Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-Plus: a double-blind, randomised, placebo-controlled phase 3 clinical trial.

Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralising IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralising antibodies. The aim of this study is to evaluate the safety and efficacy of two immunisation regimes: two doses of SOBERANA-02 and a heterologous three-dose combination with SOBERANA-Plus added to it. Methods: From March 8th to June 24th, 2021 we conducted in Havana, Cuba a multicentre randomised, double-blind, placebo-controlled, phase-3 trial evaluating a two doses SOBERANA-02 scheme and a heterologous scheme with one dose SOBERANA-Plus added to it (RPCEC00000354). Participants 19-80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose. Findings: We included 44,031 participants (52.0% female, 48.0% male; median age 50 years, range 19-80 years; 7.0% black, 24.0% mixed-race, 59.0% white) in a context of initial Beta VOC predominance, with this variant being partially replaced by Delta near the trial's end. Vaccine efficacy in the heterologous combination was 92.0% (95%CI 80.4-96.7) against symptomatic disease. There were no severe COVID-19 cases in the vaccine group against 6 in the placebo group. Two doses of SOBERANA-02 was 69.7% (95%CI 56.5-78.9) and 74.9% (95%CI 33.7-90.5) efficacious against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe adverse events (AE) was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient. Interpretation: Our results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC circulation, have a favourable safety profile, and may represent an attractive option for use in COVID-19 vaccination programmes. Funding: This study received funds from the National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020-20) of the Ministry of Science, Technology and Environment of Cuba.

Gigantomastia as a Cause of Pulmonary Hypertension.

Reduction mammaplasty is the gold standard treatment for gigantomastia. We report one female patient with juvenile gigantomastia associated with severe pulmonary hypertension where her pulmonary pressure decreased significantly after the surgery, improving her quality of life. A 22-year-old female patient with gigantomastia since 10 years old, tricuspid regurgitation, and pulmonary thromboembolism antecedent was admitted to the emergency department. Her oxygen saturation was 89%. Acute heart failure management was initiated. An echocardiogram reported left ventricle ejection fraction (LVEF) of 70% with severe right heart dilation, contractile dysfunction, and arterial pulmonary pressure (PASP) of 110 mm Hg. A multidisciplinary team considered gigantomastia could generate a restrictive pattern, so a Thorek reduction mammoplasty with Wise pattern was performed. Presurgical measurements were: sternal notch to nipple-areola complex, right 59 cm, left 56 cm. Three days after surgery, the patient could breathe without oxygen support. In the outpatient follow-up, patient referred reduction of her respiratory symptoms and marked improvement in her quality of life. Six months after surgery, a control echocardiogram showed a LVEF of 62% and PASP of 85 mm Hg. Pulmonary hypertension may be present in patients with gigantomastia. Reduction mammoplasty may be a feasible alternative to improve the cardiac signs and symptoms in patients with medical refractory management.

Biophysical analysis of thermosensitive TRP channels with a special focus on the cold receptor TRPM8.

Mammals maintain homeostatic control of their body temperature. Therefore, these organisms are expected to have adaptations that confer the ability to detect and react to both self and ambient temperature. Temperature-activated ion channels have been discovered to be the primary molecular determinants of thermosensation. The most representative group of these determinants constitutes members of the transient receptor potential superfamily, TRP, which are activated by either low or high temperatures covering the whole range of physiologically relevant temperatures. This review makes a critical assessment of existing analytical methods of temperature-activated TRP channel mechanisms using the cold-activated TRPM8 channel as a paradigm.

A BK (Slo1) channel journey from molecule to physiology.

Calcium and voltage-activated potassium (BK) channels are key actors in cell physiology, both in neuronal and non-neuronal cells and tissues. Through negative feedback between intracellular Ca (2+) and membrane voltage, BK channels provide a damping mechanism for excitatory signals. Molecular modulation of these channels by alternative splicing, auxiliary subunits and post-translational modifications showed that these channels are subjected to many mechanisms that add diversity to the BK channel α subunit gene. This complexity of interactions modulates BK channel gating, modifying the energetic barrier of voltage sensor domain activation and channel opening. Regions for voltage as well as Ca (2+) sensitivity have been identified, and the crystal structure generated by the 2 RCK domains contained in the C-terminal of the channel has been described. The linkage of these channels to many intracellular metabolites and pathways, as well as their modulation by extracellular natural agents, has been found to be relevant in many physiological processes. This review includes the hallmarks of BK channel biophysics and its physiological impact on specific cells and tissues, highlighting its relationship with auxiliary subunit expression.

Cyclodextrin inclusion complex to improve physicochemical properties of herbicide bentazon: exploring better formulations.

The knowledge of the host-guest complexes using cyclodextrins (CDs) has prompted an increase in the development of new formulations. The capacity of these organic host structures of including guest within their hydrophobic cavities, improves physicochemical properties of the guest. In the case of pesticides, several inclusion complexes with cyclodextrins have been reported. However, in order to explore rationally new pesticide formulations, it is essential to know the effect of cyclodextrins on the properties of guest molecules. In this study, the inclusion complexes of bentazon (Btz) with native ßCD and two derivatives, 2-hydroxypropyl-ß-cyclodextrin (HPCD) and sulfobutylether-ß-cyclodextrin (SBECD), were prepared by two methods: kneading and freeze-drying, and their characterization was investigated with different analytical techniques including Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), X-ray diffractometry (XRD) and differential pulse voltammetry (DPV). All these approaches indicate that Btz forms inclusion complexes with CDs in solution and in solid state, with a stoichiometry of 1:1, although some of them are obtained in mixtures with free Btz. The calculated association constant of the Btz/HPCD complex by DPV was 244±19 M(-1) being an intermediate value compared with those obtained with ßCD and SBECD. The use of CDs significantly increases Btz photostability, and depending on the CDs, decreases the surface tension. The results indicated that bentazon forms inclusion complexes with CDs showing improved physicochemical properties compared to free bentazon indicating that CDs may serve as excipient in herbicide formulations.

