Incorporation of SARS-CoV-2 spike NTD to RBD protein vaccine improves immunity against viral variants.

Emerging SARS-CoV-2 variants pose a threat to human health worldwide. SARS-CoV-2 receptor binding domain (RBD)-based vaccines are suitable candidates for booster vaccines, eliciting a focused antibody response enriched for virus neutralizing activity. Although RBD proteins are manufactured easily, and have excellent stability and safety properties, they are poorly immunogenic compared to the full-length spike protein. We have overcome this limitation by engineering a subunit vaccine composed of an RBD tandem dimer fused to the N-terminal domain (NTD) of the spike protein. We found that inclusion of the NTD (1) improved the magnitude and breadth of the T cell and anti-RBD response, and (2) enhanced T follicular helper cell and memory B cell generation, antibody potency, and cross-reactive neutralization activity against multiple SARS-CoV-2 variants, including B.1.1.529 (Omicron BA.1). In summary, our uniquely engineered RBD-NTD-subunit protein vaccine provides a promising booster vaccination strategy capable of protecting against known SARS-CoV-2 variants of concern.

Ultraviolet-C Irradiation, Heat, and Storage as Potential Methods of Inactivating SARS-CoV-2 and Bacterial Pathogens on Filtering Facepiece Respirators.

The arrival of SARS-CoV-2 to Aotearoa/New Zealand in February 2020 triggered a massive response at multiple levels. Procurement and sustainability of medical supplies to hospitals and clinics during the then upcoming COVID-19 pandemic was one of the top priorities. Continuing access to new personal protective equipment (PPE) was not guaranteed; thus, disinfecting and reusing PPE was considered as a potential alternative. Here, we describe part of a local program intended to test and implement a system to disinfect PPE for potential reuse in New Zealand. We used filtering facepiece respirator (FFR) coupons inoculated with SARS-CoV-2 or clinically relevant multidrug-resistant pathogens (Acinetobacter baumannii Ab5075, methicillin-resistant Staphylococcus aureus USA300 LAC and cystic-fibrosis isolate Pseudomonas aeruginosa LESB58), to evaluate the potential use of ultraviolet-C germicidal irradiation (UV-C) or dry heat treatment to disinfect PPE. An applied UV-C dose of 1000 mJ/cm2 was sufficient to completely inactivate high doses of SARS-CoV-2; however, irregularities in the FFR coupons hindered the efficacy of UV-C to fully inactivate the virus, even at higher UV-C doses (2000 mJ/cm2). Conversely, incubating contaminated FFR coupons at 65 °C for 30 min or 70 °C for 15 min, was sufficient to block SARS-CoV-2 replication, even in the presence of mucin or a soil load (mimicking salivary or respiratory secretions, respectively). Dry heat (90 min at 75 °C to 80 °C) effectively killed 106 planktonic bacteria; however, even extending the incubation time up to two hours at 80 °C did not completely kill bacteria when grown in colony biofilms. Importantly, we also showed that FFR material can harbor replication-competent SARS-CoV-2 for up to 35 days at room temperature in the presence of a soil load. We are currently using these findings to optimize and establish a robust process for decontaminating, reusing, and reducing wastage of PPE in New Zealand.

Characterization of the First SARS-CoV-2 Isolates from Aotearoa New Zealand as Part of a Rapid Response to the COVID-19 Pandemic.

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has wreaked havoc across the globe for the last two years. More than 300 million cases and over 5 million deaths later, we continue battling the first real pandemic of the 21st century. SARS-CoV-2 spread quickly, reaching most countries within the first half of 2020, and New Zealand was not an exception. Here, we describe the first isolation and characterization of SARS-CoV-2 variants during the initial virus outbreak in New Zealand. Patient-derived nasopharyngeal samples were used to inoculate Vero cells and, three to four days later, a cytopathic effect was observed in seven viral cultures. Viral growth kinetics was characterized using Vero and VeroE6/TMPRSS2 cells. The identity of the viruses was verified by RT-qPCR, Western blot, indirect immunofluorescence assays, and electron microscopy. Whole-genome sequences were analyzed using two different yet complementary deep sequencing platforms (MiSeq/Illumina and Ion PGM™/Ion Torrent™), classifying the viruses as SARS-CoV-2 B.55, B.31, B.1, or B.1.369 based on the Pango Lineage nomenclature. All seven SARS-CoV-2 isolates were susceptible to remdesivir (EC50 values from 0.83 to 2.42 µM) and ß-D-N4-hydroxycytidine (molnupiravir, EC50 values from 0.96 to 1.15 µM) but not to favipiravir (>10 µM). Interestingly, four SARS-CoV-2 isolates, carrying the D614G substitution originally associated with increased transmissibility, were more susceptible (2.4-fold) to a commercial monoclonal antibody targeting the spike glycoprotein than the wild-type viruses. Altogether, this seminal work allowed for early access to SARS-CoV-2 isolates in New Zealand, paving the way for numerous clinical and scientific research projects in the country, including the development and validation of diagnostic assays, antiviral strategies, and a national COVID-19 vaccine development program.

