Efficacy of Persian barley water on clinical outcomes of hospitalized moderate-severity COVID-19 patients: a single-blind, add-on therapy, randomized controlled clinical trial.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a debilitating disease with numerous medical and non-medical consequences. Our study aimed to evaluate the efficacy of Persian barley water in controlling the clinical outcomes of hospitalized COVID-19 patients. PATIENTS AND METHODS: This was a single-blind, add-on therapy, randomized controlled clinical trial conducted in Shiraz, Iran, from January to March 2021. One hundred hospitalized COVID-19 patients with moderate disease severity were randomly allocated to receive routine treatment (per local protocols) with or without 250 ml of Persian barley water (PBW) daily for two weeks. Clinical outcomes and blood tests were recorded before and after the study period. Multivariable modeling was applied using Stata software for data analysis. RESULTS: The PBW product passed our standardization and safety assessments. Length of hospital stay (LHS) was 4.5 days shorter in the intervention group than the control group regardless of history of cigarette smoking (95% confidence interval: -7.22, -1.79 days). Also, body temperature, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and creatinine significantly dropped in the intervention group compared to the control group. No adverse events related to PBW occurred. CONCLUSIONS: This clinical trial demonstrated the efficacy of PBW in minimizing the LHS, fever, and levels of ESR, CRP, and creatinine among hospitalized COVID-19 patients with moderate disease severity. More robust trials can help find safe and effective herbal formulations as treatments for COVID-19.

Evidence on yoga for health: A bibliometric analysis of systematic reviews.

OBJECTIVE: To support the research agenda in yoga for health by comprehensively identifying systematic reviews of yoga for health outcomes and conducting a bibliometric analysis to describe their publication characteristics and topic coverage. METHODS: We searched 7 databases (MEDLINE/PubMed, Embase, PsycINFO, CINAHL, AMED, the Cochrane Database of Systematic Reviews, and PROSPERO) from their inception to November 2019 and 1 database (INDMED) from inception to January 2017. Two authors independently screened each record for inclusion and one author extracted publication characteristics and topics of included reviews. RESULTS: We retrieved 2710 records and included 322 systematic reviews. 157 reviews were exclusively on yoga, and 165 were on yoga as one of a larger class of interventions (e.g., exercise). Most reviews were published in 2012 or later (260/322; 81 %). First/corresponding authors were from 32 different countries; three-quarters were from the USA, Germany, China, Australia, the UK or Canada (240/322; 75 %). Reviews were most frequently published in speciality journals (161/322; 50 %) complementary medicine journals (66/322; 20 %) or systematic review journals (59/322; 18 %). Almost all were present in MEDLINE (296/322; 92 %). Reviews were most often funded by government or non-profits (134/322; 42 %), unfunded (74/322; 23 %), or not explicit about funding (111/322; 34 %). Common health topics were psychiatric/cognitive (n = 56), cancer (n = 39) and musculoskeletal conditions (n = 36). Multiple reviews covered similar topics, particularly depression/anxiety (n = 18), breast cancer (n = 21), and low back pain (n = 16). CONCLUSIONS: Further research should explore the overall quality of reporting and conduct of systematic reviews of yoga, the direction and certainty of specific conclusions, and duplication or gaps in review coverage of topics.

Pathways to post-traumatic growth in cancer patients: moderated mediation and single mediation analyses with resilience, personality, and coping strategies.

BACKGROUND: Cancer diagnosis is a potentially traumatic experience, which could generate significant long-lasting emotional distress, but also positive changes linked to post-traumatic growth (PTG). This study aimed to analyze the role of resilience, coping, and personality in determining PTG or post-traumatic symptoms, and to test a moderated mediation model and a single mediation model in a sample of individuals diagnosed with cancer. METHODS: A sample of 154 individuals diagnosed with cancer (Mage = 51.4, SD = 11.25) completed the Post-Traumatic Growth Inventory, Impact of Event Scale, Connor-Davidson Resilience Scale, Ten Item Personality Inventory, and Coping Orientation to Problems Experienced after providing written informed consent. RESULTS: Results showed that the impact of resilience in PTG is partially mediated by positive attitude, with a significant and negative moderating effect of openness on the relationship between resilience and positive attitude. Furthermore, resilience negatively predicted the impact of trauma, with a partial mediation of avoidance strategies. LIMITATIONS: The cross-sectional nature of the study, the use of only self-report measures, heterogeneity of the sample, and the risk of influence of unobserved prognostic variables should be kept in mind while interpreting the results. CONCLUSIONS: The findings showed that the level of resilience predicted PTG or post-traumatic symptoms, both directly and indirectly, with different coping strategies as mediators. Furthermore, the lower the level of openness reported by participants, the higher the resilience induced by positive attitude. These findings may significantly contribute toward tailoring interventions for improving the mental health of cancer patients.

