Novel mutations in the toll like receptor genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection

Toll like receptors play a central role in the recognition of pathogen associated molecular patterns (PAMPs). Mutations in TLR1, TLR2 and TLR4 genes may change the PAMP reorganization ability which causes altered responsiveness to the bacterial pathogens. A case control study, performed to assess the association between TLR gene mutations and susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP), revealed novel mutations (TLR1 - Ser150Gly and Val220Met; TLR2 - Phe670Leu) that hindered either PAMP recognition or further downstream TLR pathway activation. A cytokine expression experiments (IL-4, IL-8, IL-10, IL-12 and IFN-γ) in the challenged mutant and wild type moDCs (mocyte derived dendritic cells) confirmed the negative impact of these mutations and altered TLR downstream activation. Further In silico analysis of the TLR1 and TLR4 ectodomains (ECD) revealed the polymorphic nature of the central ECD and irregularities in the central LRR motifs. The most critical positions that may alter the pathogen recognition ability of TLR were: the 9th amino acid position in LRR motif (TLR1, LRR10) and 4th residue downstream to LRR domain (exta LRR region of TLR4). The study describes novel mutations in the TLRs and presents their association with the MAP infection

Elektrofiziološke metode u dijagnostici vrtoglavica

The role of neurophysiologic tests in the diagnostics of vertigo primarily consists of assessing the functional status of the sensory systems responsible for the concept of space. They also have a limited application in assessing the functional status of structures responsible for the integration of this information. The data obtained by neurophysiological testing are purely functional giving no information considering the etiology of the disturbance, and only point to the localization and type of the disturbance that lead to vertigo. That is why they always need to be combined with neuroradiologic, neurosonologic and laboratory tests. The brain relies on three sensory systems to maintain spatial orientation: the vestibular system (the inner ear), the visual system (the eyes), and the somatosensory system (which conveys information from the skin, joint, and muscle receptors). These three systems overlap, allowing the brain to assemble an accurate sense of spatial orientation. Information from these systems is integrated in the cerebrum and cerebellum. However, a compromised system or conflicting signals can cause vertigoUloga neurofizioloških pretraga u dijagnostici vrtoglavica primarno se sastoji u utvrđivanju funkcionalnog statusa senzornih sustava odgovornih za stvaranje koncepta prostora. Primjenjive su donekle i u određivanju stanja integrativnih neuralnih struktura, koji objedinjuju informacije dobivene iz istih senzornih sustava. Podaci dobiveni neurofiziološkim pretragama isključivo su funkcijskog karaktera i ne daju nikakvu informaciju o etiologiji poremećaja, već upućuju samo na lokalizaciju i vrstu poremećaja koji je doveo do vrtoglavice, te se uvijek moraju kombinirati s neuroradiološkim, neurosonološkim i laboratorijskim ispitivanjima. Obzirom na način stvaranja koncepta prostora u ljudskom mozgu, potencijalni generatori vrtoglavice su oči (koje prenose vidnu informaciju), unutarnje uho (koje prenosi slušnu i vestibularnu informaciju), cervikalni receptori (koji prenose proprioceptivnu informaciju), te mali i veliki mozak (čija je uloga u integraciji ovih informacija). Ovi sustavi se nadopunjavaju, omogućavajući mozgu da stvori točnu informaciju o položaju u prostoru. Neurofiziološka ispitivanja ovih struktura predstavljaju temelj neurofiziološke dijagnostike vertiginoznih smetnji

