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Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p

We compared paired serum specimens from household contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases with detectable SARS-CoV-2 seroconversion with contacts who remained seronegative. No protection from SARS-CoV-2 infection was associated with human coronavirus antibodies; however, an increase in common betacoronavirus antibodies was associated with seroconversion to SARS-CoV-2 in mild to moderately ill cases.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (RT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of RT-PCR confirmed COVID-19 patients’ sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4%-96.6%. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698-0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.

A severe consequence of adult Zika virus (ZIKV) infection is Guillain-Barré Syndrome (GBS), where autoreactive antibodies attack peripheral and central nervous systems (CNS) resulting in neuro-ocular pathology and fatal complications. During virally induced GBS, autoimmune brain demyelination and macular degeneration correlate with low virus neutralization and elevated antibody-mediated infection among Fcγ-R bearing cells. The use of interferon-deficient mice for ZIKV studies limits elucidation of antibody-dependent enhancement (ADE) and long-term pathology (≥120 days), due to high lethality post-infection. Here we used immunocompetent BALB/c mice, which generate robust humoral immune responses, to investigate long-term impacts of ZIKV infection. A high infectious dose (1x106 FFU per mouse) of ZIKV was administered intravenously. Control animals received a single dose of anti-IFNAR blocking monoclonal antibody and succumbed to lethal neurological pathology within 13 days. Immunocompetent mice exhibited motor impairment such as arthralgia, as well as ocular inflammation resulting in retinal vascular damage, and corneal edema. This pathology persisted 100 days after infection with evidence of chronic inflammation in immune-privileged tissues, demyelination in the hippocampus and motor cortex regions of the brain, and retinal/corneal hyperplasia. Anti-inflammatory transcriptional responses were tissue-specific, likely contributing to differential pathology in these organs. Pathology in immunocompetent animals coincided with weakly neutralizing antibodies and increased ADE among ZIKV strains (PRVABC59, FLR, and MR766) and all Dengue virus (DENV) serotypes. These antibodies were autoreactive to GBS-associated gangliosides. This study highlights the importance of longevity studies in ZIKV infection and confirms the role of anti-ganglioside antibodies in ZIKV-induced neuro-ocular disease.

Global Down Syndrome Foundation stated that “More research is needed to determine how to most effectively teach children with Down syndrome,” (Development…) directly identifying a need for increased research in the respective field. A debate persisting surrounding which teaching style is most effective for children with Down syndrome will be addressed through the incorporation of a kinesthetic and visual approach to teaching visual-spatial constructs in an effort to find one so-called “best” form of teaching. Understanding whether a kinesthetic or visual approach to teaching is more beneficial for children with Down syndrome is a step towards revising an education system that oftentimes does not sufficiently educate children with special needs. This study seeks to assist in finding the most efficient ways to teach children with Down syndrome so that their education will become more effective and impactful.

We quantify antibody and memory B-cell responses to severe acute respiratory syndrome coronavirus 2 at 6 and 12 months postinfection among 7 unvaccinated US coronavirus disease 2019 cases. All had detectable S-specific memory B cells and immunoglobulin G at both time points, with geometric mean titers of 117.2 BAU/mL and 84.0 BAU/mL at 6 and 12 months, respectively.

