As these paradigms use chronic administration of estrogens, the classical estrogen receptor (ER) isoforms, ERα and ERβ, are thought to slowly regulate anxiety via transcription (Nilsson et al. 2001). However, administration of 10 μg/kg 17β estradiol exerted anxiolytic effects in the elevated T-maze within 30 min in OVX rats (Kalandakanond-Thongsong et al. 2012),

whereas administration of 25 μg/kg 17β estradiol to female mice was an anxiogenic in the EPM and open field (Kastenberger et al. 2012) tasks within 2 h of a single injection. These studies implicate a rapid, possibly Inhibitors,research,lifescience,medical nongenomic, mode of signaling by 17β estradiol that contributes to state anxiety. One candidate for nongenomic signaling by 17β estradiol is the GPR30, a former orphan G-protein coupled receptor that binds 17β estradiol with a Kd value of 6 nmol/L (Thomas et al. 2005). The expression of GPR30 Inhibitors,research,lifescience,medical in the hippocampus and the central amygdala (Hazell et al. 2009) suggests that this receptor contributes to some of 17β estradiol’s Inhibitors,research,lifescience,medical effect on the limbic system. In OVX rats, chronic administration of the

specific GPR30 agonist, G-1 at 5 μg/day improved memory on a delayed matching to place (DMP) task that requires hippocampally encoded spatial memory (Hammond et al. 2009). In OVX acutely stressed mice, GPR30 expression increased in the basolateral amygdala and G-1 regulated the NMDA receptor system to increase inhibitory synaptic transmission (Tian et al. 2013), thus decreasing anxiety. Contrary

to this anxiolytic effect of GPR30 activation, Kastenberger et al. (2012) showed that 1 mg/kg body weight of G-1 given 2 h before testing to OVX female Inhibitors,research,lifescience,medical mice increased anxiety in the EPM and OFT, but not in the LDT. Hence, similar to the studies that show both anxiolytic and anxiogenic effects of 17β estradiol, GPR30 SB431542 concentration activation by the use of a selective agonist also leads to differing effects on state anxiety that are dependent on dose and timing. As recent studies suggest that enhanced performance on spatial tasks is correlated with lower anxiety Inhibitors,research,lifescience,medical (Kheirbek et al. 2013; Olsen et al. 2013), we hypothesized that the enhancement seen in the DMP task Rutecarpine in OVX rats with chronic administration of G-1 (Hammond et al. 2009) could be due to an anxiolytic effect of GPR30 activation. Hence, adult ovariectomized mice chronically administered, via silastic implants, EB, G-1, or vehicle were tested on the EPM task and the open field test. Our second hypothesis was that the anxiolytic effect exerted by G-1 would correlate with increased extracellular-regulated kinase (ERK) activation as well as the subsequent phosphorylation of an ERK target – the serine 118 of the ERα itself (Kato et al. 1995) – in the hippocampus. This is because GPR30 activation increased ERK activation in a breast cancer (MCF-7) cell line (Filardo et al.

3.5. Drug Release Kinetics The ability of implants to continuously release drug over extended period of time is crucial especially for glaucoma that requires chronic drug administration. It is highly desirable to avoid erratic drug release with potential implications in therapeutic effectiveness and toxicity. Over-all, biodegradable systems are more prone to nonlinear drug release kinetics and increased Inhibitors,research,lifescience,medical burst effects compared to nonbiodegradable systems [29]. Also, burst release patterns are more pronounced with hydrophilic

drugs in polymer matrices that are usually hydrophobic due to their poor drug-polymer interaction. Considering biodegradable systems, drug release pattern may follow three phases involving initial burst, diffusive release (regulated by polymer degradation rate, surface area, and solubility of loaded drug), and the final burst from Inhibitors,research,lifescience,medical disintegrating polymer matrices [46]. The solubility of the drug determines its loading capacity and the higher the Inhibitors,research,lifescience,medical solubility the more uniform the distribution of drug within the polymer matrix.

