Soluble cytokeratin-19 and E-selectin biomarkers: their relevance for lung cancer detection when tested independently or in combinations

OBJECTIVES: Determination of tumor biomarkers in serum has been proposed as an alternative and noninvasive way of establishing diagnosis for lung cancer. The aim of this study was to assess the combined use of Cyfra 21-1; the soluble fragment of cytokeratin 19, and soluble E-selectin; endothelial adhesion molecule, for improving the accuracy of diagnosing and screening lung cancer. MATERIALS AND METHODS: Serum Cyfra 21-1 and sE-selectin were determined using electrochemiluminescent immunoassay and enzyme linked immunosorbent assay, respectively, in 52 patients with histologically proven lung cancer, 40 patients with benign lung diseases and 50 healthy volunteers. RESULTS: Both markers were significantly increased in lung cancer patients as compared to healthy, for benign lung diseases Cyfra 21-1 perform well than sE-selectin. Sensitivities of Cyfra 21-1 and sE-selectin at 95th percentiles of the normal group were 96.2% and 92.3%, while at 95th percentiles of the benign lung diseases were 57.7% and 5%, respectively. In ROC curves, the diagnostic power for the detection of lung cancer was similar for Cyfra 21-1 and sE-selectin; however, when compared with benign lung diseases, Cyfra 21-1 was superior to sE-selectin. The highest sensitivity (99.8%) was reported when the two markers were combined. CONCLUSION: Cyfra 21-1 and sE-selectin show good performance in detecting lung cancer from normal groups, however, Cyfra 21-1 was superior to sE-selectin in discriminating lung cancer from benign lung diseases.     

Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

1. Download : Download high-res image (387KB)
2. Download : Download full-size image

     

A Systematic Review of HIV Risk Behaviors and Trauma Among Forced and Unforced Migrant Populations from Low and Middle-Income Countries: State of the Literature and Future Directions

The aim of the current systematic review is to examine the relationship between trauma and HIV risk behaviors among both forced and unforced migrant populations from low and middle income countries (LMIC). We conducted a review of studies published from 1995 to 2014. Data were extracted related to (1) the relationship between trauma and HIV risk behaviors, (2) methodological approach, (3) assessment methods, and (4) differences noted between forced and unforced migrants. A total of 340 records were retrieved with 24 studies meeting inclusion criteria. Our review demonstrated an overall relationship between trauma and HIV risk behaviors among migrant populations in LMIC, specifically with sexual violence and sexual risk behavior. However, findings from 10 studies were not in full support of the relationship. Findings from the review suggest that additional research using more rigorous methods is critically needed to understand the nature of the relationship experienced by this key-affected population.     

Deconstructing the Relationship Between Intimate Partner Violence and Sexual HIV Risk Among Drug-Involved Men and Their Female Partners

This study, based on data from a random sample of 322 men on methadone, examines whether traditional male gender role beliefs, male substance use, and couple drug-involvement lead to male psychological dominance, which in turn leads to perpetration of intimate partner violence (IPV) and sexual HIV risk behavior. Structural equation modelingindicated that male psychological dominance is directly associated with perpetrating both physical IPV and sexual HIV risk; however, physical IPV did not lead to sexual HIV risk as predicted originally. Stronger endorsement of traditional male gender role beliefs was associated with male psychological dominance. Couple drug-involvement was also directly associated with male psychological dominance as well as sexual HIV risk. Male substance use led to couple drug-involvement, but not to physical or sexual HIV risk as hypothesized. Study findings highlight the significance of couple drug-involvement and male psychological dominance as pathways leading to physical IPV and sexual HIV risk behavior. Implications for HIV prevention efforts targeting drug-involved men and their sexual partners are discussed.     

Couple-focused support to improve HIV medication adherence: a randomized controlled trial

OBJECTIVE: To assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems. DESIGN: A randomized controlled trial (SMART Couples Study) conducted between August 2000 and January 2004. SETTING: Two HIV/AIDS outpatient clinics in New York City. PARTICIPANTS: Heterosexual and homosexual HIV-serodiscordant couples (n = 215) in which the HIV-seropositive partner had < 80% adherence at baseline. The sample was predominantly lower-income racial/ethnic minorities. INTERVENTION: Participants were randomly assigned to a four-session couple-focused adherence intervention or usual care. The intervention consisted of education about treatment and adherence, identifying adherence barriers, developing communication and problem-solving strategies, optimizing partner support, and building confidence for optimal adherence. OUTCOME MEASURES: Medication adherence at week 8 (2 weeks after the intervention) compared with baseline, assessed with a Medication Event Monitoring System cap. RESULTS: Intervention participants showed higher mean medication adherence at post-intervention when compared with controls whether adherence was defined as proportion of prescribed doses taken (76% versus 60%) or doses taken within specified time parameters (58% versus 35%). Also, participants in the intervention arm were significantly more likely to achieve high levels of adherence (> 80%, > 90%, or > 95%) when compared with controls. However, in most cases, effects diminished with time, as seen at follow-up at 3 and 6 months. CONCLUSION: The SMART Couples program significantly improved medication adherence over usual care, although the level of improved adherence, for many participants, was still suboptimal and the effect was attenuated over time.     

