Sub-second periodicity in a fast radio burst.

Fast radio bursts (FRBs) are millisecond-duration flashes of radio waves that are visible at distances of billions of light years1. The nature of their progenitors and their emission mechanism remain open astrophysical questions2. Here we report the detection of the multicomponent FRB 20191221A and the identification of a periodic separation of 216.8(1) ms between its components, with a significance of 6.5σ. The long (roughly 3 s) duration and nine or more components forming the pulse profile make this source an outlier in the FRB population. Such short periodicity provides strong evidence for a neutron-star origin of the event. Moreover, our detection favours emission arising from the neutron-star magnetosphere3,4, as opposed to emission regions located further away from the star, as predicted by some models5.

Pendrin stimulates a chloride absorption pathway to increase CFTR-mediated chloride secretion from Cystic Fibrosis airway epithelia.

Cystic Fibrosis (CF), an inherited multi-system disease, is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that disrupt its ability to secrete anions from epithelia. Recovery of functional anion secretion may be curative for CF, so different components of the ion transport machinery have become attractive therapeutic targets. Several members of the SLC26 ion transporter family have been linked to epithelial ion flux, some through putative functional interactions with CFTR. Using a small-scale qPCR screen, we confirmed that the anion transporter SLC26A4 (pendrin) is downregulated in CF. Upregulation of pendrin using interleukins IL-4 or IL-13 increased Cl- secretion through CFTR in human bronchial epithelial cell (HBEC) derived epithelia differentiated in vitro and measured in the Ussing Chamber. Inhibition or knockdown of pendrin prevented this increased secretion. Increased CFTR activity was not driven by increases in CFTR protein or upstream regulatory pathway components. When basolateral Cl- absorption through NKCC1 was inhibited, a pendrin-dependent Cl- absorption pathway allowing CFTR to continue secreting Cl- from the epithelium was revealed. Although CFTR is often considered the bottleneck in the transepithelial Cl- transport pathway, these studies indicate that basolateral Cl- permeability becomes limiting as CFTR activity increases. Therefore, an increase of epithelial Cl- absorption via pendrin might have additional therapeutic benefit in combination with CFTR modulators.

Reduced level of synapsin I protein in the rat striatum after intraventricular administration of proteasome inhibitors: preliminary studies.

BACKGROUND: We have recently described changes present in nigrostriatal terminals after intraperitoneal administration of MG-132 and changes that occur in the walls of the rat lateral ventricle after intraventricular administration of MG-132, lactacystin and epoxomicin - different classes of proteasome inhibitors. Substances that inhibit ubiquitin-proteasome system (UPS) activity, are intensively studied due to their potential role as novel therapeutic strategies in the treatment of cancer and ischaemia-reperfusion injury in the brain. The aim of this study is to determine the influence of intraventricular administration of MG-132, lactacystin and epoxomicin on the level in the rat striatum synapsin I - one of the most prominent neuron-specific phosphoproteins in the brain. MATERIALS AND METHODS AND RESULTS: Two weeks after administration of studied proteasome inhibitors, substantial reduction (up to 80%) of synapsin I was ob-served in the rat striatum. Because neurons, and especially dopaminergic ones, are sensitive to the depletion of proteasome function, we assume that observed synapsin I decrease may reflect changes in population of striatal neurons and/or nigrostriatal terminals. CONCLUSIONS: Understanding of cellular mechanisms standing behind our findings needs further studies, and could provide valuable contribution to the discussion on the mechanisms linking UPS inhibition and survival of neurons.

The Reference Level of Serum S-100B Protein for Poor Prognosis in Patients with Intracranial Extracerebral Hematoma.

BACKGROUND: S-100B protein, blood-brain barrier permeability marker, is one of a few biochemical indicators useful in the evaluation of traumatic brain injury. Our aim was to correlate serum concentration of S-100B with clinical condition and CT head scan findings as well as to estimate the level of the protein significant for clinical outcome prediction. METHODS: The cohort of 41 subjects underwent clinical examination by the neurosurgeon, consciousness was evaluated with Glasgow Coma Scale (GCS). Diagnosis was established on the basis of CT head scans. Venous blood samples were collected before surgery. Serum concentration of S-100B protein was estimated using electrochemiluminesce immunoassays (ECLIA) on Cobas 6000 Analyzer (Roche Diagnostics). Clinical outcome was measured applying Glasgow Outcome Scale (GOS). Finally, data were analyzed with Statistica, v. 8.0 (StatSoft, Inc. 2007). RESULTS: The average S-100B concentration was 0.95 ± 1.75 µg/L. Statistical analysis revealed significant correlation between S-100B and GCS, GOS and dimers-D concentration (p<0.001, Spearman correlation test). There were statistically significant differences in the S-100B concentration depending on the presence of brain oedema (1.29±2.02 vs. 0.06±0.03; p<0.01, Mann-Whitney test) or contusion foci (1.37±1.77 vs. 0.72±1.92; p<0.01) in CT scans. The S-100B concentration of 0.288 µg/L was determined as a cut-off point for unfavorable clinical outcome prediction (ROC, p<0.001). CONCLUSIONS: Association between serum S-100B concentration and clinical, radiological or laboratory findings prove its usefulness as a diagnostic marker for assessment of brain trauma severity. The concentration of the protein >0.288 µg/L is associated with poor prognosis.