Uniform drug distribution further reduces the risk of unwanted burst release [85, 86]. Overloading of drug and nonuniform distribution of drug within the polymer matrix can result in increased release during initial burst, which can cause MS-275 cost undesirable ocular effects and inflammatory responses. The release profile of implantable delivery can be affected by the following: (1) amount of drug loaded, (2) surface area and volume of implant, (3) type of polymer and composition, (4) average molecular Inhibitors,research,lifescience,medical weight of polymer, and (5) solubility of the drug. Continuous attempts are being made to minimize the burst effects and achieve linear

drug release kinetics [28, 29]. Formulation Inhibitors,research,lifescience,medical strategies that can enhance drug dispersion in the polymer matrices using suitable drug carriers and emulsifying agents can stabilize the burst effect and result in a drug release rate that correlates with polymer degradation. Also in order to maintain constant release of drug, it is important to use geometrical shapes that will minimize reduction of surface area with PAK6 degradation [54]. The various factors that affect drug release rate from ocular implants are summarized in Figure 2. Figure 2 Schematic of the various factors that could affect drug release rate from ocular implants. A viable approach to achieving desired drug release profiles is by modifying the polymer composition. For instance, some studies have demonstrated that combining two PLA monomers of high and low molecular weights resulted in biphasic release pattern (eliminating the final burst) and achieved pseudozero order kinetics comparable to nonbiodegradable systems [29, 48, 87].

Furthermore, the need to increase clarity and pragmatic instruction for health care providers regarding how best to perform fluid resuscitation is relevant to the management of all forms

of non-cardiogenic shock. Conclusions Our results support use of 30 and 60 mL syringes for the purposes of rapid pediatric fluid resuscitation when the ‘disconnect-reconnect’ technique is utilized. Further studies are needed to evaluate the comparative efficiency of other fluid resuscitation techniques, the potential Quisinostat price problem of provider fatigability, and how fluid resuscitation is best performed in the context of multi-provider Inhibitors,research,lifescience,medical teams. An improved body of evidence should assist with generating clear best practice recommendations as to how pediatric fluid resuscitation Inhibitors,research,lifescience,medical is best performed. Key messages 1) When using a syringe for pediatric fluid resuscitation, choose a 30 – 60 mL syringe. 2) Regular infusion pumps are not adequate for performing fluid resuscitation for children in shock. 3) Further studies are needed to support comprehensive and pragmatic recommendations regarding best practice pediatric fluid resuscitation techniques. Abbreviations ACCM: American College of Critical Care Medicine; HCP: Health care provider; PALS: Pediatric Advanced Life Support. Competing

Inhibitors,research,lifescience,medical interests Greg Harvey – No competing interests to declare, Gary Foster – No competing interests to declareAsmaa Manan – No competing interests to declare, Lehana Thabane – No competing Inhibitors,research,lifescience,medical interests to declare, Melissa Parker – Dr. Parker has received research start-up funding from McMaster and some of these funds may be used if required to cover publication costs in relation to this article. McMaster University and McMaster Children’s Hospital may benefit in

reputation from publication of this article. Authors’ contributions GH was primarily responsible for developing the trial protocol, including all study instruments, under the mentorship of MP. He prepared the REB submission, responded to comments, and revised all documents as required. GH Inhibitors,research,lifescience,medical assisted with the training of the research assistants and subject recruitment and was responsible for inputting all of the study data into the database. GH was involved in the data analysis and interpretation of study findings, assisted with the preparation of figures, and he drafted the first version until of the manuscript. AM was responsible for trial logistical organization including the scheduling and coordination of all subject testing. AM worked under the supervision of MP and ensured that subject testing was conducted under the appropriate conditions and with scientific rigor. GF and LT assisted with trial design and statistical analysis planning. GF verified sample size requirements and provided feedback on study instruments such as the questionnaire. GF also was primarily responsible for the final data analyses. MP conceived of the research question, including the study objectives and hypotheses.

The main advantages of incorporate insulin into SLN would be the enhancement of transmucosal transport and protection from the degradation in the GIT. 7. Conclusions Lipids and lipid nanoparticles are promising for oral and peroral administration route for drugs, proteins, and peptides. Theses matrices are able to promoting controlled release of drugs in GIT and reducing PD173074 absorption variability. In addition, these matrices can be absorption as food lipids together with drugs improving the bioavailability. These systems present several advantages, including drug protection and excipients of GRAS status, which decreases the Inhibitors,research,lifescience,medical danger of acute and chronic

toxicity. In addition, the oral administration of lipids nanoparticles is possible as aqueous dispersion

