Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature.

Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

[Periprosthetic knee infection after a cat bite]. / Periprothetische Kniegelenkinfektion nach Katzenbiss.

BACKGROUND: Infections caused by Pasteurella multocida are extremely rare in arthroplasty. We report the case of a patient who was bitten by his domestic cat, causing an infection of his knee arthroplasty. DIAGNOSIS AND TREATMENT: The puncture of the knee resulted in putrid joint effusion. After removal of the knee prosthesis, infection with Pasteurella multocida was verified. We performed a two-stage revision combined with intravenous antibiotic therapy. DISCUSSION: Infections caused by cats and dogs should attract more attention especially as prosthesis material represents a significant "locus minoris resistentiae". Patients with domestic pets should be informed about this source of infection and possible complications. In the case of a bite, prompt and liberal antibiotic treatment should be administered.

Windows of vulnerability: maternal separation, age, and fluoxetine on adolescent depressive-like behavior in rats.

Early exposure to stressful life events plays a significant role in adolescent depression. Clinical studies have identified a number of factors that increase the risk of depression, including sex of the subject, duration of the stressor, and genetic polymorphisms that elevate serotonin levels. In this study we used the maternal separation (MS) model to investigate to what extent these factors interacted during development to manifest in depressive-like behavior in male and female rats. The triadic model of learned helplessness parses depressive-like behavior into aspects of controllable, uncontrollable, and motivational behaviors. This model was used to investigate how the timing of MS between the ages of postnatal day (P) 2-9 and P9-16 interacted with either simultaneous vehicle (saline; 1ml/kg; i.p.) or fluoxetine (10mg/kg) exposure, which was used to enhance serotonin levels; these experiments also compared the effect of a vehicle injection during these developmental periods to a no injection control. Vehicle injections alone increased helplessness in the controllable condition in male rats when injected between P9-16 only, and did not interact further with MS. MS at both ages decreased controllability in male adolescents; females demonstrated an increase in controllability after MS. Elevated serotonin at P2-9 increased escape latencies in male and female control and MS subjects. Fluoxetine exposure at P9-16 increased helplessness in controls. Fluoxetine decreased helplessness in MS males independent of age, but increases helplessness in MS females. This study highlights the importance of age of MS (MS between P2-9 increases helplessness in males more than females), the duration of the stressor (previous results show females are effected by longer MS [P2-20], but not shorter [this study]), and that elevated serotonin increases escape latencies to a greater extent in females.

Organization of telencephalotectal projections in pigeons: Impact for lateralized top-down control.

Birds display hemispheric specific modes of visual processing with a dominance of the right eye/left hemisphere for detailed visual object analysis. In pigeons, this behavioral lateralization is accompanied by morphological left-right differences in the ascending tectofugal pathway. This system is also asymmetrically modulated by descending telencephalotectal input whereby the left forebrain displays a much more pronounced physiological control over ipsilateral left and contralateral right visual thalamic processes. In the present study we aimed to answer the question if this top-down asymmetry that up to now had been demonstrated in single cell recording studies is due to anatomical asymmetries in the size of the fiber systems descending from the telencephalon to the tectum. We approached this question by means of a quantitative retrograde tracing study. Cholera toxin subunit B (CtB) was injected unilaterally into either the left or right optic tectum of adult pigeons. After immunohistochemical detection of CtB-positive cells, the number of ipsi- and contralaterally projecting neurons was estimated. Retrogradely labeled cells were located within the arcopallium, the hyperpallium apicale (HA) and the temporo-parieto-occipital area (TPO). Descending projections from HA, arcopallium, and TPO were mainly or exclusively ipsilateral with the contralateral projection being extremely small. Moreover, there was no difference between left and right hemispheric projections. These anatomical data sharply contrast with behavioral and electrophysiological ones which reveal an asymmetric and bilateral top down control. Therefore, contralateral and lateralized forebrain influences onto tectofugal processing are possibly not the direct result of asymmetrical descending axon numbers. Those influences emerge by a lateralized intra- and/or interhemispheric integration of ascending and descending input onto the rotundus.

Extracellular glutamate, aspartate and arginine increase in the ventral posterolateral thalamic nucleus during nociceptive stimulation.

Although there is evidence that the thalamus plays a remarkable role in pain processing few in vivo studies on the thalamic neurochemical correlates of pain have been done. In the present experiments a combination of capillary zone electrophoresis with laser-induced fluorescence detection (CZE-LIF) and microdialysis in freely moving rats was used to measure extracellular arginine, glutamate and aspartate in the thalamus during the formalin test. Microdialysis probes were implanted in the left ventral posterolateral (VPL) nucleus of the thalamus in rats. Samples were collected every 30 s, derivatized with fluorescein isothyocyanate and injected into a CZE-LIF instrument. After nine baseline samples, a subcutaneous formalin (5%, 50 microl) injection in the right hind paw caused an increase of arginine, glutamate and aspartate that lasted for about 3 min. These increases were calcium and nerve impulse dependent. These results indicate that the release of arginine, glutamate and aspartate may mediate rapid pain neural transmission in the VPL nucleus of the thalamus.

Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney.

We have recently demonstrated that the exposure to hyperglycemia in utero impairs nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999). Diabetic pregnancy is commonly associated with alterations in the IGF system in fetal tissues. It has also been shown that both IGF-I and IGF-II are produced within developing metanephros and promote renal organogenesis. Therefore, we investigated the effect of maternal diabetes on IGFs and their receptors in developing fetal rat kidney. Diabetes was induced in pregnant rats by a single injection of streptozotocin on day 0 of gestation. We measured the amounts of IGF and their receptors, both proteins and mRNAs, in the metanephroi of fetuses issued from diabetic subjects and in age-matched fetuses from control subjects (14-20 days of gestation). IGF-II was produced throughout fetal nephrogenesis, whereas IGF-I protein was not detected, suggesting a critical role of IGF-II in kidney development. Fetal exposure to maternal diabetes caused no change in IGF production in the early stages of nephrogenesis. Similarly, the amounts of IGF-I receptor and insulin receptor were not altered. By contrast, there was an increase in production of IGF-II/mannose-6-phosphate receptor throughout nephrogenesis. Because this receptor plays an essential role in regulating the action of IGF-II, the altered nephrogenesis in fetuses exposed to maternal diabetes may be linked to a decrease in IGF-II bioavailability.

Adverse effects of hyperglycemia on kidney development in rats: in vivo and in vitro studies.

Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of hyperglycemia on kidney development in the rat. Female rats were made hyperglycemic throughout gestation with a single injection of streptozotocin (STZ) on day 0 of gestation, or for a short period encompassing the early stage of renal organogenesis by infusing glucose from gestational days 12-16. Kidney development in the pups was assessed by determining the total number of nephrons formed in the kidney. The number of nephrons was significantly reduced (10-35%) in the pups from STZ-treated dams, as a function of hyperglycemia. There were also fewer nephrons in pups from dams given glucose infusion whose hyperglycemia was transiently higher on day 13 of gestation. The in vitro experiments were done on metanephroi removed from 14-day-old fetuses and grown for 6 days in medium containing 0, 6.9, 13.8, or 27.5 mmol/l glucose. The development of explants grown in 0, 13.8, and 27.5 mmol/l glucose was impaired compared with that of explants grown in the 6.9 mmol/l control medium, showing that the glucose concentration must be closely controlled to ensure optimum in vitro metanephros development. Thus, exposure to hyperglycemia in utero can cause a nephron deficit, which in turn may have renal consequences later in life.