Neurološke manifestacije i osobitosti spavanja u osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a rare genetic disorder leading to skeletal fragility, fractures and deformities. The main pathophysiologic eff ect of OI is reduction in either the quality or the quantity of type I collagen, aff ecting the structures that normally contain type I collagen. COL1A1 and COL1A2 genes account for 80% of cases. Our aim was to review relevant information on the neurodevelopment, sleep issues and neurologic complications in OI. The nervous system is involved in OI because of softening of bone at the base of the skull, resulting in upwards migration of the upper cervical spine and odontoid process. The disease may directly involve neurovascular structures, leading to cavernous fi stulas, dissections, or aneurysms. The brain parenchyma can be aff ected in OI, with manifestations such as cerebral atrophy, hydrocephalus and cerebellar hypoplasia. Basilar impression/invagination are serious craniocervical junction abnormalities that can be life threatening. There is still no knowledge about sleep phenotype in OI. Neurologic manifestations and sleep disorders are valuable prognostic factors and are highly important features within the phenotypic complexity of OI. The measures of prevention in OI stress the need of regular monitoring of these issues from an early age and education of both OI patients and their families.Osteogenesis imperfecta (OI) je rijedak genetički poremećaj koji dovodi do krhkosti kostiju, prijeloma i deformiteta. Glavni patofi ziološki učinak OI je smanjenje u kvaliteti ili kvantiteti kolagena tip I te su stoga zahvaćene strukture koje normalno sadrže kolagen tip I. U 80% slučajeva postoje promjene u genima COL1A1 i COL1A2. Naš cilj je bio pretražiti relevantne podatke o neurorazvoju, spavanju i neurološkim komplikacijama u OI. Živčani sustav je zahvaćen u OI zbog omekšavanja kosti na bazi lubanje, što rezultira migracijom gornjeg dijela cervikalne kralježnice i odontoidnog procesusa. Bolest može izravno zahvatiti neurovaskularne strukture pa nastaju kavernozne fi stule, disekcije ili aneurizme. Moždani parenhim je zahvaćen u OI, s kliničkim entitetima kao što su cerebralna atrofi ja, komunicirajući hidrocefalus i cerebelarna hipoplazija. Bazilarna impresija/invaginacija su ozbiljne abnormalnosti kraniocervikalne veze i mogu biti životno ugrožavajuće. Zasad postoji vrlo malo saznanja o obrascima spavanja u OI. Neurološke komplikacije i poremećaji spavanja su korisni prognostički čimbenici i izrazito važne manifestacije unutar složenog fenotipa u OI. Mjere prevencije u OI ukazuju na potrebu redovitog praćenja ove problematike od rane dobi i edukacije bolesnika s OI i njihovih obitelji

Vrijednost refleksa treptaja u ranoj dijagnostici multiple skleroze

The aim was to determine differences of blink reflex in clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) in patients presented with symptoms and signs of brainstem impairment. The study included 20 patients diagnosed with CDMS, 20 with CIS, and 20 healthy controls. We recorded latencies of early (R1) and late component ipsilaterally (R2) and contralaterally (R2’), and occurrence of irritative component (R3). We analyzed data on sex, age, signs of brainstem impairment and magnetic resonance imaging (MRI) findings for the presence of brainstem demyelinating lesions. There was no statistically significant difference between patient groups according to sex, age, symptoms of brainstem involvement and MRI findings. There was no statistically significant difference in R1 component latencies and R2 latencies on the right side. Latencies of R2 on the left and R2’ on the right were statistically longer in CDMS group. There was no difference in the appearance of R3 component. In conclusion, blink reflex was found to be a very sensitive and useful diagnostic tool in the assessment of brainstem structures, especially because abnormalities are seen not only in CDMS but also in CIS. Slowing of the late component as a sign of dysfunction in the efferent part of the reflex arc is not very specific but is a highly sensitive finding.Cilj je bio ispitati razliku refleksa treptaja u bolesnika s dijagnozom klinički definitivne multiple skleroze (CDMS) i klinički izoliranog sindroma (CIS) koji imaju simptome i znakove oštećenja moždanog debla. Istraživanje je obuhvatilo 20 bolesnika s dijagnozom CDMS, 20 s CIS i 20 zdravih ispitanika kao kontrolna skupina. Bilježili smo latencije rane (R1) i kasne komponente ipsilateralno (R2) i kontralateralno (R2’), kao i pojavu iritativne komponente (R3). Analizirali smo spol, dob, simptome i znakove oštećenja moždanog debla, nalaz magnetske rezonancije (MR) s obzirom na prisustvo demijelinizacijskih lezija u području moždanog debla. Nije utvrđena razlika među skupinama bolesnika s obzirom na spol, dob, prisustvo simptoma oštećenja moždanog debla te nalaz MR. Nije bilo razlike u latencijama komponente R1, kao ni u latencijama R2 na desnoj strani. Latencije komponente R2 na lijevoj strani i R2’ na desnoj strani bile su statistički duže u skupini ispitanika s CDMS. Nije bilo razlike u pojavnosti komponente R3. U zaključku, refleks treptaja je vrlo osjetljiv i koristan dijagnostički alat za procjenu funkcije moždanog debla, pogotovo zbog toga što se abnormalnosti ne vide samo u CDMS, nego i u CIS. Usporenje kasne komponente kao znak disfunkcije eferentnog dijela refleksnog luka, iako nije specifičan nalaz, pokazao se kao vrlo osjetljiv nalaz

Analiza srednjih brzina krvnog protoka u bazalnim moždanim arterijama pomoću transkranijskog dopplera tijekom vidne stimulacije

