Abnormal hip bone morphologies are associated with various diseases of the hip joint. Weight bearing, especially during growth, may be important to achieve normal acetabulum development. This study aimed to investigate whether hip bone morphologies were affected by hindlimb suspension (HS) in 4 week-old rats. In HS groups, tail suspension was applied for 0, 2, 4, and 8 weeks. Age-matched rats were used as controls. The complex of hip bones with lumbar and sacral vertebrae were assessed based on morphological indexes using three-dimensional reconstructed images from X-ray computed tomography. Acetabular widths (measured from cranial to caudal) unchanged and depths became larger in both groups with age. Acetabular lengths (from the ventral side to the dorsal side) became larger in control groups but unchanged in HS groups with age. In HS groups, acetabular width, length, and depths were smaller than the control groups at 4 and/or 8 weeks. Acetabular versions became enlarged (rotated inwards) with age in both groups, although this was particularly pronounced in HS groups. Histologically, triradiate cartilage layers in the acetabulum were thinner with age and almost disappeared at 8 weeks in both groups. However, HS decreased Safranin O staining and prolonged the presence of hypertrophic chondrocyte indicating alterations in the chondral ossification processes. Iliac wing angles remained unchanged and anterior superior iliac crest (ASIC) distances increased with age in controls. In contrast, HS groups showed narrowed iliac wing angles with small ASIC distances. These results suggest that reduced mechanical loading during growth can interfere with hip joint formation. Keywords Hindlimb suspension, Hip joint, Acetabular morphology, Triradiate cartilage.

• MeSH
• Acetabulum diagnostic imaging   growth & development   MeSH
• Rats MeSH
• Rats, Sprague-Dawley MeSH
• Hindlimb Suspension * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways. METHODS: A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review. RESULTS: We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development. CONCLUSIONS: Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.

• MeSH
• Pain MeSH
• Mechanotransduction, Cellular * physiology   MeSH
• Migraine Disorders * diagnosis   MeSH
• Nociception physiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Systematic Review MeSH

The acidic tumor microenvironment (TME) of pancreatic cancer affects the physiological function of pancreatic stellate cells (PSCs), which in turn promotes cancer progression. Acid-sensing ion channel 1a (ASIC1a) is responsible for acidosis-related physiopathological processes. In this study, we investigated the effect of acid exposure on the activation and autophagy of PSCs, and the role of ASIC1a in these events. The results showed that acidic medium upregulated the expression of ASIC1a, induced PSCs activation and autophagy, which can be suppressed by inhibiting ASIC1a using PcTx1 or ASIC1a knockdown, suggesting that ASIC1a involves these two processes. In addition, the acid-induced activation of PSCs was impaired after the application of autophagy inhibitor alone or in combination with ASIC1a siRNA, meaning a connection between autophagy and activation. Collectively, our study provides evidence for the involvement of ASIC1a in the acid-caused PSCs activation, which may be associated with autophagy induction.

• MeSH
• Autophagy MeSH
• Acid Sensing Ion Channels * genetics   metabolism   MeSH
• Rats MeSH
• Pancreatic Stellate Cells * metabolism   MeSH
• Rats, Sprague-Dawley MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Stray radiation produced by ultra-high dose-rates (UHDR) proton pencil beams is characterized using ASIC-chip semiconductor pixel detectors. A proton pencil beam with an energy of 220 MeV was utilized to deliver dose rates (DR) ranging from conventional radiotherapy DRs up to 270 Gy/s. A MiniPIX Timepix3 detector equipped with a silicon sensor and integrated readout electronics was used. The chip-sensor assembly and chipboard on water-equivalent backing were detached and immersed in the water-phantom. The deposited energy, particle flux, DR, and the linear energy transfer (LET(Si)) spectra were measured in the silicon sensor at different positions both laterally, at different depths, and behind the Bragg peak. At low-intensity beams, the detector is operated in the event-by-event data-driven mode for high-resolution spectral tracking of individual particles. This technique provides precise energy loss response and LET(Si) spectra with radiation field composition resolving power. At higher beam intensities a rescaling of LET(Si) can be performed as the distribution of the LET(Si) spectra exhibits the same characteristics regardless of the delivered DR. The integrated deposited energy and the absorbed dose can be thus measured in a wide range. A linear response of measured absorbed dose was obtained by gradually increasing the delivered DR to reach UHDR beams. Particle tracking of scattered radiation in data-driven mode could be performed at DRs up to 0.27 Gy/s. In integrated mode, the saturation limits were not reached at the measured out-of-field locations up to the delivered DR of over 270 Gy/s. A good agreement was found between measured and simulated absorbed doses.