Background Research on the effects of the COVID-19 pandemic on people with rare diseases is limited. Few studies compare healthcare throughout the progression of the ongoing pandemic.Aims To assess the impact of lockdown on individuals with OI (Osteogenesis Imperfecta) across two consecutive years of the pandemic, to understand what challenges were encountered, and to analyse the experience of remote consultation.Methods Two independent surveys were distributed in August 2020 and April 2021. The primary survey was distributed following the first lockdown, and the second survey built on the experiences reported from the initial survey. The surveys explored four key themes- effects on therapy, alternatives to consultation, effect on mental health, and perceived risks of COVID-19.Results In the primary 2020 survey of the 110 respondents 69 (63%) had at least one appointment delayed due to lockdown, increasing to 89 of the 124 respondents (72%) in the follow-up survey. Of the 110 initial survey participants, 57 (52%) had a remote consultation, increasing to 92 of 124 (74%) in the follow-up survey. In the primary survey 63 of 91 (69%) expressed increasing anxiety due to lockdown, compared with 76 of 124 (61%) in the follow-up survey. In the primary survey 12 of 91 respondents (13%) expressed concerns at not seeing friends and family compared with 103 of 124 (83%) in the follow-up survey. In the second survey of 124 participants there were concerns regarding weight and diet (55, 44%), mobility (70, 56%), pain (71, 57%), and keeping physically active (89, 72%). The majority of participants felt they would have a worse illness and require longer rehabilitation than someone without OI (81 of 117 respondents, and 77 of 120 respectively), and the majority of participants (68%) had been vaccinated at the time of the second survey.Conclusions The pandemic has had widespread effects on both the mental and physical health of those with OI. These repercussions are likely to be felt for years to come. On the other hand, the pandemic has also revealed that in certain situations remote consultation may prove a viable long-lasting alternative to face-to-face appointments.

Objective:To characterize and compare severe acute respiratory coronavirus virus 2 (SARS-CoV-2)–specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection.Design:Prospective cohort.Setting:Nursing home.Participants:SARS-CoV-2–infected nursing home residents.Methods:A convenience sample of 14 SARS-CoV-2–infected nursing home residents, enrolled 4–13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. After diagnosis, plasma SARS-CoV-2–specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 time points, and GCF SARS-CoV-2–specific IgG and IgA were measured at 4 time points.Results:All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12 participants. Neutralizing antibodies were positive in 11 participants; IgM was positive in 10 participants, and IgA was positive in 9 participants. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 participants and for IgA in 12 participants. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response were similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive throughout this evaluation, 46–55 days after diagnosis. All participants were viral-culture negative by the first detection of antibodies.Conclusions:Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Noninvasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized.

Serologic assays developed for SARS-CoV-2 detect different antibody subtypes and are based on different target antigens. Comparison of the performance of a SARS-CoV-2 Spike-Protein ELISA and the nucleocapsid-based Abbott ArchitectTM SARS-CoV-2 IgG assay indicated that the assays had high concordance, with rare paired discordant tests results.

While the majority of influenza-infected individuals show no or mild symptomatology, pregnant women are at higher risk of complications and infection-associated mortality. Although enhanced lung pathology and dysregulated hormones are thought to underlie adverse pregnancy outcomes following influenza infection, how pregnancy confounds long-term maternal anti-influenza immunity remains to be elucidated. Previously, we linked seasonal influenza infection to clinical observations of adverse pregnancy outcomes, enhanced lung and placental histopathology, and reduced control of viral replication in lungs of infected pregnant mothers. Here, we expand on this work and demonstrate that lower infectious doses of the pandemic A/California/07/2009 influenza virus generated adverse gestational outcomes similar to higher doses of seasonal viruses. Mice infected during pregnancy demonstrated lower hemagglutination inhibition and neutralizing antibody titers than non-pregnant animals until 63 days post infection. These differences in humoral immunity suggest that pregnancy impacts antibody maturation mechanisms without alterations to B cell frequency or antibody secretion. This is further supported by transcriptional analysis of plasmablasts, which demonstrate downregulated B cell metabolism and post-translational modification systems only among pregnant animals. In sum, these findings corroborate a link between adverse pregnancy outcomes and severe pathology observed during pandemic influenza infection. Furthermore, our data propose that pregnancy directly confounds humoral responses following influenza infection which resolves post-partem. Additional studies are required to specify the involvement of plasmablast metabolism with early humoral immunity abnormalities to best guide vaccination strategies and improve our understanding of the immunological consequences of pregnancy.

Among 249 healthcare personnel who worked in hospital units with COVID-19 patients for 1 month, 19 (7.6%) tested positive for SARS-CoV-2 antibodies. Only 11 (57.9%) of the 19 personnel with positive serology reported symptoms of a prior illness, suggesting asymptomatic healthcare personnel could be an important source of SARS-CoV-2 transmission.