Effects of high phenolic olive oil on cardiovascular risk factors: A systematic review and meta-analysis.

BACKGROUND: Cardiovascular diseases are the world's leading cause of death. Prevention by nutrition is an easy and effective approach especially by advising foods with nutraceutic properties like high phenolic olive oil (HPOO). AIM: The aim of this review was to systematically access and meta-analyse the effects of HPOO on risk factors of the cardiovascular system and thusly to evaluate its use as a nutraceutical in prevention. DATA SYNTHESIS: Medline/PubMed, EMBase, the Cochrane Library, CAMbase and CAM-QUEST were searched through July 2013. Randomized controlled trials (RCTs) comparing high vs. low (resp. non) phenolic olive oils in either healthy participants or patients with cardiovascular diseases were included. For study appraisal the Cochrane Collaboration's risk of bias tool was used. Main outcomes were blood pressure, serum lipoproteins and oxidation markers. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated and analysed by the generic inverse variance methods using a random effects model. Eight cross over RCTs comparing ingestion (21-90 d) of high vs. low (resp. non) phenolic olive oils with a total of 355 subjects were included. RESULTS: There were medium effects for lowering systolic blood pressure (n = 69; SMD -0.52; CI -0.77/-0.27; p < 0.01) and small effects for lowering oxLDL (n = 300; SMD -0.25; CI [-0.50/0.00]; p = 0.05). No effects were found for diastolic blood pressure (n = 69; SMD -0.20; CI -1.01/0.62; p = 0.64); malondialdehyde (n = 71; SMD -0.02; CI [-0.20/0.15]; p = 0.79), total cholesterol (n = 400; SMD -0.05; CI [-0.16/0.05]; p = 0.33); HDL (n = 400; SMD -0.03; CI [-0.14/0.08]; p = 0.62); LDL (n = 400; SMD -0.03; CI [-0.15/0.09]; p = 0.61); and triglycerides (n = 360; SMD 0.02; CI [-0.22/0.25]; p = 0.90). LIMITATIONS: The small number of studies/participants limits this review. CONCLUSIONS: HPOO provides small beneficial effects on systolic blood pressure and serum oxidative status (oxLDL). HPOO should be considered as a nutraceutical in cardiovascular prevention.

Responsiveness of stem-like human glioma cells to all-trans retinoic acid and requirement of retinoic acid receptor isotypes α, ß and γ.

Retinoic acid (RA) is required for development and homeostasis of the normal mammalian brain and may play a role in the initiation and progression of malignant brain tumors, such as the glioblastoma multiforme (GBM) and the gliosarcoma (Gsarc). The subpopulation of stem-like glioma cells (SLGCs) was shown to resist standard glioma radio-/chemotherapy and to propagate tumor regrowth. We used phenotypically distinct, self-renewing SLGC lines from six human GBMs, two Gsarcs, and two subcloned SLGC derivatives in order to investigate their responsiveness to all-trans retinoic acid (atRA) and to identify the RA-receptor (RAR) isotypes involved. In general, atRA exerted a pro-proliferative and pro-survival effect on SLGCs, though the efficacy was distinct. By means of RAR isotype-selective retinoids we disclosed that these effects were mediated by RARα and RARγ, except for one SLGC line, in which the pro-proliferative signal was induced by the RARß-selective retinoid. Only one GBM-derived cell line (T1338) and a subpopulation of another (T1389) displayed neural differentiation in response to atRA. Differentiation of T1338 was induced by RARα and RARγ isotype-selective retinoids, associated with down-regulation of Sox2, and the failure to induce orthotopic tumors in the brains of SCID mice. The differential responsiveness of the SLGC lines appeared unrelated to the expression of RARß, as (i) atRA augmented RAR isotype mRNA expression and particularly rarß mRNA in all SLGC lines, (ii) rarß promoter hypomethylation in the SLGC lines was not related to differentiation and (iii) the induction of T1338 differentiation was by RARα- and RARγ-selective ligands.

EUS-guided FNA cytology of pancreatic neuroendocrine tumour (PanNET): a retrospective study of 132 cases over an 18-year period in a single institution.