Changes of mean blood flow velocities (MBFV) in the posterior cerebral arteries (PCA) during visual stimulation were recorded in a group of 51 healthy, right-handed volunteers. There were 27 (52.9%) males and 24 (47.1%) females aged from 20 to 59 (mean age 36.98) years. Measurements were performed with a hand-held 2 MHz transcranial Doppler (.I.CD) probe through temporal window, while the subjects had their eyes open, closed, and when looking at white light. In half of the subjects, the right PCA was insonated first and then the left PCA, while in the other half a reverse procedure was used. Statistical analysis was performed using Wilcoxon.s matched-pair signed-rank test. In the left PCA, MBFV was 41.2±8.6 cm/s (mean ± SD) with eyes open, 27.8±8.5 cm/s with eyes closed, and 42.3±9.1 cm/s while looking at white light. In the right PCA, MBFV was 41.7±8.9 cm/s with eyes open, 28.2±9.1 cm/s with eyes closed, and 42.4±8.8 cm/s while looking at white light. In the left PCA, differences between eyes open and closed, and between eyes open and while looking at white light were statistically significant (p<0.001, z=-6.2146, and p<0.001, z=-3.4836, respectively). In the right PCA, a statistically significant difference was found between eyes open and closed (p<0.001, z=-6.2146 and p<0.001, z=-3.6928), but not between eyes open and looking at white light (p=0.03, z=-2.1693). Study results demonstrated that straightforward visual stimulation had an effect on blood flow velocities in PCA and that it could be measured with TCD.Promjene srednjih brzina krvnog protoka (MBFV) u stražnjim moždanim arterijama (PCA) bilježene su tijekom vidne stimulacije u skupini od 51 zdravog desnorukog dobrovoljca. Skupina se sastojala od 27 (52,9%) muških i 24 (47,1%) ženskih ispitanika u dobi od 20 do 59 (srednja dob 36,98) godina. Mjerenja su se izvodila pomoću ručne sonde od 2 MHz za transkranijski Doppler (TCD) kroz temporalni prozor, dok su ispitanici oči držali otvorenima, zatvorenima i dok su gledali u bijelo svjetlo. U polovice ispitanika najprije je ispitana desna PCA, a potom lijeva PCA, a u druge polovice primijenjen je obrnuti postupak. Statistička analiza je provedena pomoću Wilcoxonova parnog rank testa. U lijevoj PCA je MBFV bila 41,2±8,6 cm/s (srednja vrijednost ± SD) uz otvorene oči, 27,8±8,5 cm/s uza zatvorene oči i 42,3±9,1 cm/s dok su gledali u bijelo svjetlo. U desnoj PCA je MBFV bila 41,7±8,9 cm/s uz otvorene oči, 28,2±9,1 cm/s uza zatvorene oči i 42,4±8,8 cm/s dok su gledali u bijelo svjetlo. Razlike u MBFV između zatvorenih i otvorenih očiju, te između otvorenih očiju i gledanja u bijelo svjetlo bile su statistički značajne za lijevu PCA (p<0,001, z=-6,2146, odnosno p<0,001, z=-3,4836). U desnoj PCA je razlika u MBFV bila statistički značajna između otvorenih i zatvorenih očiju (p<0,001, z=-6,2146, odnosno p<0,001, z=-3,6928), ali ne između otvorenih očiju i gledanja u bijelo svjetlo (p=0,03, z=-2,1693). Rezultati su pokazali da izravna vidna stimulacija utječe na brzinu krvnog protoka u PCA te da se to može mjeriti pomoću TCD

Les peuplements de millipèdes et de centipèdes résultant du type de gestion des pâturages : résultats préliminaires en République tchèque

The aim of this study was to compare distribution and assemblage structures in centipedes and millipedes in pastures with different management arrangements. The evaluated types of management included sheep grazing, mowing, mulching and various combinations of these treatments. Different foundation modes of pasture were also evaluated – commercial mixtures of fodder crops, local mixtures of seeds with different proportions of dicotyledonous herbs, and spontaneous fallow land. Despite low abundance of both centipedes and millipedes, the most positive effect observed in millipedes was in mulching due to the surplus of dead organic matter. The best way to manage pasture is to use a mixture of local seeds with a high proportion of dicotyledonous herbs as food of highe r substantiality compared to grassLe but de cette étude était de comparer la répartition et les structures des groupements de centipèdes et de millipèdes dans les pâturages en fonction de différents types de gestion. Les types de gestion évalués étaient le pâturage de moutons, le fauchage et le paillage dans diverses combinaisons. Différents modes de fondations de pâturages ont également été évalués - mélange commercial des cultures fourragères, semences locales mélangées avec des proportions différentes de plantes dicotylédones, et une jachère spontanée. Malgré la rareté des centipèdes et des millipèdes, l'effet le plus positif pour les millipèdes a été observé dans le cadre du paillage car celui-ci offre de la matière organique morte. La meilleure façon de gérer le pâturage est d'utiliser un mélange local de semences à forte proportion de plantes dicotylédones comme nourriture de qualité supérieure en comparaison du gazon