In 2013, the Australian oil and gas company, Woodside Petroleum, and its multinational joint venture partners announced that they would not be proceeding with a $40 billion liquefied natural gas (LNG) processing facility on the coast of the Kimberley, north-western Australia. The corporations’ decision was made after a five-year campaign against the gas hub by Indigenous, community and environmental groups. The limited academic literature on this case has focused on particular sets of actors and stages of the conflict. This paper applies a broader perspective by examining the positions of a range of actors over a longer time period. It argues that i) the concept of the politics of time provides a useful lens for understanding the dynamics of the conflict ii) the state attempted to exercise control over the development using temporal strategies, but this facilitated alliances between Indigenous and non-Indigenous people and iii) the state also exercised control over corporate actors, but was ultimately unable to compel investment in an increasingly globalized market featuring new floating LNG technology (FLNG).

Since emergence of SARS-CoV-2 in late 2019, there has been a critical need to understand prevalence, transmission patterns, to calculate the burden of disease and case fatality rates. Molecular diagnostics, the gold standard for identifying viremic cases, are not ideal for determining true case counts and rates of asymptomatic infection. Serological detection of SARS-CoV-2 specific antibodies can contribute to filling these knowledge gaps. In this study, we describe optimization and validation of a SARS-CoV-2-specific-enzyme linked immunosorbent assay (ELISA) using the prefusion-stabilized form of the spike protein [1]. We performed receiver operator characteristic (ROC) analyses to define the specificities and sensitivities of the optimized assay and examined cross reactivity with immune sera from persons confirmed to have had infections with other coronaviruses. These assays will be used to perform contact investigations and to conduct large-scale, cross sectional surveillance to define disease burden in the population.

Brazil, a key mining producer globally, has a comprehensive system of environmental laws and institutions. Nevertheless, their effectiveness has been questioned. We examined the perception of regulatory effectiveness of the environmental licensing process for mining from a range of actors involved in these processes in Brazil. Firstly, we found that in line with past research, participants characterized the environmental licensing system as being beset by administrative and legal complexity, a lack of systematization of these processes, and insufficient resources being devoted to enforcement. The workload of environmental agency officers was also noted as a problem as was political influence. In addition, informants raised concerns around environmental agency officers being personally liable for environmental crimes. Furthermore, although interviewees noted that public hearings, environmental impact documents and having the Public Prosecutor's Office (PPO) as a resource were useful state-led ways to mitigate environmental risks from mining, they highlighted longstanding issues around the effectiveness of the hearings and the quality and quantity of the environmental impact documents. These findings are important because despite having comprehensive environmental laws and institutions in place for decades including the presence of a dedicated actor – the PPO – past problems with environmental regulation of mining in Brazil continue.

Purpose : Osteosarcoma is an aggressive primary bone cancer characterized by expression of platelet-derived growth factor (PDGF) and its cognate receptor. Coexpression of the growth factor and receptor suggests their role in autocrine or paracrine growth mechanisms. It has been reported previously that STI571 has specific activity in inhibiting select tyrosine kinase receptors, including PDGF and c-Kit. Osteosarcomas express low levels of c-Kit but abundant levels of PDGF receptor (PDGFR). Experimental Design : To investigate the potential of STI571 as therapy for osteosarcoma, we studied its effects on PDGF-mediated cell growth in vitro and in an in vivo mouse model. Results : PDGF acted as a potent mitogen in a dose-dependent manner in two osteosarcoma cell lines. STI571 (1.0 μm) inhibited both PDGFR-α and PDGFR-β phosphorylation and the downstream phosphorylation targets extracellular signal-regulated kinase and Akt. STI571 also inhibited PDGF-mediated growth and induced apoptosis in vitro as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. To study the effect of STI571 alone or in combination with Taxol in an in vivo model, an osteosarcoma cell line (KRIB) was transplanted into the tibia of athymic nude mice. Mice were treated with STI571 (50 mg/kg p.o. q M-F), Taxol (8 mg/kg i.p. weekly), or STI571 plus Taxol for 6 weeks. There was no significant difference in tumor size between treatment and control mice. Aberrant signaling pathways downstream of the PDGFR in the v-Ki- ras oncogene-transformed KRIB cell line may in part explain this finding. Conclusions : Our data demonstrate that STI571 inhibits PDGF-mediated growth and leads to apoptosis of osteosarcoma cells in vitro by selective inhibition of the PDGFR tyrosine kinase. The effectiveness of STI571 in our studies suggests targeting of PDGFRs as a novel treatment for osteosarcoma.

