Positronium Laser Cooling via the 1

We report on laser cooling of a large fraction of positronium (Ps) in free flight by strongly saturating the 1^{3}S-2^{3}P transition with a broadband, long-pulsed 243 nm alexandrite laser. The ground state Ps cloud is produced in a magnetic and electric field-free environment. We observe two different laser-induced effects. The first effect is an increase in the number of atoms in the ground state after the time Ps has spent in the long-lived 2^{3}P states. The second effect is one-dimensional Doppler cooling of Ps, reducing the cloud's temperature from 380(20) to 170(20) K. We demonstrate a 58(9)% increase in the fraction of Ps atoms with v_{1D}<3.7×10^{4} ms^{-1}.

Regulatory Mechanisms of Muscle Mass: The Critical Role of Resistance Training in Children and Adolescent.

Muscle mass and strength are subjected to several regulations. We found endocrine signals such as growth hormone, insulin-like growth factor 1, testosterone, thyroid hormones, and glucocorticoids among them. Neural inputs also influence muscle development, modulating mass and strength. Among the external stimuli that modulate these muscular features is physical training such as resistance and endurance training. Specifically, resistance training can mediate an increase in muscle mass by hypertrophy in adults, but the effects in children and adolescents are full of myths for most of the population. However, the evidence shows that the impact of resistance training on children and adolescents is clear and provides a wide range of benefits. However, qualified professionals must be available since exercise prescription and subsequent supervision must follow this population's abilities, needs, and interests.

Impact of hypogonadism on bone mineral density and vertebral fractures in HIV-infected men.

PURPOSE: Hypogonadism and osteoporosis are frequently reported in HIV-infected men and, besides multifactorial pathogenesis, they might be directly linked because of testicular involvement in bone health. We evaluated the prevalence of osteoporosis and vertebral fractures (VFs) in HIV-infected men, and assessed their relationship with gonadal function. METHODS: We enrolled 168 HIV-infected men (median age 53). Osteoporosis and osteopenia were defined with T-score ≤ - 2.5SD and T-score between - 1 and - 2.5SD, respectively. VFs were assessed by quantitative morphometric analysis. Total testosterone (TT), calculated free testosterone (cFT), Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were obtained; overt hypogonadism was defined on symptoms and low TT or cFT, and classified into primary and secondary according to gonadotropins; compensated hypogonadism was defined as normal TT and cFT with high LH levels. RESULTS: Overall, osteoporosis and osteopenia were found in 87.5% of patients, and VFs were detected in 25% of them; hypogonadism was identified in 26.2% of cases. Osteoporotic patients had higher SHBG vs those with normal bone mineral density (BMD). Fractured patients were more frequently hypogonadal and with higher SHBG. SHBG showed negative correlation with both spine and femoral BMD, and positive correlation with VFs. In multivariate models, FSH showed negative impact only on femoral BMD, whereas older age and higher SHBG predicted VFs. CONCLUSION: We found a high burden of bone disease and hypogonadism in HIV-infected men, and we showed that the impact of gonadal function on bone health is more evident on VFs than on BMD.

Hypogonadism and liver fibrosis in HIV-infected patients.

PURPOSE: Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. METHODS: We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. RESULTS: Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. CONCLUSION: Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

Lymphocyte homeostasis is maintained in perinatally HIV-infected patients after three decades of life.

BACKGROUND: While immunosenescence, defined as reduced production of new lymphocytes, restriction of T-cell receptor repertoire and telomeres shortening, has been extensively evaluated in HIV-infected children and adults, no data about these parameters are available in perinatally-infected patients with very long-lasting HIV infection. METHODS: We compared thymic and bone marrow output, telomere length (measured by Real-Time PCR) and T-cell receptor repertoire (determined by spectratyping) of 21 perinatally HIV-infected subjects (with a median of 27 years of infection) with those of 19 age-matched non-perinatally HIV-infected patients and 40 healthy controls. All patients received a combined antiretroviral therapy. RESULTS: While thymic and bone marrow output were not different among the analyzed groups, telomere length in peripheral blood cells and T-cell receptor diversity were significantly lower in HIV-perinatally and non-perinatally infected individuals compared to healthy controls. CONCLUSIONS: In HIV-infected subjects, a normal thymic output together with a reduced telomere length and a restricted T-cell receptor repertoire could be explained by the shift of newly produced cells into memory subsets. This phenomenon may allow to control viral infection and maintain peripheral homeostasis.

AEgIS at ELENA: outlook for physics with a pulsed cold antihydrogen beam.

