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}.

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.

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.

Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling.

Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5-deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5-deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm. Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages.

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.

Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir?

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of neurological impairment for which, currently, there are no approved antenatal treatment options. OBJECTIVES: The aim of this article was to summarize the available evidence on the use of valacyclovir during pregnancy to prevent and treat congenital CMV infection and disease. SOURCES: Two databases (PubMed and ClinicalTrial.gov) were reviewed. CONTENT: Six relevant documents were identified, namely one observational study, three clinical trials, two case reports. Most relevant findings were those from two clinical trials. A phase 2/3 placebo-controlled study showed a decrease of 71% (5 of 45 vs 14 of 47) in rate of CMV vertical transmission in women treated with 8 g/day valacyclovir following primary CMV infection in pregnancy. A phase 2, single-arm clinical trial, showed that 8 g/day valacyclovir administered to mothers of symptomatic infected foetuses increased the portion of asymptomatic neonates to 82% (34 of 41), compared with 43% (20 of 47) in untreated pregnancies from a historical cohort. IMPLICATIONS: Studies in favour of using valacyclovir during pregnancy for prevention and treatment of congenital CMV infection are emerging but are still few. Randomized clinical trials on large cohorts of patients investigating the efficacy on prevention and treatment of congenital CMV are required. Unfortunately, this will be probably not be feasible at least in the short period. In the meantime, data on the 'off label' use of valacyclovir for CMV in pregnancy could be collected within a multicentre observational study.

Formal calculation of exchange correlation effects on annihilation lifetimes of positronium confined in small cavities.

Positronium atoms (Ps) are widely used as a probe to characterize voids or vacancies in non-metallic materials. The annihilation lifetime of trapped Ps is strongly modified by pickoff, depending on the cavity size and on the appropriate external electron density. The connection between these material characteristics and Ps annihilation lifetimes is usually based on models that do not consider the requirements of full electron indistinguishability, that must be taken into account for a correct description of pickoff annihilation processes. In this report, we provide a formal theoretical framework in which exchange correlation effects between confined Ps and surrounding electrons are introduced in a natural way, giving a clear and versatile picture of the various contributions to pickoff annihilation. Moreover, our results provide a simple explanation of the lowering of the contact density (the Ps-electron density at the positron position) as a direct consequence of the electrons indistinguishability, at variance with previous interpretation based on spatial deformations of Ps wavefunction. Calculations are performed within the 'symmetry adapted perturbation theory' approach, and the results are compared with available experimental data on Ps lifetimes for polymers and molecular solids. Finally, our analysis gives a formal justification to the approximations involved in early models based on the well known Tao-Eldrup approach, and gives a simple interpretation of Ps properties in subnanometric voids.

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.

Preparedness against mobility disruption by floods.

Civil responders currently have limited information available to them to support flood incident planning. A new generation of tools are emerging that produce more detailed understanding of flood impacts on people and accessibility during floods. These are typically applied in isolation, proving only a partial assessment of impacts. This paper integrates analysis of flood hydraulics, transport accessibility and human safety to explore the impact of flooding on pedestrians and drivers, and its implications on emergency routes and service areas. A reference scenario, developed and used by the local Civil Protection Agency, is applied to Galluzzo in Florence (Italy). Results shows that 37% of inhabitants live close to roads where they can be swept away, and 78% live in locations where parked vehicles can be transported by floodwaters. Furthermore, at its worst 22.5% of road extension is inaccessible; and all hospitals, fire and police stations cannot be reached, highlighting the need to take preventative action from the outset of an event that is predicted to lead to substantial inundation. Integration of multiple indicators of flood impacts, especially those most relevant to human safety, is fundamental to civil responders if they are to successfully planning and implement emergency response operations in urban environments.

Risk of congenital toxoplasmosis in women with low or indeterminate anti-Toxoplasma IgG avidity index in the first trimester of pregnancy: an observational retrospective study.

