased choline phospholipid biosynthesis, led to increased GPC and decreased PC levels. However, in nonmalignant HMECs, activation of the anabolic pathway alone was detected following indomethacin treatment. Following indomethacin treatment in breast cancer cells, several candidate genes, such as interleukin 8, NGFB, CSF2, RHOB, EDN1, and JUNB, were differentially expressed, which may have contributed to changes in choline metabolism through secondary effects or signaling cascades leading to changes in enzyme activity.


Protein interactions of MADS box transcription factors involved in flowering in Lolium perenne.
Regulation of flowering time is best understood in the dicot model species Arabidopsis thaliana. Molecular analyses revealed that genes belonging to the MADS box transcription factor family play pivotal regulatory roles in both the vernalization- and photoperiod-regulated flowering pathways. Here the analysis of three APETALA1 (AP1)-like MADS box proteins (LpMADS1-3) and a SHORT VEGETATIVE PHASE (SVP)-like MADS box protein (LpMADS10) from the monocot perennial grass species Lolium perenne is reported. Features of these MADS box proteins were studied by yeast two-hybrid assays. Protein-protein interactions among the Lolium proteins and with members of the Arabidopsis MADS box family have been studied. The expression pattern for LpMADS1 and the protein properties suggest that not the Arabidopsis AP1 gene, but the SUPPRESSOR OF CONSTANS1 (SOC1) gene, is the functional equivalent of LpMADS1. To obtain insight into the molecular mechanism underlying the regulation of LpMADS1 gene expression in vernalization-sensitive and -insensitive Lolium accessions, the upstream sequences of this gene from a winter and spring growth habit variety were compared with respect to MADS box protein binding. In both promoter elements, a putative MADS box transcription factor-binding site (CArG-box) is present; however, the putative spring promoter has a short deletion adjacent to this DNA motif. Experiments using yeast one-hybrid and gel retardation assays demonstrated that the promoter element is bound by an LpMADS1-LpMADS10 higher order protein complex and, furthermore, that this complex binds efficiently to the promoter element from the winter variety only. This strongly supports the model that LpMADS1 together with LpMADS10 controls the vernalization-dependent regulation of the LpMADS1 gene, which is part of the vernalization-induced flowering process in Lolium.


Single-bicycle crashes: An in-depth analysis of self-reported crashes and estimation of attributable hospital cost.
Cyclists' awareness of their risk of single-bicycle crashes is limited. Thus, knowledge of the most common contributory factors of single-bicycle crashes is required. Similarly, single-bicycle crashes and their costs to society are under-recognized by the public. The aim of this study was to conduct an analysis of single-bicycle crashes occurring in a cohort of cyclists in Denmark and supplement it with estimation of some attributable costs of single-bicycle crashes among all injured cyclists during one year treated in a hospital or emergency room in Denmark. We conducted a one-year follow-up of 6,793 active cyclists (mean age: 45.8 years) encountering 349 single-bicycle crashes (single-bicycle crash rate: 55 per 1,000 person-years). An in-depth analysis of the crashes suggested that daily winter road maintenance is crucial in colder climates and that the current cyclist infrastructure design gives rise to many single-bicycle crashes. Further analysis of the co-occurrence of the factors contributing to the crashes indicated that when the weather is warmer, the factors pertaining to the individual cyclist (and not the road authorities) dominate. The risk of sustaining a more severe injury (i.e. other than light bruises) once in a single-bicycle crash was 18 %. However, for cyclists above 50 years, this risk doubled compared with their younger counterparts, wholly due to a 4.7 times higher risk during the warm season. Among cyclists treated in hospital or emergency room, we estimated the attributable hospital cost of single-bicycle crashes at €1,701 and the attributable cost of municipality care at €417 in the first year after the injury (2019 prices). In cyclists aged 18-60 years and treated in hospital or emergency room, the estimated attributable risk of sickness benefit was 5.2 percentage points in the first year after the injury. We concluded that to increase cyclist safety, the road authorities should improve winter road maintenance and redesign cyclist infrastructure.


Nasal glioma: a case report.
Here we describe a rare case of nasal glioma in a 14 year old boy who presented with history of right nasal obstruction and nasal discharge since 6 months. On examination a pale mass was seen filling the right nasal cavity and extending down in the oropharynx. Clinical impression was antrochoanal polyp. Excision of the mass was carried out and sent for histopathology which showed presence of glial tissue and the diagnosis was made as nasal glioma.


Immunohistochemical detection of deposits of eosinophil-derived neurotoxin and eosinophil peroxidase in the myocardium of patients with Chagas' disease.
An immunohistochemical study of eosinophil distribution in the inflammatory cell infiltrates of four different types of myocardial lesions associated with Chagas' disease--caused by Trypanosoma cruzi--showed larger numbers of these cells in areas presenting tissue necrosis and degeneration, most notably in patients with the most severe myocarditis from a histopathological stand-point. Using antisera specific for human eosinophil-derived neurotoxin or eosinophil peroxidase, we detected deposits of these secretion products on myofibres and in the interstitium of chagasic myocardium displaying necrosis and degeneration but rarely in other types of lesions. These deposits were not detectable in the myocardium of non-chagasic patients who had died from myocardial infarction (acute or in the scarring stage) or myocarditis secondary to bacterial endocarditis. When human eosinophil-derived neurotoxin was incubated with myoblast monolayers there was a significant cell injury, detachment and lysis. These effects were abrogated by yeast RNA, added as a competitive ribonuclease substrate, and inhibited by the ribonuclease inhibitor RNasin, suggesting that the ribonuclease activity of the eosinophil-derived neurotoxin was involved in the effect. These results suggest a link between eosinophil infiltration and necrosis in chagasic myocardial lesions and point to EDN, and perhaps other toxic eosinophil secretion products, as possible mediators of tissue damage.


Craniocervical spinal instability after type 1 Arnold Chiari decompression: a case report.
To present and describe an unusual case of spinal instability after craniocervical spinal decompression for a type-1 Chiari malformation. Type-1 Chiari malformation is a craniocervical disorder characterized by tonsillar displacement greater than 5 mm into the vertebral canal; posterior fossa decompression is the most common surgical treatment for this condition. Postoperative complications have been described: cerebrospinal fluid leak, pseudomeningocele, aseptic meningitis, wound infection, and neurological deficit. However, instability after decompression is unusual. A 9-year-old female presented with symptomatic torticollis after cervical decompression for a type-1 Chiari malformation. Spinal instability was diagnosed; craniocervical stabilization was performed. After a 12-month follow-up, spinal stability was achieved, with a satisfactory clinical neck alignment. We present a craniocervical instability secondary to surgical decompression; clinical and radiological symptoms, and definitive treatment were described.


Cementless hip arthroplasty with a modular neck.
The authors report the preliminary results obtained in 347 prosthetic implants with hip arthroplasty with a modular neck. The advantages to using this method are related to the chance to adapt to different anatomical conditions: in particular, in primary arthroplasty a straight neck was used in the majority of cases (83%), while in dysplastic hips a straight neck was used in 47.5% of cases and a retroverse neck (8 degrees or 15 degrees) overall in 40% of cases.


β-Blockers on Discharge From Acute Atrial Fibrillation Are Associated With Decreased Mortality and Lower Cerebrovascular Accidents in Patients With Heart Failure and Reduced Ejection Fraction.
The benefits of β-blockers in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) are controversial. The Gulf Survey of Atrial Fibrillation Events was a prospective, multinational, observational registry of consecutive patients with AF recruited from the emergency department (ED). We studied the incidence of 6- and 12-month mortality, hospitalization for HF or AF, and stroke/transient ischemic attacks (TIAs) in patients with HFrEF, in relation to β-blockers on discharge from the ED or the subsequent hospital stay. Of the 344 patients with HFrEF and AF in the GULF-SAFE, 177 patients (53%) were discharged on β-blockers. Mortality was lower in those patients compared with the non-β-blockers group at 6 and 12 months (odds ratios [ORs] 0.31, 95% CI [0.16-0.61]; OR 0.30, 95% CI [0.16-0.55]; P = .001 for both, respectively), so was the risk of stroke/TIAs. However, hospitalizations for AF increased in the β-blockers group. Even after adjustment for several risk variables in 2 different models, the beneficial effect of β-blockers on mortality persisted, at the cost of more hospitalization for AF.