OBJECTIVE: To determine the diagnostic accuracy and pitfalls of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology of pancreatic neuroendocrine tumour (PanNET). METHODS: A search of our laboratory information system was performed from July 1992 to June 2010 to identify all FNA cytology and corresponding surgical specimens in which the diagnosis of PanNET was rendered or considered. RESULTS: One hundred and thirty-two cases diagnosed by EUS-guided FNA were collected. Histological correlation was available for 77 (58%) of FNAs; 55 patients may have been treated elsewhere or had no surgery because of advanced disease or co-morbidity. Among 56 cases diagnosed as PanNET on FNA, 54 (96%) were confirmed histologically; the remaining two were poorly differentiated adenocarcinoma with focal neuroendocrine features in one case and no tumour was found in the other. Follow-up histology of nine patients diagnosed as suspicious for PanNET on FNA showed four PanNETs, two pancreatic ductal adenocarcinomas (PDA), one solid pseudopapillary tumour (SPT) and two cases of chronic pancreatitis. Nine cases rendered by FNA as atypical (n = 3), no atypical cells identified (n = 4) or unsatisfactory (n = 2) were PanNETs on histology. Lastly, three cases of oncocytic variant of PanNET were misdiagnosed on FNA as either adenocarcinoma (n = 2) or as suspicious for carcinoma (n = 1). CONCLUSIONS: Overall, 54 of the 70 histologically confirmed PanNET cases (77%) were correctly diagnosed by preoperative FNA as PanNET. FNA cases designated as no atypical cells identified and unsatisfactory (7/132, 5%) were attributable to sampling error. Diagnostic pitfalls in our study mainly included PDA, SPT and chronic pancreatitis.

[Error reporting from a nurse's point of view: results of a survey in nursing homes and hospitals]. / Fehlermeldungen aus Sicht stationär Pflegender: Ergebnisse einer Befragung in Pflegeheimen und Krankenhäusern.

AIM OF THE STUDY: The aim of this study was to gain insight into the reporting of errors as perceived by nurses employed in inpatient health-care facilities. METHOD: A representative written survey of nurses working in German nursing homes and hospitals was conducted. RESULTS: The 1100 respondents reported an average of 1.9 errors in the last half year, with nurses working in nursing homes reporting more errors than hospital-employed ones. They estimated that 20.5% of all errors are reported. One third of the participants did not know what events should be reported; more than 20% feared repercussions and mentioned a lack of feedback on error reports. RESULTS are not statistically associated to the presence or absence of an error reporting system, but there are hints for organisational advantages and workload-related disadvantages of systematic forms of reporting. Reporting behaviour was also related to the perception of factors concerning the organisation of the actual reporting of errors. CONCLUSION: Defining reportable error events, organisational barriers to report errors and deficits in the dealing with errors and error reports have to be tackled to augment error reporting rates and profit from reporting systems.

A systematic review and meta-analysis of exercise interventions for colorectal cancer patients.

The aim of this systematic review and meta-analysis was to investigate the effectiveness of exercise for colorectal cancer patients. PubMed/Medline, Scopus and the Cochrane Library were searched through December 2012 without language restrictions. Randomised controlled trials (RCTs) comparing exercise interventions to control conditions were analysed when they assessed health-related quality of life, fatigue, physical fitness, survival and/or tumour-associated biomarkers in colorectal cancer patients. Risk of bias was assessed using the risk of bias tool recommended by the Cochrane Back Review Group. Literature search identified 342 non-duplicate records of which five RCTs with a total of 238 patients were included; three RCTs had low risk of bias. No evidence was found for short-term effects on quality of life [standardised mean difference (SMD) = 0.18; 95% confidence interval (CI) -0.39, 0.76; P = 0.53] or fatigue (SMD = 0.18; 95% CI -0.22, 0.59; P = 0.38). There was strong evidence for short-term improvements of physical fitness after aerobic exercise compared with controls (SMD = 0.59; 95% CI 0.25, 0.93; P < 0.01). One RCT each assessed immune parameters and oxidative DNA damage. No study reported survival rates or safety data. Given this insufficient evidence and the lack of safety data, no recommendation can be made regarding exercise interventions as a routine intervention for colorectal cancer patients.

