bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opportunities and Challenges of Sexual Health Services Among Young People: A Study in Nepal
Authors: Regmi Krishna 
Published: April 2008

ABSTRACT

Introduction
It has been well documented that young people are more likely to engage in high-risk sexual activity. Appropriate understanding of safe sex, sexual practices, and related behaviors must recognize the importance of socioeconomic and cultural factors in prevention efforts related to HIV and other sexual transmitted infections (STIs).

Aim
To examine and summarize the opportunities and challenges of sexual health services among young people in Nepal.

Main Outcome Measures
Review of literature—assessing knowledge, attitudes, and understanding of sex, sexual health, and related sexual risk behaviors, among young people (15–24), in line with the current sociocultural and health service practices.

Methods
Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Science, Cochrane database, and Google were searched. Similarly, documents published at the WHO, United Nations Population Fund, United Nations Development Program, and at national/local level—Ministry of Health, National Center for AIDS, and STD Control were also assessed to access the relevant reports and articles. Published and gray articles were also reviewed.

Results
This study contends growing expansion of communication and transportation networks, urbanization, and urban in-migration is creating a different sociocultural environment, which is conducive to more social interactions between young girls and boys in Nepal. Rising age at marriage opens a window of opportunity for premarital and unsafe sexual activity among young people and this creates risks of unwanted pregnancy, STIs/HIV and AIDS. Socioeconomic, demographic, and cultural factors have been identified as encouraging factors for risk-taking behaviors among young people.

Conclusions
Understanding safer sex and responsible sexual/reproductive behavior is important. Effective and appropriate interventions on sexual and reproductive health education directed at young people and the whole family, including fathers, could have significant effect on reducing risk and related risk practices in the context of Nepal.
Impact of Premature Ejaculation: The Psychological, Quality of Life, and Sexual Relationship Consequences
Authors: Rosen Raymond C. , Althof Stanley 
Published: April 2008

Abstract

Introduction
Premature ejaculation (PE) has been associated with a range of negative psychological effects, including anxiety, depression, and distress in men and their female partners.

Aim
To review evidence of the psychosocial concomitants of premature ejaculation in recent observational studies, and to consider the psychosocial and quality of life outcomes associated with PE, including effects on the partner relationship.

Main Outcome Measure
Psychosocial and quality of life consequences related to premature ejaculation.

Methods
A literature search was performed to retrieve publications relating to management or treatment of PE or male sexual dysfunction. Publications were included if they reported the impact of PE on the man, his partner or relationship, or the impact of male sexual dysfunction and included PE in the analysis.

Results
Eleven observational studies were selected. All these studies found evidence for an association between PE and adverse psychosocial and quality of life consequences, including detrimental effects on the partner relationship. Comparative analyses were restricted by major differences across the studies.

Conclusions
PE significantly negatively impacts men and their partners and may prevent single men forming new partner relationships. Men are reluctant to seek treatment from their physicians, although they may be more encouraged to do so through their partner's support and the availability of effective treatments. There is a need for validated diagnostic screening criteria and validated, reliable, brief patient-reported outcome measures that can be used to assess men with PE and their partners. These factors would allow further studies with more complete and accurate assessment of the impact of PE.
Detection ofLeishmania infantumby real‐time PCR in a canine blood bank
Authors: Tabar M. D. , Roura X. , Francino O. , Altet L. , Ruizde Gopegui R. 
Published: April 2008

Objectives:Risk for transmission ofLeishmania infantumfrom blood products has been largely demonstrated in human and veterinary literature. Appropriate screening of canine blood donors is important especially in an endemic area such as Barcelona (Spain). The purpose of this study was to evaluate the presence ofL infantumDNA parasites by real‐time quantitative PCR in our canine blood bank.Methods:Samples from blood products obtained from 92 canine blood donors were assayed forL infantumby means of real‐time PCR amplification and quantification.Results:The prevalence of quantitative PCR‐positive blood samples among healthy seronegative blood donors was 19·6 per cent.ClinicalSignificance:The results of this study show thatL infantuminfection is common in canine blood donors and their blood products in an endemic area, despite a negative commercial serological screening for infectious diseases. Therefore, screening by PCR should be included in an integrated approach to evaluateL infantuminfection among potential blood donors.
A retrospective study of the clinical presentation of 140 dogs and 39 cats with bacteraemia
Authors: Greiner M. , Wolf G. , Hartmann K. 
Published: April 2008

