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Background: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)–piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. Methods: Participants were recruited through Health Care Provider’s safety registry in 15 centres across 6 European countries in the period 2013–2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett’s (QTcB) or Fridericia’s (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. Results: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). Conclusions: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942, SCOPUS: ar.j, info:eu-repo/semantics/published

Objective The Saudi government requires that all pilgrims receive a quadrivalent meningococcal vaccine at least 10 days before the Hajj. We conducted a study to determine the uptake of meningococcal vaccine and antibiotic use. We also investigated risk factors of meningococcal carriage and carriage of Neisseria meningitidis pathogenic serogroups A, C, W and Y. Methods A cross‐sectional oropharyngeal carriage survey was conducted in 2973 Hajj pilgrims in September 2017. A real‐time polymerase chain reaction (rt‐PCR) assay was used to identify N. meningitidis from the oropharyngeal swabs. A questionnaire investigated potential risk factors for carriage of N. meningitidis. Results Two thousand two hundred forty nine oropharyngeal swabs were obtained. The overall prevalence of carriage of N. meningitidis was 4.6% (95% CI: 3.4%–6%). Carriage of pathogenic serogroups was not associated significantly with any of the meningococcal risk factors evaluated. 77% of pilgrims were vaccinated but 22.58 % said they were carrying unofficial vaccination cards. Conclusion Carriage of serogroups A, C, W and Y was not significantly associated with any of the risk factors investigated. Almost a quarter of pilgrims were unlikely to have been vaccinated, highlighting a need to strengthen compliance with the current policy of vaccination to prevent meningococcal disease outbreaks during and after the Hajj.

Replacement of lost cranial bone (partly mesodermal and partly neural crest‐derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow‐derived mesenchymal stromal cells (mesoderm‐derived BM‐MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) improves implant‐to‐bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC‐MPCs. BM‐MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (μCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC‐MPC‐Luc2 vs BM‐MSC‐Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, μCT analysis showed enhanced structural parameters in the iNCC‐MPC‐Luc2 group and increased bone volume in the BM‐MSC‐Luc2 group compared to controls. Histology demonstrated improved integration of iNCC‐MPC‐Luc2 allografts compared to BM‐MSC‐Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft‐host interphase in cell‐seeded groups. The iNCC‐MPC‐Luc2 group also demonstrated improved biomechanical properties compared to BM‐MSC‐Luc2 implants and cell‐free controls. Our results show an improved integration of iNCC‐MPC‐Luc2‐coated allografts compared to BM‐MSC‐Luc2 and controls, suggesting the use of iNCC‐MPCs as potential cell source for cranial bone repair., Bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) were obtained from human bone marrow. Induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) were generated from induced pluripotent stem cell‐derived iNCCs. Cells were luciferase transfected and seeded onto decellularized allografts, which were implanted into 5 mm circular calvarial defects in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Allograft only was used as controls. Mice were followed for a duration of 8 weeks. Cell survival, allograft integration, and tissue morphology and transplanted cell contribution were monitored via bioluminescence imaging (BLI), micro‐computed tomography (μCT), and histology and immunofluorescence (IF). Green arrow: BLI; yellow arrow: μCT; Orange arrow: histology and IF; Blue arrow: biomechanical test.

Cytokine-induced memory-like (CIML) NK cells generated in response to proinflammatory cytokines in vitro and in vivo can also be generated by vaccination, exhibiting heightened responses to cytokine stimulation months after their initial induction. Our previous study demonstrated that in vitro human NK cell responses to inactivated influenza virus were also indirectly augmented by very low doses of IL-15, which increased induction of myeloid cell–derived cytokine secretion. These findings led us to hypothesize that IL-15 stimulation could reveal a similar effect for active influenza vaccination and influence CIML NK cell effector functions. In this study, 51 healthy adults were vaccinated with seasonal influenza vaccine, and PBMC were collected before and up to 30 d after vaccination. Myeloid and lymphoid cell cytokine secretion was measured after in vitro PBMC restimulation with low-dose IL-15, alone or in combination with inactivated H3N2 virus; the associated NK cell response was assessed by flow cytometry. PBMC collected 30 d postvaccination showed heightened cytokine production in response to IL-15 compared with PBMC collected at baseline; these responses were further enhanced when IL-15 was combined with H3N2. NK cell activation in response to IL-15 alone (CD25) and H3N2 plus IL-15 (CD25 and IFN-γ) was enhanced postvaccination. We also observed proliferation of less-differentiated NK cells with downregulation of cytokine receptors as early as 3 d after vaccination, suggesting cytokine stimulation in vivo. We conclude that vaccination-induced “training” of accessory cells combines with the generation of CIML NK cells to enhance the overall NK cell response postvaccination.