The efficient production of cold antihydrogen atoms in particle traps at CERN's Antiproton Decelerator has opened up the possibility of performing direct measurements of the Earth's gravitational acceleration on purely antimatter bodies. The goal of the AEgIS collaboration is to measure the value of g for antimatter using a pulsed source of cold antihydrogen and a Moiré deflectometer/Talbot-Lau interferometer. The same antihydrogen beam is also very well suited to measuring precisely the ground-state hyperfine splitting of the anti-atom. The antihydrogen formation mechanism chosen by AEgIS is resonant charge exchange between cold antiprotons and Rydberg positronium. A series of technical developments regarding positrons and positronium (Ps formation in a dedicated room-temperature target, spectroscopy of the n=1-3 and n=3-15 transitions in Ps, Ps formation in a target at 10 K inside the 1 T magnetic field of the experiment) as well as antiprotons (high-efficiency trapping of [Formula: see text], radial compression to sub-millimetre radii of mixed [Formula: see text] plasmas in 1 T field, high-efficiency transfer of [Formula: see text] to the antihydrogen production trap using an in-flight launch and recapture procedure) were successfully implemented. Two further critical steps that are germane mainly to charge exchange formation of antihydrogen-cooling of antiprotons and formation of a beam of antihydrogen-are being addressed in parallel. The coming of ELENA will allow, in the very near future, the number of trappable antiprotons to be increased by more than a factor of 50. For the antihydrogen production scheme chosen by AEgIS, this will be reflected in a corresponding increase of produced antihydrogen atoms, leading to a significant reduction of measurement times and providing a path towards high-precision measurements.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

Positronium Confinement in Small Cavities: A Two-Particle Model for the Lowering of Contact Density.

Positronium (Ps) is widely used as a probe for studying nanometric porosities in condensed matter. Accessible experimental measurements concern annihilation rates by pickoff processes and contact densities (the electron density at the positron position). Existing models for describing Ps properties in small cavities do not justify the lowering of the contact density with respect to that of Ps in vacuum, as found in most materials. We formulate a two-particle model in which only the electron is confined in the cavity, while the positron is moving freely and feels the medium via a positive work function. Our calculation fully explains experimental data for a large class of materials and suggests a way to gain information on pore sizes and positron work functions.

Infective endocarditis in patients with hepatic diseases.

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD- patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species (S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD- patients (p = 0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p < 0.001); embolization (43.3 % versus 26.1 %, p < 0.001) and congestive heart failure (42 % versus 34.1 %, p = 0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD- and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required.

Role of bone mineral density in predicting morphometric vertebral fractures in patients with HIV infection.

UNLABELLED: This study investigated the bone of HIV patients both in terms of quantity and quality. It was found that HIV-infected patients did fracture independently of the degree of bone demineralization as in other forms of secondary osteoporosis. INTRODUCTION: We aimed to determine the prevalence of vertebral fractures (VFs) in HIV patients who were screened by bone mineral density (BMD) and to explore possible factors associated with VFs. METHODS: This is a cross-sectional study that included HIV-infected patients recruited in the Clinic of Infectious and Tropical Diseases and that underwent BMD measurement by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and hip (Lunar Prodigy, GE Healthcare). For the assessment of VFs, anteroposterior and lateral X-ray examinations of the thoracic and lumbar spines were performed and were centrally digitized. Logistic regression models were used in the statistical analysis of factors associated with VFs. RESULTS: One hundred thirty-one consecutive patients with HIV infection (93 M, 38 F, median age 51 years; range, 36-75) underwent BMD measurement: 25.2 % of patients showed normal BMD, while 45 % were osteopenic and 29.7 % osteoporotic. Prevalence of low BMD (osteopenia and osteoporosis) was higher in females as compared to males (90 vs 69 %) with no significant correlation with age and body mass index. VFs occurred more frequently in patients with low BMD as compared to patients with normal BMD (88.5 vs. 11.4 %; p < 0.001) without any significant difference between osteopenia and osteoporosis (43 vs. 46 %; p = 0.073). VFs were significantly associated with older age and previous AIDS events. CONCLUSIONS: These results suggest a BMD <-1 threshold to identify patients at risk of skeletal fragility and, therefore, good candidates for morphometric evaluation of spine X-ray in line with other forms of secondary osteoporosis with impaired bone quality.

New Italian guidelines for malaria prophylaxis in travellers to endemic areas.