OBJECTIVES: Congenital toxoplasmosis (CT) affects one to ten fetuses per 10 000 live newborns in western countries. Without knowing pre-conception serostatus, it is hard to date the infection when anti-Toxoplasma IgG and IgM antibodies are positive at first screening. Although a high IgG avidity index (AI) in the first trimester excludes CT, the same cannot be said of intermediate and low AI. The aim of this study was to estimate the risk of CT when intermediate or low AI is detected in the first trimester of pregnancy. METHODS: Our observational retrospective study enrolled women with positive anti-Toxoplasma IgG and IgM, and low/intermediate AI in the first trimester of gestation seen at two reference centres in northern Italy between 2006 and 2015. All women received spiramycin. When requested by women, a sample of fluid obtained through amniocentesis was tested with a commercial real-time PCR. CT was defined by positive PCR result confirmed on aborted materials or by newborn follow up. RESULTS: Overall, 778 first-trimester pregnant women were included; AI was low in 532/778 (68%) and intermediate in 246/778 (32%). Amniocenteses were performed in 528/778 (67.9%), with no fetal loss. In all, 19/778 (2.4%) miscarriages and 15/778 (1.9%) pregnancy terminations were recorded; 9/778 (1.6%) were lost to follow up. In two women, PCR on amniotic fluid was positive, but CT was confirmed in only 1/747 cases (0.13%, 95% CI 0.02%-0.75%). CONCLUSION: In our study, the risk of CT was much lower than anticipated. These data must be considered when counselling these women.

Peripheral loss of regulatory T cells and polyautoimmunity in an HIV-infected patient.

We report a case of a human immunodeficiency virus (HIV)/hepatitis C virus-co-infected patient with an optimal virological status but with a poor CD4+ cell profile, followed up in the University Department of Infectious and Tropical Diseases of Brescia, Italy. He presented several autoimmune diseases (ADs) over the years concomitant with CD4+ cell increase episodes following severe immune depression of unknown cause. We studied T- and B-cell subsets and found low levels of K-deleting Recombination Excision Circles, T-cell Receptor Excision Circles and B and T memory subpopulations, which indicated that the bone marrow and thymic outputs were lower than in healthy controls. The most relevant phenotypic alteration was in the regulatory T-cell (Treg) population, because total Tregs as well as naïve, central memory and effector memory cells were detected at very low levels. This was the first case of polyautoimmunity defined as the presence of more than one AD in the same individual, occurring in an HIV patient. Several factors may be implicated, including genetic susceptibility, environmental factors, concomitant therapies and dysregulation of immune system cells. The extremely low number of Tregs found in our patient may play a major role in the regulation of the immune response and the development of all ADs.

Simultaneous Diagnosis of Acute Crohn's Disease and Endometriosis in a Patient Affects HIV.

This is the case report of a 45-year-old woman affected by HIV, who was hospitalized for diffuse abdominal pain, constipation, and weight loss present for over one month. A colonoscopy showed the presence of a nontransitable stenosis of the ascending colon. A right hemicolectomy was performed. The histological examination reports CD with outbreaks of endometriosis. CD and the HIV infection may coexist in the same individual and it seems that HIV reduces the relapse rate in IBD patients. CD and intestinal endometriosis can also occur simultaneously. The diagnosis is often only made after surgical resection of the diseased segment. These patients were more likely to have stricturing CD but endometriosis does not seem to impact the natural history of CD.

TMS Over the Cerebellum Interferes with Short-term Memory of Visual Sequences.

Growing evidence suggests that the cerebellum is not only involved in motor functions, but it significantly contributes to sensory and cognitive processing as well. In particular, it has been hypothesized that the cerebellum identifies recurrent serial events and recognizes their violations. Here we used transcranial magnetic stimulation (TMS) to shed light on the role of the cerebellum in short-term memory of visual sequences. In two experiments, we found that TMS over the right cerebellar hemisphere impaired participants' ability to recognize the correct order of appearance of geometrical stimuli varying in shape and/or size. In turn, cerebellar TMS did not affect recognition of highly familiar short sequences of letters or numbers. Overall, our data suggest that the cerebellum is involved in memorizing the order in which (concatenated) stimuli appear, this process being important for sequence learning.

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'.