Insects have attracted much attention as a novel food source because of their environmental and nutritional advantages. In Latin America, some traditional groups consume insects; but the urban areas of Brazil resist adopting insects as food, like most Western countries. Thus, this study investigated the social representation of edible insects to understand the barrier behind this avoidance and to identify their segmentation in the Brazilian population. Seven hundred and eighty individuals were interviewed in all the Brazilian regions. The interview was composed of a word association task, a risk perception evaluation and two open-ended questions about the subject. According to the structural approach of social representation, Disgust was the primary association with edible insects. Three segments of consumers were identified using the risk perception of eating insects. The first segment, composed mainly of young men with higher educational levels, had the lowest risk perception, and the most positive attitude about entomophagy, their associations were also positive, such as Acceptance and Sustainability; the second had average risk perception and neutral attitude towards edible insects, with neutral and positive associations (e.g., Flavor and Culture); and the third, formed mostly by older women with lower educational level, presented the highest risk perception and the most negative attitude, and exhibited negative associations (Disgust, and Fear). The insect consumption in Brazil would be favored by using species of crickets, grasshoppers, ants, and their fried and roasted styles of preparations. Also, participants would eat insects mainly because of survival and curiosity.

As physicians, we strive to meet the needs of our patients. In doing so, we are often exposed to hazards that have the potential to not only compromise our health, but also our ability to deliver the best possible healthcare. Occupational hazards specific to the field of orthopaedics include infectious organisms, radiation, surgical smoke, chemicals, hazardous noise, musculoskeletal injury, and psychosocial stressors. Even though orthopaedic surgeons acknowledge the risk, most lack in-depth knowledge of the associated long-term harm associated with these hazards and ways of reducing risk of exposure. Orthopaedic surgeons should increase awareness, follow established guidelines, and integrate preventative measures to create the safest possible work environment. It is our hope that by improving our own health, we will be better equipped to address the health concerns of those we serve-our patients.

Background: Klippel-Feil syndrome (KFS) is defined by multiple abnormal segments of the cervical spine with congenital synostosis of two or more cervical vertebrae. KFS patients who demonstrate progressive symptomatic instability and/or neurologic sequelae are traditionally managed with operative decompression and arthrodesis. Case Description: A 44-year-old female with chronic neck pain and radiculopathy and a C7-T1 KFS presented with adjacent segment degenerative disc disease at the C5-6 and C6-7 levels. She was successfully managed with a two-level cervical disc arthroplasty (CDA). Conclusion: Patients with KFS and disease at two contiguous, adjacent levels (e.g., cervical disc disease) may be safely and effectively managed with two-level CDA.

Background The Hajj is one of the world’s largest pilgrimage and gathers millions of Muslims from different nationalities every year. Communicable diseases have been reported frequently, during and following the Hajj, and these have been linked to individual behavioural measures. This study aimed to measure the effect of personal preventive measures, such as face mask use, hand hygiene and others, adopted by pilgrims in reducing the acquisition of infectious diseases. Methods We conducted a cross-sectional study at the Hajj terminal in King Abdulaziz International Airport in Jeddah, Saudi Arabia. Pilgrims were approached in the airport lounges after the 2017 Hajj season and prior to the departure of their flights from Jeddah to their home countries. An electronic data collection tool (‘Open Data Kit’) was used to gather survey data in regards to health problems and preventive measures during the Hajj. Results A total of 2973 Hajj pilgrims were surveyed. In all, 38.7% reported symptoms of upper respiratory tract infections (URTIs) and 5.4% reported symptoms of travel diarrhoea. Compliance with face mask use was 50.2%. Changing a face mask every 4 h was found to be significantly associated with lower prevalence of URTIs [adjusted odds ratio 0.56 (95% confidence interval 0.34–0.92), P = 0.02]. There was no statistical difference between overall face mask use and URTI acquisition. The main sources of food, eating raw vegetables/food, frequency of hand washing or use of hand sanitizers were not found to be significantly associated with reported travellers’ diarrhoea. Unlicensed barbers were used by 12% of pilgrims and 9.2% of pilgrims reported using blades that were reused by other pilgrims. Conclusion Preventive measures are the most effective way to prevent infections. Pilgrims can benefit from face masks by changing them frequently. There is still limited information on the effect of the use of face mask in decreasing the risk of URTI in mass gatherings.