BACKGROUND AND METHODS: As a consequence of the rapid evolution of malaria prophylaxis recommendations throughout the world, the Italian Society of Tropical Medicine (SIMET-Società Italiana di Medicina Tropicale) has set up a working group in charge of preparing a new national guideline. Other scientific societies interested in the topic were also involved in the project. RESULTS AND CONCLUSIONS: The group stated that awareness about malaria risk and characteristics, as well as protection from mosquito bites, are recommended for all travellers visiting malaria-endemic countries. The risk and benefit of malaria chemoprophylaxis must be carefully balanced before prescribing drugs: the disease-related risk must outweigh the possibility of drugs' side effects. As a general rule, malaria pills are the first choice for travellers to high-risk areas, such as sub-Saharan Africa, Eastern India, Myanmar, Eastern Indonesia, Papua New Guinea and, with some limitations, South-East Asia, and the Amazon part of Venezuela, Guyana and French Guyana. However, several other factors, such as itinerary, season, duration of trip, availability of insect bite protection, pre-existing conditions and compliance, must be taken into account. In low-risk areas, stand-by emergency treatment is the first option. In minimal-risk areas and in Plasmodium vivax areas, a prompt diagnosis only is advised (Central America, South America outside the Amazon basin, Middle East, China, Thailand, Nepal). Recommendations may be modified when particular groups of travellers are concerned, such as long-term residents, visiting friends and relatives, patients with pre-existing conditions, pregnant women and children.

Clinical and epidemiological features of HIV/AIDS infection among migrants at first access to healthcare services as compared to Italian patients in Italy: a retrospective multicentre study, 2000-2010.

PURPOSE: Migrants account for approximately 8.7% of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians. METHODS: We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000-2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models. RESULTS: The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8%; adjusted odds ratio [(AOR) = 1.55, 95% confidence interval (CI) 1.34-1.78]. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95% CI 0.97-2.04), though of borderline significance. CONCLUSIONS: Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.

Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group.

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.

Incidence of AIDS-defining cancers and virus-related and non-virus-related non-AIDS-defining cancers among HIV-infected patients compared with the general population in a large health district of Northern Italy, 1999-2009.

OBJECTIVES: The aim of the study was to investigate the incidence of AIDS-defining cancers (ADCs) and virus-related and non-virus-related non-AIDS-defining cancers (NADCs) in HIV-infected patients compared with the general population, and to assess the risk factors associated with these malignancies. METHODS: We performed a retrospective cohort study for the period from 1999 to 2009 of HIV-infected patients residing in the Local Health Authority of Brescia (northern Italy). Observed cancers in patients with HIV infection were compared with expected cancers in the population living in the same area using standardized incidence ratios (SIRs). Risk factors were assessed using Poisson regression analysis. RESULTS: A total of 5090 HIV-infected patients were included in the study, with 32 390 person-years of follow-up. We recorded 416 tumours in 390 HIV-infected patients. Two hundred of these (48.1%) were ADCs, 138 (33.2%) were non-virus-related NADCs and 78 (18.7%) were virus-related NADCs. An increased risk (SIR = 4.2) of cancers overall was found in HIV-infected patients. A large excess of ADCs (SIR = 31.0) and virus-related NADCs (SIR = 12.3) was observed in HIV-infected patients, while the excess risk for non-virus-related NADCs was small (SIR = 1.6). The highest SIRs were observed for Kaposi sarcoma among ADCs and for Hodgkin lymphoma among virus-related NADCs. Conversely, among non-virus-related NADCs, SIRs for a broad range of malignancies were close to unity. In multivariate analysis, increasing age and CD4 cell count < 50 cells/µL were the only factors independently associated with all cancers. CONCLUSIONS: Among HIV-infected people there was an excess of ADCs and also of NADCs, particularly those related to viral infections. Ageing and severe immunodeficiency were the strongest predictors.

Characteristics of the population with mild COVID-19 symptoms eligible for early treatment attended in a single center in Northern Italy.

After more than two years from the first COVID-19 detected case in Brescia, Northern Italy, monoclonal antibodies and antiviral therapy aimed at early treatment of mild COVID-19 in patients at risk of progression and of hospitalization has been approved in Italy. Here we report the characteristics of the population eligible for the COVID-19 early treatments at our COVID-19 Early Therapy Unit of the Infectious Diseases Department of the ASST Spedali Civili of Brescia, with the aim to evaluate the characteristics of the foreign and native groups. Up to March the 31st, 2022, a total of 559 patients were referred to our Unit for COVID-19 early treatment, where 7.6% were foreigners, a group significantly younger than natives (p < 0.05). Particular differences are noticed between the native and the foreign population, where people aged > 65 years old were significantly more frequent among italians (39.7% vs 16.3%, p < 0.01), while primary or acquired immunodeficiencies were more frequent in foreigners (55.8% vs 38.9%, p = 0.03). Substantial differences are noted between native and foreign populations, where 14% and 26% (p < 0.05) respectively have never been vaccinated for COVID-19. Overall, 71% of the referred patients received an early treatment for mild COVID-19, with no differences between the two groups. Overall, on day 28 after treatment, 23 (4%) patients had been hospitalized due to COVID-19 related complications and four died (0,7%), no one was foreigner. In conclusion, while the treatment offered for mild COVID-19 appears to be rather uniform between the native and the foreign populations, some differences, especially in preventive vaccination COVID-19, must be taken into account.