Rot and SaeRS cooperate to activate expression of the staphylococcal superantigen-like exoproteins.
Staphylococcus aureus is a significant human pathogen that is capable of infecting a wide range of host tissues. This bacterium is able to evade the host immune response by utilizing a repertoire of virulence factors. These factors are tightly regulated by various two-component systems (TCS) and transcription factors. Previous studies have suggested that transcriptional regulation of a subset of immunomodulators, known as the staphylococcal superantigen-like proteins (Ssls), is mediated by the master regulators accessory gene regulator (Agr) TCS, S. aureus exoprotein expression (Sae) TCS, and Rot. Here we demonstrate that Rot and SaeR, the response regulator of the Sae TCS, synergize to coordinate the activation of the ssl promoters. We have determined that both transcription factors are required, but that neither is sufficient, for promoter activation. This regulatory scheme is mediated by direct binding of both transcription factors to the ssl promoters. We also demonstrate that clinically relevant methicillin-resistant S. aureus (MRSA) strains respond to neutrophils via the Sae TCS to upregulate the expression of ssls. Until now, Rot and the Sae TCS have been proposed to work in opposition of one another on their target genes. This is the first example of these two regulators working in concert to activate promoters.


Gold(I)-mediated C-H activation of arenes.
We demonstrate the first Au(I)-mediated C-H activation of arenes. Au(I) salts undergo C-H activation with electron-poor arenes, in stark contrast to Au(III) salts, which activate electron-rich arenes. This operationally simple and highly regioselective process occurs under very mild conditions and gives access to a variety of Au(I)-arene complexes in excellent yields.


Incremental cost-effectiveness of evidence-based non-surgical weight loss strategies.
Recent medical advancements have led to new modes of treatment for non-surgical weight loss, including several new medications. Our aim was to conduct an incremental cost-effectiveness analysis for all commercially available, evidence-based non-surgical weight loss interventions for people with excess weight. We identified interventions through a systematic review of randomized controlled trials that reported weight loss 12 months from baseline. We then meta-analysed the results, sourced costs and performed an incremental cost-effectiveness analysis from the payer perspective. Cost-effectiveness was presented in terms of cost per kilogram lost and quality-adjusted life years (QALY) gained. We further performed sensitivity analyses on costs and duration of benefits, and a probabilistic sensitivity analysis. Ten interventions were identified for inclusion: six pharmaceutical products (Alli, Xenical, Qsymia, Contrave, Belviq and Saxenda), two lifestyle modification programmes (Weight Watchers Meetings and Online), one food replacement and lifestyle programme (Jenny Craig) and one intragastric balloon system (Orbera). At an incremental cost-effectiveness ratio of $30 071 per additional QALY gained, only Weight Watchers Meetings was cost-effective. Sensitivity analyses revealed that for the medications to become incrementally cost-effective, costs would have to decrease by as much as 91%. Results are highly dependent on duration that benefits are maintained. Despite several newly available interventions, Weight Watchers Meetings is currently the only evidence-based, commercially available, cost-effective option for non-surgical weight loss. Other interventions, specifically medications, are more effective but priced too high to be cost-effective.


Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians.
In an examination of disease-free aging and neurodegenerative disease in 100-year-olds, the New England Centenarian Study compared data from neuropsychological evaluations with postmortem brain studies of fourteen 100-year-olds to ascertain if the presence or absence of Alzheimer disease changes correlated with measured cognitive abilities. Fourteen of 74 centenarians who underwent annual extensive neuropsychological evaluation proceeded to postmortem neuropathological examination. CERAD criteria, emphasizing neuritic amyloid plaques and Braak and Braak staging of neurofibrillary tangles were used to assess the 14 brains. Neuropsychological and neuropathological findings correlated well for four subjects with no dementia on testing (CDR = 0) and for six subjects with CDR scores in the dementia range (CDR = 1-5). In the latter group, Alzheimer's disease was diagnosed in four brains; Pick's disease was an etiological factor in the fifth and hippocampal sclerosis in the sixth. Correlation was low for four subjects: two subjects with no dementia on neuropsychological testing met CERAD neuropathological criteria for possible AD; two subjects with dementia on testing did not meet CERAD criteria for definite Alzheimer's disease and had otherwise minimal changes to correlate with the cognitive findings. Lack of correlation between level of cognitive functioning and brain pathology in two subjects with no dementia raised the question of whether a functional reserve delayed the functional expression of pathological changes. For two subjects with dementia on testing, there appeared to be no sufficient pathological explanation for the extent of the cognitive changes; depression and such factors as environment, sensory impairment, and medical illness may all have played a role. There may also have been neuropathologic changes not detected by current methods.


Pharmacokinetic study of the variability of indinavir drug levels when boosted with ritonavir in HIV-infected children.
The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clinical routine practice in HIV-infected children, whose antiretroviral treatment includes IDV boosted with ritonavir (RTV), and (2) describe a possible relationship between IDV pharmacokinetics and MDR1 genotypes. In 21 ambulatory pediatric patients receiving IDV plus RTV, IDV plasma levels and MDR1 genotypes on exon 26 (C3435T) were determined. Nine of the 21 patients initially receiving 250 mg/m(2) IDV yielded trough levels below 0.10 microg/ml (median: 0.21, range: 0.04-1.31 microg/ml). When the dosage was increased to 400 mg/m(2) IDV plus 100 mg/m(2) RTV b.i.d., all, except 1 patient, achieved levels above 0.10 microg/ml. Pharmacokinetic analysis showed higher volume of distribution median values related to the C/C genotype in comparison with C/T or T/T genotypes for exon 26 (4.57 vs. 1.20 and 1.50 l/kg, respectively; p = 0.002). Although a higher median value of clearance was observed with the C/C genotype, the difference was not statistically significant (1.43 vs. 0.27 and 0.42 l/h, respectively; p = 0.052). These results may be explained by a reduced absorption of the drug, related with lower plasma IDV levels in patients carrying the C/C genotype in exon 26.


Chemical composition of Schinus molle essential oil and its cytotoxic activity on tumour cell lines.
The leaf essential oil hydrodistilled from Schinus molle grown in Costa Rica was characterised in terms of its chemical composition, antioxidant activity, ability to induce cytotoxicity and the mechanism of cell death involved in the process. As a result, 42 constituents, accounting for 97.2% of the total oil, were identified. The major constituents of the oil were beta-pinene and alpha-pinene. The antioxidant activity showed an IC(50) of 36.3 microg mL(-1). The essential oil was cytotoxic in several cell lines, showing that it is more effective on breast carcinoma and leukemic cell lines. The LD(50) for cytotoxicity at 48 h in K562 corresponded to 78.7 microg mL(-1), which was very similar to the LD(50) obtained when apoptosis was measured. The essential oil did not induce significant necrosis up to 200 microg mL(-1), which together with the former results indicate that apoptosis is the main mechanism of toxicity induced by S. molle essential oil in this cell line. In conclusion, the essential oil tested was weak antioxidant and induced cytotoxicity in different cell types by a mechanism related to apoptosis. It would be interesting to elucidate the role that different components of the oil play in the effect observed here, since some of them could have potential anti-tumoural effects, either alone or in combination.


