Long-term Microglial Phase-specific Dynamics During Single Vessel Occlusion and Recanalization

Vascular occlusion leading to brain dysfunctions is usually considered evoking microglia-induced inflammation response. However, it remains unclear how microglia interact with blood vessels in the development of vascular occlusion-related brain disorders. Here, we illuminate long-term spatiotemporal dynamics of microglia and their activation pattern during single vessel occlusion and recanalization. The results show that microglia display remarkable response characteristics in different phases, including acute reaction, rapid diffusion, transition and chronic effect. Microglial cell body represents a unique filament-shape migration and has slower motility compared to the immediate reaction of processes to occlusion. We capture single microglia with few processes moves out of the cluster and redistributes territory with increasing ramified processes. Microglial cluster resolves gradually until microglial number and morphology become stabilized. Therefore, our study offers a comprehensive analysis of spatiotemporal dynamics of microglia to both vessel occlusion and recanalization. Microglial phase-specific response suggests the morphological feature-oriented phased intervention would be an attractive option for vascular occlusion-related diseases treatments.

Magnetic Resonance Imaging in Diagnosis of Complications of Renal and Ureteral Injuries in Different Periods of Traumatic Disease

The aim of this study was to evaluate the effectiveness of MRI in diagnosing combined renal and ureteral injuries at different periods of traumatic disease (TD). Methods and Results: We analyzed the results of diagnostics and treatment of 139 patients (80 women and 59 men) with renal and ureteral injuries aged between 18 and 72 years. There were 67(48.2%) patients in the period of acute reaction to trauma, 40(28.8%) patients with early manifestations, and 32(23%) patients in the period of late manifestations. In 127(91.4%) patients, an urgent plain abdominal X-ray was performed without any preliminary preparation. USI of the abdominal and retroperitoneal space was performed in 108(77.7%) patients in the stage of the primary assessment of renal injury as it was a rapid non-invasive investigation. A whole-body MSCT was performed in 131(94.2%) patients, using the nonionic contrast agents Ultravist (350mg I/ml) and Omnipaque (350mg I/ml). MRI was performed in 125(89.9%) patients, including cases of pregnancy and a medical history of allergies. Contrast-enhanced MSCT had a high diagnostic efficiency in assessing complications in kidney and ureteral injuries at different periods of TD (accuracy of 89.2% for acute reaction, 88.8% for early manifestations, and 89.5% for late manifestations). MRI of the kidneys and ureters was indicated in periods of early and late manifestations of TB to detect renal complications in cases with a discrepancy between clinical manifestations and the results obtained by ultrasound and MSCT (accuracy of 87.5% for early manifestations and 89.9% for late manifestations).

Pseudo-Anaphylactic Reactions to Pfizer BNT162b2 Vaccine: Report of 3 Cases of Anaphylaxis Post Pfizer BNT162b2 Vaccination

Anaphylactic reactions were observed after Singapore’s national coronavirus disease 2019 (COVID-19) vaccination programme started in December 2020. We report the clinical and laboratory features of three patients in our institution who developed anaphylactic reactions after receiving the Pifzer BNT162b2 vaccine. IgM and IgG antibodies, but not IgE antibodies to the Pfizer BNT162b2 vaccine, were detected in all subjects. Similarly, mild to high elevated levels of anti-polyethylene glycol (PEG) IgG (1035–19709 U/mL, vs. vaccine-naive < 265 U/mL, vaccine-tolerant < 785 U/mL) and IgM (1682–5310 U/mL, vs. vaccine-naive < 1011 U/mL, vaccine-tolerant < 1007 U/mL) were detected in two out of three patients via commercial ELISA. High levels of serum anaphylatoxin C3a (79.0 ± 6.3 μg/mL, mean ± SD, vs. normal < 10 μg/mL) were observed in all three patients during the acute phase of the reaction, while tryptase levels, a marker of mast cell activation, were not elevated. Finally, one patient with the highest levels of anti-PEG IgG, IgM, and anti-Pfizer BNT162b2 IgG and IgM exhibited an enhanced Th2 cytokine serum profile during an acute reaction, with high levels of IL-4 (45.7 pg/mL, vs. vaccine-naive/tolerant < 2.30 pg/mL), IL-33 (86.4 pg/mL, vs. vaccine-naive/tolerant < 5.51 pg/mL) and IL-10 (22.9 pg/mL, vs. vaccine-naive/tolerant < 12.49 pg/mL) diminishing over time following corticosteroid treatment. Taken together, we propose these cases of anaphylaxis described are driven by a complement activation-related pseudoallergy (CAPRA), rather than classical IgE-mediated mechanisms.

