BACKGROUND: Advancing the retrograde microcatheter (MC) into the antegrade guide catheter during retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be challenging or impossible, preventing guidewire externalization. OBJECTIVES: To detail and evaluate all the techniques focused on wiring to achieve intubation of the distal tip of a microcatheter, balloon, or stent with an antegrade or retrograde guidewire, aiming to reduce complications by minimizing tension on fragile collaterals during externalization and enabling rapid antegrade conversion in various clinical scenarios. METHODS: We describe the two main techniques, tip-in and rendezvous, and their derivatives such a facilitated tip-in, manual MC-tip modification, tip-in the balloon, tip-in the stent, deep dive rendezvous, catch-it and antegrade microcatheter probing. We provide case studies that demonstrate the effectiveness of these techniques in complex scenarios involving extreme vessel angulation, severe calcification, fragile collaterals, and challenging retrograde MC crossing without externalization. CONCLUSION: The development of advanced variants along with traditional techniques to establish retrograde guidewire connection and antegrade conversion has led to the establishment of a cohesive group of methods known as portal techniques. These approaches serve as strategic advantages in retrograde CTO-PCI, providing a valuable and feasible alternative to conventional retrograde connection techniques, particularly when those techniques fail. Their ability to avoid the externalization process reduces potential damage to collateral channels and the ostium of the donor artery, potentially leading to a reduction in complication rates.

• MeSH
• Angioplasty, Balloon, Coronary instrumentation   adverse effects   MeSH
• Chronic Disease MeSH
• Equipment Design MeSH
• Percutaneous Coronary Intervention instrumentation   adverse effects   MeSH
• Coronary Occlusion * diagnostic imaging   therapy   physiopathology   MeSH
• Humans MeSH
• Miniaturization MeSH
• Cardiac Catheters * MeSH
• Stents * MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Bacterial resistance has become a global concern for public health agencies. Various resistance mechanisms found in Staphylococcus aureus strains grant this bacterium resistance to a wide range of antibiotics, contributing to the rise in human mortality worldwide. Resistance mediated by efflux pumps is one of the most prevalent mechanisms in multi-resistant bacteria, which has aroused the interest of several researchers in the search for possible efflux pump inhibitors. In view of the aforementioned considerations, it is important that new strategies, such as the synthesis of chalcones, be made available as a viable strategy in antimicrobial therapy. In this study, the synthesized chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one was tested for its antibacterial activity, focusing on antibiotic modification and the inhibition of the MepA efflux pump present in S. aureus strain K2068. The broth microdilution method, using microdilution plates, was employed in microbiological tests to determine the minimum inhibitory concentration of the chalcone, antibiotics, and ethidium bromide. The results show that while the chalcone did not exhibit direct antibacterial activity, it synergistically enhanced the effects of ciprofloxacin and ethidium bromide, as evidenced by the reduction in MICs. In addition, computer simulations of molecular docking demonstrate that the tested chalcone acts on the same binding site as the efflux pump inhibitor chlorpromazine, interacting with essentially the same residues. These data suggest that the chalcone may act as a MepA inhibitor.

• MeSH
• Anti-Bacterial Agents * pharmacology   chemistry   chemical synthesis   MeSH
• Bacterial Proteins * metabolism   genetics   chemistry   antagonists & inhibitors   MeSH
• Chalcone * pharmacology   chemistry   MeSH
• Chalcones * pharmacology   chemistry   MeSH
• Humans MeSH
• Membrane Transport Proteins * metabolism   genetics   chemistry   MeSH
• Microbial Sensitivity Tests MeSH
• Multidrug Resistance-Associated Proteins * metabolism   genetics   chemistry   MeSH
• Molecular Docking Simulation MeSH
• Staphylococcus aureus * drug effects   genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Obézní 69letý muž s rezistentní arteriální hypertenzí a orgánovými komplikacemi, diabetem 2. typu a kombinovanou dyslipidemií nedosahoval cílových hodnot krevního tlaku ani lipidových parametrů. Bylo nově diagnostikováno srdeční selhání se zachovalou ejekční frakcí (heart failure with persisted ejection fraction, HFpEF). Po modifikaci životního stylu a změně terapie hypertenze (ponechán amlodipin 10 mg, zavedena fixní kombinace telmisartanu 80 mg s indapamidem 2,5 mg v léčivém přípravku YLPIO®), dyslipidemie (atorvastatin 40 mg a ezetimib 10 mg) a diabetu / srdečního selhání (přidán empagliflozin 10 mg) došlo ke zlepšení klinického stavu pacienta, kardiovaskulárních i laboratorních parametrů. Kombinace telmisartanu s indapamidem, amlodipinem a gliflozinem potencuje antihypertenzní účinek i nefroprotektivitu a kardioprotektivitu u tohoto plymorbidního pacienta.