Objectives: To evaluate retrospective data from 140 dogs and 39 cats with positive blood cultures that were presented to the Clinic for Small Animal Medicine in Munich from 1995 to 2004. Methods: The identity of bacteria isolated from blood cultures of dogs and cats with bacteraemia was determined, and clinical and laboratory findings and outcome of animals with Gram‐negative versus Gram‐positive bacteraemia were compared. Results: Sepsis was diagnosed in 81·7 per cent of dogs and 59·5 per cent of cats with bacteraemia. Escherichia coli was isolated in one third of the animals. Dogs with bacteraemia more often showed monocytosis and increased alkaline phosphatase activity, while in cats, hyperglycaemia was found more commonly. Dogs with Gram‐negative bacteraemia had hypoalbuminaemia significantly more often than dogs with Gram‐positive bacteraemia, while among the remaining parameters, there were no statistically significant differences. Clinical Significance: Not all dogs and cats with a positive blood culture met the criteria for sepsis. Bacteraemia caused by Gram‐positive versus Gram‐negative bacteria cannot be distinguished based on clinical or laboratory parameters, and bacterial culture and susceptibility testing have to be performed for the right choice of antibiotic treatment.
Activities of Clindamycin, Daptomycin, Doxycycline, Linezolid, Trimethoprim-Sulfamethoxazole, and Vancomycin against Community-Associated Methicillin-Resistant
Staphylococcus aureus
with Inducible Clindamycin Resistance in Murine Thigh Infection and In Vitro Pharmacodynamic Models
Authors: LaPlante Kerry L. , Leonard Steven N. , Andes David R. , Craig William A. , Rybak Michael J. 
Published: April 2008

ABSTRACT

Controversy exists about the most effective treatment options for community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) and about the ability of these strains to develop inducible resistance to clindamycin during therapy. Using both in vitro pharmacodynamic and murine thigh infection models, we evaluated and compared several antimicrobial compounds against CA-MRSA. Strains with inducible macrolide lincosamide-streptogramin type B (iMLS
B
) resistance and strains in which resistance was noninducible were evaluated. Two levels of inocula (10
5
and 10
7
) were evaluated for clindamycin activity in the in vivo model. In both models, the antimicrobial evaluation was performed in triplicate, and bacterial quantification occurred over 72 h, with drug doses that were designed to simulate the free drug area-under-the-concentration-time curve values (
f
AUCs) obtained from human samples. When the activity of clindamycin against the iMLS
B
strains was evaluated, constitutive resistance was noted at 24 h (MIC of >256), and failure was noted at an inoculum of ≥10
6
in the in vivo models. However, at a low inoculum (10
5
) in the murine thigh-infection model, clindamycin demonstrated modest activity, reducing the CFU/thigh count for clindamycin resistance-inducible strains at 72 h (0.45 to 1.3 logs). Overall, administration of daptomycin followed by vancomycin demonstrated the most significant kill against all strains in both models. Against the clindamycin noninducible strain, clindamycin and doxycycline demonstrated significant kill. Doxycycline, linezolid, and trimethoprim-sulfamethoxazide (not run in the murine model) demonstrated bacteriostatic activity against clindamycin resistance-inducible isolates. This study demonstrates that clindamycin's activity against the iMLS
B
strains tested is partially impacted by inoculum size. At present, there are several alternatives that appear promising for treating clindamycin resistance-inducible strains of CA-MRSA.
β-Hydroxybutyrate Abrogates Formation of Bovine Neutrophil Extracellular Traps and Bactericidal Activity against Mammary PathogenicEscherichia coli
Authors: Grinberg Navit , Elazar Sharon , Rosenshine Ilan , Shpigel Nahum Y. 
Published: April 2008

ABSTRACTEscherichia coliis an important bacterial species isolated from bovine mastitis. The rate of neutrophil recruitment into the mammary gland and their bactericidal activity largely affect the severity and outcome of the disease. Ketosis is a common metabolic disease, and affected dairy cows are known to have increased risk for mastitis and other infectious conditions. The disease is associated with high blood and milk levels of β-hydroxybutyrate (BHBA), previously shown to negatively affect neutrophil function by unknown mechanisms. We show here that the mammary pathogenicE. colistrain P4 activates normal bovine neutrophils to form neutrophil extracellular traps (NETs), which are highly bactericidal against this organism. Preincubation of these neutrophils with increasing concentrations (0.1 to 8 mmol/liter) of BHBA caused a fivefold decrease ofE. coliP4 phagocytosis, though intracellular killing was unaffected. Furthermore, BHBA caused a 10-fold decrease in the NETs formed byE. coliP4-activated neutrophils and a similar decrease in NET bactericidal activity against this organism. These negative effects of BHBA on bovine neutrophils might explain the increased susceptibility of ketotic cows to mastitis and other infectious conditions.
Initial Delay in the Immune Response to
Francisella tularensis
Is Followed by Hypercytokinemia Characteristic of Severe Sepsis and Correlating with Upregulation and Release of Damage-Associated Molecular Patterns
Authors: Mares Chris A. , Ojeda Sandra S. , Morris Elizabeth G. , Li Qun , Teale Judy M. 
Published: April 2008