On the occasion of the 13th International Conference on Osteogenesis imperfecta in August 2017 an expert panel was convened to develop an international consensus paper regarding physical rehabilitation in children and adolescents with Osteogenesis imperfecta. The experts were chosen based on their clinical experience with children with osteogenesis imperfecta and were identified by sending out questionnaires to specialized centers and patient organizations in 26 different countries. The final expert-group included 16 representatives (12 physiotherapists, two occupational therapists and two medical doctors) from 14 countries. Within the framework of a collation of personal experiences and the results of a literature search, the participating physiotherapists, occupational therapists and medical doctors formulated 17 expert-statements on physical rehabilitation in patients aged 0-18 years with osteogenesis imperfecta. ispartof: ORPHANET JOURNAL OF RARE DISEASES vol:13 issue:1 ispartof: location:England status: published

An in vitro Particle Based Biofilm (PBB) model was developed to enable high throughput screening tests to predict clinical plaque reduction. Multi-species oral biofilms were cultured from pooled stimulated human saliva on continuously-colliding hydroxyapatite particles. After three days PBBs were saline washed prior to use in screening tests. Testing involved dosing PBBs for 1 min followed by neutralization of test materials and rinsing. PBBs were then assayed for intact biofilm activity measured as ATP. The ranking of commercial dentifrices from most to least reduction of intact biofilm activity was Crest ProHealth Clinical Gum Protection, Crest ProHealth, Colgate Total and Crest Cavity Protection. We demonstrated five advantages of the PBB model: 1) the ATP metric had a linear response over ≥ 1000-fold dynamic range, 2) potential interference with the ATP assay by treatments was easily eliminated by rinsing PBBs with saline, 3) discriminating power was statistically excellent between all treatment comparisons with the negative controls, 4) screening test results were reproducible across four tests, and 5) the screening test produced the same rank order for dentifrices as clinical studies that measured plaque reduction. In addition, 454 pyrosequencing of the PBBs indicated an oral microbial consortium was present. The most prevalent genera were Neisseria, Rothia, Streptococcus, Porphyromonas, Prevotella, Actinomyces, Fusobacterium, Veillonella and Haemophilus. We conclude these in vitro methods offer an efficient, effective and relevant screening tool for reduction of intact biofilm activity by dentifrices. Moreover, dentifrice rankings by the in vitro test method are expected to predict clinical results for plaque reduction.

In Mexico, the measurement of maternal death has demonstrated the extent to which the risk to women’s lives is determined by their class, location, and ethnicity. In this paper, I examine how the Mexican federal government has implemented measurement and monitoring regimes to track and respond to maternal deaths. Drawing on field research and interviews conducted at various times between 2004 and 2010, I consider some of the contradictory knowledge and governance effects that this turn to measurement has generated in the Mexican health-care system. Measurement and monitoring regimes, I argue, have given maternal health advocates the evidence to argue that it is failings within the health-care system which have made high levels of mortality so intractable. At the same time, measuring mortality has rendered broader aspects of sexual and reproductive rights less visible, while also generating a politics of responsibility and culpability. I trace in this paper a tendency by some health-care professionals to resist what they see as the punitive nature of maternal health monitoring regimes, by either ‘gaming’ the numbers, and/or shifting responsibility other, usually more vulnerable, populations. This analysis highlights the importance of attending to the context in which measurement regimes are introduced. In the context of a deeply flawed system, measurement regimes will generate tensions around responsibility which cannot easily be resolved, and may be resisted by those on whom the regime depends for its reliability.