Mindfulness-based stress reduction for breast cancer-a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the effectiveness of mindfulness-based stress reduction (mbsr) and mindfulness-based cognitive therapy (mbct) in patients with breast cancer. METHODS: The medline, Cochrane Library, embase, cambase, and PsycInfo databases were screened through November 2011. The search strategy combined keywords for mbsr and mbct with keywords for breast cancer. Randomized controlled trials (rcts) comparing mbsr or mbct with control conditions in patients with breast cancer were included. Two authors independently used the Cochrane risk of bias tool to assess risk of bias in the selected studies. Study characteristics and outcomes were extracted by two authors independently. Primary outcome measures were health-related quality of life and psychological health. If at least two studies assessing an outcome were available, standardized mean differences (smds) and 95% confidence intervals (cis) were calculated for that outcome. As a measure of heterogeneity, I(2) was calculated. RESULTS: Three rcts with a total of 327 subjects were included. One rct compared mbsr with usual care, one rct compared mbsr with free-choice stress management, and a three-arm rct compared mbsr with usual care and with nutrition education. Compared with usual care, mbsr was superior in decreasing depression (smd: -0.37; 95% ci: -0.65 to -0.08; p = 0.01; I(2) = 0%) and anxiety (smd: -0.51; 95% ci: -0.80 to -0.21; p = 0.0009; I(2) = 0%), but not in increasing spirituality (smd: 0.27; 95% ci: -0.37 to 0.91; p = 0.41; I(2) = 79%). CONCLUSIONS: There is some evidence for the effectiveness of mbsr in improving psychological health in breast cancer patients, but more rcts are needed to underpin those results.

[Nursing errors and the consequences. Results of a survey of nurses from inpatient care institutions]. / Pflegefehler und die Folgen. Ergebnisse einer Befragung von Pflegendenin stationären Versorgungseinrichtungen.

Internationally, research on the consequences of errors caused by nurses is quite comprehensive. In contrast, the body of knowledge on the effects that errors have on the nurses themselves is rather small. It is well known that errors can have profoundly negative outcomes on nurses. In some cases, however, errors can have useful ramifications. This paper shows the research results of a representative cross-sectional survey that covers 1,100 nurses working in German hospitals and nursing homes and illustrates the effects of errors on them. Most participants in the sample mentioned feelings of regret/remorse and irritation/annoyance/stress as an effect when they made a mistake. More than half of the nurses state that they also learnt from their errors. Hospital nurses frequently suffer from psychological effects while nursing home nurses experience more often professional or legal consequences. With increasing age and professional experience the nurses indicate a lower error impact. The answers given by nurse assistants differ from those of nurses with a three-year training course. The results suggest an amount of stress that may reduce efficiency and increase susceptibility to mistakes and which, therefore, needs to be remedied.

Diffusion-weighted imaging in characterization of cystic pancreatic lesions.

AIM: To evaluate whether apparent diffusion coefficient (ADC) measurements from diffusion-weighted imaging (DWI) can characterize or predict the malignant potential of cystic pancreatic lesions. MATERIALS AND METHODS: Retrospective review of the magnetic resonance imaging (MRI) database over a 2-year period revealed 136 patients with cystic pancreatic lesions. Patients with DWI studies and histological confirmation of cystic mass were included. In patients with known pancreatitis, lesions with amylase content of >1000 IU/l that resolved on subsequent scans were included as pseudocysts. ADC of cystic lesions was measured by two independent reviewers. These values were then compared to categorize these lesions as benign or malignant using conventional MRI sequences. RESULTS: Seventy lesions were analysed: adenocarcinoma (n=4), intraductal papillary mucinous neoplasm (IPMN; n=28), mucinous cystic neoplasm (MCN; n=9), serous cystadenoma (n=16), and pseudocysts (n=13). There was no difference between ADC values of malignant and non-malignant lesions (p=0.06), between mucinous and serous tumours (p=0.12), or between IPMN and MCN (p=0.42). ADC values for low-grade IPMN were significantly higher than those for high-grade or invasive IPMN (p=0.03). CONCLUSION: ADC values may be helpful in deciding the malignant potential of IPMN. However, they are not useful in differentiating malignant from benign lesions or for characterizing cystic pancreatic lesions.

Human papillomavirus detection and typing in thin prep cervical cytologic specimens comparing the Digene Hybrid Capture II Assay, the Roche Linear Array HPV Genotyping Assay, and the Kurabo GeneSquare Microarray Assay.