• MeSH
• Silicon MeSH
• Linear Energy Transfer MeSH
• Proton Therapy * methods   MeSH
• Protons MeSH
• Radiometry * methods   MeSH
• Water MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Cardiovascular Diseases MeSH
• Heart Diseases MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• kardiologie

Počas gastroezofágového refluxu (GER) dochádza k výraznému poklesu pH v lumen pažeráka. V úrovniach nervových zakončení sliznice pažeráka je ale vďaka jej bariérovej funkcii pH oveľa vyššie (pH 5,5–6,5). Napriek tomu, že bariérová funkcia sliznice je pri pažerákovej refluxovej chorobe (GERD) čiastočne porušená, dostatočne zabraňuje difúzii kyseliny do tkaniva a nedochádza k následnej deštrukcii buniek. Predpokladá sa, že pažerákové nociceptívne neuróny, ktoré sprostredkujú bolesť a pyrózu, exprimujú receptory vysoko senzitívne na kyselinu, a sú teda stimulované už pri miernom poklese pH. V recentných modelových štúdiách na morčatách sme dokázali, že už slabá kyselina (pH 5,5–6,5) môže masívne stimulovať spinálne nociceptívne C-vlákna. V súlade s týmto pozorovaním sme pomocou génovej analýzy zistili, že pažerákové aferentné nervové vlákna redundantne exprimujú viaceré receptory, ktoré sú vysoko citlivé na kyselinu. Identifikovali sme iónové kanály citlivé na kyselinu (ASICs – acid sensing ion channels), receptory spriahnuté s G-proteínom reagujúce na kyselinu (OGR1 – proton sensing G-protein coupled receptor) a TASK1 zo skupiny drasíkových kanálov zo skupiny K2P. Vysoká vnímavosť nociceptívnych nervov na kyselinu pri oslabenej báriérovej funkcii sliznice (napr. pri GERD) prispieva k vzniku ezofágových senzácií, ako je pyróza a bolesť pažerákového pôvodu. Receptory, ktoré sprostredkúvajú citlivosť na kyselinu, môžu v budúcnosti slúžiť ako nové terapeutické ciele pre aditívnu alebo alternatívnu liečbu k antisekrečnej liečbe.

The pH in the esophageal lumen can be very low (pH 1) during acidic reflux. However, the pH in the esophageal mucosa where the esophageal afferent nerves terminate is predicted to be much higher (pH 5.5–6.5). This is because the esophageal mucosal barrier, even when reduced in gastroesophageal reflux disease, still prevents most acid from diffusing into the esophageal tissue and causing widespread cellular death. It has therefore been predicted that the esophageal nociceptive (pain- and heartburn-mediating) nerves are stimulated by modest acid (pH 5.5–6.5) and express highly sensitive acid receptors. Recent studies in a guinea pig model demonstrated that weak acid (pH 5.5–6.5) robustly stimulates esophageal spinal nociceptive C-fibers. Consistent with this observation, gene expression analysis revealed that esophageal C-fibers redundantly express multiple acid sensing ion channels (ASICs), proton-sensing G-protein coupled receptor OGR1, and the highly acid sensitive two-pore-domain (K2P) TASK1-family potassium channel. The high acid sensitivity of esophageal nociceptive nerves contributes to heartburn and pain in conditions of reduced mucosal barrier function (e. g. GERD), suggesting that the receptors mediating this high acid sensitivity could be targeted by novel drugs as a combinatorial therapy with, or an alternative to acid suppression.