BackgroundThe impact of CD4+ T-cell count and highly active antiretroviral therapy (HAART) on the rate of surgical site infection (SSI) in patients with human immunodeficiency virus (HIV) undergoing total hip arthroplasty is still unclear. The goals of this study were to assess the rate of perioperative infection at a large tertiary care referral center and to identify risk factors in HIV+ patients undergoing total hip arthroplasty (THA).MethodsThis study was a prospective, observational study at a single medical center from 2000–2017. Patients who were HIV+ and underwent THA were followed from the preoperative assessment period, through surgery and for a 2-year follow-up period.ResultsSixteen of 144 HIV+ patients (11%) undergoing THA developed perioperative surgical site infections. Fourteen patients (10%) required revision THA within a range of 12 to 97 days after the initial surgery. The patients’ mean age was 49.6 ± 4.5 years, and the most common diagnosis prompting THA was osteonecrosis (96%). Patients who developed SSI had a lower waist-hip ratio (0.86 vs. 0.93,p= 0.047), lower high density lipoprotein cholesterol (45.8 vs. 52.5,p= 0.015) and were more likely to have post-traumatic arthritis (12.5% vs. 0%,p= 0.008). Logistic regression analysis demonstrated that current alcohol use and higher waist-hip ratio were significant protectors against infection (p< 0.05). No other demographic, medical, immunologic parameters, or specific HAART regimens were associated with perioperative infection.ConclusionsImmunologic status as measured by CD4+ cell count, HIV viral load, and medical therapy do not appear to influence the development of SSI in HIV+ patients undergoing THA. Metabolic factors and post-traumatic arthritis may influence the increased rate of infection in HIV+ patients following THA.

Introduction Synthetic bone grafts are often used to achieve a well-consolidated fusion mass in spinal fusion procedures. These bone grafts function as scaffolds, and ideally support cell function and facilitate protein binding. Objective The aim was to characterize an electrospun, synthetic bone void filler (Reb) for its bone morphogenetic protein (BMP)-2 release properties and support of human mesenchymal stem cell (hMSC) function in vitro, and its efficacy in promoting BMP-2-/bone marrow aspirate-(BMA)-mediated posterolateral spinal fusion (PLF) in vivo. Methods BMP-2 release kinetics from Reb versus standard absorbable collagen sponge (ACS) was determined. hMSC adhesion and proliferation on Reb was tested using cell counting, fluorescence microscopy and MTS. Cell osteogenic differentiation was quantified via cellular alkaline phosphatase (ALP) activity. For in vivo analysis, 18 Lewis rats were treated during PLF surgery with the following groups: (I) Reb + BMA, (II) Reb + BMA + BMP-2 and (III) BMA. A safe, minimally effective dose of BMP-2 was used. Fusion consolidation was followed for 3 months using radiography and micro-CT. After sacrifice, fusion rate and biomechanical stiffness was determined using manual palpation, biomechanical tests and histology. Results In vitro, BMP-2 release kinetics were similar between Reb versus ACS. MSC proliferation and differentiation were increased in the presence of Reb. At 3 months post-surgery, fusion rates were 29% (group I), 100% (group II), and 0% (group III). Biomechanical stiffness was higher in group II versus I. Micro-CT showed an increased bone volume and connectivity density in group II. Trabecular thickness was increased in group I versus II. H&E staining showed newly formed bone in group II only. Conclusions Reb possesses a high protein binding affinity and promotes hMSC function. Combination with BMA and minimal dose BMP-2 allowed for 100% bone fusion in vivo. This data suggests that a minimally effective dose of BMP-2 can be used when combined with Reb.