Evaluation of treatment-associated eye toxicity after irradiation in childhood and adolescence—results from the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK)

Purpose The aim of the study is to evaluate treatment-related acute and late eye toxicity associated with radiation therapy in childhood and adolescence as correlated with RT (radiotherapy) doses. Methods From 2001 to 2016, a total of 1725 children and adolescents undergoing radiation therapy were prospectively documented in the Registry of the Evaluation of Side Effects after Radiotherapy in Childhood and Adolescence (RiSK). The RTOG/EORTC criteria were used to classify ocular acute and late effects. Uni- and multivariate analyses were carried out to evaluate the impact of patient age, pre-existing impairments, and radiation dose on ocular toxicity. Results Of all documented patients, 593 received dose to the eye and formed the basis of this analysis. In 435 patients, information on acute reaction was available and graded 1, 2, 3, and 4 in 49, 17, 0, and 2 patients, respectively. Information on late toxicity was available in 268 patients and graded 1, 2, 3, and 4 in 15, 11, 11, and 5 patients, respectively. The acute toxicity rate was significantly higher in children who received a maximum dose > 50 Gy to the eye (p < 0.001) and who had a pre-existing eye impairment (p < 0.001 in multivariate analysis). The development of late toxicity was significantly higher for patients experiencing acute toxicity and having received a radiation dose > 50 Gy. Conclusion Acute and late toxicity both correlate with high radiation dose to the eye (> 50 Gy) and acute toxicity additionally with pre-existing eye impairments.

Cyclosporin A but not FK506 activates the integrated stress response in human cells

Cyclosporin A (CsA) and tacrolimus (FK506) are valuable immunosuppressants for a range of clinical settings, including (but not limited to) organ transplantation and the treatment of autoimmune diseases. They function by inhibiting the activity of the Ca2+/calmodulin-dependent phosphatase calcineurin toward nuclear factor of activated T-cells (NF-AT) in T-lymphocytes. However, use of CsA is associated with more serious side effects and worse clinical outcomes than FK506. Here we show that CsA, but not FK506, causes activation of the integrated stress response (ISR), an event which is normally an acute reaction to various types of intracellular insults, such as nutrient deficiency or endoplasmic reticulum stress. These effects of CsA involve at least two of the stress-activated protein kinases (GCN2 and PERK) that act on the translational machinery to slow down protein synthesis via phosphorylation of the eukaryotic initiation factor (eIF) 2α and thereby induce the ISR. These actions of CsA likely contribute to the adverse effects associated with its clinical application.

Correlated factors of acute oral mucosal and skin reaction induced by radiotherapy in hypopharyngeal carcinoma

Background This present retrospective single center study was intended to investigate the factors associated with acute radiation oral mucositis or dermatitis during hypopharyngeal carcinoma radiotherapy.Methods From May 2012 to December 2018, previously untreated 93 patients with hypopharyngeal squamous cell carcinoma received radiotherapy in Affiliated Cancer Hospital of Zhengzhou University were enrolled. Radiation Therapy Oncology Group (RTOG) scoring criteria were used for assessing the severity of toxicities. Patients are therefore classified into “mild reaction group” (G0~G1) and “acute reaction group” (G2~G4). Single variate was applied to screen out factors with significant difference between mild and acute reaction groups, multivariate analysis was used to detect independent risk factors from those related. A total of 16 medical and laboratory indexes were included to examine, i.e., gender, age, smoking history, primary site, history of hypotension and diabetes, treatment modalities, dose, T (tumor) staging, N (reginal lymph node) staging, as well as hemoglobin value (1 week before radiotherapy). Relevant data used for the study were collected from clinical records.Results Total of 93 subjects completed radiotherapy. Acute mucositis occurred in 75 patients, and 27 cases developed acute radiation dermatitis. Smoking history, post-operative radiotherapy, concurrent chemotherapy, T staging, N staging, total dose (Gy) for GTV, single fraction dose (Gy) for GTV, and hemoglobin value (1 week before radiotherapy) showed significant differences between G0~G1 and G2~G4 groups of oral mucosa reaction; significant differences between mild and acute dermatitis reaction groups were found in diabetes history, hemoglobin value, age, total dose (Gy). Multivariate analysis showed that higher hemoglobin value ( OR = 1.120, P = 0.031), smoking history ( OR = 0.070, P = 0.031) were independent risk factor of acute OM; significant relationships for acute skin reaction were found with hemoglobin value ( OR = 1.059, P = 0.034) and older age ( OR = 1.068, P = 0.036).Conclusion Multivariate analysis showed higher hemoglobin value and smoking history to be the most relevant factors independently predicting grades 2 or higher OM; higher hemoglobin value and older age were found to be significantly associated with acute skin reaction.