or alternatively transformed Inhibitors,research,lifescience,medical into a traditional dosage forms such as tablets, pellets, capsules, or powders in sachets. Acknowledgments The authors wish to acknowledge Fundação para a Ciência e Tecnologia do Ministério da Ciência e Tecnologia, under reference no. ERA-Eula/0002/2009. Sponsorship of P. Severino was received from CAPES (Coordenação Inhibitors,research,lifescience,medical Aperfeiçoamento de Pessoal de Nivel Superior) and FAPESP (Fundação de Amparo a Pesquisa). Sponsorship of T. Andreani was received from Fundação para Ciência e Tecnologia (SFRH/BD/60640/2009).
Lipid nanocapsules (LNCs) Inhibitors,research,lifescience,medical are a new generation of biomimetic nanovectors composed of an oily core of medium-chain triglycerides of capric and caprylic acids known under the commercial name of Labrafac that is surrounded by a shell composed of lecithin and a pegylated surfactant called Solutol HS 15. Solutol is a mixture of free PEG 660 and PEG 660 hydroxystearate and oriented towards the water phase. Lecithin is composed of 69% phosphatidylcholine soya bean

and is generally Inhibitors,research,lifescience,medical used in small proportions to significantly increase LNC stability [1, 2]. Their structure mimics lipoproteins [3, 4] while have a hybrid structure between polymer nanocapsules and liposomes. LNCs present a great physical stability up to 18 months with size ranges from 20 to 100nm. They are prepared by a phase inversion of an oil/water emulsion due to from thermal manipulation and in the absence of organic solvents with good monodispersion [5]. The aqueous phase consists of MilliQ water plus sodium chloride salt, which helps to decrease the phase-inversion temperature (PIT) [5, 6]. Preparation of LNCs involves two steps. In the first step all mixed components are heated from room temperature up to T2 temperature, above the PIT, to obtain a W/O emulsion. Then the temperature is dropped to T1 below the PIT, by a cooling process that leads to the formation of an O/W emulsion.

Girls were recruited inhibitors through posters, leaflets and adverts

which were placed in a range of community settings including educational, community, and leisure and sport facilities. Adverts in local newspapers and strategically chosen websites, such as Facebook, Bebo, and Jo’s Trust (a cervical cancer support website) invited interested parties to contact the researcher. Girls were also recruited through community group leaders such as Girl Guide leaders, community workers running youth groups in socially deprived areas, school teachers or parents who been contacted by the researchers or who had viewed an advert indicated they would be interested in getting their youth group, class or daughters involved. Each girl was given a £10 voucher for taking Epigenetic inhibitor nmr part. A topic guide, which was developed from the literature and pilot work, explored the following themes: knowledge and understandings about HPV infection and its link to cervical cancer; beliefs about safer sex and personal risk in relation to HPV; understandings and concerns about HPV vaccination; vaccination experiences; and understandings of the importance of cervical cancer screening. The group discussions were facilitated by ES and lasted between 1 and 2 h. All discussions were audio recorded (with participants’ permission) and transcribed verbatim. To

enable systematic comparisons to be made across the large amounts of data, each transcript was checked learn more and imported into NVivo 7. Data were thematically coded and systemically charted, following the principles of framework analysis [17]. One of the benefits of framework analysis is that it allows a team of researchers to rigorously examine and cross-compare data to identify common reasoning and themes, and ideas that are less common or specific to certain subgroups or individuals. Throughout the analysis attention was paid to any deviant or contradictory

cases [18] and to group dynamics using the full transcripts supplemented by field-note observations [19]. To report the data we have selected quotes attributed to an individual which are expressed concisely and typify responses around key themes. We have also selected some extracts which convey the types of interactions which occurred in mafosfamide the group discussion to give a sense of the rich data gathered from group discussions, whilst being mindful of group effects and the fact that all conversation is influenced by the context in which it is generated [20]. An advantage of the focus group method is that it can generate dynamic data by encouraging discussion between group members [21]; however the chaotic nature of conversation in more animated groups can make it difficult to identify all the individual speakers and this was a particularly challenging aspect of this study. Ethical approval for the study was obtained from the research ethics committee of the University of Glasgow’s Law, Business and Social Sciences Faculty.