Three methods for the detection of HPV DNA were compared in cervical cytologic specimens: the Digene Hybrid Capture II Assay (HC), the Roche Linear Array HPV Genotyping Assay (LA) and the Kurabo GeneSquare Microarray (GS). The main goals of the study were to correlate cytology with HPV detection and to determine agreement between assay pairs for HPV detection. Thin-prep Pap smears were performed and supernates were tested by HC, LA, and GS. For specimens reacting with the HPV 52/33/35/58 probe in the LA assay, type-specific PCR was performed for HPV types 52, 33, 35, or 58. Binomial proportions and kappa coefficients were calculated for agreement between assays. Cytology results and supernatant were available for 202 subjects. HPV detection increased with worsening cytologic abnormality in all three assays. For all cytologic groups, LA and GS detected more HPV (all and oncogenic) than HC. However, for detection of oncogenic HPV types represented in all three assays, differences between assays were less pronounced. The highest agreement was between LA and GS. In four of 12 specimens reacting with the HPV 52/33/35/58 probe in the LA assay but deemed HPV 52-LA-negative using an algorithm provided by the manufacturer, the presence of HPV 52 was confirmed using type-specific HPV 52 PCR. All four of these specimens were also GS-positive for HPV 52.

A prospective study comparing rapid assessment of smears and ThinPrep for endoscopic ultrasound-guided fine-needle aspirates.

BACKGROUND AND STUDY AIMS: ThinPrep is often used for endoscopic ultrasound fine-needle aspiration (EUS-FNA) samples but the sensitivity of this method is unknown. The objective of the study was to compare sensitivity and accuracy of ThinPrep versus the smear method in pancreas and lymph node samples obtained by EUS-FNA. PATIENTS AND METHODS: Patients with suspected malignancy in the pancreas or lymph node underwent EUS-FNA. On-site rapid assessment of all aspirates using the smear method was performed. After rapid assessment, three additional passes from each site were submitted into ThinPrep liquid medium. Cytopathologists interpreting the smear method and ThinPrep slides were blinded to each other. The gold standard was final cytology or pathology results. RESULTS: A total of 130 patients (36 % women, mean age 63 years) underwent EUS-FNA of 139 sites (50 pancreas, 89 lymph node). Malignancy was confirmed in 47 pancreas samples (94 %) and 48 lymph node samples (54 %). Mean +/- SD number of passes made for the smear method was 2.6 +/- 1.3. For pancreatic cancer, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the ThinPrep versus the smear method were: 62 % versus 98 %, 100 % versus 100 %, 100 % versus 100 %, 14 % versus 75 %, and 64 % versus 98 %, respectively. For lymph nodes the values were 67 % versus 92 %, 100 % versus 98 %, 100 % versus 98 %, 72 % versus 72 %, and 82 % versus 94 %, respectively. CONCLUSIONS: The smear method is more sensitive and accurate than ThinPrep in detecting malignancy from EUS-FNA samples of the pancreas and lymph nodes. Smear method with on-site rapid assessment should be favored over ThinPrep in suspected malignancy.

Fabrication of homogeneously cross-linked, functional alginate microcapsules validated by NMR-, CLSM- and AFM-imaging.

Cross-linked alginate microcapsules of sufficient mechanical strength can immunoisolate cells for the long-term treatment of hormone and other deficiency diseases in human beings. However, gelation of alginate by external Ba(2+) (or other divalent cations) produces non-homogeneous cross-linking of the polymeric mannuronic (M) and guluronic (G) acid chains. The stability of such microcapsules is rather limited. Here, we show that homogeneous cross-linking can be achieved by injecting BaCl(2) crystals into alginate droplets before they come into contact with external BaCl(2). The high effectiveness of this crystal gun method is demonstrated by confocal laser scanning microscopy and by advanced nuclear magnetic resonance imaging. Both techniques gave clear-cut evidence that homogeneous cross-linkage throughout the microcapsule is only obtained with simultaneous internal and external gelation. Atomic force microscopy showed a very smooth surface topography for microcapsules made by the crystal gun method, provided that excess Ba(2+) ions were removed immediately after gelation. In vitro experiments showed greatly suppressed swelling for crystal gun microcapsules. Even alginate extracted from Lessonia nigrescens (highly biocompatible) yielded microcapsules with long-term mechanical stability not hitherto possible. Encapsulation of rat islets, human monoclonal antibodies secreting hybridoma cells and murine mesenchymal stem cells transfected with cDNA encoding for bone morphogenetic protein (BMP-4) revealed that injection of BaCl(2) crystals has no adverse side effects on cell viability and function. However, the release of low-molecular weight factors (such as insulin) may be delayed when using alginate concentrations in the usual range.

Significance of benign endometrial cells in Pap smears from postmenopausal women.