Phylogeny and pathogenicity of Fusarium solani species complex (FSSC) associated with potato tubers

Potato (Solanum tuberosum L.) is one of the known five crops cultivated throughout the world after corn, barley, cereals, rice, and wheat, due to its content of high carbohydrates. In developing countries, potatoes are especially had valuable contents as a rich source of starch, vitamins C and B6, and essential amino acids. Fusarium solani species complex (FSSC) is one of the prevalent pathogens of potato, causing dry rot in Upper Egypt. In this study, FSSC were isolated and identified from potato tubers based on the morphological and molecular characteristics. F. solani isolates (187) were isolated from infected and noninfected potato tubers collected from various markets in Upper Egypt. Based on the morphology observations, sequence data from amplifying β-tubulin, and specific translation elongation factor (TEF-1α) genes, all of the chosen 88 FSSC isolates were grouped into three major groups (F. keratoplasticum, F. falciforme, and F. solani). All the tested FSSC were able to produce amylases. The selected isolates were examined for their pathogenic ability on healthy potato tubers, which exhibited pathogenic effects; with lesions sizes were quite variable. F. solani SVUFs73 showed a highly virulent effect.     

TRPV4 Dysfunction Promotes Renal Cystogenesis in Autosomal Recessive Polycystic Kidney Disease

The molecular mechanism of cyst formation and expansion in autosomal recessive polycystic kidney disease (ARPKD) is poorly understood, but impaired mechanosensitivity to tubular flow and dysfunctional calcium signaling are important contributors. The activity of the mechanosensitive Ca²⁺-permeable TRPV4 channel underlies flow-dependent Ca²⁺ signaling in murine collecting duct (CD) cells, suggesting that this channel may contribute to cystogenesis in ARPKD. Here, we developed a method to isolate CD-derived cysts and studied TRPV4 function in these cysts laid open as monolayers and in nondilated split-open CDs in a rat model of ARPKD. In freshly isolated CD-derived cyst monolayers, we observed markedly impaired TRPV4 activity, abnormal subcellular localization of the channel, disrupted TRPV4 glycosylation, decreased basal [Ca²⁺]_i, and loss of flow-mediated [Ca²⁺]_i signaling. In contrast, nondilated CDs of these rats exhibited functional TRPV4 with largely preserved mechanosensitive properties. Long-term systemic augmentation of TRPV4 activity with a selective TRPV4 activator significantly attenuated the renal manifestations of ARPKD in a time-dependent manner. At the cellular level, selective activation of TRPV4 restored mechanosensitive Ca²⁺ signaling as well as the function and subcellular distribution of TRPV4. In conclusion, the functional status of TRPV4, which underlies mechanosensitive Ca²⁺ signaling in CD cells, inversely correlates with renal cystogenesis in ARPKD. Augmenting TRPV4 activity may have therapeutic potential in ARPKD.Polycystic kidney disease (PKD) is a cohort of monogenic disorders that result in development and subsequent growth of renal cysts filled with fluid.^1–5 Cyst enlargement compromises function of surrounding nephrons and progresses to ESRD.^1,6 In the more common form of PKD, autosomal dominant PKD (ADPKD), which is caused by mutations of polycystin 1 (PC1) and polycystin 2 (PC2), renal cysts are formed along the full length of the nephron with prevalence to the collecting duct (CD).^1,7 In the rarer and more severe autosomal recessive PKD (ARPKD), renal cyst formation is virtually restricted to the CD.^1,2,5,8 Mutations of the PKHD1 gene encoding fibrocystin underlie the genetic basis of the disease.^6,8,9 Although the exact function of the protein is unknown, fibrocystin was shown to be expressed in primary cilia where it can interact and form complexes with PC2, possibly participating in mechanotransduction.^10–12It is accepted that the CD cells elevate [Ca²⁺]_i in response to mechanical stress arising from variations in tubular flow or tubular composition.^13–23 Impaired mechanosensitive [Ca²⁺]_i responses, reported for both cultured ADPKD²⁴ and ARPKD^25,26 cells, point to a possible fundamental role of disrupted [Ca²⁺]_i signaling in cystogenesis. The central cilia and cilia-associated PC1 and PC2 were proposed to mediate flow-induced cellular responses.^19,27 However, homomeric PC2 channels are not mechanosensitive and fail to increase [Ca²⁺]_i in response to flow and hypotonicity.^28,29 Furthermore, intercalated cells, which lack primary cilia, respond to flow changes with comparable increases in [Ca²⁺]_i as observed in principal cells, which have primary cilia.^16,30 Therefore, additional mechanisms conferring mechanosensitivity to the CD cells need to be considered.Transient receptor potential (TRP) channels are known to participate in cellular responses to a variety of environmental stimuli, including thermosensation, chemosensation, and mechanical forces (reviewed in Song and Yuan³¹). Several TRP channels, including TRPC3, TRPC6, and TRPV4, can be detected in the native CD cells and CD-originated cultured lines.^19,32–34 Among these channels, TRPV4 has routinely been shown to be activated by mechanical stimuli.^34–38 Indeed, we documented that endogenous TRPV4 in M-1 CD cells is stimulated by increases in flow, a response that is abolished by TRPV4 small interfering RNA knockdown.^34,38 We further demonstrated a lack of flow-mediated [Ca²⁺]_i elevations in CD from TRPV4−/− mice.³⁰ Consistently, flow-mediated Ca²⁺-dependent K⁺ secretion in the CD is disrupted in TRPV4 knockout animals.³⁹ TRPV4 directly interacts with PC2 to form mechanosensitive heteromeric complexes.^28,29 The fact that PC2 interacts with both PC1⁴⁰ and fibrocystin^10–12 suggests that TRPV4 could be an essential part of this mechanotransducing sensory complex.Current PKD management is directed toward pharmacologic interference with abnormal signaling pathways causing exaggerated cell proliferation, dedifferentiation, apoptosis, and cyst growth.⁴¹ Specifically, PKD is associated with elevated circulating vasopressin levels, increased basal cellular cAMP levels, and strong upregulation of cAMP-dependent fluid secretion and proliferation.^42,43 V2 antagonism greatly diminishes disease progression in rodent models of both ADPKD and ARPKD.^42,44 Elevated cAMP levels might be directly related to the reduced [Ca²⁺]_i, possibly due to impaired ability to sense changes in flow.^42,44,45 This raises the possibility that manipulation with the mechanosensitivity in the CD along the TRPV4 axis modulates [Ca²⁺]_i signalization and, in turn, renal cystogenesis.In this study, we developed a new approach to isolate native CD-derived cyst monolayers and nondilated CDs from a rat model of ARPKD to thoroughly investigate how functional TRPV4 status determines the development and growth of renal cysts. We found that the disease leads to disruption of mechanosensitive [Ca²⁺]_i signaling and impaired TRPV4 activity specifically in CD cysts but not in nondilated CDs. Long-term pharmacologic potentiation of TRPV4 activity gradually restores mechanosensitivity in cyst cells and greatly blunts renal ARPKD progression. From a global prospective, this study establishes a temporal link between disruption of TRPV4-based mechanosensitivity in the CD and cystogenesis. This also suggests pharmacologic potential of targeting TRPV4 activity as a treatment strategy in retarding development of ARPKD.     