Obese 69 years old man with resistant arterial hypertension and end-organ damage, type 2 diabetes and mixed dyslipidemia had not reached the aims of blood pressure and lipid parameters. Heart failure with preserved ejection fraction (HFpEF) was newly diagnosed. The clinical status and all cardiovascular and laboratory parameters have improved after a lifestyle modification and pharmacothertapy of hypertension (Amlodipine 10 mg, telmisartan 80 mg plus indapamid 2,5 mg in the medicinal preparation YLPIO®), dyslipidemia (atorvastatin 40 mg plus ezetimibe 10 mg) and diabetes / heart failure (empagliflozin 10 mg). The combination of telmisartan with indapamid, amlodipine and empagliflozin raises antihypertensive effect, cardioprotenction and nephroprotection in that polymorbid patient.

Our aim is to determine the number of leukocytes, T lymphocytes and B lymphocytes and the expression of activation markers CD200 and CD23 on B lymphocytes in atopic dermatitis (AD) patients (treated and not treated with dupilumab) during the pollen season. We examined 29 patients not treated with dupilumab, 24 patients treated with dupilumab and 40 healthy subjects as a control group. The count of T and B lymphocytes and their subsets were assessed by flow cytometry. The non-parametric Kruskal-Wallis one-factor analysis of variance with post hoc by Dunn's test with Bonferroni's modification was used for statistical processing. Although there was a significant improvement in skin findings in patients treated with dupilumab, the changes in immunological profile show a persistent altered immune response characterized by dysregulation and overactivation of B lymphocytes. Dupilumab therapy leads to normalization of relative T regulatory lymphocytes and total memory B lymphocytes and to decreased count of absolute CD8+ T lymphocytes. Why carry out this study?Studies investigating the immunological profile of atopic dermatitis (AD) patients during the pollen season are rare. There are no studies investigating the count of B lymphocytes (CD5+, CD22+ and CD73+ B lymphocytes) and the expression of activation markers CD23 and CD200 on B lymphocytes and on their subsets during pollen season in AD patients treated and non-treated with dupilumab therapy.What was learned from the study?In atopic dermatitis (AD) patients with and without dupilumab therapy, we confirmed the significantly higher count of absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, non-switched B lymphocytes, transitional B lymphocytes, CD23 memory, naive, non-switched, switched and total CD23 B lymphocytes, the relative count of CD200 memory and CD200 switched B lymphocytes.In dupilumab treated patients, we confirmed the significantly higher count of relative eosinophils, relative CD16+ eosinophils, relative CD200 non-switched B lymphocytes and lower count of absolute CD8+ T lymphocytes. Further studies should focus on investigating the effect of dupilumab on CD8+ T lymphocytes and their subpopulations.In patients without dupilumab therapy, we confirmed the significantly higher count of relative neutrophils, relative T regulatory lymphocytes and total memory B lymphocytes.The changes in the count of CD5+, CD22+ and CD73+ B lymphocytes were not observed during pollen season in both groups of AD patients.

• MeSH
• Dermatitis, Atopic * drug therapy   immunology   MeSH
• B-Lymphocytes immunology   MeSH
• Antigens, CD MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Pollen immunology   MeSH
• Receptors, IgE MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Obezita a diabetes mellitus 2. typu (DM2T) sú významnými rizikovými faktormi rozvoja kognitívnej dysfunkcie a neurodegeneratívnych ochorení. Ich spoločný patofyziologický základ zahŕňa inzulínovú rezistenciu, chronický subklinický systémový zápal a neurozápal, poruchy mikrobiómu, hormonálnu dysreguláciu a štrukturálne zmeny mozgu. Tieto faktory vedú k zhoršeniu pamäte, exekutívnych funkcií a k akcelerácii neurodegenerácie. Pozitívne účinky úpravy životného štýlu – vrátane zníženia telesnej hmotnosti, zvýšenia fyzickej aktivity a úpravy výživy a stravovacích návykov – sa prejavujú zlepšením inzulínovej senzitivity v mozgu, zvýšením neurotrofických faktorov, redukciou systémového zápalu a neurozápalu a zlepšením metabolizmu. Kombinácia behaviorálnych a farmakologických intervencií môže spomaliť kognitívny pokles a znížiť riziko demencie u populácie s obezitou a poruchou metabolizmu glukózy.

