Raman Spectroscopy Can Identify Acute and Persistent Biochemical Changes in Leukocytes From Patients With COVID-19 and Non-COVID-19-Associated Sepsis.

Nine children, 7-16 years of age, were studied repeatedly during an acute asthmatic attack, from acute deterioration to recovery. The transcutaneous blood gases, forced expiratory volume in 1 s (FEV1) and maximum expiratory flow when 25% of vital capacity remained to be expelled (MEF25) were monitored before and after salbutamol inhalation. The flow-volume variables were markedly impaired in the acute phase but improved gradually by the time of recovery. The transcutaneous PO2 (tcPO2) decreased in the acute and early recovery phase but improved by the late recovery phase. In the acute phase, the salbutamol inhalations increased the FEV1, indicating an improvement in central airway function, but also reduced the MEF25 and tcPO2 in some of the children. The changes in tcPO2 after the inhalations correlated with the changes in MEF25 (p < 0.001), thereby indicating a common denominator, probably the condition of the peripheral airways. In the recovery phase, the FEV1, MEF25 and tcPO2 improved after the inhalations (p < 0.05). In conclusion, transcutaneous PO2 can be used to evaluate the effects of treatment in children with acute asthmatic symptoms and may add information about peripheral airway function which may prove particularly valuable in small children where few methods are available for such measurements.

Objective To evaluate the changes of C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in cerebrospinal fluid and serum of patients with intracranial infection,in order to explore their significance.Methods The levels of CRP and MMP-9 in 43 cases patients with intracranial infection of the acute and recovery phase and 21 normal people (control group) were determined by immunohistochemical turbidimetric method and radioimmunity method.In 43 patients,24 cases of viral encephalitis (viral encephalitis group),12 cases of tuberculous meningitis (tuberculous meningitis group) and 7 cases of purulent meningitis (purulent meningitis group).Results The levels of CRP of cerebrospinal fluid and serum in the acute phase in tuberculous meningitis group [(7.12 ±2.32),(28.84 ±4.91) μg/L] and purulent meningitis group [(8.68 ± 2.32),(32.60 ± 6.94) μg/L] were significantly higher than those in control group [(3.20 ± 1.62),(9.96 ± 3.45) μ g/L] (P ＜0.05);the levels of CRP had no significantly statistical difference in the acute and recovery phase between viral encephalitis group and control group (P＞0.05),and there was no significant difference in the levels of CRP of cerebrospinal fluid and serum in the recovery phase between tuberculous meningitis group or purulent meningitis group and control group (P＞0.05).There was no significant difference in the levels of CRP in tuberculous meningitis group and purulent meningitis group between the acute phase and recovery phase (P＞0.05).The levels of MMP-9 in the acute and recovery phase of all the groups were significantly higher than those in control group (P ＜0.05).The levels of MMP-9 in the recovery phase of all the groups were significantly decreased,compared with those in the acute phase (P＜0.05).Especially the levels of MMP-9 in the acute and recovery phase in tuberculous meningitis group and purulent meningitis group were significantly higher than those in viral encephalitis group (P＜0.05).There were no significant difference in the levels of MMP-9 in tuberculous meningitis and purulent meningitis group between the acute phase and the recovery phase (P＞0.05).Conclusions There is no significant relationship between CRP and viral encephalitis,however the levels of CRP are significantly increased in the acute phase of bacterial intracranial infections.The levels of MMP-9 in the three kinds of intracranial infection are signifcanfiy increased,especially in tuberculous meningitis and purulent meningitis patients,and they gradually decrease during the recovery procedure.The changes of CRP and MMP-9 would help to determine the phases,the kinds,the severity and the prognosis of intracranial infection. Key words: C-reactive protein; Matrix metalloproteinase-9; Intracranial infection

Exercise training improves functional recovery and motor nerve conduction velocity after sciatic nerve crush lesion in the rat

