Succinate dehydrogenase (SDH), formed by four subunits SDHA, SDHB, SDHC, SDHD, and an assembly factor SDHAF2, functions as a key respiratory enzyme. Biallelic inactivation of genes encoding any of the components, almost always in the presence of a germline mutation, causes loss of function of the entire enzyme complex (so-called SDH deficiency) and subsequent development of SDH-deficient neoplasms which include pheochromocytoma/paraganglioma, gastrointestinal stromal tumor, and renal cell carcinoma (RCC). These tumors may occur in the same patient or kindred. SDH-deficient RCC shows distinctive morphological features with vacuolated eosinophilic cytoplasm due to distinctive cytoplasmatic inclusions containing flocculent material. The diagnosis is confirmed by loss of SDHB on immunohistochemistry with positive internal control. The majority of tumors occur in the setting of germline mutations in one of the SDH genes, most commonly SDHB. The prognosis is excellent for low-grade tumors but worse for high-grade tumors with high-grade nuclei, sarcomatoid change, or coagulative necrosis. Awareness of the morphological features and low-threshold for applying SDHB immunohistochemistry help identify patients with SDH-deficient RCC and hereditary SDH-deficient tumor syndromes. In this review we summarize recent development on the clinical and genetic features, diagnostic approach, and pitfalls of SDH-deficient syndrome, focusing on SDH-deficient renal cell carcinomas.

• MeSH
• Neoplastic Syndromes, Hereditary * genetics   MeSH
• Carcinoma, Renal Cell * genetics   MeSH
• Humans MeSH
• Kidney Neoplasms * genetics   pathology   MeSH
• Sarcoma * MeSH
• Succinate Dehydrogenase genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Complex II (CII) activity controls phenomena that require crosstalk between metabolism and signaling, including neurodegeneration, cancer metabolism, immune activation, and ischemia-reperfusion injury. CII activity can be regulated at the level of assembly, a process that leverages metastable assembly intermediates. The nature of these intermediates and how CII subunits transfer between metastable complexes remains unclear. In this work, we identify metastable species containing the SDHA subunit and its assembly factors, and we assign a preferred temporal sequence of appearance of these species during CII assembly. Structures of two species show that the assembly factors undergo disordered-to-ordered transitions without the appearance of significant secondary structure. The findings identify that intrinsically disordered regions are critical in regulating CII assembly, an observation that has implications for the control of assembly in other biomolecular complexes.

• MeSH
• Catalytic Domain * MeSH
• Protein Structure, Secondary MeSH
• Publication type
• Journal Article MeSH

Po 10 rokoch vychádza dôkladne prepracované a rozšírené vydanie vysokoškolskej učebnice. Kolektív 20 slovenských klinických psychológov podáva erudovaný prehľad o súčasnom stave výskumu a klinickej praxe tejto oblasti aplikovanej psychológie. V jednotlivých kapitolách všeobecnej časti sa zaoberá históriou, predmetom a metodológiou klinickej psychológie, ako vo výskume, tak v prístupe k jednotlivému klientovi. Definuje problém normality duševného zdravia, rozoberá príčiny psychických a psychosomatických porúch a analyzuje ich zvláštnosti v jednotlivých vývinových obdobiach. V špeciálnej časti je každá kapitola venovaná inej oblasti psychických porúch (úzkostné poruchy, poruchy osobnosti, schizofrénne psychózy, afektívne poruchy, poruchy príjmu potravy). Osobitne sa venuje jednotlivým psychosomatickým ochoreniam (srdcovocievne, dýchacie, interné, onkologické ochorenia) a psychológii ľudí s rôznymi postihnutiami (poruchy zraku, sluchu, komunikácie, mentálne postihnutia). Zvláštny dôraz je kladený na poruchy detského vývinu i klinickú problematiku vyššieho veku. Samostatné kapitoly sú venované neuropsychológii (diagnostike a rehabilitácii poškodenia mozgu) a psychologickej sexuológii. Nová je kapitola o psychofarmakológii, ktorá mapuje súčasný stav tejto oblasti terapie duševných porúch. Kniha je určená nielen na pre- a postgraduálne vzdelávanie klinických psychológov, ale aj odborníkom z viacerých medicínskych odvetví a v neposlednej rade vzdelaným laikom so záujmom o problematiku duševného zdravia.

