Muon g-2 and B Anomalies from Dark Matter

In light of the recent result of the muon g−2 experiment and the update on the test of lepton flavor universality RK published by the LHCb Collaboration, we systematically study for the first time a set of models with minimal field content that can simultaneously give (i) a thermal dark matter candidate; (ii) large loop contributions to b→sℓℓ processes able to address RK and the other B anomalies; (iii) a natural solution to the muon g−2 discrepancy through chirally enhanced contributions. Moreover, this type of model with heavy particles and chiral enhancement can evade the strong limits from direct searches but can be tested at present and future colliders and direct-detection searches

Systematic approach to B-physics anomalies and t-channel dark matter

We study renormalizable models with minimal field content that can provide a viable dark matter candidate through the standard freeze-out paradigm and, simultaneously, accommodate the observed anomalies in semileptonic B-meson decays at one loop. Following the hypothesis of minimality, this outcome can be achieved by extending the particle spectrum of the Standard Model either with one vectorlike fermion and two scalars or two vectorlike fermions and one scalar. The dark matter annihilations are mediated by t-channel exchange of other new particles contributing to the B anomalies, thus resulting in a correlation between flavor observables and dark matter abundance. Again based on minimality, we assume the new states to couple only with left-handed muons and second and third generation quarks. Besides an ad hoc symmetry needed to stabilize the dark matter, the interactions of the new states are dictated only by gauge invariance. We present here for the first time a systematic classification of the possible models of this kind, according to the quantum numbers of the new fields under the Standard Model gauge group. Within this general setup we identify a group of representative models that we systematically study, applying the most updated constraints from flavor observables, dedicated dark matter experiments, and LHC searches of leptons and/or jets and missing energy, and of disappearing charged tracks

Pertussis in infants and the resurgence of a vaccine preventable disease: what to do?

Pertussis or whooping cough remains one of the most poorly controlled vaccine-preventable diseases across the world. Universal vaccination has dramatically reduced its incidence but has failed to bring it completely under control. In the last decades, changes in pertussis epidemiology have been noted, likely related to the introduction of acellular pertussis vaccines. Increasing incidence is recorded among adolescents and adults who have become a reservoir for transmission to unimmunized infants, who are at risk of severe disease and death. In Italy, experimental evidences suggest a sustained circulation of Bordetella pertussis in the adult population and a significant health burden of pertussis among infants less than six months of age. Public health systems are currently exploring new vaccination strategies, including a cocooning strategy to prevent the transmission of the disease from family members to the newborn and vaccination of pregnant mothers to transmit protective antibodies to the offspring, and neonatal vaccination. An integrated approach for pertussis control and prevention need to enhance the current surveillance system providing an accurate estimate of the real burden of pertussis in our Country, particularly among infants

A utilidade da terapia de oxigenação hiperbárica e própolis em potencializar a atividade leishmanicida do glucantime

In this study we investigated the efficacy of hyperbaric oxygen (HBO) therapy, alone or combined with the pentavalent antimonial glucantime on Leishmania amazonensis infection. In parallel, the effect of Brazilian red propolis gel (propain) alone or combined with glucantime on L. amazonensis infection was evaluated. The inhibition of the infection in macrophages treated with glucantime in combination with HBO exposition was greater than that of macrophages treated with glucantime alone or HBO alone. The susceptible mouse strain BALB/c infected in the shaved rump with L. amazonensis treated with glucantime and exposed to HBO showed: time points in the course of the disease in which lesions were smaller than those of mice treated with glucantime alone and revascularization of the skin in the lesion site; interferon-gamma (IFN-g) levels were not elevated in lymph node cells from these animals. Propain alone was not efficient against lesions, although less exudative lesions were observed in animals treated with propain alone or combined with glucantime. These results reveal the potential value of HBO and red propolis in combination with glucantime for treating cutaneous leishmaniasis and encourage further studies on the effect of more aggressive HBO, propolis and glucantime therapies on different mouse models of leishmaniasis.Nesse trabalho foi avaliada a eficácia da terapia da oxigenação hiperbárica (HBO), aplicada em combinação ou não com o tratamento com glucantime, durante a infecção com Leishmania amazonensis. O efeito de gel da própolis vermelha de origem brasileira (propaina) aplicado em combinação ou não com o tratamento com glucantime, também foi avaliado durante infecção com esse parasita. A inibição da infecção de macrófagos tratados com glucantime em combinação com HBO foi maior que a de macrófagos tratados apenas com glucantime ou HBO. A linhagem murina susceptível, BALB/c, infectada no dorso com L. amazonensis, tratada com glucantime e exposta a HBO, mostrou durante o curso da doença, fases em que as lesões eram menores do que a de camundongos apenas tratados com glucantime; observou-se revascularização da pele da lesão e baixa produção de interferon-gama em células de linfonodos desses animais. O tratamento com propaina não foi eficiente na cura das lesões, apesar de lesões menos exsudativas serem observadas em animais tratados com propaina ou propaina combinada ao tratamento com glucantime. Os resultados demonstram que tanto HBO como a própolis vermelha em combinação com glucantime, são promissoras no tratamento da leishmaniose cutânea. Novos estudos devem ser realizados para avaliar tratamentos e outros protocolos em diferentes modelos murinos da leishmanios