INTERPARTIAL BOAT CONTINUATION- THE NOSLOVAN CITY HOUSE AT THE END OCTOBER 1917

In article interparty opposition in the Ekaterinoslav City Council concerning events 24 - on October, 25th, 1917 in Petrograd is considered and analyzed. In Ekaterinoslav, as well as on all country, overthrow of Provisional government and coming to power of Bolsheviks in Petrograd has caused an acute reaction of party-political forces of a city. The City Council became one of places of their opposition. Collision in its walls of different party-political forces on this question was inevitable. The selected works on August, 13th, 1917 city self-management of Ekaterinoslav have been generated mainly under party lists and was most completely displayed party-political sympathies of electorate of the provincial centre. By this criterion members of the City Council approximately have been half presented by moderate socialist parties, on the one fifth Bolsheviks and on one third conservative figures. In this situation party-political forces a City Council position in an estimation of events 24 - on October, 25th, 1917 in Petrograd it was predicted, as have confirmed sessions on October, 26th and 27.Attracts attention the first day of session of the City Council, devoted basically to the informing on occurring events. It is indicative that from 12 Bolsheviks present at this session (it is more than half of all fraction) nobody has acted. We weed fights on this point in question there was a session on October, 27th. As one would expect, only the lecturer from Bolsheviks has completely supported and has approved events in Petrograd, moderate socialists, cadets, the Jewish fraction have opposed, condemning actions of Bolsheviks, calling for Constituent assembly protection, creation of the homogeneous socialist government and a unification of forces of revolutionary democracy. From the offered resolutions, which have been taken out on voting, the majority was received by the resolution of Mensheviks and Socialists-revolutionaries. The analysis of interparty opposition in the Ekaterinoslav City Council in the end of October, 1917 at regional level of the large provincial industrial centre confirms the basic laws and tendencies which were showed in development of revolutionary process in Russia in the autumn of 1917, in a sharp aggravation of a general-political situation in the country.

ALLERGIC ALVEOLITIS

Allergic alveolitis (AA) is a group of diseases with an immunologic background evoked by chronic antigen inhalation. The diagnosis is difficult due to the diversity and non-specific character of symptoms and different clinical severity. AA is the third most often interstitial-lung-disease, comprising 4−15% of all interstitial diseases. It’s often related to professional exposure. Farmer’s lung, a hypersensitivity pneumonitis is the most common AA. By binding precipitins to form immunologic complexes, antigens trigger an early phase acute reaction in the lung tissue thus initiating disease’s progression. In the chronic phase endolobular fibrosis located in the upper lobes prevails. Disease differs in course depending the type and time of antigen exposition. Thus, avoiding antigen exposition is the first-line-therapy. Acute form is characterized by fever, chills, dyspnea, and cough. It usually starts 4-8 hours after intensive exposure. Early diagnosis leads to a good prognosis. When the exposition to the antigen stops, acute form of AA usually self-limits within 24−48 hours. Only in severe cases 0.5−1.0 mg/kg/d (up 60 mg/d) can be required for 1−2 weeks with a subsequent dose reduction. Long-term usually leads to chronic form with more serious deteriorations, including severe dyspnea and chronic cough (it takes months-years for them to develop, however). There is no effective therapy, in rapidly progressing cases 40−60 mg/g of prednisone repeated in 4-week-cycles can be recommended. Usually it does not stop the progression, and pulmonary fibrosis followed by respiratory insufficiency develop. Symptoms duration at diagnosis and effectiveness of antigen elimination are the known prognostic factors.

Immunofluorescent microscopy in patients with IgA nephropathy

The aim of the study was to evaluate relations between the deposition of IgA, IgG, IgM, C3, C1q and baseline clinical features and pathological findings.According to exclusion criteria, 72 patients with diagnosed primary IgAN who were biopsied from 2015 to 2017 in the district of the Minsk city, Belarus were included for retrospective analysis. All biopsy had to be reviewed according to the Oxford classification (MEST-C). We examined the immunofluorescence staining with antibodies against IgG, IgA, IgM, C3, C1q.Mean age was 32 (26; 42.5) years, 72.2% was men, 48.6% of the patients had arterial hypertension. Median of proteinuria was 870 (355; 1420) mg/day, 8.4% of the patients had isolated hematuria, serum creatinine – 104 (89; 126.5) µmol/l.The patients with 3+ IgA deposits showed a significantly higher percentage of crescents (C1-2) than those with 2+ IgA deposits (p = 0.028). The presence of C3 deposits showed a gradual increase in the percentage of endothelial proliferation (E1) (p = 0.007). The degree of IgA deposits showed a significant negative relation to the IgM deposits (p = 0.01) and a positive relation to the C3 deposits (p = 0.001).We found that the intensity of IgA and C3 deposits is associated with histopathology markers of the acute reaction (C1-2 and E1) according to the Oxford classification. At the same time, the appearance of the IgM deposits testifies the acute phase of the disease as well as the advanced sclerotic stage in some patients.