The role of the Community Pharmacist in promoting vaccinations among general population according to the National Vaccination Plan 2017-2019: results from a survey in Sicily, Italy.

INTRODUCTION: The 2017-2019 Italian National Vaccination Plan promotes the improvement of knowledge and attitudes of healthcare workers about vaccine prevention, in order to spread a vaccination culture among general population. Similarly to the General Practitioner, the Pharmacist represents a fundamental forefront for both patients and healthy people, also in promoting vaccine acceptance. This research aims to analyze knowledge and attitudes about vaccines of Community Pharmacists and to evaluate the burden of vaccination counselling during their work activities. MATERIAL AND METHODS: A standardized, self-administered and previously validated questionnaire, including 5 sections and 28 items, was submitted to a sample of Community Pharmacists working in Western Sicily. The survey was carried out through an online questionnaire, that investigated socio-demographic data, knowledge and attitudes towards vaccination and the role of the Pharmacist as vaccination counselor during his work. RESULTS: A total of 120 Pharmacists were surveyed. 99.2% of them were definitely agreed with the Regional Vaccination Schedule. A large majority (n = 114, or 95%) were fully vaccinated and have vaccinated, or would vaccinate in future, their children. According to Community Pharmacists interviewed, at least 90% of clients asked for further explanations about vaccination, and the citizens' trust towards vaccination increased (30%) or remained stable (54.2%) over time in the last 5 years. Finally, as reported by interviewed Pharmacists, a correct counselling provided by General Practitioners (GPs) and Family Pediatricians was the main boost in increasing vaccination confidence, instead of mass-media and web misinformation that has led to skepticisms among general population. CONCLUSION: The study demonstrated the key role of the Community Pharmacist for their consumers in vaccination counselling. In future, a strong collaboration between Community Pharmacists and all the actors promoting vaccination themes (GPs, family Pediatricians, public health workers) will be essential, as well as a uniform and standardized University training on vaccination themes for all these categories.

Safety and efficacy of vaccinations in patients with multiple sclerosis: a systematic review.

OBJECTIVE: The study aims to show the efficacy/effectiveness and safety of vaccinations in patients with multiple sclerosis. MATERIALS AND METHODS: This systematic review was conducted following the guidelines of the Cochrane Collaboration and the meta-analysis of observational studies in epidemiology (MOOSE). RESULTS: At the end of the review process, 133 studies were included; the bibliographic search was conducted on PubMed/Medline and Scopus, combining free text and words. CONCLUSIONS: In general, vaccinations do not seem to aggravate multiple sclerosis (MS) or increase the probability of relapse, particularly for inactivated vaccines and, in general, for the rest of the vaccines. However, it is advisable, especially for vaccines with a live attenuated virus, to carefully evaluate the risks and benefits of these vaccinations; as regards the effectiveness in relation to the drug taken, there is great variability in response. In particular, vaccinations are less effective in patients undergoing therapy with anti-CD20 and S1P modulators. At the same time, a small response is likely to be better than none. Whenever possible, vaccinations should be offered and recommended to patients with multiple sclerosis.

Completely isolated enteric duplications cysts: a survey of four cases.

Enteric duplication cysts are uncommon congenital abnormalities with epithelial lining. They are cystic or tubular structures intimately attached to a portion of the gastrointestinal tract; they are usually located on the mesenteric site of the digestive tract sharing common blood supply. Isolated cystic duplications are an extremely rare variant with their own blood supply: in literature only five cases have been reported. We present our four cases series of this uncommon anomaly.

Ice volume and climate changes from a 6000 year sea-level record in French Polynesia.

Mid- to late-Holocene sea-level records from low-latitude regions serve as an important baseline of natural variability in sea level and global ice volume prior to the Anthropocene. Here, we reconstruct a high-resolution sea-level curve encompassing the last 6000 years based on a comprehensive study of coral microatolls, which are sensitive low-tide recorders. Our curve is based on microatolls from several islands in a single region and comprises a total of 82 sea-level index points. Assuming thermosteric contributions are negligible on millennial time scales, our results constrain global ice melting to be 1.5-2.5 m (sea-level equivalent) since ~5500 years before present. The reconstructed curve includes isolated rapid events of several decimetres within a few centuries, one of which is most likely related to loss from the Antarctic ice sheet mass around 5000 years before present. In contrast, the occurrence of large and flat microatolls indicates periods of significant sea-level stability lasting up to ~300 years.

Structural features and anti-HIV-1 activity of novel polysaccharides from red algae Grateloupia longifolia and Grateloupia filicina.