Rapid Response to SARS-CoV-2 in Aotearoa New Zealand: Implementation of a Diagnostic Test and Characterization of the First COVID-19 Cases in the South Island.

It has been 20 months since we first heard of SARS-CoV-2, the novel coronavirus detected in the Hubei province, China, in December 2019, responsible for the ongoing COVID-19 pandemic. Since then, a myriad of studies aimed at understanding and controlling SARS-CoV-2 have been published at a pace that has outshined the original effort to combat HIV during the beginning of the AIDS epidemic. This massive response started by developing strategies to not only diagnose individual SARS-CoV-2 infections but to monitor the transmission, evolution, and global spread of this new virus. We currently have hundreds of commercial diagnostic tests; however, that was not the case in early 2020, when just a handful of protocols were available, and few whole-genome SARS-CoV-2 sequences had been described. It was mid-January 2020 when several District Health Boards across New Zealand started planning the implementation of diagnostic testing for this emerging virus. Here, we describe our experience implementing a molecular test to detect SARS-CoV-2 infection, adapting the RT-qPCR assay to be used in a random-access platform (Hologic Panther Fusion® System) in a clinical laboratory, and characterizing the first whole-genome SARS-CoV-2 sequences obtained in the South Island, right at the beginning of the SARS-CoV-2 outbreak in New Zealand. We expect that this work will help us and others prepare for the unequivocal risk of similar viral outbreaks in the future.

Nanofluid based on self-nanoencapsulated metal/metal alloys phase change materials with tuneable crystallisation temperature.

Nanofluids using nanoencapsulated Phase Change Materials (nePCM) allow increments in both the thermal conductivity and heat capacity of the base fluid. Incremented heat capacity is produced by the melting enthalpy of the nanoparticles core. In this work two important advances in this nanofluid type are proposed and experimentally tested. It is firstly shown that metal and metal alloy nanoparticles can be used as self-encapsulated nePCM using the metal oxide layer that forms naturally in most commercial synthesis processes as encapsulation. In line with this, Sn/SnOx nanoparticles morphology, size and thermal properties were studied by testing the suitability and performance of encapsulation at high temperatures and thermal cycling using a commercial thermal oil (Therminol 66) as the base fluid. Secondly, a mechanism to control the supercooling effect of this nePCM type based on non-eutectic alloys was developed.

Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia.

Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM).

Increment of specific heat capacity of solar salt with SiO2 nanoparticles.

Thermal energy storage (TES) is extremely important in concentrated solar power (CSP) plants since it represents the main difference and advantage of CSP plants with respect to other renewable energy sources such as wind, photovoltaic, etc. CSP represents a low-carbon emission renewable source of energy, and TES allows CSP plants to have energy availability and dispatchability using available industrial technologies. Molten salts are used in CSP plants as a TES material because of their high operational temperature and stability of up to 500°C. Their main drawbacks are their relative poor thermal properties and energy storage density. A simple cost-effective way to improve thermal properties of fluids is to dope them with nanoparticles, thus obtaining the so-called salt-based nanofluids. In this work, solar salt used in CSP plants (60% NaNO3 + 40% KNO3) was doped with silica nanoparticles at different solid mass concentrations (from 0.5% to 2%). Specific heat was measured by means of differential scanning calorimetry (DSC). A maximum increase of 25.03% was found at an optimal concentration of 1 wt.% of nanoparticles. The size distribution of nanoparticle clusters present in the salt at each concentration was evaluated by means of scanning electron microscopy (SEM) and image processing, as well as by means of dynamic light scattering (DLS). The cluster size and the specific surface available depended on the solid content, and a relationship between the specific heat increment and the available particle surface area was obtained. It was proved that the mechanism involved in the specific heat increment is based on a surface phenomenon. Stability of samples was tested for several thermal cycles and thermogravimetric analysis at high temperature was carried out, the samples being stable. PACS: 65.: Thermal properties of condensed matter; 65.20.-w: Thermal properties of liquids; 65.20.Jk: Studies of thermodynamic properties of specific liquids.