Obesity and type 2 diabetes (T2D) are important risk factors for the development of cognitive dysfunction and neurodegenerative diseases. Their common pathophysiological substrate includes insulin resistance, chronic subclinical systemic inflammation, neuroinflammation, shifts in the intestinal microbiome composition, hormonal dysregulation, and structural changes of the brain. These factors lead to impaired memory, executive functions, and accelerated neurodegeneration. The positive effects of lifestyle modifications — including weight loss, increased physical activity, and improved dietary composition — are manifested by improved insulin sensitivity in the brain, increased neurotrophic factors, reduced systemic inflammation and neuroinflammation, and improved metabolism. A combination of behavioral and pharmacological interventions may slow cognitive decline and reduce the risk of dementia in patients with obesity, prediabetes and T2D.

• MeSH
• Exercise MeSH
• Diabetes Mellitus, Type 2 complications   MeSH
• Weight Loss MeSH
• Cognition Disorders * etiology   MeSH
• Humans MeSH
• Neurodegenerative Diseases etiology   MeSH
• Obesity * complications   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Non-tuberculous mycobacteria (NTM) are pathogens that are widely distributed in the environment and cause increasing rates of human infections. High levels of antimicrobial resistance shown by these bacteria complicate infection management and limit treatment options. The complex structure of cell walls and features such as biofilm formation are responsible for intrinsic resistance in NTMs. Antimicrobial resistance can be explained by four basic mechanisms: (i) limitation of drug uptake, meaning antibiotic entry is limited due to the presence of a hydrophobic and low permeability cell wall and a small number of porin channels, (ii) enzymatic modification of antibiotics, (iii) target site modification, (iv) efflux pumps, which prevent drug accumulation by actively expelling antibiotics from the cell and reduce treatment efficacy. For effective management of NTM infections, detailed understanding of resistance mechanisms, development of species-specific treatment protocols, and discovery of new antimicrobial agents are of great importance. In this review, the mechanisms causing drug resistance in NTMs will be reviewed.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Mycobacterium Infections, Nontuberculous * microbiology   drug therapy   MeSH
• Drug Resistance, Bacterial * MeSH
• Bacterial Proteins metabolism   genetics   MeSH
• Biofilms MeSH
• Cell Wall metabolism   MeSH
• Humans MeSH
• Nontuberculous Mycobacteria * drug effects   genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The circadian clock in choroid plexus (ChP) controls processes involved in its physiological functions, but the signals that synchronize the clock have been sparsely studied. We found that the ChP clock in the fourthventricle (4V) is more robust than that in the lateral ventricle (LV) and investigated whether both clocks use information about mealtime as a signal to synchronize with the current activity state. Exposure of mPer2Luc mice to a 10-day reverse restricted feeding (rRF) protocol, in which food was provided for 6 h during daytime, advanced the phase of the ChP clock in 4V and LV, as evidenced by shifted (1) PER2-driven bioluminescence rhythms of ChP explants ex vivo and (2) daily profiles in clock gene expression in both ChP tissues in vivo. In contrast, clocks in other brain regions (DMH, ARC, LHb) of the same mice did not shift. The 4V ChP responded more strongly than the LV ChP to rRF by modulating the expression of genes to ensure a decrease in resistance to cerebrospinal fluid drainage and increase the secretory capacity of ChP cells. Mechanistically, rRF affects the ChP clock through food-induced increases in insulin, glucose and temperature levels, as in vitro all three signals significantly shifted the clocks in both ChP tissues, similar to rRF. The effect of glucose was partially blocked by OSMI-1, suggesting involvement of O-linked N-acetylglucosamine posttranslational modification. We identified mechanisms that can signal to the brain the time of feeding and the associated activity state via resetting of the ChP clock.

• MeSH
• Circadian Clocks * physiology   genetics   MeSH
• Period Circadian Proteins metabolism   genetics   MeSH
• Circadian Rhythm physiology   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Transgenic MeSH
• Mice MeSH
• Choroid Plexus * metabolism   physiology   MeSH
• Gene Expression Regulation MeSH
• Feeding Behavior * physiology   MeSH
• Lateral Ventricles metabolism   physiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Menopauza je přirozený biologický stav, kdy končí reprodukční období života ženy. Hormonální změny, hlavně pokles estrogenu, významně ovlivňují všechny tkáně, kde jsou estrogenové receptory, včetně kůže. Tento článek shrnuje, jak menopauza ovlivňuje zdraví kůže a popisuje současné dostupné terapeutické přístupy ke zvládnutí těchto změn, které se projevují jako stárnutí pleti, suchost, ztráta kolagenu a zvýšeného rizika některých dermatologických problémů. Zkoumá dostupné možnosti zmírnění těchto účinků, včetně hormonální substituční terapie (HRT), lokální léčby, úprav životního stylu a nových terapií.