2010; Lu et al. 2006]. Guo and colleagues showed that mice without the long form of the leptin receptor (Lepr), which are selectively distributed in the PFC and hippocampus, demonstrated normal growth and body weight but depression-like behaviour and NMDA-induced hippocampal long-term synaptic depression [Guo et al. 2012]. These mice were very sensitive to antidepressant-like effects of the selective NMDA receptor GluN2B (NR2B) antagonist Ro25-6981 but resistant to leptin. The authors argue that defective Lepr signalling in Glu neurons may play a role in the pathogenesis

of depressive disorders Inhibitors,research,lifescience,medical and long-term synapse depression mediated through NMDA GluN2B receptors; Inhibitors,research,lifescience,medical further, the therapeutic actions of NMDA antagonists might be through facilitation of normal leptin-Glu functioning. A systematic review of the efficacy of ketamine as an antidepressant Materials and methods Data acquisition We attempted to identify all randomized controlled trials (RCTs) and non-RCTs available to review up to January 2013, in which the potential efficacy of hallucinogen drugs in the treatment of depression was analysed. Search strategy References Inhibitors,research,lifescience,medical were retrieved through searching electronic databases and manual searches through reference lists of identified literature. The following data sources were searched:

PSYCINFO (1806 to 26 June 2013), MEDLINE (1946 to 26 June 2013), Inhibitors,research,lifescience,medical EMBASE (1980 to 26 June 2013). Although the primary

aim was to explore the efficacy of ketamine, to ensure the fullest data collection the search criteria were as follows: “hallucinogen” OR “lsd” OR “lysergic acid diethylamide” OR “ketamine” OR “mescaline” OR “psilocybin” OR “magic mushroom” OR “mdma” OR “ecstasy” OR “psychedelic” OR “dissociative” OR “phenethylamine” OR “phencyclidine” combined with AND “antidepressant” OR “depression*” OR “mood disorder” OR “bipolar” OR “depressive-disorder” OR “unipolar”. Inhibitors,research,lifescience,medical Eligibility criteria The following inclusion and exclusion criteria were established those prior to the literature search. Participants Studies that looked at adult populations (≥18 years old) with a diagnosis of a MDD or BPAD based on a structured diagnostic interview (DSM or ICD) were included. Interventions All designs evaluating the effect of ketamine on depressed mood were included. Investigations on addiction, ketamine misuse or specifically looking at psychedelic effects of ketamine were excluded. Comparators No comparators were required for inclusion in this review. Outcomes Studies investigating the effect of ketamine on mood symptoms and/or suicidality were included. Studies that failed to use a validated assessment scale for the Olaparib supplier evaluation of mood changes were excluded.

Analyses were performed using SAS version 9.2. In 2009, there were 14,562 hospitalizations among patients with GISTs at a rate of 44/100,000 admissions. Hospitalization rates

among patients with GISTs varied by patient-, hospital-, and discharge-level characteristics. Patients with GISTs had longer length of stay (LOS), total charges, and mortality rate as compared to the control group. Total charges for hospitalizations among patients with GISTs varied by household income, hospital location and region, LOS, and number of diagnoses on record, Inhibitors,research,lifescience,medical respectively. When examining the predictors of mortality, household income, hospital region, and number of diagnoses on record emerged significant. By examining the inpatient burden among patients with GISTs, this study fills a critical gap in this area of research. Future studies could merge medical Selleck Nutlin-3a services claims data with cancer registry data to study in-depth the

humanistic and economic burden associated with GISTs. Key Words: Inhibitors,research,lifescience,medical Gastrointestinal stromal tumors, inpatient, charges, mortality Introduction Gastrointestinal Stromal Tumors (GISTs) are the Inhibitors,research,lifescience,medical most common tumors of the gastrointestinal (GI) tract that arise from mesenchymal cells, and are considered to be a subset of soft tissue sarcomas (1). GISTs account for less than 1% of all GI tumors (2). The prevalence of GISTs has been found to be 129 per million adults while the incidence is reported to be 3000-4000 adults per year (3-5). Though the incidence and prevalence numbers of GISTs are lower as compared to other more common cancers, the disease burden associated with these tumors is significant (6). The 3-year survival rate for patients with GISTs is 79%, while the 5-year Inhibitors,research,lifescience,medical survival rate is 63% (7,8). Besides leading to significant morbidity and mortality, GISTs cause

considerable economic burden. Inhibitors,research,lifescience,medical In their study of costs associated with GISTs using the SEER-Medicare database, Rubin et al. (2011) reported the first-year total medical costs after surgical resection of GISTs to be $35,478. A few studies have reported found the survival rates and costs associated with GISTs; however, there is currently no information available regarding the inpatient burden associated with these tumors. Information concerning total charges and mortality among patients hospitalized with GIST is currently unknown. The purpose of this study was to determine the hospitalization burden associated with GISTs in the United States (US) using a nationally representative database. Specific objectives of the study were to: (I) assess the hospitalization rates of GISTs by different patient-, hospital- and discharge-level characteristics; (II) compare the hospitalization characteristics of patients with GISTs to those without GISTs; and (III) identify the factors predicting total charges and mortality, respectively, among patients with GISTs.