Since sulphated polysaccharides have antiviral activity in vitro, we examined the structure and antiretroviral activity of native sulphated galactans extracted from the red algae, Grateloupia filicina (GFP) and Grateloupia longifolia (GLP). The sulphate contents of GFP and GLPE (the 1,4-alpha-d-glucan-glucanohydrolase digest of GLP) were 25.7 and 18.5%, respectively. The sulphate ester groups were located at carbon 2 for GFP and at carbon 2 and 6 for GLPE. Antiretroviral activity was investigated with a primary isolate (PI) of HIV-1 and human peripheral blood mononuclear cells (PBMCs) rather than T-cell line adapted (TCLA) HIV-1 and T-cell lines because it is more representative of the in vivo situation. Both compounds and their derivatives had potent anti-HIV-1 activity when added at the time of infection, and 2h post-infection (EC50s 0.010-0.003microM, EC(90s) 0.87-0.33microM) and low cytotoxicity. Their potential medical application as virucidal vaginal formulations is discussed.

Life in the fat lane: seasonal regulation of insulin sensitivity, food intake, and adipose biology in brown bears.

Grizzly bears (Ursus arctos horribilis) have evolved remarkable metabolic adaptations including enormous fat accumulation during the active season followed by fasting during hibernation. However, these fluctuations in body mass do not cause the same harmful effects associated with obesity in humans. To better understand these seasonal transitions, we performed insulin and glucose tolerance tests in captive grizzly bears, characterized the annual profiles of circulating adipokines, and tested the anorectic effects of centrally administered leptin at different times of the year. We also used bear gluteal adipocyte cultures to test insulin and beta-adrenergic sensitivity in vitro. Bears were insulin resistant during hibernation but were sensitive during the spring and fall active periods. Hibernating bears remained euglycemic, possibly due to hyperinsulinemia and hyperglucagonemia. Adipokine concentrations were relatively low throughout the active season but peaked in mid-October prior to hibernation when fat content was greatest. Serum glycerol was highest during hibernation, indicating ongoing lipolysis. Centrally administered leptin reduced food intake in October, but not in August, revealing seasonal variation in the brain's sensitivity to its anorectic effects. This was supported by strong phosphorylated signal transducer and activator of transcription 3 labeling within the hypothalamus of hibernating bears; labeling virtually disappeared in active bears. Adipocytes collected during hibernation were insulin resistant when cultured with hibernation serum but became sensitive when cultured with active season serum. Heat treatment of active serum blocked much of this action. Clarifying the cellular mechanisms responsible for the physiology of hibernating bears may inform new treatments for metabolic disorders.

Mechanisms of enrichment of natural radioactivity along the beaches of the Camargue, France.

A field study was carried out along the Golfe du Lion, that focussed on the beaches of the Camargue, to locate the main areas where enriched U and Th are found, and to better understand the processes that concentrate radioactivity on beaches. Indeed enriched areas are observed on some Camargue beaches, where high-dose rates are recorded due to excess U and Th activity (>1000 Bq kg(-1)). The coastline was mapped by means of an aerial gamma survey and the results indicated that the main actinides deposits occurred in the Camargue area. This concentrating effect is possibly due to a greater sedimentary contribution from the River Rhone relative to other minor Mediterranean rivers. Across the along-shore profile, the variability in actinides observed at the eastern part of Beauduc spit is mainly explained by variations in heavy and light mineral contents. Such variability can be accounted for by redistribution of the sand caused by erosion/deposition processes occurring in the eastern part of the spit. Further parameters such as grain size and heavy minerals content were studied in connection with the distribution of U, Th and (40)K in the field at a more localised level (i.e. across-shore beach profile). The <200-micro m fraction contains more than 50% of the radioactivity and heavy minerals (especially zircon) are the main contributors to the high levels of external radiation. Therefore the enriched areas, where U and Th exceed 1000 Bq kg(-1), presumably result from the sorting of sand grains according to their size and density.

A review of the stroke volume response to upright exercise in healthy subjects.

Traditionally, it has been accepted that, during incremental exercise, stroke volume plateaus at 40% of Vo(2)max. However, recent research has documented that stroke volume progressively increases to Vo(2)max in both trained and untrained subjects. The stroke volume response to incremental exercise to Vo(2)max may be influenced by training status, age, and sex. For endurance trained subjects, the proposed mechanisms for the progressive increase in stroke volume to Vo(2)max are enhanced diastolic filling, enhanced contractility, larger blood volume, and decreased cardiac afterload. For untrained subjects, it has been proposed that continued increases in stroke volume may result from a naturally occurring high blood volume. However, additional research is needed to evaluate the importance of blood volume, or other mechanisms, that influence the stroke volume response to exercise in untrained subjects.