The impact of time-of-day reperfusion on remote ischemic conditioning in ST-elevation myocardial infarction: a RIC-STEMI substudy.
Daytime variation affects the tolerance of cardiomyocytes to ischemia-reperfusion injury (IRI). This study aims to evaluate the impact of time-of-day reperfusion on clinical outcomes of remote ischemic conditioning (RIC) as an adjuvant to primary percutaneous coronary intervention(PPCI) in ST-elevation myocardial infarction(STEMI) patients. A post-hoc analysis of a prospective, single-center parallel 1:1 randomized trial (RIC-STEMI) was performed. This analysis included 448 STEMI patients previously randomized to either PPCI alone (PPCI group) (n = 217) or RIC as an adjuvant to PPCI (RIC + PPCI group) (n = 231). Moreover, the sample was divided according to the time of PPCI: night-morning (22 h-11h59min) (n = 216) or afternoon (12 h-21h59min) (n = 232) groups. The primary follow-up endpoint was a composite of cardiac death and hospitalization due to heart failure. There were no significant differences in the clinical characteristics and the follow-up outcomes between groups. The afternoon period (HR = 0.474; 95% CI 0.230-0.977; p = 0.043) and RIC (HR = 0.423; 95% CI 0.195-0.917; p = 0.029) were independent predictors of the primary follow-up endpoint. An univariate analysis showed a lower frequency of primary follow-up endpoint, just in the afternoon period (10.3%vs0.9%; p = 0.002), in the RIC + PPCI group. A multivariate analysis revealed that RIC was an independent predictor of the primary follow-up endpoint in the afternoon group (HR = 0.098; 95% CI 0.012-0.785; p = 0.029), but not in the night-morning group. In addition, the afternoon period was not an independent predictor of the primary follow-up endpoint when the multivariate analysis was performed in the PPCI group. In conclusion, this study showed an important cardioprotective effect of RIC, namely in the afternoon period, suggesting that the afternoon period enhances the cardioprotection induced by RIC.


[Current epidemiological status of salmonellosis of humans in Germany].
Infections caused by Salmonella typhi and Salmonella paratyphi B have special epidemiological significance. However, the enteritis caused by Salmonella enteritidis and Salmonella typhimurium dominates. A complex typing of these serovars is the prerequisite for both, an effective surveillance of salmonellosis and the detection of occurring replacements and variations of the pathogens. The increasing occurrence of Salmonella in spices since 1993 is epidemiologically remarkable. In this connection, serotypes such as Salmonella javiana, S. rubislaw, and monophasic, KCN-positive serovars dominate. The transmission route man-man is of no special epidemiological importance at present in Germany.


Empirical mean curve decomposition with multiwavelet transformation for eye movements recognition using electrooculogram signals.
Many research works are in progress in classification of the eye movements using the electrooculography signals and employing them to control the human-computer interface systems. This article introduces a new model for recognizing various eye movements using electrooculography signals with the help of empirical mean curve decomposition and multiwavelet transformation. Furthermore, this article also adopts a principal component analysis algorithm to reduce the dimension of electrooculography signals. Accordingly, the dimensionally reduced decomposed signal is provided to the neural network classifier for classifying the electrooculography signals, along with this, the weight of the neural network is fine-tuned with the assistance of the Levenberg-Marquardt algorithm. Finally, the proposed method is compared with the existing methods and it is observed that the proposed methodology gives the better performance in correspondence with accuracy, sensitivity, specificity, precision, false positive rate, false negative rate, negative predictive value, false discovery rate, F1 score, and Mathews correlation coefficient.


Relative potencies of anti-herpes compounds.
Assessment of the relative potencies of compounds that inhibit the multiplication of herpesvirus is rendered difficult by the fact that they have been investigated by different workers who were not using comparable test systems. The relative and absolute potencies of idoxuridine, cytarabine, vidarabine, trifluorothymidine, and ara-DAP have therefore been evaluated by plaque inhibition, plaque reduction, and yield reduction tests, the most satisfactory dose-response lines being obtained by plaque reduction. The results obtained for five strains of type 1 and five of type 2 herpesvirus indicated that cytarabine was the most active compound, followed by idoxuridine and trifluorothymidine; vidarabine and ara-DAP were found to be the least active compounds. From comparisons of ED50 values derived from the dose-response lines it was found that the greater sensitivity of type 1 strains reported in the literature could only be confirmed with idoxuridine, since considerable overlaps in type sensitivity were observed with the other compounds.


Outcomes in Endoscopic and Operative Transgastric Pancreatic Debridement.
Select patients with anatomically favorable walled off pancreatic necrosis may be treated by endoscopic (Endo-TGD) or operative (OR-TGD) transgastric debridement (TGD). We compared our experience with these 2 approaches. Select necrotizing pancreatitis (NP) patients are suitable for TGD which may be accomplished endoscopically or surgically. Limited experience exists contrasting these techniques exists. Patients undergoing Endo-TGD and OR-TGD at a single, high-volume pancreatic center between 2008 and 2019 were identified from a prospective database. Patient characteristics, procedural details, and outcomes of these 2 groups were compared. Among 498 NP patients undergoing necrosis intervention, 160 (32%) had TGD: 59 Endo-TGD and 101 OR-TGD. The groups were statistically similar in age, comorbidity, pancreatitis etiology, necrosis anatomy, pancreatitis severity, and timing of TGD from pancreatitis insult. OR-TGD required 1.1 ± 0.5 and Endo-TGD 3.0 ± 2.0 debridements/patient. Fewer hospital readmissions and repeat necrosis interventions, and shorter total inpatient length of stay were observed in OR-TGD patients. New-onset organ failure [Endo-TGD (13%); OR-TGD (13%); P = 1.0] was similar between groups. Hospital length of stay after TGD was significantly longer in patients undergoing Endo-TGD (13.8 ± 20.8 days) compared to OR-TGD (9.4 ± 6.1 days; P = 0.047). Mortality was 7% in Endo-TGD and 1% in OR-TGD (P = 0.04). Operative and endoscopic transgastric debridement achieve necrosis resolution with different temporal and procedural profiles. Clear multidisciplinary communication is essential to determine appropriate approach to individual necrotizing pancreatitis patients.


Audiologist availability and supply in the United States: A multi-scale spatial and political economic analysis.
This study employs statistical modeling and mapping techniques to analyze the availability and accessibility of audiologists (practitioners who diagnose and treat hearing loss) in the United States at the county scale. The goal is to assess the relationships between socio-demographic and structural factors (such as health policy and clinical programs which train audiologists) and audiologist availability. These associations are analyzed at the county level, via a mixed effects hurdle model. At the county level, the proportion of older adults reporting difficulty hearing is negatively associated with audiologist supply. The findings show that audiologists tend to locate in metropolitan counties with higher median household incomes, younger populations, and lower proportions of older adults reporting hearing difficulty, suggesting an inverse care-type relationship between audiologist availability and need for hearing health services. Notably, neither state legislation requiring insurance plan coverage of hearing services for adults or Medicaid coverage of audiology services were significant predictors of audiologist supply at the county level.


Translocator Protein (TSPO) Expression in Platelets of Depressed Patients Decreases during Antidepressant Therapy.
Introduction: A promising candidate in the field of pharmacological treatment options regarding major depressive disorder (MDD) is the mitochondrial translocator protein (18 kDa) (TSPO). TSPO is crucial for neurosteroid synthesis, which is in turn important for the regulation of emotions. It has already been shown that TSPO expression in platelets of depressed patients is reduced compared to healthy subjects. Methods: We measured TSPO levels in platelets of 37 depressed patients before and after 6 weeks of pharmacological treatment to test the hypotheses that i) such treatment would increase TSPO expression and ii) that this increase would be correlated with therapeutic response. Results: Surprisingly, TSPO levels in platelets of all patients were significantly reduced after 6 weeks of treatment (p=0.044). Within the responder group, a non-significant trend towards greater TSPO level reduction could be observed. Discussion: These results challenge our hypotheses that TSPO levels might increase during antidepressant therapy along with a decrease in depressive symptoms. Thus, we assume that TSPO expression in platelets is not a suitable state marker for MDD.


Pd-catalyzed deoxygenation of mandelate esters.
A new approach to the synthesis of phenylacetic acids and esters has been developed via the palladium-catalyzed deoxygenation of mandelate esters.