Menopause is a natural biological state when the reproductive period in a woman's life ends. Hormonal changes, particularly a decrease in oestrogen levels, significantly affect all tissues with oestrogen receptors, including the skin. The present article summarizes how menopause affects skin health and describes the currently available therapeutic approaches to managing these changes that are manifested as skin ageing, dryness, loss of collagen, and increased risk of some dermatological conditions. It also explores the options available to mitigate these effects, including hormone replacement therapy (HRT), topical treatments, lifestyle modifications, and novel therapies.

• MeSH
• Estrogens metabolism   deficiency   MeSH
• Hormone Replacement Therapy methods   MeSH
• Skin Diseases diagnosis   classification   prevention & control   MeSH
• Humans MeSH
• Menopause * metabolism   MeSH
• Interdisciplinary Communication MeSH
• Skin Aging * physiology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Review MeSH

Reconstruction of the anatomic defect following extra-articular shoulder resection is a challenging problem, particularly in cases when function of the deltoid muscle and rotator cuff are compromised. Standard reconstruction techniques often result in either instability or rigidity. Constrained implants have been used to overcome these problems; however, they have been associated with a high rate of aseptic loosening. Recently, a novel double-constrained implant has been introduced, yielding promising functional results. Nonetheless, this implant exhibited a cosmetic defect related to protrusion of the humeral component that becomes apparent with time as result of surrounding muscle atrophy. An updated improved design of the implant has been developed to counteract this.We report the case of a 15-year-old patient who underwent an extra-articular (Malawer type V) shoulder resection due to osteosarcoma and received an innovated custom-made double-constrained implant. Moreover, we describe a new modification of the Malawer utilitarian approach to the shoulder girdle that enhances tumor visibility and allows safer dissection. The patient recovered well with satisfactory outcomes at 18 months follow-up, highlighting the potential benefits of this implant design and surgical approach.

• MeSH
• Arthroplasty, Replacement, Shoulder * methods   MeSH
• Humans MeSH
• Adolescent MeSH
• Bone Neoplasms * surgery   pathology   MeSH
• Shoulder Prosthesis * MeSH
• Osteosarcoma * surgery   pathology   MeSH
• Proof of Concept Study MeSH
• Prognosis MeSH
• Prosthesis Design * MeSH
• Shoulder Joint * surgery   pathology   MeSH
• Treatment Outcome MeSH
• Plastic Surgery Procedures * methods   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Cílem léčby dyslipidemií je maximální redukce kardiovaskulárního (KV) rizika pomocí snižování koncentrace LDL-cholesterolu (LDL-C); u osob s vyšší koncentrací triglyceridů (> 1,7 mmol/l) především non-HDL cholesterolu (non-HDL-C). Pro každou kategorii KV rizika existují doporučené cílové hodnoty LDL-C, apolipoproteinu B i non-HDL-C. V posledních letech došlo k výraznému vývoji na poli diagnostiky i léčby dyslipidemií. Po téměř 40 letech od zavedení statinové léčby jsou k dispozici nové účinné léčebné metody, např. inhibitory propotein konvertázy subtilisin kexin typu 9 (iPCSK9), kyselina bempedoová a další. Častěji je zvažováno použití eliminačních metod (lipoproteinová aferéza) a máme již první zkušenosti s novými léky pro léčbu smíšené dyslipidemie a redukci lipoproteinu (a). Základem léčby všech dyslipidemií jsou režimová opatření; nejsou-li dostatečně účinná ke snížení aterogenních lipidů, je doplněna farmakoterapie. Základními léky kontroly dyslipidemií jsou statiny, často v kombinaci s ezetimibem.

The aim of dyslipidemia treatment is to reduce cardiovascular (CV) risk as much as possible by lowering LDL-cholesterol (LDL-C) concentrations; in persons with higher triglyceride concentration (>1.7 mmol/l), especially non-HDL cholesterol (non-HDL-C). For each CV risk category there are recommended target values for LDL-C, apolipoprotein B and non-HDL-C. In recent years, there have been significant developments in the diagnosis and treatment of dyslipidemias. After almost 40 years since the introduction of statin therapy, new effective treatments are available, such as propotein convertase subtilisin kexin type 9 inhibitors (iPCSK9), bempedoic acid and others. The use of elimination methods (lipoprotein apheresis) is being considered more frequently and there is already initial experience with new drugs for the treatment of mixed dyslipidemia and lipoprotein(a) reduction. The cornerstone of treatment for all dyslipidemias is lifestyle modification; in the case of insufficient effect in reducing atherogenic lipoproteins in combination with pharmacotherapy. The first line drugs to control dyslipidemias are statins, often in combination with ezetimibe.

• Keywords
• aterogenní lipidy,
• MeSH
• Dyslipidemias * diagnosis   therapy   MeSH
• Humans MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH
• Publication type
• Practice Guideline MeSH