Parp mutations protect from mitochondrial toxicity in Alzheimer's disease.

Alzheimer's disease is the most common age-related neurodegenerative disorder. Familial forms of Alzheimer's disease associated with the accumulation of a toxic form of amyloid-β (Aβ) peptides are linked to mitochondrial impairment. The coenzyme nicotinamide adenine dinucleotide (NAD+) is essential for both mitochondrial bioenergetics and nuclear DNA repair through NAD+-consuming poly (ADP-ribose) polymerases (PARPs). Here we analysed the metabolomic changes in flies overexpressing Aβ and showed a decrease of metabolites associated with nicotinate and nicotinamide metabolism, which is critical for mitochondrial function in neurons. We show that increasing the bioavailability of NAD+ protects against Aβ toxicity. Pharmacological supplementation using NAM, a form of vitamin B that acts as a precursor for NAD+ or a genetic mutation of PARP rescues mitochondrial defects, protects neurons against degeneration and reduces behavioural impairments in a fly model of Alzheimer's disease. Next, we looked at links between PARP polymorphisms and vitamin B intake in patients with Alzheimer's disease. We show that polymorphisms in the human PARP1 gene or the intake of vitamin B are associated with a decrease in the risk and severity of Alzheimer's disease. We suggest that enhancing the availability of NAD+ by either vitamin B supplements or the inhibition of NAD+-dependent enzymes such as PARPs are potential therapies for Alzheimer's disease

Severe pertussis infection in infants less than 6 months of age: clinical manifestations and molecular characterization

We conducted a study to determine the main traits of pertussis among unimmunized infants less than 6 months of age. From August 2012 to March 2015, 141 nasopharyngeal aspirates (NPAs) were collected from infants with respiratory symptoms attending 2 major hospitals in Rome. Clinical data were recorded and analyzed. Lab-confirmation was performed by culture and realtime PCR. B. pertussis virulence-associated genes (ptxP, ptxA and prn), together with multilocus variable-number tandem repeat analysis (MLVA), were also investigated by the sequence-based analysis on the DNAs extracted from positive samples. Antibiotic susceptibility with Etest was defined on 18 viable B. pertussis isolates. Samples from 73 infants resulted positives for B. pertussis. The median age of the patients was 45 d (range 7–165); 21 infants were treated with macrolides before hospital admission. Cough was reported for a median of 10 d before admission and 18 d after hospital discharge among infected infants, 84% of whom showed paroxysmal cough. No resistance to macrolides was detected. Molecular analysis identified MT27 as the predominant MLVA profile, combined with ptxP3-ptxA1-prn2 associated virulence genes. Although our data may not be generalized to the whole country, they provide evidence of disease severity among infants not vaccinated against pertussis. Moreover, genetically related B. pertussis strains, comprising allelic variants of virulence associated genes, were identified

Protection against pertussis in humans correlates to elevated serum antibodies and memory B cells

Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies

Pertussis prevention: reasons for resurgence, and differences in the current acellular pertussis vaccines