OBJECTIVE: To assess the significance of benign exfoliated endometrial epithelial or stromal cells on cervicovaginal Pap smears obtained from postmenopausal women not receiving exogenous hormones. STUDY DESIGN: A computerized search of the cytology database at two institutions was performed for a five-year period, and all cervical cytology cases from postmenopausal patients diagnosed with benign endometrial cells were identified. Those cases with histologic follow-up within 12 months of the original cytologic evaluation were selected for analysis, and their cytology and surgical pathology slides were reviewed. RESULTS: A total of 227 postmenopausal women with benign endometrial cells were identified. Of the 61 patients with histologic follow-up, 25 (41%) had significant endometrial diseases, including hyperplasia without atypia (11), atypical endometrial hyperplasia (5), well-differentiated adenocarcinoma (8) and high grade serous carcinoma (1). Benign diagnoses, including atrophy (15), weakly proliferative endometrium (9) and proliferative endometrium (6), were noted in 30 patients (49%). Endometrial polyp was identified in three patients (5%). There were three cases of nondiagnostic histologic specimens that lacked endometrial tissue (5%). Two of nine women (22%) with proven carcinoma were asymptomatic. CONCLUSION: The diagnosis of endometrial cells, cytologically benign, in a postmenopausal woman not receiving hormone on Pap smears is associated with a significant number of cases of endometrial hyperplasia, atypical hyperplasia and carcinoma.

Coupling of endothelin receptors to the ERK/MAP kinase pathway. Roles of palmitoylation and G(alpha)q.

Endothelins are potent mitogens that stimulate extracellular signal-regulated kinases (ERK/MAP kinases) through their cognate G-protein-coupled receptors, ET(A) and ET(B). To address the role of post-translational ET receptor modifications such as acylation on ERK activation and to identify relevant downstream effectors coupling the ET receptor to the ERK signaling cascades we have constructed a panel of palmitoylation-deficient ET receptor mutants with differential G(alpha) protein binding capacity. Endothelin-1 stimulation of wild-type ET(A) or ET(B) induced a fivefold to sixfold increase in ERK in COS-7 and CHO cells whereas full-length nonpalmitoylated ET(A) and ET(B) mutants failed to stimulate ERK. A truncated ET(B) lacking the C-terminal tail domain including putative phosphorylation and arrestin binding site(s) but retaining the critical palmitoylation site(s) was still able to fully stimulate ERK activation. Using mutated ET receptors with selective G-protein-coupling we found that endothelin-induced stimulation of G(alpha)q, but not of G(alpha)i or G(alpha)s, is essential for endothelin-mediated ERK activation. Inhibition of protein kinases A and C or epidermal growth factor receptor kinase failed to prevent ET(A)- and ET(B)-mediated ERK activation whereas blockage of phospholipase C-beta completely abrogated endothelin-promoted ERK activation through ET(A) and ET(B) in recombinant COS-7 and native C6 cells. Complex formation of Ca2+ or inhibition of Src family tyrosine kinases prevented ET-1-induced ERK-2 activation in C6-cells. Our results indicate that endothelin-promoted ERK/MAPK activation criticially depends on palmitoylation but not on phosphorylation of ET receptors, and that the G(alpha)q/phospholipase C-beta/Ca2+/Src signaling cascade is necessary for efficient coupling of ET receptors to the ERK/MAPK pathway.

Detection of multiple human papillomavirus types in the lower genital tract correlates with cervical dysplasia.

Some human papillomavirus (HPV) types, such as HPV 16, are clearly associated with cervical dysplasia; however, the role played by other HPV types occasionally found in dysplasia is less certain. In addition, most methods used to detect HPV in clinical specimens cannot easily distinguish among more than two or three HPV types in a single specimen. Therefore, the significance of infection with multiple HPV types is not known. To address this question, we analyzed cervicovaginal lavage specimens from three cohorts of women for HPV DNA using a PCR/reverse blot assay system that permits the detection and partial quantitation of 26 genital HPV types. As expected, 94.1% of women who had dysplasia (n = 34) and 71.4% of women who had atypical squamous cells of uncertain significance (ASCUS) (n = 21) on cytology had HPV DNA detected compared to 54.5% of age matched women with normal cytology. HPV 16 DNA was detected in 35% of dysplasia patients compared to 9% of cytologic normals (P = 0.0044). Dysplasia patients had a mean of 3.29 (range 0-10) different HPV types detected compared to 1.04 (range 0-7) HPV types among those with normal cytology (P < 0.0001). These data support a possible role for multiple HPV types in the development or progression of cervical dysplasia.