A Complex Relationship between TRAF3 and Non-Canonical NF-κB2 Activation in B Lymphocytes.
The adaptor protein TRAF3 restrains B cell activating factor receptor (BAFFR) and CD40-mediated activation of the NF-κB2 pathway in B cells. Mice lacking TRAF3 specifically in B cells revealed the critical role of TRAF3 in restraining homeostatic B cell survival. Furthermore, loss-of-function mutations of the traf3 gene have been associated with human B cell malignancies, especially multiple myeloma (MM). It has been proposed that receptor-induced TRAF3 degradation leads to stabilization of the NF-κB inducing kinase (NIK), and subsequent NF-κB2 activation. However, it is unclear how receptor-mediated TRAF3 degradation or loss-of-function contributes to B cell-specific NF-κB2 activation. In the current study, we employed two complementary models to address this question. One utilized a mutant traf3 gene found in a human MM-derived cell line called LP1. The LP1 mutant TRAF3 protein lacks the TRAF-N and TRAF-C domains. Consistent with the paradigm described, expression of LP1 TRAF3 in B cells promoted higher basal levels of NF-κB2 activation compared to Wt TRAF3. However, LP1 did not associate with TRAF2, CD40, or BAFFR, and no LP1 degradation was observed following receptor engagement. Interestingly, LP1 showed enhanced NIK association. Thus, TRAF3 degradation becomes dispensable to activate NF-κB2 when it is unable to associate with TRAF2. In a second model, we examined several mutant forms of BAFFR that are unable to induce NF-κB2 activation in B cells. Signaling to B cells by each of these BAFFR mutants, however, induced levels of TRAF3 degradation similar to those induced by Wt BAFFR. Thus, in B cells, receptor-mediated TRAF3 degradation is not sufficient to promote NF-κB2 activation. We thus conclude that there is not a simple linear relationship in B lymphocytes between relative levels of cellular TRAF3, induced TRAF3 degradation, NIK activation, and NF-κB2 activation.


Stress-related expectations about smoking cessation and future quit attempts and abstinence - a prospective study in daily smokers who wish to quit.
Smokers who wish to quit may refrain from doing so if they expect to experience more stress after haven given up. We test if stress-related expectations about smoking cessation are associated with quit attempts and abstinence among smokers who are motivated to quit. The study included 1809 daily smokers in Denmark in 2011-2013. Stress-related expectations (do you think you will be more, less or equally stressed as a non-smoker?) were measured at baseline. Quit attempts, 30-day point prevalence abstinence and prolonged abstinence (defined as having been abstinent since baseline), were measured after 3, 8 and 14 months. We found that the association between expecting to be more stressed if giving up smoking differed between participants who had previously attempted to quit and those who had not: In participants who previously attempted to quit (47%), expecting to be more stressed was associated with significantly lower odds of abstinence compared to smokers who expected the same or a lower level of stress (odds ratios were 0.49 (95% CI: 0.31-0.79) for 30-day abstinence and was 0.28 (95% CI: 0.08-0.99) for prolonged abstinence). In participants who had not previously attempted to quit, expectations about stress were not associated with abstinence. Results indicate that expectations about stress in relation to smoking cessation are an important determinant of cessation in smokers who previously attempted to quit. Addressing stress and how to handle stressful situations may increase the likelihood of a successful quit attempt.


Gender differences in neighborhood walking in older adults.
This study examined mobility, self-efficacy, outcome expectations, neighborhood (density, destinations, and design), and neighborhood walking in older men (n = 106, 60-99 years, M = 76.78, SD = 8.12) and women (n = 216, 60-99 years, M = 75.81, SD = 8.46). In hierarchical regression, the variables explained 32% of the variance in neighborhood walking in men (p < .001) and 27% of the variance in women (p < .01). Self-efficacy (β = .49, p < .01), density (β= .22, p < .05), and design (β= .21, p = .05) were associated with walking in men. Significant design characteristics included sidewalks (β= .25, p < .05) and crime (β= .36, p < .01). In women, self-efficacy (β= .48, p < .001) and destinations (β= .15, p < .05) were associated with walking. Walking was associated with self-efficacy for walking despite individual barriers in women (β= .38, p < .001) and neighborhood barriers in men (β= .30, p < .05). Walking interventions targeting older women should incorporate local destinations. In older men, interventions should consider neighborhood sidewalk design and crime. Walking interventions for all older adults should include enhancement of self-efficacy, but gender differences may exist in the types of self-efficacy on which to focus.


Influence of the effective microorganisms (EM) on performance, intestinal morphology and gene expression in the jejunal mucosa of pigs fed different diets.
The aim of the study was to determine the influence of the effective microorganisms (EM) on performance parameters, intestinal morphology and gene expression in the jejunal mucosa in pigs under different feeding regimes. The study group comprised of 150 piglets divided into three feeding groups: C, E1 and E2. Feeding groups included: C-standard fodder, blend with a full share of post-extracted soy meal, E1-in the phase I of fattening: pea and lupin/soybean 50/50%; in the phase II of fattening: pea and lupin/soybean 75/25%, and E2-in the phase I of fattening: pea and lupin/soybean 50/50%; in the phase II of fattening: pea and lupin 100%. The experimental factor was addition of a probiotic EM Carbon Bokashi to the diets (C + EM, E1 + EM and E2 + EM). After slaughter, histological evaluation and gene expression analysis were performed. The highest intestinal villi were reported in E2 + EM. A higher intestinal absorption area was demonstrated in groups C + EM and E2 + EM. An interaction between feeding and EM Bokashi supplementation was found in villus surface area crypt depth, villus height/crypt depth and number of goblet cells. Mucosa thickness and number of goblet cells was the largest in E2 + EM. Gene expression of FABP4 increased in E1, and GLUT2 decreased in E2. Gene expression of IL10 and FABP4 increased in E2 + EM. The results indicate that the E2 diet is more optimal for EM Bokashi supplementation, because in this group, EM positively influenced the morphological characteristics of the porcine jejunum and caused an increase in the expression of genes related to the metabolism and functioning of the gastrointestinal tract.


[Dispensary registration groups and follow-up periods of patients with silicotuberculosis].
Silicosis is the most common and most frequently tuberculosis-complicated pneumoconiosis with poor prognosis. So a procedure for following up patients with silicotuberculosis requires revision and elaboration. Long-term follow-ups have made it possible to define early signs of this disease and to propose a number of techniques for its early diagnosis, such as chest computed tomography and polarization serum crystal microscopy. Specific recommendations on follow-ups of patients with silicosis and silicotuberculosis by a phthisiologist are laid down.


Oceanihabitans sediminis gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from the Yellow Sea.
A Gram-stain-negative, rod-shaped bacterial strain, designated S9-10T, was isolated from a sediment sample from the Yellow Sea near China. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain S9-10T was a member of the family Flavobacteriaceaeand formed a distinct lineage. The genomic DNA G+C content of strain S9-10T was 34.2 mol%. The major respiratory quinone was MK-6. The predominant cellular fatty acids were iso-C15 : 0 (21.1 %), iso-C15 : 1G (16.3 %) and iso-C17 : 0 3-OH (12.0 %). The polar lipid profile contained phosphatidylethanolamine, aminophospholipid, aminoglycolipid, two unidentified aminolipids and five unidentified polar lipids. On the basis of phenotypic, genotypic, chemotaxonomic and phylogenetic analyses, strain S9-10T represents a novel species of a novel genus of the family Flavobacteriaceae, for which the name Oceanihabitans sediminis gen. nov., sp. nov. is proposed. The type strain of Oceanihabitans sediminis is S9-10T (=DSM 28133T =LMG 28074T).