Background Acute mitral valve regurgitation is known to be associated with a severe prognosis in patients affected by Takotsubo syndrome (TTS). The mechanisms involved are different and related to various pathogenesis such as cordal or mitral anterior leaflet (LAM) systolic anterior motion (SAM) and tethering of the mitral valve. Aim of the study to compare mitral valve morpho-functional features and concomitant left ventricle (LV) abnormalities by transthoracic echocardiography in patients during the acute and recovery phase of Takotsubo syndrome. Methods 24 consecutive patients were enrolled from a multicenter prospective registry of TTS from July 2007 to February 2022. Through transthoracic echocardiography, LV ejection fraction, LV end-diastolic and end-systolic diameters and volumes, left atrium antero-posterior diameter and end-systolic volume, mitral anulus diameter, prevalence of mitral valve regurgitation, of LV outflow tract obstruction (LVOTO), coaptation depth and tenting area were collected during the acute and recovery phase of takotsubo syndrome. Results LVEF at admission was 39.6 ± 7.8% vs 60.5 ± 4% at functional recovery (p&amp;lt;0.001). LVEDV, LVESV and LVESVi were found to be higher during the acute phase when compared to the recovery phase (103.8 ± 28.9 vs 89.7 ± 23.4 ml, p=0.012; 59.8 ± 17.2 vs 35.1 ± 10.1 ml, p&amp;lt; 0.001; and 36.1 ± 9 vs 20.6 ± 5.4 ml/m2, p&amp;lt;0.001 respectively). No statistically significant differences were found between admission and recovery phase in term of mitral annular dimension (32.3 ± 4.6 vs 32.5 ± 4.1 mm, p=0.825), tenting area (2.3 ± 0.6 vs 2.2 ± 0.7 cm2, p=0.445), proximal thickness and length of both of the mitral leaflets, while coaptation depth was higher during the acute phase in comparison to functional recovery (1.1 ± 0.2 vs 1 ± 0.3 cm, p=0.018). 10 patients (41%) presented with moderate/ severe mitral insufficiency and 5 patients of them (20% of the general population) downgraded to mild at recovery. Among the patients with values of LVEDV higher than 104 mL, LVESV higher than 43 mL, LVESVi higher than 25 mL/m2 and coaptation depth higher than 1.1 cm during the acute phase, 4 out of 5 patients experienced a downgrade of the severity of mitral valve regurgitation. Conclusions Left ventricle end-diastolic volume and coaptation depth are statistically different during the acute and recovery phase. Among the patients who experienced a downgrading of the severity of mitral valve regurgitation, higher values of LVEDV, LVESV, LVESVi and coaptation depth during the acute phase were found.

The relationship between mechanistic target of rapamycin complex 1 (mTORC1) activation after resistance exercise and acetylcholine receptor (AChR) subunit gene expression remains largely unknown. Therefore, we aimed to investigate the effect of electrical stimulation-induced intense muscle contraction, which mimics acute resistance exercise, on the mRNA expression of AChR genes and the signalling pathways involved in neuromuscular junction (NMJ) maintenance, such as mTORC1 and muscle-specific kinase (MuSK). The gastrocnemius muscle of male adult Sprague-Dawley rats was isometrically exercised. Upon completion of muscle contraction, the rats were euthanized in the early (after 0, 1, 3, 6 or 24h) and late (after 48 or 72h) recovery phases and the gastrocnemius muscles were removed. Non-exercised control animals were euthanized in the basal state (control group). In the early recovery phase, Agrn gene expression increased whereas LRP4 decreased without any change in the protein and gene expression of AChR gene subunits. In the late recovery phase, Agrn, Musk, Chrnb1, Chrnd and Chrne gene expression were altered and agrin and MuSK protein expression increased. Moreover, mTORC1 and protein kinase B/Akt-histone deacetylase 4 (HDAC) were activated in the early phase but not in the late recovery phase. Furthermore, rapamycin, an inhibitor of mTORC1, did not disturb changes in AChR subunit gene expression after muscle contraction. However, rapamycin addition slightly increased AChR gene expression, while insulin did not impact it in rat L6 myotube. These results suggest that changes in the AChR subunits after muscle contraction are independent of the rapamycin-sensitive mTORC1 pathway.

The role of the limbic system in the acute phase and during the recovery of takotsubo syndrome needs further clarification. In this longitudinal study, anatomical and task-based functional magnetic resonance imaging of the brain was performed during an emotional picture paradigm in 19 postmenopausal female takotsubo syndrome patients in the acute and recovery phases in comparison to sex- and aged-matched 15 healthy controls and 15 patients presenting with myocardial infarction. Statistical analyses were performed based on the general linear model where aversive and positive picture conditions were included in order to reveal group differences during encoding of aversive versus positive pictures and longitudinal changes. In the acute phase, takotsubo syndrome patients showed a lower response in regions involved in affective and cognitive emotional processes (e.g., insula, thalamus, frontal cortex, inferior frontal gyrus) while viewing aversive versus positive pictures compared to healthy controls and patients presenting with myocardial infarction. In the recovery phase, the response in these brain regions normalized in takotsubo syndrome patients to the level of healthy controls, whereas patients 8–12 weeks after myocardial infarction showed lower responses in the limbic regions (mainly in the insula, frontal regions, thalamus, and inferior frontal gyrus) compared to healthy controls and takotsubo syndrome patients. In conclusion, compared to healthy controls and patients suffering from acute myocardial infarction, limbic responses to aversive visual stimuli are attenuated during the acute phase of takotsubo syndrome, recovering within three months. Reduced functional brain responses in the recovery phase after a myocardial infarction need further investigation.