Non-linear relationships between central cardiovascular variables and VO2 during incremental cycling exercise in endurance-trained individuals.

AIM: The purpose of this study was to examine the relationships between the central cardiovascular variables (cardiac output, stroke volume and heart rate) and oxygen uptake (VO2) during continuous, incremental cycle exercise to maximal aerobic capacity (VO2max). METHODS: Twenty-one moderately to highly trained males (n=19) and females (n=2) participated in the study. A baseline maximal exercise test was performed to measure VO2max. Following the initial VO2max test, cardiac output was measured (CO2 rebreathing technique) at rest and 3 times during each of 4 exercise trials (2 submaximal tests to 90% VO2max and 2 maximal tests). Stroke volume and arteriovenous O2 difference were calculated using standard equations. RESULTS: Significant non-linear relationships were found between all central cardiovascular variables and VO2 (P<0.01). A plateau in cardiac output at VO2max was identified in 3 subjects. Stroke volume plateaued at an average of 37+/-12.5% of VO2max in 18 subjects and increased continuously to VO2max in 3 subjects. The arteriovenous O2 difference progressively increased to VO2max in 17 subjects and revealed a plateau response in 4 subjects. CONCLUSIONS: Our data suggest that there is a significant non-linear relationship between the central cardiovascular variables and VO2 during incremental exercise to VO2max. Furthermore, depending on the person, VO2max may be limited by cardiac output (evidence of cardiac output[Q] plateau) or peripheral factors (continued increase in Q).

Restriction of serum antibody reactivity to the V3 neutralizing domain of HIV gp120 with progression to AIDS.

OBJECTIVE: To identify epitopes on HIV-1 gp120 that correlate with disease resistance and/or prognostic indication. DESIGN: The identification of epitopes on HIV-1 gp120 was determined by testing the reactivity by immunoblotting of anti-HIV-positive human sera against partially cleaved Chinese hamster ovary (CHO) cell-derived recombinant gp120. Cleavage of recombinant gp120 occurs in the V3 loop region resulting in 70 and 50K cleavage bands if the protein is subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. Antibodies reactive with the 120 Mr band alone on immunoblotting indicate that binding is restricted to this cleavage site. Reactivity to either of the cleavage products is independent of gp120 cleavage and indicates that binding occurs in sites other than the V3 cleavage region. METHODS: A panel of anti-HIV-positive human sera was tested for virus neutralizing activity and reactivity by immunoblotting against CHO cell-derived gp120. RESULTS: All sera reacted with the uncleaved from of gp120 but reacted either weakly or did not react with its cleavage products. There was a statistically significant correlation between serum reactivity to cleavage products and clinical stage of disease [Centers for Disease Control (CDC) criteria]. Sera of asymptomatic individuals (CDC stage II/III) were more likely to recognize either one or both of the cleavage products compared with sera from patients presenting with symptoms of disease (CDC stage IV). Furthermore, sera reacting with either one or both of the cleavage products were more likely to have higher neutralizing antibody titres than those that were unreactive. CONCLUSIONS: There is a restriction of serum antibody reactivity (when tested by immunoblotting) to the V3 loop with progression to disease. Raised neutralizing antibody titres may be dependent on regions outside the V3 cleavage site.

Recognition of poliovirus/HIV chimaeras by antisera from individuals with HIV infection.

The neutralization of five poliovirus/HIV chimaeras by serum from HIV-infected individuals was examined to evaluate the presentation of HIV envelope sequences, to assess the immune response of individuals to specific epitopes, and to relate it to the stage of disease. The sera were unable to differentiate between four of the chimaeras and the Sabin vaccine strain. With a fifth construct containing an immunodominant gp41 sequence, significant differential recognition was observed in approximately 67% of individuals with asymptomatic HIV infection [groups II and III of the Centers for Disease Control (CDC) classification of HIV infection] and 37% of patients with symptomatic disease (CDC group IV). Furthermore, among patients with CDC stage IV disease antibody levels against this construct and the titre achieved decreased with progression to further disease from approximately 40% in AIDS-related complex (ARC) patients (CDC group IVA and IVC-2 to 14% in those with AIDS (other group IV diseases). Loss of antibody to this construct did not result from a reduction in the anti-polio or anti-envelope response, but from a decline in antibody levels to the HIV sequence inserted in antigenic site 1.

Construction and biological characterization of an infectious molecular clone of HIV type 1GB8.

