Scalar sector properties of two-Higgs-doublet models with a global U(1) symmetry

We analyze the scalar sector properties of a general class of two-Higgs-doublet models which has a global U(1) symmetry in the quartic terms. We find constraints on the parameters of the potential from the considerations of unitarity of scattering amplitudes, the global stability of the potential and the $\rho$-parameter. We concentrate on the spectrum of the non-standard scalar masses in the decoupling limit which is preferred by the Higgs data at the LHC. We exhibit charged-Higgs induced contributions to the diphoton decay width of the 125\,GeV Higgs boson and its correlation with the corresponding $Z\gamma$ width.Comment: 12 pages, 15 eps figure files; minor modifications made and a few references adde

Atrioventricular block related to liposomal amphotericin B

Atrioventricular block can occur in normal children, young adults or athletes. It is also associated with underlying heart disease or occurs as a drug adverse effect. Amphotericin B is used in the treatment of invasive fungal infections. Cardiac toxicity is a rare adverse reaction. We report the case of a 9-month girl, admitted in the paediatric intensive care unit with cytomegalovirus pneumonitis. During hospitalisation the patient developed a systemic fungic infection and was medicated with liposomal amphotericin B. On the third day of treatment she began repeated episodes of bradycardia with spontaneous reversion. The investigation revealed a second-degree atrioventricular block. We excluded the misplacement of the central catheter, myocarditis or structural cardiomyopathy and suspended amphotericin. After 8 days, the bradycardia episodes ceased what was consistent with the drug's half-life. Amphotericin cardiotoxic mechanism is still unclear. It may be related with alteration of myocardial membrane depolarisation.info:eu-repo/semantics/publishedVersio

Novel strategies for preventing dysbiosis in the oral cavity

Oral diseases affect over three billion people worldwide, making it one of the most common infections. Recent studies show that one approach to reducing the risk of chronic infections, such as caries, gingivitis, periodontitis, and halitosis, is to control the ecology of the oral microbiome instead of completely removing both the harmful and beneficial microorganisms. This is based on the knowledge that oral diseases are not caused by a single pathogen but rather by a shift in the homeostasis of the entire microbiota, a process known as dysbiosis. Consequently, it is of the utmost importance to implement strategies that are able to prevent and control oral dysbiosis to avoid serious complications, including heart, lung, and other systemic diseases. Conventional treatments include the use of antibiotics, which further disrupt the equilibrium in the oral microbiota, together with the mechanical removal of the decayed cavity area following its formation. Therefore, it is imperative to implement alternative strategies with the potential to overcome the disadvantages of the current therapy, namely, the use of broad-spectrum antibiotics. In this sense, probiotics and postbiotics have received particular attention since they can modulate the oral microbiota and decrease the dysbiosis rate in the oral cavity. However, their mechanisms of action need to be addressed to clarify and drive their possible applications as preventive strategies. In this sense, this review provides an overview of the potential of probiotics and postbiotics, focusing on their antimicrobial and antibiofilm activities as well as their ability to modulate the inflammatory response. Finally, it also showcases the main advantages and disadvantages of orodispersible films—a promising delivery mechanism for both probiotics and postbiotics to target oral dysbiosis.info:eu-repo/semantics/publishedVersio

Drug repurposing opportunities in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgently needed. Drug repurposing is a strategy for the development of novel treatments using approved or investigational drugs outside the scope of the original clinical indication. Since repurposed drugs have already completed several stages of the drug development process, a broad range of data is already available. Thus, when compared with de novo drug development, drug repurposing is timeefficient, inexpensive and has less risk of failure in future clinical trials. Several repurposing candidates have been investigated in the past years for the treatment of PDAC, as single agents or in combination with conventional chemotherapy. This review gives an overview of the main drugs that have been investigated as repurposing candidates, for the potential treatment of PDAC, in preclinical studies and clinical trials.Cristina P. R. Xavier was supported by the Fundação para a Ciência e Tecnologia (FCT) and Fundo Social Europeu (FSE), Portugal, through the post-doc grant SFRH/BPD/122871/2016. This research group is supported by FEDER-Fundo Europeu de Desenvolvimento Regional through COMPETE 2020 and by FCT-Foundation for Science and Technology in the framework of project POCI-01-0145-FEDER-030457 and project POCI-01-0145-FEDER- 016390:CANCEL STEM

Pheochromocytomas and paragangliomas in von hippel–lindau disease: Not a needle in a haystack

Objective: Pheochromocytomas are a hallmark feature of von Hippel–Lindau disease (vHL). To our knowledge, this is the first systematic review with meta-analysis evaluating the frequency of pheochromocytomas and/or paragangliomas (PPGLs) in patients with vHL, as well as among patients with different vHL subtypes. Design: Systematic review with meta-analysis. Methods: We searched on MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with vHL and reporting on the frequency of PPGL. We performed random-effects meta-analysis to quantitatively assess the frequency of PPGL, followed by meta-regression and subgroup analysis. Risk of bias analysis was performed to assess primary studies’ methodological quality. Results: We included 80 primary studies. In 4263 patients with vHL, the pooled frequency of PPGL was 19.4% (95% CI = 15.9–23.6%, I2 = 86.1%). The frequency increased to 60.0% in patients with vHL type 2 (95% CI = 53.4–66.3%, I2 = 54.6%) and was determined to be of 58.2% in patients with vHL type 2A (95% CI = 49.7–66.3%, I2 = 36.2%), compared to 49.8% in vHL type 2B (95% CI = 39.9–59.7%, I2 = 42.7%), and 84.1% in vHL type 2C (95% CI = 75.1–93.1%, I2 = 0%). In meta-regression analysis, more recent studies were associated with a higher frequency of PPGL. All studies had at least one internal validity item classified as 'high risk of bias,' with 13% studies having low risk of bias in all external validity items. Conclusions: PPGLs are a common manifestation of vHL. Despite methodological limitations and differences across primary studies, our results point to the importance of PPGL screening in patients with vHL