• MeSH
• Afferent Pathways MeSH
• Esophagus * innervation   metabolism   MeSH
• Gastroesophageal Reflux * physiopathology   MeSH
• Acid Sensing Ion Channels * MeSH
• TRPV Cation Channels MeSH
• Hydrogen-Ion Concentration MeSH
• Humans MeSH
• Neurons, Afferent MeSH
• Nociceptors MeSH
• Heartburn physiopathology   MeSH
• Esophageal Mucosa innervation   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Integrovat žáky se speciálními vzdělávacími potřebami do hodin školní tělesné výchovy je proces, který naráží na mnoho postojových a architektonických barier, který se neobejde bez kvalitně připravených pedagogických pracovníků a podpůrných systémů. Jednou z možností jak zajistit budoucím učitelům tělesné výchovy (TV) adekvátní kompetence, potřebné k úspěšné práci s osobami se zdravotním postižením (ZP), je zařazení předmětů z oblasti aplikovaných pohybových aktivit/aplikované tělesné výchovy (APA/ATV) do kurikul studijních oborů učitelství tělesné výchovy. Cílem tohoto výstupu je analýza nabídky předmětů z oblasti APA/ATV pro studenty bakalářských a navazujících magisterských tělovýchovných oborů. Výsledky této analýzy naznačují, že oblasti aplikovaných pohybových aktivit, není ve studiu tělovýchovných oborů na českých vysokých školách, věnován dostatečný prostor, potřebný pro zabezpečení integrovaného prostředí ve výukovém procesu na základních a středních školách.

BACKGROUND: The inclusion of students with special educational needs is a process, which faces many challenges. An essentia l condition for the success of inclusion is the competence of physical educators. We suggest that it is necessary to establish courses focused on adapted physical ac tivity as part of the university education for physical education (PE) teachers. OBJECTIVES: The aim of this study is to analyze courses focuse d on adapted phy sical activity within teacher preparation programs. METHODS: We conducted quantitative and qualitative content an alysis of subjects which was focused on adapted physical acti vity at selected public uni- versities in t he Czech Republic. In total, subjects from the six faculties met the conditions. RESULTS: The results show the lack of emphasis for this are a in the current PE teacher preparations programs, which is one of b asic requirements for success of the inclusion process.

• Keywords
• inkluze, integrace, učitel tělesné výchovy, žák, zdravotní postižení,
• MeSH
• Child MeSH
• Curriculum MeSH
• Humans MeSH
• Motor Activity MeSH
• Persons with Disabilities education   MeSH
• Social Isolation MeSH
• Education, Special * methods   manpower   MeSH
• Physical Education and Training * MeSH
• Check Tag
• Child MeSH
• Humans MeSH

Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a nonselective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 oC). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does not require an intact cell, as capsaicin-induced currents were also inhibited in the excised outside-out configuration. The antagonism of the capsaicin and proton action on native TRPV1 by MCS-18 may be of interest for pain therapy.

• MeSH
• Acrolein analogs & derivatives   pharmacology   MeSH
• Biological Products pharmacology   MeSH
• Pain drug therapy   metabolism   MeSH
• Financing, Organized MeSH
• Helleborus MeSH
• Capsaicin metabolism   MeSH
• TRPV Cation Channels antagonists & inhibitors   metabolism   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Acids pharmacology   MeSH
• Membrane Potentials drug effects   MeSH
• Patch-Clamp Techniques MeSH
• Sensory Receptor Cells cytology   metabolism   drug effects   MeSH
• Ganglia, Spinal cytology   MeSH
• Calcium metabolism   MeSH
• Hot Temperature MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH

• MeSH
• Analgesia MeSH
• Pain diagnosis   drug therapy   MeSH
• Treatment Outcome MeSH
• Publication type
• Congress MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• anesteziologie a intenzivní lékařství