The widely used influenza subunit vaccine would benefit from increased protection rates in vulnerable populations. Skin immunization by microneedle (MN) patch can increase vaccine immunogenicity, as well as increase vaccination coverage due to simplified administration. To further increase immunogenicity, we used granulocyte-macrophage colony stimulating factor (GM-CSF), an immunomodulatory cytokine already approved for skin cancer therapy and cancer support treatment. GM-CSF has been shown to be upregulated in skin following MN insertion. The GM-CSF-adjuvanted vaccine induced robust and long-lived antibody responses cross-reactive to homosubtypic and heterosubtypic influenza viruses. Addition of GM-CSF resulted in increased memory B cell persistence relative to groups given influenza vaccine alone and led to rapid lung viral clearance following lethal infection with homologous virus in the mouse model. Here we demonstrate that successful incorporation of the thermolabile cytokine GM-CSF into MN resulted in improved vaccine-induced protective immunity holding promise as a novel approach to improved influenza vaccination. To our knowledge, this is the first successful incorporation of a cytokine adjuvant into dissolvable MNs, thus advancing and diversifying the rapidly developing field of MN vaccination technology.

Chemoresistance is a major reason that patients with osteosarcoma fail to achieve a lasting chemotherapy response, and it contributes to disease relapse, progression, and death. Human glutathione S-transferase P1 (GSTP1), a phase II detoxification enzyme, contributes to chemoresistance in many cancers. However, the role of GSTP1 in osteosarcoma chemoresistance is ill defined. We hypothesized that GSTP1 has cytoprotective effects in human osteosarcoma. To assess this possibility, we used GSTP1 cDNA transfection or RNA interference to overexpress or suppress GSTP1 in osteosarcoma cells, and assessed the cytotoxic effect of chemotherapeutic agents on these cells. Our results showed that GSTP1 expression was up-regulated in osteosarcoma cells when they were treated with doxorubicin or cisplatin. GSTP1 overexpression in SAOS-2 osteosarcoma cells caused the cells to be more resistant to doxorubicin and cisplatin. In contrast, GSTP1 suppression in HOS cells caused more apoptosis and extensive DNA damage in response to doxorubicin and cisplatin. The cytotoxicity assay also showed that GSTP1 suppression caused a 2.5-fold increase in cell growth inhibition resulting from doxorubicin and cisplatin treatments [the IC50s are ∼0.16 μmol/L (doxorubicin) and 1.8 μmol/L (cisplatin) for parental HOS versus 0.06 μmol/L (doxorubicin) and 0.75 μmol/L (cisplatin) for GSTP1-silenced HOS]. Moreover, GSTP1 suppression decreased the activation of extracellular signal–regulated kinase 1/2, which is induced by cisplatin and doxorubicin. Taken together, these findings show that GSTP1 contributes to doxorubicin and cisplatin resistance in osteosarcoma, which may be mediated in part by the activation of extracellular signal–regulated kinase 1/2. Targeting of GSTP1 combined with chemotherapy may have synergistic therapeutic effects on osteosarcoma. [Mol Cancer Ther 2007;6(5):1610–9]

Purpose: To characterize current practices and attitudes regarding testing adolescents for carrier status. Methods: Electronic survey of 294 genetic service providers from various professional organizations. Testing for predisposition and presymptomatic conditions was excluded from this study. Results: Eighty-three percent of providers had received requests to test adolescents for carrier status. Of these, 84% have performed testing. Providers cited adolescent desire, sexual activity/pregnancy, and adolescent competence as the main reasons for testing. Some providers who performed testing found the current guidelines unhelpful. Conclusion: Testing adolescents for carrier status is common for at least some conditions. The guidelines regarding genetic testing of adolescents may need to be updated to reflect current concerns and practices.

Since 1987, international organizations have accorded greater attention to the problem of maternal mortality, particularly with the inclusion of its reduction in the Millennium Development Goals. This article examines maternal health policies in Mexico, focusing on interactions between the international, national, and local scales and considering the case of local projects in two states, Chiapas and Guerrero. Although the discourse of maternal health expressed at the international level has facilitated the creation of networks dedicated to maternal health, the restructuring of health services in Mexico and the rescaling of their provision have often conflicted with the realization of this goal. The impact of decentral- izing health services has differed according to (a) the timing and nature of decentralization; (b) the number and expertise of nongov- ernmental organizations (NGOs) working on maternal health issues, and the connections between these NGOs and international networks; and (c) the responsiveness of the state governments to maternal health issues. During the 1980s and 1990s, there were two contradictory