How to Improve Fault Tolerance in Disaster Predictions: A Case Study about Flash Floods Using IoT, ML and Real Data.
The rise in the number and intensity of natural disasters is a serious problem that affects the whole world. The consequences of these disasters are significantly worse when they occur in urban districts because of the casualties and extent of the damage to goods and property that is caused. Until now feasible methods of dealing with this have included the use of wireless sensor networks (WSNs) for data collection and machine-learning (ML) techniques for forecasting natural disasters. However, there have recently been some promising new innovations in technology which have supplemented the task of monitoring the environment and carrying out the forecasting. One of these schemes involves adopting IP-based (Internet Protocol) sensor networks, by using emerging patterns for IoT. In light of this, in this study, an attempt has been made to set out and describe the results achieved by SENDI (System for dEtecting and forecasting Natural Disasters based on IoT). SENDI is a fault-tolerant system based on IoT, ML and WSN for the detection and forecasting of natural disasters and the issuing of alerts. The system was modeled by means of ns-3 and data collected by a real-world WSN installed in the town of São Carlos - Brazil, which carries out the data collection from rivers in the region. The fault-tolerance is embedded in the system by anticipating the risk of communication breakdowns and the destruction of the nodes during disasters. It operates by adding intelligence to the nodes to carry out the data distribution and forecasting, even in extreme situations. A case study is also included for flash flood forecasting and this makes use of the ns-3 SENDI model and data collected by WSN.


Genetic variations in the alanine-glyoxylate aminotransferase 2 (AGXT2) gene and dimethylarginines levels in rheumatoid arthritis.
Rheumatoid arthritis (RA) is associated with high rates of cardiovascular events mainly due to coronary and cerebrovascular atherosclerotic disease. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines are endogenous inhibitors of nitric oxide synthase and have been repeatedly linked with adverse cardiovascular outcomes in the general population and various disease settings. Alanine-glyoxylate aminotransferase 2 (AGTX2) is considered an alternative metabolic pathway contributing to the clearance of dimethylarginines in humans. The aim of the current study was to investigate the effect of specific AGXT-2 gene polymorphisms on circulating levels of ADMA or SDMA in patients with RA. Serum ADMA and SDMA levels were measured in 201 individuals with RA [median age: 67 years (IQR: 59-73), 155 females]. Two single nucleotide polymorphisms (SNPs) in the AGXT-2 gene-rs37369 and rs28305-were genotyped. Distributions of SDMA and ADMA were skewed, hence comparisons across the gene polymorphisms were performed using Kruskal-Wallis tests, and summarized using medians and interquartile ranges. Univariable analysis did not demonstrate a significant difference in the levels of SDMA or ADMA amongst the different genotypic groups of either rs37369AGXT2 (p = 0.800, 0.977) or rs28305AGXT2 (p = 0.463, 0.634). In multivariable analyses, ADMA levels were found to be significantly associated with erythrocyte sedimentation rate and estimated glomerular filtration rate, whilst SDMA levels were significantly associated with estimated glomerular filtration rate and quantitative insulin sensitivity check index. After adjustments for these factors, the relationship between the AGXT2 gene variants and both ADMA and SDMA remained non-significant. Our study in a well-characterized RA population did not show an association between serum concentrations of dimethylarginines and genetic variants of the AGXT2 gene.


Effects of Prepartum Dietary Energy Level and Nicotinic Acid Supplementation on Immunological, Hematological and Biochemical Parameters of Periparturient Dairy Cows Differing in Parity.
The periparturient period is critical according to health, productivity and profitability. As this period is fundamental for the success of the lactation period, the interest in improving periparturient health by dietary supplements increased in recent years. The present study investigated the effects of feeding nicotinic acid (NA) combined with varying dietary energy densities on immunological, hematological and biochemical parameters of periparturient cows differing in parity. Thirty-six multiparous and 20 primiparous dairy cows were enrolled in the study 42 days before expected parturition date until 100 days postpartum with the half of the cows being supplemented with 24 g of NA/d. After parturition a diet with 30% concentrate was fed to all cows which was followed by different concentrate escalation strategies. Dietary NA supplementation was ceased on day 24 postpartum. Dietary NA increased (P = 0.010) serum nicotinamide concentrations (mean of 3.35 ± 1.65 µg/mL), whereas NA could not be detected. Present data emphasize that periparturient cows are faced with major physiological challenges and that both parity-groups have different prerequisites to adapt to those changes irrespective of NA supplementation. The overfeeding of energy to cows which were similar in body condition score had only minor effects on periparturient immune system function and the metabolism of those cows.


Management of Chronic Lymphocytic Leukemia in Less-Resourced Countries.
Despite the practice-changing advances achieved in the prognostic stratification and treatment of chronic lymphocytic leukemia (CLL), a large fraction of the world population resides in countries where access to many of these advances remains unavailable or subject to severe constraints. Although some of these countries display incidence rates of CLL that are lower than those of developed Western countries, a large number of patients are expected to be diagnosed with CLL in these regions every year. In this article, we review issues regarding management of CLL in some less-resourced countries, with a focus on the evidence basis for epidemiological and clinical information on this disease, the availability of diagnostic and therapeutic resources, and participation in clinical trials. Going forward, challenges that still need to be addressed include the development of unified countrywide registries, guidelines for management applicable to each country, wider availability of prognostic tools, access to new drugs, and policies that ensure these drugs are affordable to all patients worldwide.


Long Non-Coding RNA SNHG14 Contributes to the Development of Hepatocellular Carcinoma via Sponging miR-217.
Thousands of long non-coding RNAs (lncRNAs) have been functionally verified as crucial regulators of physiological processes and disease progressions, yet their roles in hepatocellular carcinoma (HCC) have not been clearly illuminated. We analyzed the expression of lncRNA-SNHG14 in TCGA data via bioinformatic analysis and detected its expression in HCC specimens by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Loss-of-function experiments were used to study the biological function of SNHG14 in HCC cells. RT-qPCR, Western blotting and dual-luciferase reporter assay were carried out to investigate the molecular mechanism of SNHG14 in HCC. The upregulation of lncRNA-SNHG14 was observed in HCC tissues compared with normal tissues via RT-qPCR and bioinformatic analysis of TCGA data. Silencing of SNHG14 inhibited cell proliferation and induced cell apoptosis in HCC cells. microRNA-217 (miR-217), the tumor-suppressive miRNA in HCC, was predicted and confirmed as a miRNA sponged by SNHG14 in HCC cells. Via downregulation of miR-217, SNHG14 increased the expression of several miR-217-related oncogenes and subsequently activated oncogene-related signaling pathways in HCC cells. In addition, inhibition of miR-217 reversed SNHG14 silencing induced decrease of cell proliferation and increase of cell apoptosis. Their association was verified in the published microarray dataset and the collected HCC samples. In summary, SNHG14 is involved in the development of HCC via sponging miR-217 and it may be a biomarker for patients with HCC.


Mechanism of action of mRNA-based vaccines.
The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines. Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration and effects of mRNA delivery systems. Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine.


Factors resulting in postoperative dysphagia following esophagectomy: a narrative review.
Esophagectomy is a technically involved surgery and can have significant postoperative morbidity. Although the mortality rate following esophagectomy has decreased in recent years, this surgical procedure has a relatively high complication rate compared to other surgeries to resect cancer. One of the most common complaints after esophagectomy is dysphagia. Dysphagia after esophagectomy can significantly affect quality of life. Dysphagia is a complication following esophagectomy that can lead to respiratory deterioration and death. The most common sites of postoperative dysphagia are the gastroesophageal anastomosis, gastric conduit, pylorus and the hiatus. Without appropriate treatment of dysphagia, malnutrition and dehydration can develop. These factors can lead to significant impacts to the overall health of a patient and increase mortality. A detailed literature review provided data to support diagnostic modalities and management strategies to treat postoperative dysphagia at these common areas. A systematic, evidence-based approach to diagnosis and treatment of postoperative dysphagia allows for prompt intervention and a decrease in morbidity and mortality. Treatment options for dysphagia vary, depending on the etiology. Based on the location and mechanism of dysphagia, options include stenting, dilation and surgical revision. Early treatment of dysphagia after esophagectomy can lessen the morbidity from this complication and improve quality of life.