[Rare case of the cervical vagal neurinoma]. / Rzadki przypadek nerwiaka odcinka szyjnego nerwu blednego.

Neurinoma is the most common tumor of the neurogenic origin. Primary location in the neck with the vagal nerve as a source is very rare clinical situation (less than 100 cases published in the literature). The authors would like to present a case of 35 old men with vagal neurinoma. Main symptoms included painless neck tumor found on palpation. Differential diagnosis included the pedicled cyst and metastatic neck mass. The ultrasound picture was unclear. The intraoperative findings suggested the tumor arising from the vagal nerve. In first day after the surgery hoarseness appeared with paresis of the right vocal cord in the examination. The final histological evaluation revealed neurinoma.

Fluoride alters type I collagen expression in the early stages of odontogenesis.

Fluoride alters the expression and post-translational modifications of extracellular matrix proteins in dentin. The aim of our study was to determine the effects of fluoride on type I collagen expression during the early stages of tooth germ development in rats. Pregnant dams were divided into three groups and fed a standard diet. From the fifth day of pregnancy the three groups received tap water with, respectively, trace amounts of fluoride (C), a low fluoride concentration (FL) or and a high fluoride concentration (FH). Changes in type I collagen expression and distribution were evaluated. The expression of type I collagen was restricted to the extracellular spaces of cells of mesenchymal origin. In the youngest animals the most intense immunoreactivity for type I collagen was detected in predentin of the FL group. Although the intensity of immunostaining increased in proportion to the age of the animals, the largest increase in the groups investigated was detected in the FL group. We concluded that a low concentration of fluoride can act as a stimulator of type I collagen deposition in the extracellular matrix of dentin, while high concentrations of fluoride have an opposite effect, acting as an inhibitor of type I collagen formation in dentin.

TATA-binding protein (TBP)-like factor (TLF) is a functional regulator of transcription: reciprocal regulation of the neurofibromatosis type 1 and c-fos genes by TLF/TRF2 and TBP.

The lack of direct targets for TATA-binding protein (TBP)-like factors (TLFs) confounds the understanding of their role in gene expression. Here we report that human TLF (also called TBP-related factor 2 [TRF2]) activates a number of different genes, including the neurofibromatosis type 1 (NF1) gene. The overexpression of TLF increases the amount of NF1 mRNA in cells. In vivo, TLF binds to and upregulates transcription from a fragment of the NF1 promoter. In vitro, purified TLF-TFIIA binds directly to the same NF1 promoter fragment that is required for TLF responsiveness in cells. Furthermore, targeted deletion of TLF in mice reduces NF1 levels. In contrast, TLF inhibits transcription driven by a fragment from the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription. We conclude that TLF is a functional regulator of transcription with targets distinct from those of TBP.

[The Lublanska classification of precancerous lesions of the larynx]. / Klasyfikacja Lublanska stanów przedrakowych krtani.

Laryngeal carcinomas are preceded by precancerous lesions in about 20% of cases. The macroscopical appearance of these lesions is not enough characteristic to define their malignant potential. The accurate identification of epithelial abnormalities of the laryngeal mucosa requires biopsy and microscopic evaluation. There are many histological classifications of laryngeal precancerous lesions used at present. Many of them are highly subjective and have low reproducibility. Moreover, the different grades of these classifications not always give distinct guidelines for clinician concerning the treatment modality. The Ljubljana classification seems to be easier, more readily applied and more reproducible. It uses the name "epithelial hyperplastic laryngeal lesion" (EHLL) which includes all alterations in laryngeal squamous epithelium. The four grades of EHLL are: 1. simple hyperplasia (thickening of epithelium due to augmentation of normal prickle cells), 2. abnormal hyperplasia (with increase of basal-like cells), 3. atypical, or risky hyperplasia (epithelium thickened by increase of basal-like cells with pronounced atypical features), and 4. carcinoma in situ (i.e. full thickness change with the features of malignancy but without stromal invasion). The criteria of Ljubljana classification are precise and gives a possibility to make a more clear-cut separation of cases with risk of developing carcinoma from those without it.

