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We have examined the location of cholinergic and GABAergic neurons that project to the rat main olfactory bulb by combining choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) immunohistochemistry with retrograde fluorescent tracing. Since many of the projection neurons are located in subcortical basal forebrain structures, where the delineation of individual regions is difficult, particular care was taken to localize projection neurons with respect to such landmarks as the ventral pallidum (identified on the basis of GAD immunoreactivity), the diagonal band, and medial forebrain bundle. In addition, sections with fluorescent tracers or immunofluorescence were counterstained for Nissl substance in order to correlate tracer or immunopositive neurons with the cytoarchitecture of the basal forebrain. The majority of the cholinergic bulbopetal neurons are located in the medial half of the nucleus of the horizontal limb of the diagonal band (HDB), whereas only a few are located in its lateral half. A substantial number of cholinergic bulbopetal cells are also found in the sublenticular substantia innominata. A small number of cholinergic bulbopetal neurons, finally, are located in the ventrolateral portion of the nucleus of the vertical limb of the diagonal band. At the level of the crossing of the anterior commissure, approximately 17% of the bulbopetal neurons in the HDB are ChAT-positive. The noncholinergic bulbopetal cells are located mainly in the lateral half of the HDB. GAD-containing bulbopetal neurons are primarily located in the caudal part of the HDB, especially in its lateral part. About 30% of the bulbopetal projection neurons in the HDB are GAD-positive. A few GAD-positive bulbopetal cells, furthermore, are located in the ventral pallidum, anterior amygdaloid area, deep olfactory cortex, nucleus of the lateral olfactory tract, lateral hypothalamic area, and tuberomamillary nucleus. The topography of bulbopetal neurons was compared to other projection neurons in the HDB. After multiple injections of fluorescent tracer in the neocortex, retrogradely labeled neurons were concentrated in the most medial part of the HDB, while neurons projecting to the olfactory and entorhinal cortices were located in the ventral part of the HDB. These results show that the cells of the HDB can be divided into subpopulations based upon projection target as well as transmitter content. Furthermore, these subpopulations correspond, at least to a considerable extent, to areas that can be defined on cyto- and fibroarchitectural grounds.
Aims The present study had two aims: (i) compare echocardiographic parameters in COVID-19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID-19 related death. Methods and results In this prospective multicentre cohort study, 214 consecutive hospitalized COVID-19 patients underwent an echocardiographic examination (by predetermined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID-19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 ± 0.4 vs. 2.6 ± 0.5, P < 0.001), and RV strain (19.8 ± 5.9 vs. 24.2 ± 6.5, P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow-up (median: 40 days), 25 COVID-19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR) = 1.18, 95% confidence interval (CI) [1.07-1.31], P = 0.002, per 1 mm decrease], RV strain (HR = 1.64, 95%CI[1.02;2.66], P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI[1.07-1.35], P = 0.002, per 1% decrease) were significantly associated with COVID-19-related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease. Conclusions RV and LV function are significantly impaired in hospitalized COVID-19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID-19-related death.
We have examined the location of cholinergic and non-cholinergic neurons that project to the rat basolateral amygdaloid nucleus by using choline acetyltransferase (ChAT) immunohistochemistry in combination with retrograde fluorescent tracing on the same tissue section. Since many tracer-and ChAT-positive neurons were identified in basal forebrain areas, including the ventral pallidum, we also stained many of the sections for glutamate decarboxylase, a suitable marker for the delineation of pallidal areas. Cholinergic neurons projecting to the basolateral amygdaloid nucleus were observed in a continuous territory stretching from the dorsal part of ventral pallidum, through sublenticular substantia innominata to ventral parts of globus pallidus and peripallidal areas. Non-cholinergic neurons projecting to the basolateral amygdaloid nucleus were found intermixed within the same structures and constitute approximately 25% of the amygdalopetal projection neurons in these ventral forebrain structures. Since amygdalopetal cholinergic neurons were demonstrated in areas generally recognized as giving rise to cholinergic projections to cerebral cortex, several retrograde double-labeling experiments with two different fluorescent tracers were performed for the purpose of detecting the possible existence of collateral projections. The results obtained showed that the cholinergic basal forebrain neurons in general project to only one forebrain region, and, furthermore, that the cholinergic system consists of partially overlapping subsets of neurons that project to various neocortical and allocortical areas and to the amygdaloid body.
Lung transplant recipients experience a particularly high incidence of Aspergillus infection in comparison with other solid-organ transplantations. This study was conducted to determine the incidence of Aspergillus colonisation and invasive aspergillosis, and the impact on long-term survival associated with Aspergillus infection. A retrospective study of 362 consecutive lung transplant patients from a single national centre who were transplanted 1992-2003 were studied. Twenty-seven patients were excluded due to incomplete or missing files. A total of 105/335 (31%) patients had evidence of Aspergillus infection (colonisation or invasion), including 83 (25%) patients with colonisation and 22 (6%) patients with radiographic or histological evidence of invasive disease. Most of the infections occurred within the first 3 months after transplantation. Cystic fibrosis (CF) patients had higher incidences of colonisation and invasive disease [15 (42%) and 4 (11%) of 36 patients] than non-CF patients [68 (23%) and 18 (6%) of 299 patients] (P = 0.01). Invasive aspergillosis was associated with 58% mortality after 2 years, whereas colonisation was not associated with early increased mortality but was associated with increased mortality after 5 years compared to non-infected patients (P < 0.05). An analysis of demographic factors showed that donor age [OR 1.40 per decade (95% CI 1.10-1.80)], ischaemia time [OR 1.17 per hour increase (95% CI 1.01-1.39)], and use of daclizumab versus polyclonal induction [OR 2.05 (95% CI 1.14-3.75)] were independent risk factors for Aspergillus infection. Invasive aspergillosis was associated with early and high mortality in lung transplant patients. Colonisation with Aspergillus was also associated with a significant increase in mortality after 5 years. CF patients have a higher incidence of Aspergillus infection than non-CF patients.
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