To evaluate whether abdominal ultrasound (US) with a gallbladder (GB) contractility study or motor function test can be used as a diagnostic tool in patients with dengue and warning signs in acute and recovery phases. Fifty-one individuals in the acute phase of dengue presenting with warning signs (dengue group) and 49 healthy individuals without a history of dengue or hepatobiliary disease (control group) were studied with abdominal US and a GB contractility study. Statistical differences in US measurements of the liver (right lobe, P = .012; left lobe, P = .001) and spleen (P = .008) dimensions, GB wall thickness (P < .001), and the GB emptying fraction (P < .001) were observed in dengue during the acute phase compared with the control group. After 60 days, abdominal US of the dengue group showed a statistical difference in liver (right lobe, P < .001; left lobe, P = .078) and spleen (P < .001) dimensions, GB wall thickness, and the GB emptying fraction (P < .001) compared with the results obtained during the acute phase. Furthermore, a statistical difference in the spleen volume and GB emptying fraction (P < .001) was observed when comparing dengue after clinical recovery and the control group. Abdominal pain in patients with dengue was positively associated with hepatomegaly (P = .031), splenomegaly (P = .008), increased GB wall thickness (P = .016), and a reduced GB emptying fraction (P = .038) during the acute phase and with splenomegaly (P = .001) and a reduced GB emptying fraction (P = .003) after clinical recovery. Abdominal US with a GB motor function test can be used as a diagnostic tool in patients with dengue during acute and recovery phases.

Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis

Influenza patients show a high incidence of T lymphocytopenia in the acute phase of the illness. Since CD8+ T cells play an important role in influenza virus infection, we investigated which subset of CD8+ T cells was involved in this lymphocytopenia. CD8+ T cells from eight patients with influenza A were studied for lymphocyte count, surface marker, and intracellular IFN-gamma production in the acute (days 1-3) and recovery phases (days 9-12). Total and T lymphocyte counts in the acute phase were approximately three times less than in the recovery phase; however, the CD4/8 ratio was the same in both phases. The cell count reduction in the acute phase was attributed predominantly to the CD28+ CD8+ subset, compared with the CD28- CD8+ subset. The memory/activation marker CD45RO on the CD8+ T cells was assessed. The CD28+ CD45RO- subset, a naive phenotype, was reduced significantly in number in the acute phase compared with the recovery phase. The CD28+ CD45RO+ subset, a memory phenotype, was also reduced in the acute phase, but the reduction was not statistically significant. Intracellular IFN-gamma in the CD8+ subset after mitogenic stimulation was measured by flow cytometry; the percentage of CD28+ IFN-gamma-/CD8+ subset in the acute phase was significantly less than in the recovery phase. These results indicated that the predominant reduction of peripheral CD8+ T cells in the acute phase of influenza was from naive-type lymphocytes, suggesting that these quantitative and qualitative changes of CD8+ T cells in influenza are important for understanding the immunological pathogenesis.

To examine biopterin fractions and biogenic amine metabolites in cerebrospinal fluid in aseptic meningitis, the concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and the total, the oxidized form, and the reduced form of biopterin were determined in cerebrospinal fluid specimens from 15 children with aseptic meningitis in the acute phase, 15 children with aseptic meningitis in the recovery phase, and six other children as controls. The concentration of each substance was significantly higher in the acute phase than in the recovery phase. Homovanillic acid in the acute phase was significantly increased compared to that in the control group. The concentrations of the total, the oxidized form, and the reduced form of biopterin, and 5-hydroxyindoleacetic acid were higher in the acute phase than those in the controls; however, the differences were not significant. The concentration of each substance in the recovery phase was not significantly different from that in the controls. There was no difference in the 5-hydroxyindoleacetic acid/homovanillic acid ratio or in the reduced form/total biopterin ratio among the patients in acute and recovery phases and the controls. These results suggested that levels of biopterin and biogenic amine metabolites in cerebrospinal fluid are increased in the acute phase of aseptic meningitis and return to normal during the recovery phase. This is the first report of increased concentrations of biopterin fractions and biogenic amine metabolites in aseptic meningitis.