[Treatment of chronic hepatitis C virus infection. A study of best predictors for response]. / Tratamiento de la infección crónica por elvirus de la hepatitis C. Factores predictoresde respuesta.

OBJECTIVE: The aim of this study was evaluate the rate of sustained viral response (SVR) and the influence of different factors on the SVR in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon alfa 2a and ribavirin. METHODS: We retrospectively analysed 272 naïve patients with chronic hepatitis C who had been treated for 24 weeks or 48 weeks and had been followed for an additional 6 months thereafter. RESULTS: Out of 272 patients, 243 completed the entire treatment. The overall SVR rate in intent-to-treat analysis was 66.5% and in treated patients was 74.5%. In an univariate analysis, the SVR was associated with age <40 years (84.4%),pre-treatment viral load <500.000 IU/ml (86.9%), non-1 genotype HCV (86.4%), non cirrhosis or pre-cirrhosis (76.5%), rapid virologic response (RVR) (91.4%) and early virologic response (EVR) (83.8%). In the multivariate logistic regression analysis, the presence of an infection caused by a non-1 genotype and to achieve ERV were independent predictors of SVR. The RVR and histological stage of liver disease were not included in the multivariate analysis because these data were not available in most of the patients. The PPV and NVP of RVR were 91.5% and 48.7% respectively, of EVR were 83.8% and 95.8% respectively and of complete EVR were 91.3% and 78.7%, respectively. CONCLUSIONS: The SVR was higher than in other studies. The genotype and EVR were independent factors to predict the effect of antiviral therapy. The EVR had a high NPV and the complete EVR a high PPV.

La Terapia Floral en el contexto de las secuelas psicológicas de la violencia intrafamiliar / Floral therapy in the context of the intrafamiliar violence psychological sequels

El presente trabajo consistió en insertar la Terapia Floral como alternativa de tratamiento en personas que sufren las secuelas psicológicas que trae apareada la violencia familiar. Partiendo de consideraciones generales que hoy en día se expresan como una epidemia galopante que contamina la humanidad y sus secuelas psicológicas pueden llevar incluso al suicidio, siendo el manejo de este fenómeno en cuanto a alternativas de mejora un tanto difícil. Se implantó esta modalidad de tratamiento en pacientes que acudían al servicio de Medicina Natural y Tradicional del Hospital Faustino Pérez Hernández, de Matanzas, refiriendo que presentaban insomnio, miedo, preocupación, tristeza, decepción, baja autoestima, entre otros síntomas. Se trabajó con una muestra de 20 pacientes del municipio de Matanzas, se aplicó una metodología integrada por cuestionarios, análisis de documentos y la entrevista floral, lo que permitió seleccionar las esencias casuísticamente, arribando a importantes resultados.

This work consisted in insert the floral therapy as an alternative treatment in persons suffering the psychological sequels of the familiar violence. Beginning with the particular considerations that nowadays familiar violence is an increasing epidemic contaminating the human being, and its psychological sequels could lead even to the suicide, the management of this phenomenon is a little difficult, according to the ameliorating alternatives. We implanted this treatment modality in patients assisting to the Traditional and Natural Medicine Service at the Hospital Faustino Perez, of Matanzas They referred insomnia, fear, preoccupation, sadness, deception, low selfsteem, and other symptoms. We worked with a sample of 20 patients from the municipality of Matanzas , an applied a methodology integrated by questionnaires, documents analyses and the floral enquiry, which allowed us to select casuistically the essences. We achieved important results.

Función diastólica en sujetos con serología positiva para enfermedad de Chagas procedentes del estudio CHICAMOCHA / Diastolic function in subjects with positive Chagas’ disease serology from the Chicamocha study

Se presenta un estudio ecocardiográfico en 430 donantes de banco de sangre, de los cuales 120 fueron negativos para Trypanosoma cruzi (controles), 231 fueron seropositivos sin cambios en el electrocardiograma (estadio I) y 79 fueron seropositivos con cambios en el electrocardiograma (estadio II). Se estudió la función diastólica y, a través del flujo mitral, se encontró un aumento significativo de la velocidad de la onda A con relación al grupo control (54 vs. 50,5 cm/seg). Con relación al flujo de las venas pulmonares, no hubo cambios significativos en las velocidades sistólicas pero sí aumento de las velocidades diastólicas de los sujetos estadio II con relación a los controles (48,7 vs. 46,7 cm/seg). El parámetro más significativo se halló en la duración de la onda A de las venas pulmonares, la cual aumentó en los sujetos estadio I y mucho más en los sujetos estadio II (0,13 seg para el grupo control, 0,14 seg para el grupo estadio I y 0,15 seg respectivamente). La diferencia entre la duración de la onda A mitral y la duración de la onda A de las venas pulmonares, mostró menor significancia en los sujetos estadio I y mayor aún (resultado negativo) en los sujetos estadio II, expresando así un aumento de la presión capilar pulmonar de estos últimos (control 0,012 seg, estadio I 0,009 seg y estadio II-0,007). La relación entre la duración de la onda A de las venas pulmonares y de la onda A mitral (Ap/Am), mostró, igualmente, un aumento progresivo con respecto a los controles (control 0,94, estadio I 0,96 y estadio II 1,08). El tiempo de relajación isovolumétrica aumentó significativamente en los sujetos estadio II con relación al grupo control (0,084 seg vs. 0,076 seg). En lo que concierne a las velocidades del anillo mitral, se encontró un aumento significativo en la velocidad de la onda A en los sujetos estadio II con respecto a los controles (17,9 cm/seg vs. 15,9 cm/seg). No hubo diferencias significativas en la velocidad sistólica ni en la velocidad de la...

An echographic study of 430 blood bank donors is presented. 120 were negative for Trypanosoma cruzi (controls), 231 were serum-positive without changes in the electrocardiogram (state I) and 79 were positive with electrocardiographic changes (state II). The diastolic function was studied and through the mitral flow a significant increase in the A wave velocity in relation to the control group, was found (54 vs. 50.5 cm/s). In relation to the pulmonary veins’ flow, there were no significant changes in the systolic velocities but there was an increase in the diastolic velocity in state II subjects (48.7 vs. 46.7 cm/s). The most signifying parameter was that of the pulmonary veins’ A wave duration, that increased in state I subjects and even more in state II subjects (0.13 s for the control group, 0.14 s for state I group and 0.15 s for state II, respectively). The difference between the duration of the mitral A wave and the duration of the pulmonary veins’ A wave showed less significance in state I subjects and even less (negative) in state II subjects, expressing in this way an increment in pulmonary capillary tension in these last ones (control: 0.012 s, state I: 0.09 s and state II: 1.08 s). The relation between the pulmonary veins’ A wave and that of the mitral A wave (Ap/Am) showed a progressive increment as well, in regard to the control group (17.9 cm/s vs. 15.9 cm/s). There were no significant differences in the systolic velocity, or in the velocity of the E ring wave. When observing the M-colour flow propagation behaviour, a significant decrease was noticed in state I subjects and even more in state II subjects in relation to the control group (72.7, 66.8 and 62.6 cm/s respectively).

Perfil farmacocinetico y eficacia terapéutico de la famotidina / The farmacocinetic profile and eficacy therapeutic of the famotidine

La famotidina es una droga que ha demostrado su eficacia en el tratamiento de la úlcera gastroduodenal y en el reflujo gastro-esofágico, requiriéndose además menores cantidades de la droga para lograr su efecto terapeútico, siendo bien tolerada, sin reacciones adversas significativas y económicamente razonables

HIV-Sida: actualidad y experiencia quirúrgica en el Hospital de Clínicas Caracas 1985-1997 / HIV-AIDS: actuality and surgical experience in the Clinicas Caracas Hospital 1985-1997

La infección por el Virus de la Inmunodeficiencia Humana fue descubierta recientemente posterior a un brote epidémico en las ciudades de Nueva York y San Francisco en los años 1981-1982 y cuya identificación se hizo en 1983. La ausencia de una vacuna eficaz nos lleva a que la prevención de la infección por HIV sea un aspecto fundamental en la actualidad. En los últimos años, cada día se ha venido agregando mayor información en lo que respecta al HIV-SIDA, convirtiéndose actualmente en una enfermedad no solamente relacionada al ámbito médico (como Internistas, Infectólogos, Neumonólogos, etc.), sino también Quirúrgico (Cirujanos, Traumatólogos, Urólogos, etc.). La educación de la población y la aplicación de medidas de prevención deben ser aplicadas por el personal de salud dentro de las diferentes esferas de una institución hospitalaria, como lo son las salas de hospitalización, el área quirúrgica, laboratorio, banco de sangre y personal Médico y Paramédico en general. En la actualidad, el tratamiento del HIV-SIDA está fundamentado en la combinación de drogas de efecto retroviral y el tratamiento tanto preventivo como curativo de todos los Síndromes que vienen relacionados al diagnóstico de SIDA, buscando en un futuro el hallazgo de una droga o la combinación de varias drogas que logren erradicar la enfermedad