Emergency Department (ED) crowding (and access block) has been described as the most serious issue currently confronting EDs [1-3]. The demand for ED services exceeds any growth that can be explained by population increase [4]. A recent Australian Institute of Health and Welfare (AIHW) report identified that “between 2009–10 and 2010–11, ED presentations increased in all states and territories, with increases ranging from 1.6% in Tasmania to 8.1% in Western Inhibitors,research,lifescience,medical Australia” [5], p vii. ED crowding has been linked to a range of adverse outcomes for

patients and staff, including increased medical errors, increased patient mortality, patient dissatisfaction, high levels of work-related stress, decreased morale among ED staff and decreased capacity of EDs to respond to mass casualty incidents [2,3,6,7]. EGFR inhibitors list Ambulance usage is also increasing annually. In Western Australia (WA), St John Ambulance Western Australia (SJA-WA) activity in the Perth metropolitan area increased by 23% to 171,462 cases attended in the 2010/11 financial year from138,996 cases in 2006/07 [8]. Inhibitors,research,lifescience,medical For the year 2012, SJA-WA paramedic crews in metropolitan Perth attended a total of 132,862 cases and 105,327 (79.3%) were transported to ED. (“unpublished data” provided

to Prof I. Jacobs by SJA-WA.) Increasing numbers of ambulance arrivals are one of the key drivers of ED demand and also increased episodes Inhibitors,research,lifescience,medical of ramping [9]. There is growing recognition that not all patients attended by paramedics actually need to be transported to ED. As part of a major overhaul of emergency services in the UK [10], the concept of ‘emergency

care practitioners’ (EmCPs) emerged as an alternative model of ambulance Inhibitors,research,lifescience,medical paramedic response [10-12]. Initial reports showed that EmCPs were dealing with “54% of patients without the need for an immediate referral to another healthcare professional or emergency transportation Inhibitors,research,lifescience,medical to ED” [11]. A cluster randomised trial in the UK reported reduced ED attendance associated with Paramedic Practitioner (a similar role to EmCP) attendance, whilst maintaining patient satisfaction and safety [13]. Notwithstanding reports of the apparent success of the EmCP role in the UK, the structure of the health system, both in relation to primary care and emergency services, is different to that in both Australia and New Zealand. Extended care paramedics (ECPs) have been introduced in New Zealand [14], NSW [15] and SA [16]. In 2009 the Wellington (New Zealand) Ambulance service initiated a new model of care for a rural district with old approximately 50,000 residents and a high proportion of over 65 year olds. Ambulance staff, trained in additional clinical skills, are sent to patients with conditions considered amenable to treatment in their own homes or local communities [14]. As explained, “this has shifted the focus of the ambulance service towards taking healthcare to the patient and away from automatically transporting the majority of patients to hospital” [14, p11].

Given that receptor PTKs are thought to be activated by extracellular cues and transduce such stimuli into cytoplasmic signaling, this observation is surprising. However, downregulation of Dok-7 using RNA interference technique demonstrated that Dok-7 is required for activation of MuSK at least in cultured myotubes (14). Furthermore, the RNA interference experiments revealed that even neural Agrin requires Dok-7 to activate MuSK in myotubes (14). Indeed, E18.5 embryos of mice lacking Dok-7 do not form AChR clusters nor NMJs in the diaphragm muscles as Inhibitors,research,lifescience,medical was observed in MuSK-deficient mice (14, 17). It is of note that both mutant mice showed abnormal extension of motor nerve

axons at the medial area of the skeletal muscle possibly due to the lack of retrograde signaling from the postsynaptic apparatus (14, 17). Together, these data indicate that Dok-7 is a cytoplasmic activator of MuSK essential for MuSK-dependent postsynaptic Inhibitors,research,lifescience,medical specialization of NMJ (Fig. ​(Fig.11). Figure 1 A