Purpose To describe the main provisions of the US Department of Labor’s final “fiduciary” rule and its related prohibited transaction exemptions and the key challenges the rule poses for financial advisers. Design/methodology/approach This article describes the impact of the new “fiduciary” rule on broker-dealers, banks and other financial organizations who will, for the first time since the passage of ERISA, be subject to ERISA’s fiduciary standards and remedies when providing investment and asset management recommendations to individual retirement accounts and other retail retirement clients. Findings The most immediate impact of the rule will be on the compensation practices at broker-dealers and other financial institutions and on the fee and revenue sharing arrangements among funds, fund sponsors and the financial institutions that offer investment advice to retail retirement clients. Although the new rule responds to many of the concerns raised by the financial services industry, compliance with the rule will require the restructuring of pay and compliance policies at financial institutions servicing retail clients. Originality/value Practical guidance from experienced ERISA lawyers.

Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2–dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV−) individuals than in HCMV-seropositive (HCMV+) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV+ and HCMV− subjects. In addition to these IL-2–dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57− NK cells and was most evident in HCMV+ subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection.

Recombinant human bone morphogenic protein-2 (BMP-2)-loaded absorbable collagen sponges (ACS) have been successfully used to enhance bone formation and to induce spinal fusion in humans. However, side effects, such as soft tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. In this study, we investigated NBD's potential to reduce BMP-2-induced soft tissue inflammation without affecting BMP-2-mediated spinal fusion in rat. For evaluation of soft tissue inflammation, ACS containing BMP-2, BMP-2+NBD, NBD, or ACS only were implanted into intramuscular paraspinal sites of 32 rats. At day 2 postsurgery, edema formation at the implant sites was assessed using magnetic resonance imaging. T2-weighted relaxation time (T2-RT) values were increased in the BMP-2 group compared with BMP-2+NBD, NBD, and ACS groups. No difference in T2-RT values was detected between BMP-2+NBD versus NBD and ACS controls. Postsacrifice, histological analysis of the implant-surrounding zones showed increased mononuclear cell infiltration in the BMP-2 group compared with BMP-2+NBD and controls. The presence of BMP-2 increased relative NF-κB binding and gene expression of inflammatory markers, interleukin (IL)1β, IL6, IL18, and chemokine ligand (CCL)2 and CCL3 compared with controls. In the BMP-2+NBD group, cytokine expression was blocked. No differences were found between BMP-2+NBD and control groups. For evaluation of spinal fusion, posterolateral intertransverse lumbar fusion procedures were performed on 16 rats. ACS were loaded with BMP-2 or BMP-2+NBD. After sacrifice at week 12, microcomputed tomographic assessment of the fusion site detected a higher bone volume and reduced trabecular spacing in the BMP-2+NBD group compared with BMP-2. Histological analysis did not show any differences in newly formed bone microarchitecture. In summary, addition of NBD to BMP-2-loaded ACS reduces BMP-2-induced soft tissue edema formation and mononuclear cell infiltration, diminishes NF-κB binding, and thus blocks transcription of NF-κB-regulated cytokines in rat. Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion.

Background Existing travel health guidelines are based on a variety of data with underpinning evidence ranging from high‐quality randomized controlled trials to best estimates from expert opinion. For strategic guidance and to set overall priorities, data about average risk are useful. The World Health Organization (WHO) plans to base future editions of “International Travel and Health” on its new “Handbook for Guideline Development.” Methods Based on a systematic search in PubMed, the existing evidence and quality of data on vaccine‐preventable disease (VPD) risks in travelers was examined and essentials of vaccine efficacy were briefly reviewed. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used to evaluate the quality of the data. Results Moderate‐quality data to determine the risk of VPD exist on those that are frequently imported, whereas in most others the level of confidence with existing data is low or very low. Conclusions In order for the WHO to produce graded risk statements in the updated version of “International Travel and Health,” major investment of time plus additional high‐quality, generalizable risk data are needed.