• Conspectus
• Psychologie

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

• MeSH
• Adult MeSH
• Hyperplasia MeSH
• Immunohistochemistry MeSH
• Carcinoma, Renal Cell * genetics   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Kidney Neoplasms * genetics   pathology   MeSH
• Necrosis MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Succinate Dehydrogenase genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Publikace se zaměřuje na hippoterapii a dějiny České hiporehabilitační společnosti. Vydáno při příležitosti 30. výročí založení společnosti. Určeno široké veřejnosti.; Publikace vzniklá ke 30. výročí založení České hiporehabilitační společnosti

• MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Organizations history   MeSH
• Persons with Disabilities MeSH
• Human-Animal Bond MeSH
• Equine-Assisted Therapy history   MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Publication type
• Pictorial Work MeSH
• Popular Work MeSH
• Ephemera MeSH
• Geographicals
• Czech Republic MeSH

• Conspectus
• Fyzioterapie. Psychoterapie. Alternativní lékařství
• NML Fields
• dějiny lékařství
• rehabilitační a fyzikální medicína
• psychoterapie

• About
• Česká hiporehabilitační společnost Authority

S pacientmi po lumbálnej punkcii a po neuroaxiálnej anestézii sa stretávame naprieč mnohými odbormi. Medzi najčastejšie komplikácie daných výkonov patrí postpunkčná cefalea, pričom subdurálny hematóm patrí medzi ich zriedkavé komplikácie s možným závažným až letálnym dopadom. Vzhľadom na rovnakú, resp. podobnú manifestáciu týchto dvoch diagnóz môže dôjsť často k oneskorenému rozpoznaniu SDH a jeho liečbe, eventuálne aj k jeho prehliadnutiu. Na túto diagnózu treba pomýšľať pri prolongovaných bolestiach hlavy nereagujúcich na klasickú analgetickú liečbu, pri strate väzby na ortostatickú polohu, prípadne pri pridružených parézach hlavových nervov či poruche vedomia. Nasledujúci článok dokumentuje kazuistiku bilaterálneho subdurálneho hematómu po epidurálnej pôrodnej analgézii a poskytuje literárny prehľad o danej problematike.

We come across with patients after lumbar puncture and neuraxial anesthesia athwart many disciplines. Among the most frequent complications of these procedures are post-operative cephalea, whereas subdural hematoma is one of its rarest complications with a potentially severe or even lethal impact. Given the same resp. a similar manifestation of the two diagnoses there may often be a delay in the recognition of SDH and its treatment, eventually to its overlooking. This diagnosis should be considered with prolonged headaches unresponsive to classical analgesic treatment, loss of binding to the orthostatic position, prospectively associated paresis of the cranial nerves or consciousness disorder. The following article documents the case study of bilateral subdural hematoma following epidural birth analgesia and provides a literally overview of the issue concerned.

• MeSH
• Headache etiology   MeSH
• Adult MeSH
• Anesthesia, Epidural * adverse effects   MeSH
• Humans MeSH
• Neuroimaging methods   MeSH
• Anesthesia, Obstetrical adverse effects   MeSH
• Hematoma, Subdural * diagnosis   etiology   therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Zastavení nebo zpomalení rentgenové progrese u pacientů s ankylozující spondylitidou (AS) patří k jednomu z důležitých cílů léčby. Bylo prokázáno, že sekukinumab zpomaluje u pacientů s AS rentgenovou progresi během čtyř let podávání. Také u adalimumabu bylo zjištěno, že při dlouhodobém podávání dochází ke zpomalení vývoje radiografických změn. Biosimilární adalimumab GP2017 (SDZ‑ADL) byl Evropskou lékovou agenturou schválen v červnu 2018 pro léčbu stejných indikací, pro které je schválen originální adalimumab, včetně AS. Dosud nebylo provedeno přímé srovnání působení přípravků s inhibitory IL‑17 a anti‑TNFα na rozvoj radiografických změn. SURPASS je první prospektivní studií, která byla přímo koncipována tak, aby srovnávala jejich působení na spinální radiografickou progresi.

Cessation or slowing of radiographic progression in patients with ankylosing spondylitis (AS) is one of the important goals of the treatment. Secukinumab was proven to slow down radiographic progression in patients with AS during a 4‑year period of administration. Adalimumab was proven to slow down the progression of radiographic changes after long‑term administration as well. Adalimumab biosimilar GP2017 (SDZ‑ADL) was approved by the European Medicine Agency in June 2018 for the treatment of the same indications for which the original adalimumab was approved, including AS. So far, no direct efficacy comparison of products with IL‑17 inhibitors and anti‑TNFα on radiographic changes has been performed. SURPASS is the first prospective study designed to compare their effects on spinal radiographic progression.