Ultraviolet relaxation dynamics in uracil: Time-resolved photoion yield studies using a laser-based thermal desorption source

Wavelength-dependent measurements of the RNA base uracil, undertaken with nanosecond ultraviolet laser pulses, have previously identified a fragment at m/z = 84 (corresponding to the C3H4N2O+ ion) at excitation wavelengths ≤232 nm. This has been interpreted as a possible signature of a theoretically predicted ultrafast ring-opening occurring on a neutral excited state potential energy surface. To further investigate the dynamics of this mechanism, and also the non-adiabatic dynamics operating more generally in uracil, we have used a newly built ultra-high vacuum spectrometer incorporating a laser-based thermal desorption source to perform time-resolved ion-yield measurements at pump wavelengths of 267 nm, 220 nm, and 200 nm. We also report complementary data obtained for the related species 2-thiouracil following 267 nm excitation. Where direct comparisons can be made (267 nm), our findings are in good agreement with the previously reported measurements conducted on these systems using cold molecular beams, demonstrating that the role of initial internal energy on the excited state dynamics is negligible. Our 220 nm and 200 nm data also represent the first reported ultrafast study of uracil at pump wavelengths 3(1ππ*) state. These measurements do not, however, provide any evidence for the appearance of the m/z = 84 fragment within the first few hundred picoseconds following excitation. This key finding indicates that the detection of this specific species in previous nanosecond work is not directly related to an ultrafast ring-opening process. An alternative excited state process, operating on a more extended time scale, remains an open possibility

A Bridge between CP violation at Low Energies and Leptogenesis

We discuss the possibility of relating the size and sign of the observed baryon asymmetry of the universe to CP violation observable at low energies, in a framework where the observed baryon asymmetry is produced by leptogenesis through the out of the equilibrium decay of heavy Majorana neutrinos. We identify the CP violating phases entering in leptogenesis as well as those relevant for CP violation at low energies in the minimal seesaw model. We show that although in general there is no relation between these two sets of phases, there are specific frameworks in which such a connection may be established and we give a specific grand unification inspired example where such a connection does exist. We construct weak-basis invariants related to CP violation responsible for leptogenesis, as well as those relevant for CP violation at low energies

Analysis of a model with a common source of CP violation

We work in a model where all CP violating phenomena have a common source. CP is spontaneously broken at a large scale $V$ through the phase of a complex singlet scalar. An additional $SU(2)_L$ singlet vector-like down-type quark relates this high scale CP violation to low energy. We quantitatively analyze this model in the quark sector. We obtain the numerical values of the parameters of the Lagrangian in the quark sector for a specific ansatz of the $4\times4$ down-type quark mass matrix where the weak phase is generated minimally. $Z \bar b b$ vertex will modify in presence of the extra vector-like down-type quark. From the experimental lower bound of the partial decay width $Z\to \bar b b$ we find out the lower bound of the additional down-type quark mass. Tree level flavor changing neutral current appears in this model due to the presence of the extra vector-like down-type quark. We give the range of values of the mass splitting $\Delta m_{B_q}$ in $B^0_q-{\bar B}^0_q$ system using SM box, $Z$ mediating tree level and $Z$ mediating one loop diagrams together for both $q=d, s$. We find out the analytical expression for $\Gamma_{12}^q$ in this model from standard box, $Z$ and Higgs mediated penguin diagrams for $B^0_q-{\bar B}^0_q$ system, $q=d,s$. From this we numerically evaluate the decay width difference $|\Delta\Gamma_{B_q}/\Gamma_{B_q}|$. We also find out the numerical values of the CP asymmetry parameters $a_J$ and $a_\pi$ for the decays $B^0_d\to J/\psi K_s$ and $B^0_d\to \pi^+ \pi^-$ respectively. We get the lower bound of the scale $V$ through the upper bound of the strong CP phase.Comment: 20 pages, no figures New materials and references have been added. Text has been modified. To be appear in J.Phys.

Идентификация опасностей и оценка профессиональных рисков на АЭС

Приведены методические основы идентификации опасностей и оценки профессиональных рисков в системе управления АЭС. Сделан обзор основных стандартов риск-менеджмента. Приведены также некоторые примеры форм документов для идентификации опасностей и оценки профессиональных рисков.Наведено методичні основи ідентифікації небезпек та оцінки професійних ризиків у системі управління АЕС. Зроблено огляд основних стандартів ризик-менеджменту. Наведено також деякі приклади форм документів для ідентифікації небезпек і оцінки професійних ризиків.In the article the methodical bases of authentication of hazards and assessment occupational safety and health in the management system of NPP are resulted. The review of basic risk management standards is done. Some examples of forms of documents for authentication of hazards and assessment occupational safety and health are resulted also