Airway management during resuscitation is pivotal for treating hypoxia and inducing reoxygenation. This German Resuscitation Registry (GRR) analysis investigated the influence of the type of airway used in patients treated with manual chest compression (mCC) and automated chest compression devices (ACCD) after out-of-hospital cardiac arrest (OHCA). Out of 42,977 patients (1 January 2010–30 June 2016) information on outcome, airway management and method of chest compressions were available for 27,544 patients. Hospital admission under cardiopulmonary resuscitation (CPR), hospital admission with return of spontaneous circulation (ROSC), hospital discharge and discharge with cerebral performance categories 1 and 2 (CPC 1,2) were used to compare outcome in patients treated with mCC vs. ACCD, and classified by endotracheal intubation (ETI), initial supraglottic airway device (SAD) changed into ETI, and only SAD use. Outcomes for hospital admission under ongoing CPR, hospital admission with ROSC, hospital discharge and neurologically intact survival (CPC 1,2) for mCC (84.8%) vs. ACCD (15.2%) groups were: 8.4/38.6%, 39.2/27.2%, 10.6/6.8%, 7.9/4.7% (p < 0.001), respectively. Only mCC with SAD/ETI for ever ROSC (OR 1.466, 95% CI: 1.353–1.588, p < 0.001) and mCC group with SAD/ETI for hospital admission with ROSC showed better outcomes (odds ratio [OR] 1.277, 95% confidence interval [CI]: 1.179–1.384, p < 0.001) in comparison to mCC treated with ETI. Compared to mCC/ETI, all other groups were associated with a decrease in neurologically intact survival. Better outcomes were found for mCC in comparison to ACCD and ETI showed better outcomes in comparison to SAD only. This observational registry study raised the hypothesis that SAD only should be avoided or SAD should be changed into ETI, independent of whether mCC or ACCD is used.

The recommendation for carriage standby emergency treatment (SBET) for malaria is now becoming more widespread across Europe. This follows as a replacement to the withdrawal of recommendations for use of malaria chemoprophylaxis, predominantly therefore to falling transmission of Plasmodium falciparum malaria on the successful malaria control programmes across South East Asia and South America.1 Travellers are prescribed SBET antimalarial medication to carry during their journey. The policy is aimed at travel to areas of low falciparum malaria transmission in the above continents, not at travellers to Sub Saharan Africa. They are advised to use the medication when malaria is suspected and prompt medical attention is unavailable, but ideally, to attend a medical centre within 24 h of onset of symptoms for a diagnosis, and if malaria is confirmed, use the medication secure in the knowledge that it is not counterfeit.

Paediatric travellers face most of the infectious risks that adults face during travel, but their different immunological maturity and response to infection make them more vulnerable to disease.

Background Despite many travelers receiving at least one vaccination during the pre-travel consultation, little is known about travelers' fear of injections and the impact this may have on educating travelers about health risks associated with their trip. This study aimed to investigate: (1) the prevalence of injection anxiety in travelers attending a pre-travel consultation, (2) whether anxiety due to anticipating a vaccination adversely affects recall of information and advice, and (3) whether clinicians can recognize travelers' anxiety, and how they respond to anxious travelers. Methods Consecutive adult travelers (N = 105) attending one of two inner-city travel clinics completed self-report measures of state anxiety, injection anxiety, and symptoms of needle phobia immediately before and after their pre-travel consultation. Clinicians were also asked to rate travelers' anxiety and report any anxiety management strategies. Standardized information was presented during the consultation and recall of information and advice was assessed immediately post-consultation. Delayed recall (24 hours) was assessed for a subsample (20%) of participants. Results More than one third of travelers reported feeling nervous or afraid when having an injection (39%). Travelers' state anxiety was related to their psychological and physiological reactions to needles, and reduced significantly post-consultation. Recall of information and advice varied, with failure of recall ranging from 2 to 70% across 15 items, and delayed recall being significantly lower. No relationship was found between recall and anxiety. Clinician-rated anxiety moderately correlated with travelers' self-reported anxiety. Conclusions A significant proportion of travelers experienced injection anxiety when attending the pre-travel consultation, with some travelers reporting symptoms consistent with criteria for Blood Injection Injury phobia. There were important gaps in recall of information and advice about common travel risks. Although no relationship was found between recall and anxiety, this may have been due to the sample and setting.