ABSTRACT

“
Francisella tularensis
subsp.
novicida
” intranasal infection causes a rapid pneumonia in mice with mortality at 4 to 6 days with a low dose of bacteria (10
2
bacteria). The short time to death suggests that there is a failure of the innate immune response. As the neutrophil is often the first cell type to infiltrate sites of infection, we focused on the emigration of neutrophils in this infection, as well as cytokines involved in their recruitment. The results indicated that there was a significant delay in the influx of neutrophils into the bronchoalveolar lavage fluid of
F. tularensis
subsp.
novicida
-infected mice. The delay in neutrophil recruitment in
F. tularensis
subsp.
novicida
-infected mice correlated with a delay in the upregulation of multiple proinflammatory cytokines and chemokines, as well as a delay in caspase-1 activation. Strikingly, the initial delay in the upregulation of cytokines through 1 day postinfection was followed by profound upregulation of multiple cytokines and chemokines to levels consistent with hypercytokinemia described for severe sepsis. This finding was further supported by a bacteremia and the cellular relocalization and release of high-mobility group box-1 and S100A9, both of which are damage-associated molecular pattern molecules and are known to be mediators of severe sepsis.
Fas/CD95-Mediated Apoptosis of Type II Cells Is Blocked byToxoplasma gondiiPrimarily via Interference with the Mitochondrial Amplification Loop
Authors: Hippe Diana , Lytovchenko Oleksandr , Schmitz Ingo , Lüder Carsten G. K. 
Published: April 2008

ABSTRACTThe intracellular protozoanToxoplasma gondiiinduces persistent infections in various hosts and is an important opportunistic pathogen of humans with immature or deficient immune responses. The ability to survive intracellularly largely depends on the blocking of different proapoptotic signaling cascades of its host cell. Fas/CD95 triggers an apoptotic cascade that is crucial for immunity and the outcome of infectious diseases. We have determined the mechanism by whichT. gondiicounteracts death receptor-mediated cell death in type II cells that transduce Fas/CD95 ligation via caspase 8-mediated activation of the mitochondrial amplification loop. The results showed that infection withT. gondiisignificantly reduced Fas/CD95-triggered apoptosis in HeLa cells by inhibiting the activities of initiator caspases 8 and 9 and effector caspase 3/7. Parasitic infection dose dependently diminished cleavage of caspase 8, the BH3-only protein Bid, and the downstream caspases 9 and 3. Importantly, interference with Fas/CD95-triggered caspase 8 and caspase 3/7 activities after parasitic infection was largely dependent on the presence of caspase 9. Within the mitochondrial amplification loop,T. gondiisignificantly inhibited the Fas/CD95-triggered release of cytochromecinto the host cell cytosol. These results indicate thatT. gondiiinhibits Fas/CD95-mediated apoptosis in type II cells primarily by decreasing the apoptogenic function of mitochondria.
Peroxisome Proliferator-Activated Receptor γ–Mediated Up-regulation of Syndecan-1 by n-3 Fatty Acids Promotes Apoptosis of Human Breast Cancer Cells
Authors: Sun Haiguo , Berquin Isabelle M. , Owens Rick T. , O'Flaherty Joseph T. , Edwards Iris J. 
Published: April 2008