[Diagnostic problems in a rapid course of Wegener's disease with sudden sensorineural hearing loss]. / Trudnosci diagnostyczne w przypadku choroby Wegenera o gwaltownym przebiegu z objawami usznymi.

A rapid course of Wegener's disease with a sudden sensorineural hearing loss was described. The definitive diagnosis was established post mortem.

[Primary malignant melanoma of the larynx]. / Pierwotny czerniak zlosliwy krtani.

Primary malignant melanoma of the larynx is very rare. The case of larynx malignant melanoma in 71-years old men is presented. Hoarseness was the main complaint that encouraged the patient to visit a doctor. The patient was heavy smoker, he had been smoking 40 cigarettes for the last 50 years. He used to drink about 200 ml of pure alcohol per day. In the direct laryngoscopy gluish had cyanotic tumor, extending to the true vocal cord, ventricle, ventricle fold and subglottic space was seen. Enlarged cervical lymph nodes, laterally to the main vessels were found both in palpation and in US examination. Total laryngectomy and neck dissection was performed. The histological examination of surgical specimen revealed; Malignant melanoma. Metastases in the lymph nodes. Neoplastic infiltration of the nodal capsule. The patient was admitted to the complementary radiotherapy. At the moment the follow up in outpatient. The article contains the review of literature concerning the diagnosis, treatment and prognosis in cases of laryngeal malignant melanoma.

[The role of PKC isoforms in tumorigenicity and apoptotic cell death]. / Rola izoform PKC w nowotworzeniu i apoptotycznej smierci komórek.

Protein kinase C comprises a family of at least 13 distinct serine/threonine kinase isoenzymes that have important actions in transmembrane signal transduction pathways and have been reported to regulate cell proliferation, differentiation, cell-to-cell interaction, cytoskeletal functions, gene transcription, apoptosis and drug resistance. The results of investigations show differential redistribution isoenzymes in each organ and their specific activity in determined diseases.

[TNF-alpha binding ability as a sign of peripheral blood neutrophils preactivation in the course of multiple sclerosis]. / Zdolnosc do wiazania czynnika martwicy nowotworu--alpha przez neutrofile krwi obwodowej chorych na stwardnienie rozsiane.

Usually neglected is the role of neutrophils in causing of immunological disturbances in patients with multiple sclerosis (MS). Nevertheless, it has been indicated over the recent years that these cells possess a sufficient potential to affect both immune response and inflammation. This potential may result in MS through the process of priming of these cells by proinflammatory cytokines like TNF. We studied TNF and its soluble receptors sp55 and sp75 serum levels and binding of fluorescein isothiocyanate (FITC)-stained TNF by neutrophils. We studied three different groups of MS patients: 10 patients in relapse of the disease, 13 in its remission, and 11 in its chronic progressive form (CP-MS). The control was provided by 14 neurological patients (OND) with non-inflammatory diseases. The performed studies showed higher TNF sp55 and sp75 soluble TNF receptors serum levels in the patients with relapse, comparing with other MS patients and OND. TNF binding by neutrophils of MS patients during relapse was also higher, than other MS patients and OND. These result suggest the preactivation of neutrophils in the relapse of MS.

[Prognosis of the skin UV-incidence increase in Poland]. / Wzrost zachorowan na schorzenia skóry uwarunkowane oddzialywaniem promieniowania ultrafioletowego--prognoza dla Polski.

The degradation of the ozone layer causes a real menace to human health. One of the most dangerous effects is the possibility of evoking skin cancer by the intensified UV-radiation level. The authors analysed the influence of ongoing changes on the increase in skin cancer cases in Polish conditions. Following the analysis, a 16-per cent increase in morbidity can be anticipated within the next decade.

[Absorption and dispersion of ultraviolet radiation in human skin]. / Pochlanianie i rozpraszanie promieniowania ultrafioletowego na skórze czlowieka.

The study was carried out in a group composed of 48 men. The linear coefficient and linear coefficient of dispersion of ultraviolet radiation (UVR) in the skin was measured for different wavelengths. The mean values were determined for four types of the skin in both ultraviolet A (UVA) and ultraviolet B (UVB) ranges from 280 to 400 nm. The skin ability to absorb UVR decreases rapidly with decreasing wavelength. At wavelength of 280 nm, the coefficient of absorption changed within the range from 105 cm-1 (skin type II) to 160 cm-1 (skin type V), however, at wavelength of 400 nm it accounted only for 20 cm-1. A reciprocal relationship for scattering was found. The coefficient of dispersion changed within the range from 3.5 cm-1 at wavelength of 280 nm to 12 cm-1 at wavelength of 400nm. The mechanism based on absorption predominated at a shorter wave range (UVB), while at a longer range (UVA) the scattering mechanism was more efficient.