Influence of natural seawater variables on the corrosion behaviour of aluminium-magnesium alloy.

Corrosion is an important issue for alloys in natural seawater, where microorganisms can accelerate or mitigate corrosion. Al-Mg alloys are used for marine activities and various associated technologies. Here, the behaviour of AA5083 alloy was investigated in natural seawater with marine exposure lasting up to 50 days and detailing the first 8 days in two experimental series. Experimental work was carried out, including semi-field tests in natural seawater (biotic conditions) compared with abiotic conditions. The open circuit potential (OCP) measurements, during the immersion time, exhibited significantly different behaviours: an OCP downward displacement occurred under abiotic conditions, while, in biotic conditions OCP remained generally stable since the beginning of the immersion, revealing an inhibiting effect of the biological activity on the Al-Mg corrosion. This was accompanied by different surface modifications under biotic conditions: surface and cross-section characterization, performed by scanning electron microscopy with energy dispersive X-ray spectroscopy, showed less corrosion developed on the surface after 8-day immersion and formation of a protective layer during 50-day immersion. The present study shows that marine biological activity positively influences the Al alloy corrosion process, with surface modifications resulting in a protective effect counteracting the aggressiveness of chloride ions.

Hospital-related outbreaks due to rare fungal pathogens: a review of the literature from 1990 to June 2011.

Fungi can cause severe infections. Two or more nosocomial unusual fungal infections diagnosed in a short period should be assumed as an outbreak. The review's aim was to collect data to improve their management. The free online worldwide database for nosocomial outbreaks ( http://www.outbreak-database.com ) and the PubMed/MEDLINE database were used to collect the English literature published from 1990 to June 2011. The more common Candida spp. and Aspergillus spp. infections were excluded. For each outbreak, the following data were reviewed: species, duration, source and site of infection, ward, risk factors, number of patients infected, treatment, related mortality, type of epidemiological study and time elapsed between index cases and second cases. Thirty-six reports were considered: yeasts caused the majority of the outbreaks (16 out of 36). The median values for the overall duration, number of infected people per outbreak and infection-related mortality were 5 months, 4 and 20 %, respectively. Eighteen cases were caused by contaminated substances and 13 cases were hypothesised as human-transmitted. Nosocomial outbreaks due to rare fungal pathogens involve few patients but have high related mortality. These results could be explained by the diagnostic delay, the inability of recognising the source of the infections and the challenges of the treatment. More efforts should be concentrated to implement the application of proper hygiene practices to avoid human-human transmission.

Do mosquito-associated bacteria of the genus Asaia circulate in humans?

Symbiotic bacteria of the genus Asaia have been proposed as tools for control of mosquito-borne diseases, specifically malaria. However, safety issues are a major concern for paratransgenesis strategies. The aim of this study is to investigate, with immunofluorescence assays and quantitative PCR experiments, whether Asaia spp. is circulating among humans. All human sera and whole blood samples analyzed were negative for Asaia spp., thus suggesting that this organism could be utilized, in the future, as a malaria control tool.

Chronic HCV infection: epidemiological and clinical relevance.

Hepatitis C virus (HCV), first recognized as a cause of transfusion-associated acute and chronic hepatitis in 1989, plays a major role as a cause of chronic liver injury, with potential for neoplastic degeneration. It is mainly transmitted by the parenteral route. However, although with lower efficiency, it may be also transmitted by sexual intercourses and by the mother-to-child route. Epidemiological evidence shows that a wave of infection occurred in the 1945-65 period (baby boomers) in western countries. After acute infection, as many as 50-85% of the patients fail to clear the virus resulting in chronic liver infection and/or disease. It is estimated that, on a global scale, about 170 million people are chronically infected with HCV, leading to about 350.000 deaths yearly. Among western countries southern Europe, and particularly Italy, is among the most affected areas. The impact on the public health systems is noteworthy, with high number of hospitalizations due to chronic liver disease, cirrhosis or hepatocellular carcinoma. While waiting for a safe and effective vaccine to be made available, new promising direct-acting antiviral (DAA) drugs offer a better therapeutic scenario than in the past even for the poor responder genotypes 1 and 4, provided that effective screening and care is offered. However, the long and aspecific prodromic period before clinical symptoms develop is a major obstacle to early detection and treatment. Effective screening strategies may target at-risk groups or age specific groups, as recently recommended by the CDC.