Rapid and simple analysis of disease-associated biomarkers of Taiwanese patients with schizophrenia using matrix-assisted laser desorption ionization mass spectrometry

Progranulin is a secreted glycoprotein that regulates inflammation and wound healing. However, plasma progranulin levels in the acute phase and their clinical significance in patients with acute myocardial infarction (AMI) remain to be elucidated. We aimed to investigate the relationship between the increase in plasma progranulin levels in the acute phase and the recovery of left ventricular function in the chronic phase in AMI patients. Eighteen AMI patients were followed up for 6 months. Blood samples were collected from the antecubital vein on day 0 (on admission) and day 7 in the acute phase. The control group consisted of patients without significant coronary artery stenosis, as assessed by cardiac catheterization (n = 16). Plasma progranulin levels were measured by enzyme-linked immunosorbent assay. Echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI to evaluate left ventricular ejection fraction using the modified Simpson's method. Plasma progranulin levels in the AMI group on day 0 (69.5 ± 24.6 ng/mL) were similar to those in the control group (84.2 ± 47.1 ng/mL). There was a significant increase in progranulin levels in the AMI group on day 7 (104.2 ± 52.0 ng/mL) compared with day 0. The increase in plasma progranulin levels in the acute phase was positively correlated with the increase in left ventricular ejection fraction between the acute and chronic phases. Among various factors, only plasma progranulin levels were favorably correlated with left ventricular functional recovery in the chronic phase. The increase in plasma progranulin levels in the acute phase may serve as a predictive biomarker and a contributer for the recovery of left ventricular function in the chronic phase in patients with AMI.

BackgroundMultimodal rehabilitation interventions delivered in late phase of stroke recovery involve physical (motor and sensory), social, and cognitively challenging activities. Horseback riding can be incorporated within such interventions, leading to meaningful long-term improvements when applied to individuals with moderate levels of disability. There is a lack of research illuminating stroke survivors’ experiences and perceptions of horseback riding in the context of multimodal interventions.AimTo explore stroke survivors’ experiences of participation in a multimodal group-based intervention that included horseback riding.MethodsAn explorative interview study was conducted with individual face-to-face interviews performed on a single occasion, utilising a semi-structured interview guide. Eighteen participants were purposively selected from a larger trial (mean age 62, 12 men, 6 women) within four weeks after treatment completion. The interview duration was between 17 and 50 minutes. The data was analysed using a qualitative content analysis method.FindingsFour broad themes were identified from the analysis. These themes were: transformative experiences; human–horse interaction; togetherness and belonging; and the all-in-one solution. Interacting with the horse and peers had a profound emotional impact on the participants. The participants also reported having learned new skills, increased self-efficacy and self-esteem, and improvements in balance and gait, all of which could be transferred to everyday life. The horse itself played a central role, but other components, such as the other group members, the instructors, and the challenging tasks on the horseback, were also important.ConclusionA multimodal rehabilitation intervention that includes horseback riding may provide stroke survivors in a late phase of recovery with rich pleasurable experiences that may have life-changing and profound impacts on their emotional and physical state.

137 - QRS Voltage Increases during Recovery from Fulminant Myocarditis

Objectives: Intratracheal endotoxin in rats causes acute lung injury. Here we have addressed the cellular physiopathology of lung recovery from that injury. Methods: The lungs of 5 untreated rats and rats treated with intratracheal endotoxin from 2, 3, 5, 8 (5 rats each) and 15 days (2 rats) were studied by light and electron microscopy and immunohistochemistry. Results: In the acute phase there was a reduction in the aerated spaces (p < 0.01); diffuse infiltration of granulocytes and macrophages; hyperplasia of type-II pneumocytes, and hypertrophy of interstitial cells. Aerated spaces improved during recovery. In the early recovery phase (3–8 days) the compartmentalization of infiltrating cells varied significantly (p < 0.01): macrophages remained widespread while neutrophils were inside blood vessels. Many pneumocytes were intermediate between type-I and type-II cells. In the late recovery phase (15 days) the infiltrate disappeared; myofibroblasts were significantly more than previously (p < 0.01) and extracellular matrix was abundant; type-II pneumocytes contained non-lamellated lipid inclusions. Conclusions: Macrophages play a pivotal role in the damage-repair processes of the lung following endotoxin injury, leading to an increase in extracellular matrix, differentiation of myofibroblasts and altered secretion of surfactant by newly differentiated type-II pneumocytes.