The biochemical modification of the erythrocyte membranes from women with ovarian cancer.

The aim of our work was quantitative evaluation of the protein and phospholipid fractions of mature erythrocyte membranes separated from women with ovarian cancer. Blood was sampled from 30 women with ovarian cancer, aged 24-79 years, in the third stage of clinical progression of the disease. Phospholipids were separated from membranes by Müller's acidic extraction method and analysed in thin-layer two-dimensional chromatography. On the silica gel plates nine fractions of phospholipids were separated: sphingomyelin (SPH), phosphatidylethanolamine (PE), phosphatidlyserine (PS), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidic acid (PA), phosphatidylinositol (Ptd Ins), phosphatidylinositol-4-phosphate (Ptd Ins-4-P), phosphatidylinositol-4,5-diphosphate (Ptd Ins-4,5-P2). The activity of phospholipase C in erythrocyte membranes was determined by Akhrem's spectrophotometric method. Membrane proteins were separated by polyacrylamide gel electrophoresis, SDS-PAGE. It was shown that PS, SPH, LPC and PA fractions were significantly diminished. The concentration of Ptd Ins-4-P and Ptd Ins-4,5-P2 was significantly increased with simultaneous reduction in Ptd Ins level. The inhibition of phospholipase C reached 80%. The quantitative protein evaluation showed a statistically significant decrease in spectrin and a significant increase in 4.1 protein. The quantitative changes, observed in phospholipid and protein fractions, led to the restructuring of the erythrocyte membrane cytoskeleton, which may be connected to increased susceptibility to haemolysis of red blood cells.

[An attempt of immunological monitoring of patients with laryngeal carcinoma by flow cytometry]. / Próba monitorowania immunologicznego chorych na raka krtani przy pomocy cytometrii przeplywowej.

In a group of 60 patients with surgically treated laryngeal carcinoma blood lymphocyte subsets were assessed on the day of surgery (day 0) and six weeks thereafter by means of flow cytometry. Blood cells at day 0 were also compared to tumor infiltrating lymphocytes (TIL) isolated from surgical specimens. Significant alterations were found in postoperative period as compared to day 0 manifested by the fall of B cells, increase of activated T lymphocytes and NK cells. There were also marked changes between blood cells at day 0 and TIL, evidence in rise of B cells, of activated T lymphocytes and decline of NK cells within the latter. These data suggest that the assessment of lymphocyte subsets may be of value in immunological monitoring of laryngeal carcinoma patients.

[Juvenile angiofibroma presented in the clinical materials of the Otolaryngological Department of the Academy of Medicine in Poznan in the years 1977-1993]. / Wlókniaki mlodziencze w materiale Kliniki Otolaryngologicznej Akademii Medycznej w Poznaniu w latach 1977--1993.

16 patients suffering from angiofibroma were treated in the Otolaryngological Clinic, Academy of Medicine in Poznan, in the years 1977--1993. The patients were aged from 10--36, the mean age 15. All patients were treated surgically, and the method choice was Denker's surgery. 3 patients were reoperated because of local relapse. On the bases of the described cases good results of full recovery of patients with angiofibroma treated surgically are presented.

[Metastases in the prelaryngeal (delphian) lymph nodes in the course of the laryngeal cancer]. / Przerzuty do wezlów chlonnych przedkrtaniowych (delfickich) w przebiegu raka krtani.

The metastases in the pre-laryngeal (Delphian) lymph nodes in the course of laryngeal cancer are uncommon. Between 1984 and 1994, 1573 patients with the diagnosis of laryngeal carcinoma were operated at the Department of Otolaryngology of Academy of Medicine in Poznan (Poland). Total laryngectomies were performed in 1069 cases and partial laryngectomies in 504 cases. Pre-laryngeal lymph nodes were identified in 109 patients. Histologically, metastases were found in 8 cases (7.48%). The prognosis of the patients with metastases in these lymph nodes is poor; only 2 patients are alive and free of neoplastic disease.

[Evaluation of ultraviolet radiation reflectance for human skin]. / Ocena wspólczynnika odbicia promieniowania ultrafioletowego dla skóry ludzkiej.

In a group of 20 males aged 19-20 years ultraviolet radiation reflectance of different wavelength (250-400 nm) from skin surface was measured. It was found that the reflectance increased monotonically with the decrease of wavelength. The reflectance values were compared with the coefficient of relative spectral biological effectiveness and significance of both values for evaluation of human exposure to ultraviolet radiation was discussed.