• Keywords
• Cosentyx (secukinumab),
• MeSH
• Adalimumab administration & dosage   pharmacology   MeSH
• Spondylitis, Ankylosing * diagnostic imaging   drug therapy   pathology   MeSH
• Biosimilar Pharmaceuticals MeSH
• Double-Blind Method MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   pharmacology   MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Disease Progression MeSH
• Radiography methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Trial, Phase III MeSH
• Randomized Controlled Trial MeSH

• MeSH
• History, 20th Century MeSH
• Firefighters history   MeSH
• Fires prevention & control   MeSH
• Emergency Medical Services history   MeSH
• Rescue Work history   MeSH
• Check Tag
• History, 20th Century MeSH
• Geographicals
• Czech Republic MeSH
• Czechoslovakia MeSH

• Conspectus
• Veřejné zdraví a hygiena
• NML Fields
• veřejné zdravotnictví
• urgentní lékařství
• NML Publication type
• brožury

Adaptation to chronic hypoxia renders the heart more tolerant to ischemia/reperfusion injury. To evaluate changes in gene expression after adaptation to chronic hypoxia by RT-qPCR, it is essential to select suitable reference genes. In a chronically hypoxic rat model, no specific reference genes have been identified in the myocardium. This study aimed to select the best reference genes in the left (LV) and right (RV) ventricles of chronically hypoxic and normoxic rats. Sprague-Dawley rats were adapted to continuous normobaric hypoxia (CNH; 12% O2 or 10% O2) for 3 weeks. The expression levels of candidate genes were assessed by RT-qPCR. The stability of genes was evaluated by NormFinder, geNorm and BestKeeper algorithms. The best five reference genes in the LV were Top1, Nupl2, Rplp1, Ywhaz, Hprt1 for the milder CNH and Top1, Ywhaz, Sdha, Nupl2, Tomm22 for the stronger CNH. In the RV, the top five genes were Hprt1, Nupl2, Gapdh, Top1, Rplp1 for the milder CNH and Tomm22, Gapdh, Hprt1, Nupl2, Top1 for the stronger CNH. This study provides validation of reference genes in LV and RV of CNH rats and shows that suitable reference genes differ in the two ventricles and depend on experimental protocol.

• MeSH
• Chronic Disease MeSH
• Hypoxia genetics   MeSH
• Myocardium metabolism   pathology   MeSH
• Rats, Sprague-Dawley MeSH
• Reference Standards MeSH
• Gene Expression Regulation * MeSH
• Heart Ventricles metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Background: Pheochromocytoma and paraganglioma (PHEO/PGL) are rare neuroendocrine tumors which may cause potentially life-threatening complications, with about a third of cases found to harbor specific gene mutations. Thus, early diagnosis, treatment, and meticulous monitoring are of utmost importance. Because of low incidence of succinate dehydrogenase complex subunit A (SDHA)-related metastatic PHEO/PGL, currently there exists insufficient clinical information, especially with regards to its diagnostic and treatment characteristics. Methods: Ten patients with SDHA-related metastatic PHEO/PGL were followed-up prospectively and/or retrospectively between January 2010-July 2018. They underwent biochemical tests (n = 10), 123I-MIBG (n = 9) scintigraphy, and multiple whole-body positron emission tomography/computed tomography (PET/CT) scans with 68Ga-DOTATATE (n = 10), 18F-FDG (n = 10), and 18F-FDOPA (n = 6). Results: Our findings suggest that these tumors can occur early and at extra-adrenal locations, behave aggressively, and have a tendency to develop metastatic disease within a short period of time. None of our patients had a family history of PHEO/PGL, making them appear sporadic. Nine out of 10 patients showed abnormal PHEO/PGL-specific biochemical markers with predominantly noradrenergic and/or dopaminergic phenotype, suggesting their utility in diagnosing and monitoring the disease. Per patient detection rates of 68Ga-DOTATATE (n = 10/10), 18F-FDG (n = 10/10), 18F-FDOPA (n = 5/6) PET/CT, and 123I-MIBG (n = 7/9) scintigraphy were 100, 100, 83.33, and 77.77%, respectively. Five out of 7 123I-MIBG positive patients had minimal 123I-MIBG avidity or detected very few lesions compared to widespread metastatic disease on 18F-FDG PET/CT, implying that diagnosis and treatment with 123/131I-MIBG is not a good option. 68Ga-DOTATATE PET/CT was found to be superior or equal to 18F-FDG PET/CT in 7 out of 10 patients and hence, is recommended for evaluation and follow-up of these patients. All 7 out of 7 patients who received conventional therapies (chemotherapy, somatostatin analog therapy, radiation therapy, 131I-MIBG, peptide receptor radionuclide therapy) in addition to surgery showed disease progression. Conclusion: In our cohort of patients, SDHA-related metastatic PHEO/PGL followed a disease-course similar to that of SDHB-related metastatic PHEO/PGL, showing highly aggressive behavior, similar imaging and biochemical phenotypes, and suboptimal response to conventional therapies. Therefore, we recommend careful surveillance of the affected patients and a search for effective therapies.

• Publication type
• Journal Article MeSH