Here we report the construction, sequencing, and repair of a molecular clone of HIV-1GB8, a virus representative of HIV-1 subtype B strains circulating in the UK. The phenotype of virus produced by the clone matches that of the parental virus. The molecular clone will be used in the production of attenuated virus stocks for chemical inactivation to allow development of faccines based on killed whole virus preparations.

Construction and characterization of a full-length HIV-1(92UG001) subtype D infectious molecular clone.

Here we report the construction, sequencing, and biological characterization of a molecular clone of HIV-1(92UG001), a virus representative of subtype D strains circulating in Uganda. The virus produced by the clone has an aggressive syncytium-inducing phenotype, which matches that of the parental virus. This phenotype may be related to duplication of a binding site for a transcription factor, T cell factor 1alpha (TCF-1alpha), in the long terminal repeat of the virus.

CD8+ T-cell-mediated non-cytolytic suppression of human immuno-deficiency viruses.

Major histocompatibility (MHC)-restricted cytotoxic T-lymphocytes (CTL) kill human immunodeficiency virus (HIV)-infected cells. In addition, activated CD8(+) T-lymphocytes from HIV-infected individuals suppress virus replication in vitro by producing antiviral factor (CAF). The effector mechanism(s) of CAF involves modulation of HIV gene transcription, is non-cytolytic and mediated in part by soluble antiviral factors. Initially, CAF activity was shown to be more vigorous in activated CD8(+) cells and cell free supernatants (SNs) from asymptomatic individuals compared to those with AIDS, suggesting a protective role in vivo. CAF-mediated suppression is also evident in animal models of immunodeficiency virus infection. Several soluble molecules that contribute to non-cytolytic virus suppression have been characterised, including alpha- and beta-chemokines and interleukin-16 (IL-16), but these are distinct from CAF. Two agents possessing certain CAF-like characteristics, modified antithrombin 111 (AT111) and the human alpha-defensins, have been described but their antiviral mechanisms are not fully understood. CAF-secretion may not be virus-specific as similar activity is found in activated CD8(+) cells/SNs from humans and chimpanzees seronegative for HIV-1. Recent data indicates that the secretion of CAF is MHC-restricted and both cytolytic and non-cytolytic mechanisms are mediated by CTL. If the latter is correct, a single appropriate stimulus could be used to enhance both effector mechanisms in vivo. This paper reviews research aimed at characterising HIV-suppressive factors and raises other questions that must be considered for the development of prophylactic and therapeutic strategies leading to the safe and effective control of HIV.

The physiology of the ovary: maturation of ovarian granulosa cells and a novel role for antioxidants in the corpus luteum.

During folliculogenesis the granulosa cells divide whilst in contact with each other, and so exhibit some of the characteristics of stem cells. In vitro we have shown that bovine granulosa cells from 3-7 mm follicles, like stem cells, divide without the need for a substratum, and produce colonies of cells. Growth factors, bFGF and IGF's, stimulate their division. These cells secrete and assemble a basal lamina, suggesting that the follicular basal lamina is produced by the granulosa cells. They have the morphological characteristics of follicular granulosa cells. Thus this system is ideal for studying the functions of immature granulosa cells because the cells do not spontaneously differentiate or luteinize into luteal cells, as occurs in culture on a substratum. On differentiation into luteal cells in vivo the cells express the steroidogenic enzymes for progesterone production and accumulate beta-carotene. During culture of bovine luteal cells we observed that a proportion of the steroidogenic enzyme cholesterol side-chain cleavage cytochrome P450 enzyme became chemically cross-linked to its electron donor, adrenodoxin. P450 enzymes produce oxygen free radicals and oxygen free radicals can cause cross-linking between proteins in close proximity. Cell protect against this damage by the use of antioxidant vitamins. Repleting the cultured luteal cells with beta-carotene reduced the amount of cross-linking. We conclude that the high levels of beta-carotene in corpora lutea are to protect against damage due to oxygen free radicals generated in the course of progesterone synthesis.

Enhanced replication of M-tropic HIV-1 strains in Herpesvirus saimiri immortalised T-cells which express CCR5.