[Transurethral plasma resection of the prostate for acute urinary retention in patients with advanced prostate cancer].
To compare the safety of transurethral plasma resection of the prostate (TuPkRP) in the treatment of advanced PCa (APC)-related acute urinary retention (AUR) with that in the treatment of BPH-related AUR and investigate the oncologic characteristics of the PCa patient after TuPkRP. In this retrospective study, we first compared the baseline data between the patients with APC-related AUR (group A, n = 32) and those with BPH-related AUR (group B, n = 45) as well as their surgical parameters, such as the operation time, pre- and post-operative hemoglobin levels, IPSS at 3 months after TuPkRP and length of postoperative hospital stay. Then, we observed possible TuPkRP-induced tumor progression by comparing the oncologic parameters, such as the PSA level and ECT-manifested bone metastasis, between the APC-AUR patients treated by androgen-deprivation therapy (ADT) + TuPkRP and those treated by ADT only (group C, n = 24). There were no statistically significant differences in the baseline data between the APC-AUR and BPH-AUR patients (P > 0.05). The operation time and postoperative hospital stay were significantly longer in the APC-AUR than in the BPH-AUR group (P < 0.05), but the decreases in the hemoglobin level and IPSS at 3 months after operation showed no significant differences between the two groups of patients (P > 0.05). Besides, no statistically significant differences were observed in the oncologic parameters between the APC-AUR patients treated by ADT + TuPkRP and those by ADT only (P > 0.05). The safety of TuPkRP was not significantly lower and the rates of postoperative complications and adverse events were not significantly higher in the patients with APC-related AUR than in those with BPH-related AUR. And this surgical strategy did not significantly improve the progression of APC.


Refining livestock mortality indicators: a systematic review.
Background: Livestock mortality impacts farmer livelihoods and household nutrition. Capturing trends in livestock mortality at localised or national levels is essential to planning, monitoring and evaluating interventions and programs aimed at decreasing mortality rates. However, livestock mortality data is disparate, and indicators used have not been standardised. This review aims to assess livestock mortality indicator definitions reported in literature, and define the ages where mortality has greatest impact. Methods: A systematic review was conducted, limited to articles focussed on mortality of cattle, sheep and goats. Peer-reviewed articles in Web of Science until year 2020 were assessed for inclusion of age-based definitions for mortality indicators and data on age distribution of mortality. Indicator definitions for each species were collated and similar terms and age groups most targeted were compared. The cumulative distribution of age at mortality was compared across studies graphically where possible; otherwise, age patterns for mortality were collated. Results: Most studies reported mortality risk rather than rate, and there was little agreement between indicator definitions used in the literature. The most common indicators reported were perinatal and neonatal mortality in cattle, and for perinatal, neonatal and pre-weaning mortality indicators for sheep and goats. Direct comparison of age distribution of mortality was only possible for cattle, which found that approximately 80% of all mortalities within the first 12 months had occurred by six months of age. A significant finding of the study is the variation in age groups for which mortality is reported, which impedes the comparison of mortality risk across studies, particularly for sheep and goats. Conclusions: This study demonstrates the importance and value of standardising mortality risk indicators for general use, including a young stock mortality risk indicator measuring mortality in the highest risk period of birth to six months of age in cattle, sheep and goats.


Elucidation of relaxin-3 binding interactions in the extracellular loops of RXFP3.
Relaxin-3 is a highly conserved neuropeptide in vertebrate species and binds to the Class A G protein-coupled receptor (GPCR) RXFP3. Relaxin-3 is involved in a wide range of behaviors, including feeding, stress responses, arousal, and cognitive processes and therefore targeting of RXFP3 may be relevant for a range of neurological diseases. Structural knowledge of RXFP3 and its interaction with relaxin-3 would both increase our understanding of ligand recognition in GPCRs that respond to protein ligands and enable acceleration of the design of drug leads. In this study we have used comparative sequence analysis, molecular modeling and receptor mutagenesis to investigate the binding site of the native ligand human relaxin-3 (H3 relaxin) on the human RXFP3 receptor. Previous structure function studies have demonstrated that arginine residues in the H3 relaxin B-chain are critical for binding interactions with the receptor extracellular loops and/or N-terminal domain. Hence we have concentrated on determining the ligand interacting sites in these domains and have focused on glutamic (E) and aspartic acid (D) residues in these regions that may form electrostatic interactions with these critical arginine residues. Conserved D/E residues identified from vertebrate species multiple sequence alignments were mutated to Ala in human RXFP3 to test the effect of loss of amino acid side chain on receptor binding using a Eu-labeled relaxin-3 agonist. Finally data from mutagenesis experiments have been used in ligand docking simulations to a homology model of human RXFP3 based on the peptide-bound chemokine receptor 4 (CXCR4) structure. These studies have resulted in a model of the relaxin-3 interaction with RXFP3 which will inform further interrogation of the agonist binding site.


Trends in survival rates after allogeneic hematopoietic stem-cell transplantation for acute and chronic leukemia by ethnicity in the United States and Canada.
Differences in survival among ethnic groups in the United States are reported in numerous diseases and treatment strategies. Whether survival after allogeneic hematopoietic stem-cell transplantation (HSCT) differs by ethnicity is uncertain. Patients (n = 6443) receiving HLA-identical sibling HSCT for acute or chronic leukemia in the United States or Canada between 1985 and 1999 and reported to the International Bone Marrow Transplant Registry were included. The survival of recipients reported as white, black, Hispanic, or Asian was compared using Cox proportional hazards regression adjusting for other clinical factors. Three 5-year periods were studied to evaluate changes over time. Hispanics compared with whites had lower 1-year (53% v 65%; P <.001) and 3-year adjusted survival rates (38% v 53%; P <.001) between 1995 and 1999, the most recent period studied. We failed to find significant differences in survival rates comparing whites with blacks or with Asians in any of the time periods. Overall survival for the entire cohort improved over time, from 56% to 63% at 1 year and from 43% to 51% at 3 years, with greater improvements noted among blacks (45% to 61% at 1 year and 34% to 48% at 3 years). Disparities remain in survival rates between whites and Hispanics despite adjustment for clinical factors. Factors not accounted for in this analysis, such as comorbid disease, socioeconomic status, healthcare access and delivery, and psychosocial and cultural variables, require further prospective study.


Role of uncoupling protein 3 in ischemia-reperfusion injury, arrhythmias, and preconditioning.
Overexpression of mitochondrial uncoupling proteins (UCPs) attenuates ischemia-reperfusion (I/R) injury in cultured cardiomyocytes. However, it is not known whether UCPs play an essential role in cardioprotection in the intact heart. This study evaluated the cardioprotective efficacy of UCPs against I/R injury and characterized the mechanism of UCP-mediated protection in addition to the role of UCPs in ischemic preconditioning (IPC). Cardiac UCP3 knockout (UCP3(-/-)) and wild-type (WT) mice hearts were subjected to ex vivo and in vivo models of I/R injury and IPC. Isolated UCP3(-/-) mouse hearts were retrogradely perfused and found to have poorer recovery of left ventricular function compared with WT hearts under I/R conditions. In vivo occlusion of the left coronary artery resulted in twofold larger infarcts in UCP3(-/-) mice compared with WT mice. Moreover, the incidence of in vivo I/R arrhythmias was higher in UCP3(-/-) mice. Myocardial energetics were significantly impaired with I/R, as reflected by a decreased ATP content and an increase in the AMP-to-ATP ratio. UCP3(-/-) hearts generated more reactive oxygen species (ROS) than WT hearts during I/R. Pretreatment of UCP3(-/-) hearts with the pharmacological uncoupling agent carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone improved postischemic functional recovery. Also the protective efficacy of IPC was abolished in UCP3(-/-) mice. We conclude that UCP3 plays a critical role in cardioprotection against I/R injury and the IPC phenomenon. There is increased myocardial vulnerability to I/R injury in hearts lacking UCP3. The mechanisms of UCP3-mediated cardioprotection include regulation of myocardial energetics and ROS generation by UCP3 during I/R.