Desarrollo y estructura de la Escala Dimensional del Sentido de Vida / Development and structure of the Meaning of Life Dimensional Scale / Desenvolvimento e estrutura da Escala Dimensional do Sentido de Vida

En los últimos años ha aumentado considerablemente el interés por identificar factores específicos que pueden influir en nuestra salud, principalmente aspectos como el sentido de vida, la felicidad y la búsqueda de metas. Desde las aproximaciones humanistas y logoterapéuticas, el sentido de vida es, en términos generales, uno de los factores base para una vida sana. En Latinoamérica son muy pocas las pruebas que han sido desarrolladas o validadas para medir el sentido de vida. El propósito de esta investigación fue desarrollar la Escala Dimensional de Sentido del Vida, comprendido como coherencia existencial y propósito vital. El desarrollo de la escala se realizó mediante la construcción del instrumento para evaluar su estructura y sus características psicométricas. Participaron 820 personas, mujeres y varones, entre 20 y70 años de edad.Los resultados sugieren que la prueba presenta una alta consistencia interna y una estructura de dos dimensiones, una que evalúa la coherencia existencial, y la otra, el propósito vital de las personas.

In recent years, the interest for identifying specific factors that may influence our health has greatly increased, especially issues like meaning of life, happiness and pursuit of goals. From the humanistic and logotherapeutic approaches, the meaning of life is, in general, a key factor for a healthy life. In Latin America, very few tests have been developed and validated to measure the meaning of life. The purpose of this research was to develop the Dimensional Scale of Sense of Life, understood as existential coherence and purpose in life. The development of the scale was performed by constructing the instrument to assess its structure and psychometric characteristics. 820 people, women and men, participated, aged 20 and 70 years. Results suggest that the test has high internal consistency and a two-dimensional structure, one that assesses the existential coherence, and the other, the life purpose of people.

Nos últimos anos vem aumentado consideravelmente o interesse em identificar fatores específicos que podem influir em nossa saúde, principalmente aspectos como o sentido de vida, a felicidade e a procura de metas. Desde as aproximações humanistas e logoterapêuticas, o sentido de vida é, em termos gerais, um dos fatores base para uma vida saudável. Na América Latina são muito poucas as pesquisas realizadas ou validadas para medir o sentido de vida. O propósito desta pesquisa foi desenvolver a Escala Dimensional de Sentido de Vida, compreendido como coerência existencial e propósito vital. O desenvolvimento da escala foi realizado mediante a construção do instrumento para avaliar sua estrutura e suas características psicométricas. Participaram 820 pessoas, homens e mulheres, entre 20 e 70 anos de idade. Os resultados sugerem que o teste apresenta uma alta consistência interna e uma estrutura de duas dimensões, uma que avalia a coerência existencial, e a outra, o propósito vital das pessoas.

Thermo-TRP channels: biophysics of polymodal receptors.

In this chapter we discuss the polymodal activation of thermo-TRP channels using as exemplars two of the best characterized members of this class of channels: TRPM8 and TRPV1. Since channel activation by temperature is the hallmark of thermo-TRP channels, we present a detailed discussion on the thermodynamics involved in the gating processes by temperature, voltage, and agonists. We also review recently published data in an effort to put together all the pieces available of the amazing puzzle of thermo-TRP channel activation. Special emphasis is made in the structural components that allow the channel-forming proteins to integrate such diverse stimuli, and in the coupling between the different sensors and the ion conduction pathway. We conclude that the present data is most economically explained by allosteric models in which temperature, voltage, and agonists act separately to modulate channel activity.

Neighborhood phylodiversity affects plant performance.

Facilitation and competition are ecological interactions that are crucial for the organization of plant communities. Facilitative interactions tend to occur among distantly related species, while the strength of competition tends to decrease with phylogenetic distance. The balance between both types of interactions will ultimately determine the specific composition of multispecies associations. Although multispecies patches are the arena in which coexistence develops among different phylogenetic groups within communities, the specific processes that occur across life stages have not been explored. Here we study how different species, in composing discrete patches in central Mexico, exert competitive or facilitative effects on seeds and seedlings. We relate these interactions to phylogenetic relationships among nurse species and beneficiary species, and among members of the patches. Survivorship and growth rates of the columnar cactus Neobuxbaumia mezcalaensis were highly positively related to increasing phylogenetic distance to different nurse species, to the presence of related species in patches, and to mean phylogenetic distances to the rest of the species in the patch. Each of these three elements influenced N. mezcalaensis differently, with different nurse species varying substantially in their early effects on emergence, and the nearest relatives and species composition of patches varying in their late effects on survival and growth. Our results emphasize that evolutionary relationships among co-occurring species in vegetation clumps exert direct and indirect effects on plants, affecting individual performance and species coexistence.