A better characterisation of mononuclear cell-tropic (M-tropic) HIV-1 is central to disease control as these viruses predominate in disease transmission. M-tropic viruses do not replicate in conventional T-cell lines, and virus titres obtained in peripheral blood mononuclear cells (PBMC) are low. Human T-lymphocytes which have been immortalised by Herpesvirus saimiri strain C488 (HVS T-cells) are highly permissive to the replication of T-cell tropic strains of HIV. This study aimed to determine if HVS T-cells support replication of M-tropic HIV isolates that have not been adapted to conventional T-cell lines. A panel of PBMC low passage/primary field isolates and their molecular clones was used. Results show that infection in HVS T-cells was longer lived than in PBMC. In terms of peak virus titre and duration of productive infection, the two HVS T-cell lines studied were superior to PBMC, and one supported enhanced replication of all M-tropic isolates. This is important for generating M-tropic virus pools of sufficient titre for further biological studies such as virus neutralisation, co receptor usage and testing of antivirals. Phenotypic analysis showed that HVS T-cells are CD4+-activated memory cells expressing both CXCR-4 and CCR5 co receptors. Thus, HVS immortalisation appears to select for the T-cell subset targeted by HIV-1 in vivo.

Effect of Decapeptyl, an agonistic analog of gonadotropin-releasing hormone on estrogens, estrogen sulfates, and progesterone receptors in leiomyoma and myometrium.

Estrogens (estrone [E1] and estradiol [E2]), their sulfates and progesterone receptor (PR) were evaluated in patients with uterine leiomyomata nontreated and treated with Decapeptyl (D-Trp6-gonadotropin-releasing hormone [GnRH]; Ipsen Biotech, Paris, France). Estrogen concentrations are very high in the leiomyoma (secretory phase, pg/g tissue [mean +/- SEM]: n = 10; E1: 147 +/- 24; E2: 850 +/- 116; E1-sulfate: 1,668 +/- 808; E2-sulfate: 718 +/- 126). Decapeptyl treatment provokes a significant decrease in E2 and particularly in E1 and E2 sulfates. Progesterone receptors were higher in the leiomyoma than in the myometrium; after a long treatment (3 to 4 months) a significant decrease in both tissues is observed. The decrease provoked by D-Trp6-GnRH on estrogens (unconjugated and sulfates) and in PR in the leiomyoma after long treatment, supports the hypothesis that estrogens are implicated in the cause of these tumors.

Pigeon breeder's lung in childhood: varied clinical picture at presentation.

Extrinsic allergic alveolitis occurs rarely in childhood. We present 5 cases and briefly review the literature regarding this condition in the pediatric population. This report includes all cases (n = 5) of extrinsic allergic alveolitis known to have occurred in childhood on Malta. All cases were males, and were initially misdiagnosed as having other respiratory illnesses or mental disturbances. The diagnosis was based on a history of exposure to birds, clinical findings, positive avian precipitins, a restrictive defect on pulmonary function tests, and a suggestive chest X-ray appearance. All were treated with high-dose oral steroids for 3-4 weeks, with excellent response. Although these patients appear to have suffered no long-term sequelae, delayed diagnosis can lead to irreversible pulmonary fibrosis. The diagnosis of extrinsic allergic alveolitis should be entertained early in the differential diagnosis of children presenting with unusual respiratory symptoms and signs.

Antiretroviral therapy for HIV-2 infected patients.

OBJECTIVES: To evaluate clinical and RNA load response to antiretroviral therapy amongst patients infected with HIV-2 and to study the development of drug resistance. METHODS: Seven HIV-2 seropositive patients were monitored with clinical examination, CD4 cell count and HIV-2 viral RNA load. Viruses from four subjects were genotyped and in vitro recovery of virus by co-cultivation with PBMCs and HVS T-cells was attempted. Viruses isolated from two subjects were assayed for phenotypic antiviral resistance. The main outcome measures were the relationship between disease stage, viral load, CD4 cell count, viral subtype and the clinical course of HIV-2 infection and the effect of combination antiretroviral therapy on disease progression, CD4 cell count, HIV-2 RNA viral load and drug resistance. RESULTS: The median time of follow-up was 3 years (range 0-8 years). Three patients had AIDS, and one had symptomatic disease. Of the four patients genotyped, three were infected with HIV-2 subtype B and one with subtype A. Viraemia was detectable only at CD4 counts of less than 300 x 10(6)/ml. Two patients with high viral loads failed to respond to antiretroviral therapy although their treatment may not have been optimal. One developed in vitro phenotypic antiviral resistance. The genotype of this patient's viral reverse transcriptase is being analysed. CONCLUSIONS: In contrast to HIV-1, HIV-2 RNA levels were often undetectable despite advanced disease and low CD4 cell counts. However, HIV-2 was clearly capable of causing CD4 cell depletion resulting in symptomatic disease. The principles of highly active antiretroviral therapy seem to apply to HIV-2 and suboptimal therapy may lead to drug resistance. The timing of therapy initiation, monitoring of response and the measurement of resistance remain unresolved issues and conclusions cannot be extrapolated from HIV-1.