Invasion of the choroid plexus epithelium by Neisseria meningitidis is differently mediated by Arp2/3 signaling and possibly by dynamin dependent on the presence of the capsule.
Neisseria meningitis (Nm) is a human-specific bacterial pathogen that can cause sepsis and meningitis. To cause meningitis Nm must enter the central nervous system (CNS) across one of the barriers between the blood and the brain. We have previously shown that a capsule-depleted Serogroup B strain of Nm displays enhanced invasion into human choroid plexus (CP) epithelial papilloma (HIBCPP) cells, which represent an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB). Still, the processes involved during CNS invasion by Nm, especially the role of host cell actin cytoskeleton remodeling, are not investigated in detail. Here, we demonstrate that invasion into CP epithelial cells by encapsulated and capsule-depleted Nm is mediated by distinct host cell pathways. Whereas a Serogroup B wild-type strain enters HIBCPP cells by a possibly dynamin-independent, but actin related protein 2/3 (Arp2/3)-dependent mechanism, invasion by a capsule-depleted mutant is reduced by the dynamin inhibitor dynasore and Arp2/3-independent. Both wild-type and mutant bacteria require Src kinase activity for entry into HIBCPP cells. Our data show that Nm can employ different mechanisms for invasion into the CP epithelium dependent on the presence of a capsule.


Computed tomography and cross-sectional anatomy of the head in the red fox (Vulpes vulpes).
The red fox (Vulpes vulpes) is a universally widespread wild carnivore in the world. It has an important impact on human interests and plays a vital role in conservation biology. There is no report to describe computed tomography (CT) of the red fox head and its correlation with gross anatomy. Therefore, the intent of the present study was to document, by CT, the basic anatomical structures in the head region of the red fox to lay the groundwork of an appropriate anatomical description of the head structures comparable with traditional dissection technique. Three red fox heads were imaged sagittally and transversely using CT scanner. Six red fox heads were then serially cut, sagittally and transversely, by an electric band saw, and the obtained slices were cleaned and photographed. Different anatomical structures on CT images and the corresponding anatomic sections were identified and labelled. CT images revealed an excellent three-dimensional definition of bony structures of the entire craniofacial region. Moreover, CT scans revealed different contrasts between bones, oral and nasal cavities, paranasal sinuses and pharynx which enabled good visualization of those structures. The paranasal sinus system in red fox was poorly developed and represented by a frontal sinus and a small sphenoid sinus, in addition to a maxillary recess. In conclusion, the series of CT images of the normal red fox head presented in the current study will serve as an anatomical reference for the normal head of the red fox, which in turn will improve knowledge for clinical interpretation.


Elastic critical behavior in a three-dimensional model for polymer gels.
The elastic response in polymeric gels is studied by means of a percolation dynamic model. By numerical simulations the fluctuations in the gyration radius and in the center-of-mass motion of the percolating cluster are determined. Their scaling behavior at the gelation threshold gives a critical exponent for the elastic modulus f approximately 2.5+/-0.1 in agreement with the prediction f=dnu.


Allele Frequency Changes Provide Evidence for Selection and Identification of Candidate Loci for Survival in Red Clover (Trifolium pratense L.).
Survivor populations of red clover (Trifolium pratense L.) from plots in a field experiment in southern Norway were genetically characterized using genotyping by sequencing, and compared with the original population and each other. Genetic differentiation between populations was characterized on the basis of allele frequencies of single nucleotide polymorphisms (SNPs), using principal component analysis. SNPs that had been under selection, i.e., SNPs with significantly different allele frequencies in survivor populations relative to the original population, or between survivor populations that had received different treatments, were identified by analysis of F ST values, using BayeScan and a simple and stringent F ST-based test utilizing replicate populations from the field experiment. In addition, we tested the possibility of pooling DNA samples prior to sequencing, and pooling leaf samples prior to DNA extraction and sequencing, followed by allele frequency estimation on the basis of number of variant reads. Overall, survivor populations were more different from each other than from the original population, indicating random changes in allele frequency, selection in response to local variation in conditions between plots in the field experiment, or sampling error. However, some differentiation was observed between plots sown as pure stands or species mixtures, plots sown at different densities, and plots subjected to different harvesting regimes. Allele frequencies could be accurately estimated from pooled DNA, and SNPs under selection could be identified when leaf samples were pooled prior to DNA extraction. However, substantial sampling error required replicate populations and/or a high number of sampled individuals. We identified a number of chromosomal loci that had been under selection in pure stand plots relative to the original sown population, and loci that had been under differential selection in pure stands of red clover vs. red clover grown in species mixtures. These are all candidate loci for establishment success or persistence in red clover.


Vertebral locking lesion following cervical spine fracture in ankylosing spondylitis.
Spine fractures in patients with ankylosing spondylitis frequently extend to all 3 columns, which can lead to displacement and deformity with severe instability. Cervical spine fractures occasionally cause severe kyphotic deformities, such as chin-on-chest deformities. In such cases, the patients typically exhibit a chronic progression of hyperkyphosis after the traumatic event. This article describes a unique case of ankylosing spondylitis associated with an acute chin-on-chest deformity following a spine fracture due to a vertebral locking lesion.A 60-year-old man fell while walking and sustained a compression fracture of the C6 vertebra. Two weeks later, the patient acutely developed an inability to raise his head, difficulties with chewing and swallowing, and a horizontal gaze. Radiographs demonstrated a severe kyphosis in the cervical spine with a locking lesion between the anterior wall of the C5 and C6 vertebrae. The patient also presented with neurological impairment in his hands. Because the anterior approach to the spine was anatomically impossible, halo traction was initially applied under a close observation of neurological symptoms. Three days after halo traction, release of the vertebral locking lesion and realignment of the spine were seen. The patient subsequently underwent spinal fusion using a combined anterior-posterior approach.Postoperatively, neurological dysfunction improved, and solid fusion was confirmed at 6 months. In cases of acute kyphotic deformity following cervical spine fracture in ankylosing spondylitis patients, halo traction followed by circumferential spine fusion is a safe and effective approach for improving the alignment and stability of the spine.


Human β Defensin-3 Increases CD86 Expression on Monocytes by Activating the ATP-Gated Channel P2X7.
Human β defensin-3 (hBD-3), an epithelial cell-derived antimicrobial peptide, mediates chemotaxis and activation of myeloid cells. In this study, we provide evidence that hBD-3 induces the costimulatory molecule CD86 on primary human monocytes by a mechanism involving autocrine activation of ionotropic P2X7 receptors (P2X7R) by ATP. Incubation of monocytes with hBD-3 resulted in increased expression of both the CD80 and CD86 costimulatory molecules. Treatment of monocytes with a selective P2X7R antagonist inhibited the ability of hBD-3 to induce expression of CD86 but not CD80. The hBD-3-dependent upregulation of CD86 was also attenuated in monocytes incubated with apyrase, a potent scavenger of extracellular ATP. Finally, direct activation of monocyte P2X7R by exogenous ATP mimicked the ability of hBD-3 to induce CD86 expression. These data suggest that hBD-3 induces monocyte activation by both P2X7-dependent (CD86 upregulation) and P2X7-independent (CD80 upregulation) signaling mechanisms and raise the possibility that activation of P2X7R could play an important role in shaping the inflammatory microenvironment in conditions where hBD-3 is highly expressed, such as psoriasis or oral carcinoma.


Absence of tumor growth stimulation in a panel of 16 human tumor cell lines by mistletoe extracts in vitro.
Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. The mistletoe lectins have been identified as the main active principle of mistletoe extracts. They have been shown to exhibit cytotoxic effects as well as immunomodulatory activities. The latter is exemplified by induction of cytokine secretion and increased activity of natural killer cells. Recent reports, however, indicated possible tumor growth stimulation by mistletoe extracts. Therefore, the three aqueous mistletoe extracts (Iscador M special, Iscador Qu special and Iscador P) were evaluated for antiproliferative and/or stimulatory effects in a panel of 16 human tumor cell lines in vitro using a cellular proliferation assay. The results show no evidence of stimulation of tumor growth by any of the three Iscador preparations, comprising central nervous system, gastric, non-small cell lung, mammary, prostate, renal and uterine cancer cell lines, as well as cell lines from hematological malignancies and melanomas. On the contrary, Iscador preparations containing a high lectin concentration (Iscador M special and Iscador Qu special) showed antitumor activity in the mammary cancer cell line MAXF 401NL at the 15 microg/ml dose level with a more than 70% growth inhibition compared to untreated control cells. In addition, a slight antitumor activity (growth inhibition 30-70%) was found in three tumor cell lines for Iscador M special and in seven tumor cell lines for Iscador Qu special, respectively. Iscador P, which contains no mistletoe lectin I, showed no antiproliferative activity.