Abstract
Diets enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against breast cancer but biochemical mechanisms are unclear. Our studies showed that the n-3 fatty acid docosahexaenoic acid (DHA) up-regulated syndecan-1 (SDC-1) in human breast cancer cells, and we tested the hypothesis that DHA-mediated up-regulation of SDC-1 induces apoptosis. DHA was delivered to MCF-7 cells by n-3 PUFA–enriched low-density lipoproteins (LDL) or by albumin in the presence or absence of SDC-1 small interfering RNA. The n-3 PUFA induced apoptosis, which was blocked by SDC-1 silencing. We also confirmed that SDC-1 up-regulation and apoptosis promotion by n-3 PUFA was mediated by peroxisome proliferator-activated receptor γ (PPARγ). Using a luciferase gene driven by either a PPAR response element or a DR-1 site present in the SDC-1 promoter, reporter activities were enhanced by n-3 LDL, DHA, and PPARγ agonist, whereas activity of a luciferase gene placed downstream of a mutant DR-1 site was unresponsive. Cotransfection with dominant-negative PPARγ DNA eliminated the increase in luciferase activity. These data provide strong evidence that SDC-1 is a molecular target of n-3 PUFA in human breast cancer cells through activation of PPARγ and that n-3 PUFA–induced apoptosis is mediated by SDC-1. This provides a novel mechanism for the chemopreventive effects of n-3 PUFA in breast cancer. [Cancer Res 2008;68(8):2912–9]
BH3 Mimetic ABT-737 Potentiates TRAIL-Mediated Apoptotic Signaling by Unsequestering Bim and Bak in Human Pancreatic Cancer Cells
Authors: Huang Shengbing , Sinicrope Frank A. 
Published: April 2008

AbstractTumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has been shown to induce mitochondrial apoptotic signaling that can be negatively regulated by prosurvival Bcl-2 proteins. ABT-737 is a small-molecule BH3 mimetic that binds to and antagonizes Bcl-2/Bcl-xL but not Mcl-1. We show that ABT-737 can synergistically enhance TRAIL-mediated cytotoxicity in human pancreatic cancer cell lines. ABT-737 was shown to enhance TRAIL-induced apoptosis as shown by DNA fragmentation, activation of caspase-8 and Bid, and cleavage of caspase-3 and poly(ADP-ribose) polymerase. A Bax conformational change induced by TRAIL was enhanced by ABT-737. ABT-737 disrupted the interaction of Bak with Bcl-xL in both cell lines. Furthermore, ABT-737 untethered the proapoptotic BH3-only protein Bim from its sequestration by Bcl-xL or Bcl-2. Bim small hairpin RNA (shRNA) was shown to attenuate caspase-3 cleavage and to reduce the cytotoxic effects of TRAIL plus ABT-737 compared with shRNA control cells. Finally, Mcl-1 shRNA potentiated caspase-3 cleavage by ABT-737 and enhanced its cytotoxic effects. Taken together, ABT-737 augments TRAIL-induced cell killing by unsequestering Bim and Bak and enhancing a Bax conformational change induced by TRAIL. These findings suggest a novel strategy to enhance cross-talk between the extrinsic and intrinsic apoptotic pathways to improve therapeutic efficacy against pancreatic cancer. [Cancer Res 2008;68(8):2944–51]
The Promyelocytic Leukemia Zinc Finger–MicroRNA-221/-222 Pathway Controls Melanoma Progression through Multiple Oncogenic Mechanisms
Authors: Felicetti Federica , Errico M. Cristina , Bottero Lisabianca , Segnalini Patrizia , Stoppacciaro Antonella , Biffoni Mauro , Felli Nadia , Mattia Gianfranco , Petrini Marina , Colombo Mario P. , Peschle Cesare , Carè Alessandra 
Published: April 2008

Abstract
The incidence of cutaneous melanoma is steadily increasing. Although several molecular abnormalities have been associated with melanoma progression, the mechanisms underlying the differential gene expression are still largely unknown and targeted therapies are not yet available. Noncoding small RNAs, termed microRNAs (miR), have been recently reported to play important roles in major cellular processes, including those involved in cancer development and progression. We have identified the promyelocytic leukemia zinc finger (PLZF) transcription factor as a repressor of miR-221 and miR-222 by direct binding to their putative regulatory region. Specifically, PLZF silencing in melanomas unblocks miR-221 and miR-222, which in turn controls the progression of the neoplasia through down-modulation of p27Kip1/CDKN1B and c-KIT receptor, leading to enhanced proliferation and differentiation blockade of the melanoma cells, respectively. In vitro and in vivo functional studies, including the use of antisense “antagomir” oligonucleotides, confirmed the key role of miR-221/-222 in regulating the progression of human melanoma; this suggests that targeted therapies suppressing miR-221/-222 may prove beneficial in advanced melanoma. [Cancer Res 2008;68(8):2745–10]
A Role for TAZ in Migration, Invasion, and Tumorigenesis of Breast Cancer Cells
Authors: Chan Siew Wee , Lim Chun Jye , Guo Ke , Ng Chee Peng , Lee Ian , Hunziker Walter , Zeng Qi , Hong Wanjin 
Published: April 2008