Study Objective To understand adolescent girls' use of “I don't know” within the context of discussing information related to sexual attitudes and behaviors. Design Qualitative analysis of seven focus groups with adolescent girls. Setting Urban primary care clinic. Participants Adolescent girls (n = 23) with a mean age of 16.4 years (range 14 to 18 years). Fifty-two percent were African-American, 26% were Caucasian, 17% were Hispanic/Latino, and 5% were Asian. Results The use of “I don't know” served three functions: (1) place holder, (2) lack of commitment to an opinion; and (3) reduction of commitment to an opinion or belief. Conclusions These results suggest that girls use “I don't know” when asked about their thoughts and opinions related to sexual health, and that its use can have varying implications. Discriminating the intent may help providers respond appropriately. Responses should include providing a safe and nonjudgmental environment in which girls can express their feelings and opinions regarding their sexual health.

Background Cross-sectional seroprevalence studies indicate that infections with herpes simplex virus (HSV) types 1 (HSV-1) and 2 (HSV-2) and cytomegalovirus (CMV) are common. However, data on the rates of acquisition of these infections are limited. Methods A 3-year longitudinal study of HSV-1, HSV-2, and CMV seroprevalence was conducted in a cohort of 174 adolescent girls (age at enrollment, 12-15 years). Results At study entry, 41% of the girls reported a history of sexual activity, and by the end of the study, 73% reported a history of sexual activity. At enrollment, 71% of all participants were seropositive for CMV, 44% were seropositive for HSV-1, and 7% were seropositive for HSV-2. By the end of the study, 81% of the girls were seropositive for CMV, 49% were seropositive for HSV-1, and 14% were seropositive for HSV-2. Among girls with a history of sexual activity, 15.5% were HSV-2 seropositive at the beginning of the study, and 18.9% were HSV-2 seropositive at the end of the study. The attack rates, based on the number of cases per 100 person-years, were 13.8 for CMV infection and 3.2 for HSV-1 infection (among all girls) and 4.4 for HSV-2 infection (among girls with a history of sexual activity). Participants with preexisting HSV-1 antibodies were associated with a significantly lower attack rate for HSV-2 infection. A generalized estimating equation model indicated that participants with a longer history of sexual activity and those who had more sexually transmitted diseases during the 6-month periods before the study visits were more likely to be HSV-2 seropositive. Conclusions This longitudinal study of adolescent girls found high baseline CMV and HSV-1 seroprevalence rates and substantial attack rates for all 3 pathogens.

Interleukin-8 (IL-8) has recently been shown to contribute to human melanoma progression by functioning as a mitogenic and angiogenic factor. In the present study, we investigated whether targeting IL-8 by a fully human anti-IL-8 antibody (ABX-IL8) could be a potential therapeutic strategy to control angiogenesis, growth, and metastasis of melanoma. The human melanoma cells A375SM (high IL-8 producer) and TXM-13 (intermediate IL-8 producer) were injected subcutaneously into nude mice, which were then treated with ABX-IL8 (1 mg/3 times weekly, i.p., for 3 weeks). Tumor growth of both melanomas in ABX-IL8-treated mice was significantly inhibited when compared with control IgG-treated animals. ABX-IL8 treatment also suppressed experimental metastasis when the melanoma cells were injected intravenously. IL-8 blockade by ABX-IL8 significantly inhibited the promoter activity and the collagenase activity of matrix metalloproteinase-2 in human melanoma cells, resulting in decreased invasion through reconstituted basement membrane in vitro. In vivo, ABX-IL8 treatment resulted in decreased expression of matrix metalloproteinase-2, and decreased vascularization (angiogenesis) of tumors concomitant with increased apoptosis of tumor cells. Moreover, in an in vitro vessel formation assay, ABX-IL8 directly interfered with the tubule formation by human umbilical vein endothelial cells. Taken together, these results point to the potential utility of ABX-IL8 as a modality to treat melanoma and other solid tumors either alone or in combination with conventional chemotherapy or other anti-tumor agents.