Synthetic peptides in the study of the interaction of rabies virus and the acetylcholine receptor.
The neurotropism of some viruses may be explained in part by the attachment of these viruses to host cell receptors that are present on or even largely restricted to neurons. Rabies virus is an RNA virus that, after a period of replication in muscle, gains access to the central nervous system, where it selectively infects certain neuronal populations. The nicotinic acetylcholine receptor occurs in high density at the neuromuscular junction and is present in the central nervous system. Although several different cell surface constituents may act as attachment determinants for rabies, direct binding of radioactively labeled virus to affinity-purified acetylcholine receptor has been demonstrated. Binding of virus to the receptor was saturable and inhibited by up to 50% by alpha-bungarotoxin, a snake venom neurotoxin that binds at or near the acetylcholine binding site on the receptor. The molecular basis for the virus-receptor interaction may lie in an amino acid sequence similarity between the snake venom neurotoxins and a segment of the rabies virus glycoprotein. Two peptides (10 and 13 residues) of the rabies virus glycoprotein and homologous bungarotoxin peptides were synthesized and tested for ability to compete with labeled alpha-bungarotoxin for binding to the acetylcholine receptor. The peptides were found to compete with toxin binding with affinities comparable to those of the cholinergic ligands d-tubocurarine and nicotine. These findings indicate that a segment of the rabies virus glycoprotein interacts with the acetylcholine receptor at or near the acetylcholine binding site of the receptor. The similarity between the virus glycoprotein and the neurotoxin was further evidenced by the cross reaction of antibody raised against the virus 10-mer with the bungarotoxin 10-mer. Binding of rabies virus to the acetylcholine receptor or to other neuronal bungarotoxin-binding proteins may be related to the neurotropism of this virus. In addition, knowledge of both the region of the virus involved in binding and the binding domain on the receptor may be helpful in developing new strategies for treatment, especially for viruses that infect the central nervous system or evade the immune response through genetic drift. These strategies include development of antiviral agents that cross the blood-brain barrier and inhibit viral binding and the utilization as immunogens the regions of viruses, such as their binding domains, that are highly conserved among different strains.


Focal therapy in prostate cancer: determinants of success and failure.
Focal therapy is emerging as a potential challenge to the standard of care for localized prostate cancer. Short-term quality-of-life outcomes such as genitourinary side effects, anxiety levels, and global measures of quality of life using validated questionnaires are vital although proof-of-concept trials and retrospective case series have already established lower toxicity from focal therapy in some detail. Defining what outcomes will be measured and what defines a successful focal treatment in the medium and long term is problematic. Measuring long-term efficacy or effectiveness within a randomized trial is somewhat straightforward since hard endpoints are measured such as presence or absence of metastatic disease and/or death. However, owing to the long natural history of localized prostate cancer detected in the modern prostate-specific antigen screening era, with these events usually occurring a minimum of 10 years after therapy makes such a long-term trial large, costly, and probably unfeasible now. This article discusses the optimal determinants of success or failure for focal therapy that require careful consideration within multicenter trials evaluating medium-term oncological efficacy.


Effects of insertions and deletions in a beta-bulge region of Escherichia coli dihydrofolate reductase.
The role of a beta-bulge in Escherichia coli dihydrofolate reductase (DHFR) has been explored by a series of insertion and deletion mutations. Insertion of a seven amino acid sequence from a structurally equivalent 'beta-blowout' sequence from human DHFR destabilizes E. coli DHFR by 3.6 kcal/mol and decreases catalytic efficiency (kcat/K(m)) 34-fold. Deletion of F137, delta 137, the looped out residue in the bulge, also destabilizes E. coli DHFR by 2.8 kcal/mol but only decreases catalytic efficiency threefold. Concurrent deletion of F137 and mutation of, V136 to proline to try and maintain the strand twist associated with the beta-bulge decreases protein stability by 3.4 kcal/mol and decreases catalytic efficiency 84-fold. These insertion/deletion mutations were also constructed in a D27S DHFR background. The D27S mutation has been described previously and proposed to remove the catalytic acid from the active site. The delta 137 mutation partially suppresses the effect of the D27S mutation as it decreases the K(m) for substrate, dihydrofolate, twofold. Non-additive effects are observed for the insertion/deletion mutations in wild-type versus D27S DHFR backgrounds, consistent with structural changes.


Effects of diode laser irradiation on dental pulps in rats.
To evaluate the effects of different power densities of diode laser on dental pulps in rats. In this study, we used the maxillary central incisors (n=80) of the 40 adult male Wistar albino rats. Rats were randomly divided into four groups according to power densities of diode laser (n=10). Histopathological changes in pulp and height of odontoblast layer were examined . All data were compared statistically using Mann‒Whitney U (Bonferroni) test, p<0.05. G2 displayed slight histolopathologic alterations such as odontoblast cell disorganization and irregularities in cell extensions. Alterations were more prominent in the G3 than G2. Although the lowest odontoblast layer was measured in the G4, the difference in height of odontoblast layer among the groups was not found to be statistically significant. It was concluded that the use of diode laser caused changes at the cellular level in histological examination and may induce the formation of tertiary dentin by influencing the secretory activity of odontoblasts. As long as used in accordance with the recommended procedure, the diode laser can be safely used in dental hard tissues (Tab. 1, Fig. 4, Ref. 15).


[Serological characteristic and molecular basis of A2 subgroup in Shanghai population].
To investigate the similarity and difference in blood group serology and molecular biology of A2 and A2B phenotypes between healthy blood donors and patients. The A and AB phenotypes were screened with anti-A1. Exons 1 to 7 and intron 6 of the ABO gene were analyzed with polymerase chain reaction-sequence-based typing (PCR-SBT) method. The blood type was determined by referring to the Blood Group Antigen Gene Mutation Database (BGMUT). Among 7111 tested individuals, 75 were assigned as A2 or A2B phenotypes. However, only 28 individuals still belonged to the A2-related allele group based on genetic analysis. Among these, A205/B101 was the most common genotype. Among those non-A2-related alleles, A102/B101 was the most common genotype. Based on serologic testing, there was an imbalance between the A2 and A2B subgroups. In both donor group and patient group, the proportion of A2B was significantly higher than that of the A2. There were statistical differences between different groups (χ² = 64.613, 33.137, 34.963, P< 0.01). At the gene level, the imbalance still existed in both the overall population and the donor group, though there was a statistical difference between the two (χ² = 17.678, 14.157, P< 0.01). The same imbalance did not exist in the patient group (with continuous correction, χ² = 2.351, P= 0.125). The concordance rate for blood type determined by serology and genetic analysis has been low and deserves attention. For A2 and A2B phenotypes by serological screening, A102/B101 was the most common gene among non-A2-related alleles. Further study is needed to clarify this phenomenon.


Risk management in a community Gamma Knife unit.
The records of the San Diego Gamma Knife Center were retrospectively reviewed for unprogrammed events as part of a risk management assessment. Review was made of the physicist notes of the first 1,000 patients successfully treated at the center. This encompassed 1,020 stereotactic frame placement procedures, accompanied by Gamma Knife radiosurgery in 98.0% of intended cases. A total of 7,145 Gamma Knife shots were delivered to 1,509 lesions. Of the 43 unprogrammed events documented, 8 were patient related and 14 were related to lesion growth or location; these were considered unavoidable. Further, one event was related to dose administration, 5 to diagnosis, 15 to technique; these were considered potentially avoidable. This yielded an avoidable error rate of 2.1% per patient, 1.4% per lesion treated, and 0.29% per shot. It was clear that more avoidable errors occurred early in the center's operation, consistent with a learning curve. Review of individual physician's cases revealed none appeared more likely to have an avoidable event. Consistently high quality may be achieved at a community-based Gamma Knife center if sufficient multidisciplinary involvement is achieved.