BACKGROUND CONTEXT Synthetic bone grafts are being developed to lessen the need for autograft and allograft. Electrospun bone grafts (ESBG) have a highly porous nanofibrous structure with a large surface area-to-volume ratio, potentially improving its osteoconductive and osteoinductive properties. PURPOSE We investigate the potential of ESBG to stimulate mesenchymal stem cell (MSC) function in vitro, and to facilitate BMP-2 mediated spinal fusion in a rat model. STUDY DESIGN/SETTING In vitro analysis of MSC adhesion, proliferation, and differentiation seeded in ESBG. In vitro analysis of ESBG-facilitated posterolateral spine fusion in a rat model. PATIENT SAMPLE For the in vitro study: MSCs seeded with and without ESBG. For the in vivo study: 36 Lewis rats underwent posterolateral spine fusions. OUTCOME MEASURES In vitro: adhesion, proliferation, and osteogenic differentiation of MSCs. In vivo: rat fusion rate, fusion stiffness, fusion bone volume, fusion connectivity density and histological evaluation. METHODS Adhesion, proliferation, and osteogenic differentiation of MSCs seeded with and without ESBG for 7 days was analyzed. In vivo, 36 rats underwent posterolateral spine fusions in the following groups: (I) ESBG+bone marrow aspirate (BMA), (II) ESBG+BMA+BMP-2 (low-dose), and (III) BMA. Rats were followed for 3 months and the fusion masses were characterized with manual palpation, biomechanical tests, micro-CT and histological evaluation. RESULTS Ninety percent of cultured MSCs adhered to ESBG. When seeded in ESBG, there was a significant increase in MSC proliferation (0.18 to 0.43, p CONCLUSIONS This is the first reported characterization of ESBG for spinal applications. ESBGs provide a novel scaffold that supports MSC binding, proliferation and osteogenic differentiation. In a rat spine fusion model, ESBG impregnated with BMA and low-dose BMP-2 allowed for 100% fusion with strong biomechanical properties. ESBGs represent a promising synthetic graft and should be further investigated for clinical feasibility. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

Background A patch vaccine containing heat-labile toxin (LT) from enterotoxigenic Escherichia coli (ETEC) has demonstrated to be beneficial in reducing the rate and severity of travelers' diarrhea in Latin America. To evaluate the efficacy of this transdermal vaccine system in an area with a different diarrheal pathogen profile, an additional phase 2 study was conducted in European travelers to India. Methods For this multicenter, randomized, double-blinded, placebo-controlled field study 723 subjects were recruited; 603 (299 LT vaccine, 304 placebo) were included in the per-protocol-population (PPP). Results Although the LT patch induced a measurable LT immune response in recipients, it failed to protect against LT ETEC or all-cause diarrhea. In the PPP the incidence rate of diarrhea as per primary endpoint was 6.0% (18 of 299) in the vaccine group and 5.9% (18 of 304) in the placebo group. Additionally, lower than expected rates of LT ETEC diarrheas were observed in India. The vaccine delivery system frequently produced rash and pruritus at the site of application, long term hyperpigmentation persisted in a minority of LT recipients, and also few site reactions were noted in the placebo group. Conclusions The evaluated patch vaccine failed to satisfy mainly with respect to protective efficacy. Noninvasive prophylactic agents against travelers' diarrhea, particularly vaccines against the most frequent pathogens, thus continue to be badly needed.

Background Accessible travel has led to a rapid growth in international tourism, particularly to developing countries. With the increase, travel-associated morbidity and mortality has changed. Data on traveling populations are essential for policy makers to estimate infectious and noninfectious risks in travelers. Passenger flow statistics are compiled by the World Tourism Organization (WTO) and by official institutions of some countries. This study investigates sources of passenger flow statistics, methods of data collection, and compares datasets for consistency. Methods Four national datasets of departing travelers were compared to the United Nations' World Tourism Organization (WTO) data on passenger arrivals to eight destination countries. The ratio between arrivals and departures was calculated (main destination ratio [MDR]) to estimate the proportion of direct to indirect traveler arrivals. Results With few exceptions, arrival data exceeded that of departure data for all destinations. India is a primary destination for Australian residents where arrival and departure figures were similar (MDR 1.1), while visits to Cambodia and Turkey, with 3.6- and 3.8-fold higher arrivals, respectively, are part of multidestination trips. For UK residents, arrivals exceeded departures for all destinations except India where the reverse was true (MDR 0.8). A close correlation between arrivals and departures was noted for visits to South Africa while arrivals to Singapore and Cambodia were 7- and 10-fold higher, respectively. Arrivals by Finnish residents to destination countries were 1.4- to 1.6-fold higher than departures and 2.2-fold higher for Canadians visiting China. Conclusions Different methodologies used to capture arrival and departure statistics result in different estimations of traveler numbers. Data from a single source does not provide a comprehensive picture of most tourism itineraries. Inbound statistics give a more accurate reflection of the total visits made by travelers from a source country.

Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal) influenza vaccination. CD16 downregulation persisted for at least 12 weeks after vaccination and was associated with robust enhancement of influenza-specific plasma antibodies after intramuscular (but not intranasal) vaccination. This effect could be emulated in vitro by co-culture of NK cells with influenza antigen and immune serum and, consistent with the sustained effects after vaccination, only very limited recovery of CD16 expression was observed during long-term in vitro culture of immune complex-treated cells. CD16 downregulation was most marked among normally CD16high CD57+ NK cells, irrespective of NKG2C expression, and was strongly positively associated with degranulation (surface CD107a expression). CD16 downregulation was partially reversed by inhibition of ADAM17 matrix metalloprotease, leading to a sustained increase in both CD107a and CD25 (IL-2Rα) expression. Both the degranulation and CD25 responses of CD57+ NK cells were uniquely dependent on trivalent influenza vaccine-specific IgG. These data support a role for CD16 in early activation of NK cells after vaccination and for CD16 downregulation as a means to modulate NK cell responses and maintain immune homeostasis of both antibody and T cell-dependent pathways.

We report results of searches for charmless hadronic B meson decays to pseudoscalar(pi^+-,K^+-,Pi^0 or Ks^0)-vector(Rho, K* or Omega) final states. Using 9.7 million BBbar pairs collected with the CLEO detector, we report first observation of B^- --> Pi^-Rho^0, B^0 --> Pi^+-Rho^-+ and B^- --> Pi^-Omega, which are expected to be dominated by hadronic b --> u transitions. The measured branching fractions are (10.4+3.3-3.4+-2.1)x10^-6, (27.6+8.4-7.4+-4.2)x10^-6 and (11.3+3.3-2.9+-1.4)x10^-6, respectively. Branching fraction upper limits are set for all the other decay modes investigated., 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS

We present a new determination of the Ds decay constant, f_{Ds} using 5 million continuum charm events obtained with the CLEO II detector. Our value is derived from our new measured ratio of widths for Ds -> mu nu/Ds -> phi pi of 0.173+/- 0.021 +/- 0.031. Taking the branching ratio for Ds -> phi pi as (3.6 +/- 0.9)% from the PDG, we extract f_{Ds} = (280 +/- 17 +/- 25 +/- 34){MeV}. We compare this result with various model calculations., 23 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLNS

Using 13.4 $fb^{-1}$ of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudo-scalar charmonium in the decay $\eta_c$ -> $K_S K^{\mp} \pi^{\pm}$. We have measured the $\eta_c$ mass to be (2980.4 +- 2.3 (stat) +- 0.6 (sys)) MeV and its full width as (27.0 +- 5.8 (stat) +- 1.4 (sys)) MeV. We have determined the two-photon partial width of the $\eta_c$ meson to be (7.6 +- 0.8 (stat) +- 0.4 (sys) +- 2.3 (br)) keV, with the last uncertainty associated with the decay branching fraction.

Using the CLEO~II detector, we have measured the differential cross sections for exclusive two-photon production of light pseudoscalar mesons $\pi^0$, $\eta$, and $\eta^{\prime}$. From our measurements we have obtained the form factors associated with the electromagnetic transitions $\gamma^*\gamma$ $\to$ meson. We have measured these form factors in the momentum transfer ranges from 1.5 to 9, 20, and 30 GeV$^2$ for $\pi^0$, $\eta$, and $\eta^{\prime}$, respectively, and have made comparisons to various theoretical predictions., Comment: 30 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLNS