Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination.

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.

Waning and boosting of functional humoral immunity to SARS-CoV-2.

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.

Can upwelling signals be detected in intertidal fishes of different trophic levels?

For intertidal fishes belonging to three species, the herbivore Scartichthys viridis (Blenniidae), the omnivore Girella laevifrons (Kyphosidae) and the carnivore Graus nigra (Kyphosidae), mass and body size relationships were higher in individuals from an upwelling zone compared with those from a non-upwelling zone. RNA:DNA were higher in the herbivores and omnivores from the upwelling zone. Higher biomass and RNA:DNA in the upwelling intertidal fishes may be a consequence of an increased exposure to higher nutrient availability, suggesting that increased physiological conditioning in vertebrates from upwelling areas can be detected and measured using intertidal fishes of different trophic levels.

Supplementation of University of Wisconsin solution with Nitroglycerin and Nicorandil in long-term myocardial preservation: effects on the oxidative state, endothelial function and morphology.

The purpose of this study was to assess the effects of the addition of Nitroglycerin or Nicorandil to University of Wisconsin solution in long-term myocardial preservation. In a model of heterotopic heart transplantation in pigs, the donor heart was preserved for 24 hours by means of continuous perfusion in this solution, in the presence or absence of these drugs. During this period, the oxygenation and pH of the solution were measured, as were lactate concentrations and enzyme release. At regular intervals following reperfusion we measured the concentrations of enzymes, antioxidants, glutathione peroxidase, glutathione reductase, malondialdehyde, endothelin and nitrite, and, two hours later, samples of both ventricles were taken for a morphological study. In the treated groups there was a higher lactate production during preservation and, during reperfusion, the signs of contracture and the elevation of enzyme levels were more marked than in the untreated groups. In contrast, the glutathione reductase concentrations did not decrease during the first phase of reperfusion and were directly correlated with those of antioxidants, endothelin levels increased less than in the untreated groups and, in the case of nitroglycerin, the nitrite concentration was significantly greater than in the remaining groups. We conclude that nitroglycerin and nicorandil improved the oxidative state and endothelial function and did not produce substantial morphological changes, but increased cell necrosis and contracture, possibly due to the duration of ischemia.

[Intramuscular midazolam in the initial treatment of status epilepticus]. / Midazolam intramuscular en el tratamiento inicial del estado epiléptico.

INTRODUCTION: The status epilepticus a serious complication of the epileptic syndrome with high rates of morbidity and mortality. Treatment is aimed to a fast control of the crisis. AIM: To evaluate the efficacy and security of intramuscular (IM) midazolam in the initial treatment of status epilepticus. PATIENTS AND METHODS: A prospective open clinical trial that included 43 status epilepticus in 38 adult patients. All of the cases received an initial dose of 15 mg IM of midazolam, with a simultaneous oral dose of phenytoin (15 to 20 mg/kg) or carbamazepine (15 mg/kg). If there was immediate control of the seizure but recurrence occurred during the next hours, 15 mg im of midazolam every 8 hours were given, for 24 hours. If there was immediate failure intravenous (IV) midazolam was given. RESULTS: 36 of the 43 status epilepticus were controlled: 30 with only one dose, 3 required additional IM doses, and 3 needed administration of IV midazolam, no patient had neither cardiovascular, respiratory or local complications. The only adverse effect was drowsiness in a variable grade. CONCLUSIONS: The use of IM midazolam is suggested as the initial treatment in status epilepticus in adults, especially in a low complexity setting, due to its effectiveness, quick action and security.

Midazolam intramuscular en el tratamiento inicial del estado epiléptico / Intramuscular midazolam in the initial treatment of status epilepticus

Introducción. El estado epiléptico es una complicación grave del síndrome epiléptico que presenta tasas elevadas de morbilidad y letalidad. El tratamiento se dirige a un rápido control delas crisis epilépticas. Objetivos. Evaluar la eficacia y seguridad del midazolam intramuscular (IM) en el tratamiento inicial del estado epiléptico en el adulto. Pacientes y métodos. Ensayo clínico abierto prospectivo que incluyó 43 episodios de estado epiléptico en 38enfermos. Todos los casos recibieron una dosis inicial de 15 mg IMde midazolam, con una dosis de carga oral simultánea de fenitoína (15-20 mg/kg) o carbamacepina (15 mg/kg). Si hubo control inmediato, pero con recurrencia de las crisis en las horas siguientes, se indicaron 15 mg IM cada 8 horas, durante 24 horas. Ante su fracaso inmediato se administró midazolam en infusión endovenosa (EV).Resultados. Se controlaron 36 de los 43 episodios de estado epiléptico:30 con 15 mg IM por una vez, tres necesitaron administración IM adicional y tres midazolam EV, sin complicación cardiovascular, respiratoria ni tisular local. El único efecto adverso fue somnolencia de grado variable. Conclusiones. Se sugiere el uso de midazolam IM en el tratamiento inicial del estado epiléptico en adultos, especialmente en un ambiente de baja complejidad tecnológica debido a su efectividad, rapidez de acción y seguridad (AU)

Introduction. The status epilepticus a serious complication of the epileptic syndrome with high rates of morbidity and mortality. Treatment is aimed to a fast control of the crisis. Aim. To evaluate the efficacy and security of intramuscular(IM) midazolam in the initial treatment of status epilepticus. Patients and methods. A prospective open clinical trial that included 43 status epilepticus in 38 adult patients. All of the cases received an initial dose of 15 mg IM of midazolam, with a simultaneous oral dose of phenytoin (15 to 20 mg/kg) or carbamazepine (15 mg/kg). If there was immediate control of the seizure but recurrence occurred during the next hours, 15 mg IM of midazolam every 8 hours were given, for 24 hours. If there was immediate failure intravenous (IV) midazolam was given. Results. 36 of the 43 status epilepticus were controlled: 30 with only one dose, 3 required additional IM doses, and 3 needed administration of IV midazolam, no patient had neither cardiovascular, respiratory or local complications. The only adverse effect was drowsiness in a variable grade. Conclusions. The use of IM midazolam is suggested as the initial treatment in status epilepticus in adults, especially in a low complexity setting, due to its effectiveness, quick action and security (AU)

Sympathetic sprouting in dorsal root ganglia (DRG): a recent histological finding?

During the nineties it was described, as an original finding, the existence of afferent amyelinic nerve endings in animal dorsal root ganglia (DRG) caused by diverse experimental lesions. These works do not take into account the historical studies carried out by Ehrlich (1886), Ramón y Cajal (1890) and Dogiel (1885) among others. Ramón y Cajal (1899) confirmed the existence of these nerve endings naming them after their discoverer as "Dogiel's arborisations". Ramón y Cajal claims that these endings originate from fibres of sympathetic nature, something supported by later authors devoted to this topic. In any case, the same authors remarked already a possible relationship with pathological phenomena, nonetheless always referring to the frequent occasions in which the same images appeared in healthy animals. In this work we review the bibliography about the classically named "Terminal Dogiel's nests" which in modern literature have been referred to as sprouting of sympathetic axons in dorsal root ganglia likely related with sympathetically maintained pain. Furthermore, we present the finding, not described up to date, of multiple afferent amyelinic nervous endings related with the "Terminal Dogiel's nests" observed in different DRG from young adult healthy rabbits.

Histomorphometrical study of the submandibular gland ductal system in the rat.

The duct system of murine submandibular gland is composed, in contrast with other mammals, by four types of ducts, among which the granular duct is unique for rodents. The granular duct shows a typical secretory structure with a clear intersex morphological diversity on which we carried out a morphometrical study in order to determine the relative area of each duct in rats in comparison with the rest of ducts and the whole gland. Our results, in both sexes, show that the duct with the broadest surface is the granular duct, followed by the excretory, striated and the intercalated ducts. In addition, we found a significant intersex difference between the relative surface of the granular and the excretory ducts, being bigger in males than in females. Finally, in both sexes, there is a greater variation in the data related to the excretory ducts than to the other ducts.

Heart transplantation: influence of the surgical technique on sinus function.

This study analyzes the influence of the surgical technique on the development of sinus dysfunction. Cycle length, corrected sinus node recovery time, and sinoatrial conduction time were determined in 4 groups of dogs under the following conditions: group 1, controls; group 2, subjected to heterotopic heart transplantation with conservation of atrial anatomy; group 3, subjected to orthotopic heart transplantation by using a standard technique; and group 4, treated as in group 3, but with an ischemic time of 24 hours. The cycle length was prolonged in all the treated groups when compared with the controls (P < .01), an effect attributed to the disconnection of the autonomic nervous system during the transplantation procedure. The corrected sinus node recovery time and sinoatrial conduction time were significantly longer in all the animals in groups 3 and 4 when compared with those of groups 1 and 2 (P < .01); however, there were no significant differences between groups 3 and 4 or between groups 1 and 2. These results suggest that the atrial anatomy play a more relevant role than the ischemic time in the origin of sinus dysfunction occurring after orthotopic heart transplantation.

Sepsis neonatorum and its management

1. Sepsis neonatorum is the 2nd leading cause of neonatal mortality2. The neonate is an immunologically incompetent host to infection and this statement is doubly true for the "premie."3. Good maternal and obstetrical care reduces the risk factors to sepsis4. The incidence of sepsis neonatorum increases with decreasing gestational age and birth weights5. A higher index of suspicion is vital in the early diagnosis and at best this is clinical. A diagnosis of sepsis is virtually a diagnosis of meningitis6. Early bacteriologic examination from meaningful sites is a helpful tool in diagnosis. There is no single laboratory examinations that can provide rapid and early identification of neonates with bacterial sepsis7. The increasing use of invasive technics for life support aggravated by equipment are important factors in its pathogenesis8. Manual transmission is the primary mode of spread; therefore adequate and convenient handwashing facilities should be available9. Because of multiplicity of possible aetiologic agents, an initial broad coverage with an antibiotic combination is justified10. Optimum bactericidal concentration of the drug at the sites of inflammation specifically the meninges is a must to prevent a "brain rot."11. There is an increasing incidence of resistant Gram negative pathogens including Pseudomonas and Salmonella but the staphylococcus aureus has consistently been with us due to inadequate handwashing12. The pattern of antibiotic usage in the community, the health and socio-economic characteristic of the population served accout for the difference in the pathogens13. The associated complications of sepsis must be anticipated and aggresively treated for optimum care. (Summary)

Cape Town solution in prolonged myocardial preservation: structural and ultrastructural study.

This study deals with myocardial preservation after 24 hours of continuous, hypothermic and oxygenated perfusion with Cape Town (CT) solution, focusing on the morphological changes produced by preservation and reperfusion, and their possible relationship to the composition of the solution and the immediate hemodynamic findings after orthotopic heart transplantation in dogs. After preservation, aside from mild or moderate mitochondrial changes, the most relevant lesions included edema and vasoconstriction. Reperfusion was followed by the development of areas of necrosis forming contraction bands and an increment in the mitochondrial damage; the intercalated disks conserved their normal structure; edema became more prominent and was invariably accompanied by hemorrhage; vasoconstriction was very pronounced and was accompanied on occasion by evidence of capillary rupture; and inflammatory cells were observed in the interstitium. These results indicate that colloid must be added to Cape Town solution and that reperfusion probably requires selective approaches to deal with vasoconstriction and inflammation.

Structural and ultrastructural study of the myocardium after 24-hour preservation in University of Wisconsin solution.

This study deals with myocardial preservation after 24 hours of continuous perfusion with University of Wisconsin (UW) solution, focusing on the morphological changes produced by preservation and reperfusion, and their possible relationship to the composition of the solution and the immediate hemodynamic findings after orthotopic heart transplantation in dogs. Following preservation, the histological images of the myocardium were normal in almost every case. After revascularization, although 50% of the hearts recovered preoperative functional levels, there were relevant histological changes in all of them. These changes consisted of interstitial edema, damage to at least 50% of the mitochondria, presence of contraction bands, loss of intercellular junction structure and vasoconstriction. According to these results, the association of continuous perfusion and UW solution appears to be effective during the ischemic period of prolonged myocardial preservation, but not during reperfusion. Perhaps the proportion of viable hearts could be increased by preventing vasoconstriction.

Ultrastructure of the oviductal mucosa of the rat. III. Basal and peg cells.

In an E.M. analysis of the rat oviduct the authors report the morphology of the so-called indifferent basal cells and peg cells. The hallmark of the former are desmosomes and clear cytoplasm; these elements may detach themselves from the basal membrane, migrating towards the lumen and showing prominent ciliogenesis. Peg cells appear to be the morphological image of necrobiotic cells, either ciliatd or secretory.