greatly simplified model of the Dok-7/MuSK pathway Inhibitors,research,lifescience,medical for postsynaptic specialization of the mammalian NMJ. Dok-7 can activate MuSK and induce Rapsyn-dependent AChR clustering even in the absence of neural Agrin; however MuSK requires both Dok-7 and Agrin … As previously stated, a skeletal muscle-intrinsic activator of MuSK was predicted due to existence of i) aneural, but MuSK-dependent, clustering of AChRs in mouse embryos; and ii) neuromuscular synapse Inhibitors,research,lifescience,medical CHIR-99021 price formation in mice lacking both Agrin and CHAT (5–7). Although there is no definitive proof that Dok-7 is this muscle-intrinsic activator of MuSK, there is supporting evidence: i) mice lacking Dok-7 or MuSK form no AChR clusters while those lacking Agrin can form aneural, MuSK-dependent AChR clusters (14, 17); ii) Dok-7 transcripts were preferentially expressed in the central region of the diaphragm

muscle of mouse E14.5 embryos, where the aneural, MuSK-dependent Inhibitors,research,lifescience,medical AChR clusters normally form (14). However, as we will discuss later, if Dok-7 plays a role as an essential signaling molecule downstream of MuSK, the same defects could be observed in Dok-7-deficient mice. Therefore, careful examination of kinase activity of MuSK in the skeletal muscle during embryogenesis of Dok-7-deficient mice would be important. The Dok-7/MuSK pathway How does a cytoplasmic adaptor-like protein Dok-7 activate a receptor PTK MuSK? Although the definitive Mephenoxalone answer awaits further studies, several interesting observations have been found (14). In heterologous cells, which do not express Dok-7 nor MuSK, the forced expression of these two proteins resulted in robust activation of MuSK. In addition, when ectopically expressed in heterologous cells, these proteins form a stable complex that requires the intact PTB domain of Dok-7 and its target motif encompassing Tyr-553 in the juxtamembrane region of MuSK.

As HSV-2 infection is often subclinical, measurement of clinical disease as a inhibitors primary endpoint is problematic. Autophagy Compound Library clinical trial An important feature of candidate vaccines will be modification of the construct so that an antibody assay can distinguish between vaccinated and infected persons. Secondary endpoints should include frequency of clinically apparent HSV genital disease, and in those who seroconvert, frequency of genital viral shedding. Mathematical modeling suggests that even low efficacy preventative vaccine could impact the HSV-2 epidemic

by decreasing shedding and reducing viral transmission [90]. Such a vaccine would have the highest impact in high-prevalence populations [91]; for instance, a vaccine which marginally decreases HSV-2 susceptibility but reduces shedding frequency by 75% could reduce HSV-2 incidence by 30% over a 10 year period [92]. Thus, it is important to study both acquisition, and in those who acquire, frequency of viral shedding. An effective therapeutic HSV-2 vaccine could both improve the clinical course in individual patients,

and decrease selleck inhibitor HSV transmission through reduction in shedding, for a public health benefit. The approach to efficiently evaluate such vaccines relies on evaluation of viral shedding in a cohort of highly adherent persons with clinically apparent genital HSV-2; we have found that this population is highly motivated to participate in daily genital shedding studies [93]. The participants obtain genital swabs for detection of viral shedding before and after vaccination in a one-way crossover study design. These studies are ideal for proof-of-concept, those as they can rapidly provide an answer to whether the vaccine has efficacy and can be efficiently performed with fewer than 100 persons [94]. Reduction in viral shedding is the more sensitive primary endpoint for therapeutic vaccine trials, and serves as a useful surrogate endpoint for recurrence rate

and transmission likelihood. As initial therapeutic vaccine trials should target persons with symptomatic infection, important secondary endpoints include frequency of genital lesions and prodromal symptoms. These are the clinical endpoints that have been requested in the past by FDA for licensure studies. In addition, the density of HIV receptor-positive cells in the genital mucosal following therapeutic immunization will need to be evaluated. Although prior vaccines that have been tested in human clinical trials have almost exclusively targeted glycoproteins, the HSV vaccine pipeline is rich with novel platforms that have shown efficacy in animal models (Table 1). The challenge will be quickly moving these candidate vaccines into human clinical trials. There has been concern about safety of replication-competent vaccines due to possibility of recombination with clinical strains or the establishment of latency.