Abstract
TAZ (WWTR1), identified as a 14-3-3 binding protein with a PDZ binding motif, modulates mesenchymal stem cell differentiation. We now show that TAZ plays a critical role in the migration, invasion, and tumorigenesis of breast cancer cells. TAZ is conspicuously expressed in human breast cancer cell lines in which its expression levels generally correlate with the invasiveness of cancer cells. Overexpression of TAZ in low-expressing MCF10A cells causes morphologic changes characteristic of cell transformation and promotes cell migration and invasion. Conversely, RNA interference–mediated knockdown of TAZ expression in MCF7 and Hs578T cells reduces cell migration and invasion. TAZ knockdown in MCF7 cells also retards anchorage-independent growth in soft agar and tumorigenesis in nude mice. Significantly, TAZ is overexpressed in ∼20% of breast cancer samples. These results indicate that TAZ plays a role in the migration, invasion, and tumorigenesis of breast cancer cells and thus presents a novel target for the detection and treatment of breast cancer. [Cancer Res 2008;68(8):2592–8]
Synthetic Lethality by Lentiviral Short Hairpin RNA Silencing of Thymidylate Kinase and Doxorubicin in Colon Cancer Cells Regardless of the p53 Status
Authors: Hu Chun-Mei , Chang Zee-Fen 
Published: April 2008

Abstract
Intracellular supply of dTTP is a highly regulated process and has been a key target for chemotherapeutic drug development. Thymidylate kinase (TMPK) is the key enzyme for dTTP formation in both de novo and salvage pathways. In this study, we used lentiviral-based small hairpin RNA to silence TMPK expression in p53(+/+) and p53(−/−) HCT-116 colon cancer cells. This approach was sufficient to decrease the dTTP pool gradually without affecting p53 expression and generating cytotoxicity. TMPK knockdown significantly increased doxorubicin sensitivity dramatically in p53-proficient, p53-null HCT-116, and LoVo colon cancer cells. The decrease in the dTTP pool using this approach augmented the DNA damage response and enhanced apoptotic induction after exposure to low-dose doxorubicin, leading to cell death. In contrast, silencing of thymidylate synthase which blocks the de novo pathway was incapable of sensitizing p53-null HCT-116 cells to doxorubicin-induced apoptosis because of the compensation by the salvage pathway. Our results suggest the lentiviral delivery of small hairpin RNA targeting TMPK in combination with a low dose of doxorubicin as a new approach to kill colon cancer cells regardless of p53 status. [Cancer Res 2008;68(8):2831–40]
Loss of CTL Function among High-Avidity Tumor-Specific CD8+ T Cells following Tumor Infiltration
Authors: Janicki Claire N. , Jenkinson S. Rhiannon , Williams Neil A. , Morgan David J. 
Published: April 2008

AbstractA major problem in generating effective antitumor CTL responses is that most tumors express self-antigens to which the immune system is rendered unresponsive due to mechanisms of self-tolerance induction. CTL precursors (CTLp) expressing high-affinity T-cell receptors (TCR) are often functionally deleted from the repertoire, leaving a residual repertoire of CTLp having only low-affinity TCR. Furthermore, even when unique antigens are expressed, their presentation by dendritic cells (DC) may predispose to peripheral tolerance induction rather than the establishment of CTL responses that kill tumor cells. In this study, we examined both high-avidity (CL4) and low-avidity (CL1) CD8+ T-cell responses to a murine renal carcinoma expressing, as a neoantigen, high and low levels of the hemagglutinin (HA) protein from influenza virus A/PR/8 H1N1 (PR8; RencaHAhigh and RencaHAlow). Our data show that, following encounter with KdHA epitopes cross-presented by bone marrow–derived DC, low-avidity CL1 cells become tolerized within tumor-draining lymph nodes (TDLN), and in mice bearing either RencaHAhigh or RencaHAlow tumors, very few form tumor-infiltrating lymphocytes (TIL). In marked contrast, high-avidity CL4 cells differentiate into effector CTL within the TDLN of mice bearing either RencaHAhigh or RencaHAlow tumors, and although they form TIL in both tumors, they lose CTL effector function. Critically, these results show that anticancer therapies involving either adoptive transfer of high-avidity tumor-specific CTL populations or targeting of preexisting tumor antigen–specific memory CD8+ T cells could fail due to the fact that CTL effector function is lost following tumor infiltration. [Cancer Res 2008;68(8):2993–3000]