Omega-3 fatty acids in juvenile idiopathic arthritis: effect on cytokines (IL-1 and TNF-α), disease activity and response criteria

This study aims to demonstrate the effect of omega-3 fatty acids (ω-3 FAs) supplements on the clinical manifestations, laboratory investigations, disease activity, functional capacity, response criteria as well as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) levels in juvenile idiopathic arthritis (JIA) patients. Twenty-seven JIA patients were included in this study. Dietary supplements of ω-3 FAs 2 g/day were given for 12 weeks. Juvenile arthritis disease activity score in 27 joints (JADAS-27) and pediatric American College of Rheumatology (ACR) response criteria were determined. Childhood Health Assessment Questionnaire (CHAQ) was used to measure the functional status. Assessment of serum IL-1 and TNF-α level was performed using enzyme-linked immunosorbent assay. The mean age of the patients was 12.78 ± 3.26 years, the disease duration was 5.93 ± 3.06 years, and the age at disease onset was 6.78 ± 3.26 years. The TNF-α and IL-1 were significantly higher in the JIA patients compared to the control. There was a significant improvement of active joint count, number of swollen joints, JADAS-27, CHAQ, TNF-α, and IL-1 levels. The pediatric ACR response criteria improved in 92.59% of the patients. The daily requirements of nonsteroidal anti-inflammatory drugs (NSAIDs) obviously decreased. ω-3 FAs supplements reduce the inflammatory response and improve the clinical manifestation in JIA patient. The daily intake of NSAID dose decreased thus reducing the risk of related side effects. Our results support the use of omega-3 fatty acids as an add-on therapy to conventional treatment of JIA.     

Systematic Review of Couple-Based HIV Intervention and Prevention Studies: Advantages,Gaps, and Future Directions

We conducted a systematic review of couple-based HIV biobehavioral (skills-building, VCT, and adherence) and biomedical (ART, circumcision) prevention and intervention studies designed to reduce sexual- and drug-risk behaviors and HIV transmission and acquisition. Of the 11,162 papers identified in the search, 93 peer-reviewed papers met the inclusion criteria and yielded a total of 33 studies conducted globally. Biobehavioral couple-based prevention and intervention studies have been efficacious in reducing sexual- and drug-risk behaviors, increasing access to HIV testing and care, and improving adherence. Biomedical couple-based studies were found to reduce HIV incidence among HIV-negative sex partners and viral load among HIV-positive partners. Despite much progress, couple-based HIV prevention and intervention studies remain limited; a number of methodological gaps exist and studies focusing on MSM, people who inject drugs, and sex workers are scarce.