Bordetella pertussis; Whole-cell pertussis vaccine; Pertussis preventionBordetella pertussis; Vacuna contra la tos ferina de células completas; Prevención de la tos ferinaBordetella pertussis; Vacuna contra la tos ferina de cèl·lules senceres; Prevenció de la tos ferinaPertussis is an acute respiratory disease caused by Bordetella pertussis. Due to its frequency and severity, prevention of pertussis has been considered an important public health issue for many years. The development of the whole-cell pertussis vaccine (wPV) and its introduction into the pediatric immunization schedule was associated with a marked reduction in pertussis cases in the vaccinated cohort. However, due to the frequency of local and systemic adverse events after immunization with wPV, work on a less reactive vaccine was undertaken based on isolated B. pertussis components that induced protective immune responses with fewer local and systemic reactions. These component vaccines were termed acellular vaccines and contained one or more pertussis antigens, including pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN), and fimbrial proteins 2 (FIM2) and 3 (FIM3). Preparations containing up to five components were developed, and several efficacy trials clearly demonstrated that the aPVs were able to confer comparable short-term protection than the most effective wPVs with fewer local and systemic reactions. There has been a resurgence of pertussis observed in recent years. This paper reports the results of a Consensus Conference organized by the World Association for Infectious Disease and Immunological Disorders (WAidid) on June 22, 2018, in Perugia, Italy, with the goal of evaluating the most important reasons for the pertussis resurgence and the role of different aPVs in this resurgence.This study was supported by WAidid 2018_11 grant

Novi propisi iz područja zaštite zdravlja, sigurnosti na radu i zaštite od požara - 12/17. - 2/18.

<div><p><i>couch potato</i> (<i>cpo</i>) encodes an RNA binding protein that has been reported to be expressed in the peripheral and central nervous system of embryos, larvae and adults, including the major endocrine organ, the ring gland. A polymorphism in the <i>D</i>. <i>melanogaster cpo</i> gene coding region displays a latitudinal cline in frequency in North American populations, but as <i>cpo</i> lies within the inversion <i>In(3R)Payne</i>, which is at high frequencies and itself shows a strong cline on this continent, interpretation of the <i>cpo</i> cline is not straightforward. A second downstream SNP in strong linkage disequilibrium with the first has been claimed to be primarily responsible for the latitudinal cline in diapause incidence in USA populations.Here, we investigate the frequencies of these two <i>cpo</i> SNPs in populations of <i>Drosophila</i> throughout continental Europe. The advantage of studying <i>cpo</i> variation in Europe is the very low frequency of <i>In(3R)Payne</i>, which we reveal here, does not appear to be clinally distributed. We observe a very different geographical scenario for <i>cpo</i> variation from the one in North America, suggesting that the downstream SNP does not play a role in diapause. In an attempt to verify whether the SNPs influence diapause we subsequently generated lines with different combinations of the two <i>cpo</i> SNPs on known <i>timeless</i> (<i>tim)</i> genetic backgrounds, because polymorphism in the clock gene <i>tim</i> plays a significant role in diapause inducibility. Our results reveal that the downstream <i>cpo</i> SNP does not seem to play any role in diapause induction in European populations in contrast to the upstream coding <i>cpo</i> SNP. Consequently, all future diapause studies on strains of <i>D</i>. <i>melanogaster</i> should initially determine their <i>tim</i> and <i>cpo</i> status.</p></div

Reduced GABA Content in the Motor Thalamus during Effective Deep Brain Stimulation of the Subthalamic Nucleus

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), in Parkinson's disease (PD) patients, is a well established therapeutic option, but its mechanisms of action are only partially known. In our previous study, the clinical transitions from OFF- to ON-state were not correlated with significant changes of GABA content inside GPi or substantia nigra reticulata. Here, biochemical effects of STN-DBS have been assessed in putamen (PUT), internal pallidus (GPi), and inside the antero-ventral thalamus (VA), the key station receiving pallidothalamic fibers. In 10 advanced PD patients undergoing surgery, microdialysis samples were collected before and during STN-DBS. cGMP, an index of glutamatergic transmission, was measured in GPi and PUT by radioimmunoassay, whereas GABA from VA was measured by HPLC. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in VA (−30%). Simultaneously, cGMP extracellular concentrations were enhanced in PUT (+200%) and GPi (+481%). These findings support a thalamic dis-inhibition, in turn re-establishing a more physiological corticostriatal transmission, as the source of motor improvement. They indirectly confirm the relevance of patterning (instead of mere changes of excitability) and suggest that a rigid interpretation of the standard model, at least when it indicates the hyperactive indirect pathway as key feature of hypokinetic signs, is unlikely to be correct. Finally, given the demonstration of a key role of VA in inducing clinical relief, locally administration of drugs modulating GABA transmission in thalamic nuclei could become an innovative therapeutic strategy