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.

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.

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.

Cardiac response to exercise in normal-weight and obese, Hispanic men and women: implications for exercise prescription.

AIM: The effects of obesity on cardiac function during incremental exercise to peak oxygen consumption (VO(2peak)) have not been previously described. The purpose of this study was to compare submaximal and maximal cardiac function during exercise in normal-weight and obese adults. METHODS: Normal-weight (n = 20; means ± SE: age = 21.9 ± 0.5 years; BMI = 21.8 ± 0.4 kg m(-2)) and obese (n = 15; means ± SE: age = 25.1 ± 5.2 years; BMI = 34.1 ± 01.0 kg m(-2)) participants were assessed for body composition, VO(2peak) and cardiac variables (thoracic bioimpedance analysis) at rest and at heart rates (HR) of 110, 130, 150 and 170 beats min(-1) and maximal HR during incremental cycling exercise to exhaustion. Differences between groups were assessed with mixed-model ancova with repeated measures. Cardiac variables were statistically indexed for body surface area and resting HR. VO(2) and arteriovenous oxygen difference (a-vO(2)) were statistically indexed for fat-free mass and resting HR. RESULTS: Significant main effects for group indicated obese participants had higher cardiac output (Q) index and stroke volume (SV) index but lower ejection fraction (EF) and a-vO(2) index during incremental exercise to exhaustion compared with their normal-weight peers, despite similar submaximal and maximal VO(2) and absolute power outputs (P < 0.05). CONCLUSIONS: Our findings suggest that although Q index and SV index were higher in obese, young adults, EF and a-vO(2) index were significantly lower when compared to matched, normal-weight adults.

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.

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.

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).

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.

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.

Is there a physiologic basis for creatine use in children and adolescents?

The purported ergogenic benefits of creatine for the adult population have been well documented. In able-bodied children and adolescents, there is a paucity of data on creatine use and the purported ergogenic effects of creatine. Only 1 study to date has investigated the ergogenic properties of creatine in the adolescent population. The purpose of this review was to try to establish a rationale for creatine use in the child and adolescent population. The limited literature available in this area did not provide a strong enough rationale from either a physiologic or performance perspective for creatine supplementation in these populations. However, significantly more research is required before definitive conclusions can be made.

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.

Temporary myoclonus with treatment of congenital transcobalamin 2 deficiency.

The treatment of acquired cobalamin deficiency in infants may result in the development of a syndrome defined by temporary involuntary myoclonic movements. A patient with an inborn error of metabolism resulting in transcobalamin 2 deficiency who was treated with cobalamin and then developed this syndrome is presented. Neurologic investigations were normal. The continuance of cobalamin and avoidance of antiepileptic drugs is recommended. To our knowledge this is the first such case.

Absence of bone marrow amastigotes in a child with kala-azar and acute lymphoblastic leukaemia.

Visceral leishmaniasis is suspected on the basis of clinical findings and a pancytopenic blood picture and is usually confirmed by the detection of amastigotes (Leishman-Donovan bodies) in a bone marrow aspirate. We describe a child on maintenance treatment for acute lymphoblastic leukaemia who developed visceral leishmaniasis and in whom amastigotes could not be detected in repeated bone marrow aspirates. Immunofluorescence antibody testing was positive. Immunocompromised patients in endemic areas who develop features of visceral leishmaniasis should have serological tests performed in addition to bone marrow aspiration in order to maximize the chances of making a diagnosis.

Cardiac malformations associated with the congenital nephrotic syndrome.

The association of cardiac malformation with the congenital nephrotic syndrome (CNS) has been previously reported in only one family. We report four patients with CNS: three with pulmonary valve stenosis (one requiring valvuloplasty) and one with discrete subaortic stenosis requiring surgical resection. We conclude that the cardiac status of all patients with CNS should be reviewed regularly by a paediatrician, with a low threshold for referral to a cardiologist, as flow murmurs due to chronic anaemia may obscure cardiac pathology. It is important to diagnose any associated cardiac lesions as these may require intervention, and may also predispose to the development of bacterial endocarditis if surgical or dental procedures are undertaken without appropriate antibiotic prophylaxis.

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.

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.