Slovak Medical University

Protease dysregulation, particularly involving matrix metalloproteinases (MMP-2 and MMP-9), plays a pivotal role in the progression and metastasis of tongue carcinoma. Antimicrobial peptides (AMPs) with protease inhibitory activity represent promising therapeutic candidates; however, natural peptides often require optimization for enhanced efficacy and selectivity. Here, we curated a comprehensive dataset of experimentally validated protease-inhibitory AMPs and applied machine learning models to identify key sequence and physicochemical features predictive of activity. Utilizing a genetic algorithm, we designed a novel series of anti-protease peptides, selecting GA-APP1 for synthesis and in vitro validation. GA-APP1 demonstrated potent inhibition of MMP-9 and MMP-2 with IC₅₀ values of 5.4 µM and 7.1 µM, respectively, alongside selective cytotoxicity against tongue carcinoma cell lines SCC-9 and CAL-27, while sparing normal oral keratinocytes. These findings validate the computational predictions and underscore the potential of machine learning-guided peptide design as a platform for developing targeted therapeutics against protease-driven cancers.

The management of upper cervical spine (UCS) fractures is unclear concerning the role of fusion versus non-fusion fixation and the need for implant removal following fracture healing. This international AO Spine expert survey (Level IV study) evaluated the current trends, and practice preferences among experienced surgeons in the management of UCS fractures. A structured questionnaire was answered by AO Spine Knowledge Forum Trauma and Infection (KF T I) members (n = 24). The survey collected data regarding demographics, classification use, fixation vs. fusion preferences, and implant removal practices for UCS fractures (C1, C2 odontoid, and Hangman’s fractures). Descriptive statistics were analysed. Majority were from North America and Europe (54

The European Renal Association (ERA) Registry collects data on patients with kidney failure receiving kidney replacement therapy (KRT). This paper presents a summary of the ERA Registry Annual Report 2023, and focuses specifically on comparisons by age. The complete ERA Registry Annual Report 2023 is available in the Supplementary information. For 2023, data were collected from 34 countries in Europe and countries bordering the Mediterranean Sea. Using these data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities, and expected remaining lifetimes were calculated. In 2023, the ERA Registry covered 519 million people in the participating countries. The incidence of KRT was 151 per million population (pmp). Among incident patients, 29% were aged ≥75 years, 64% were male, and the most common primary renal disease (PRD) was diabetes mellitus (22%). Most patients (83%) started KRT with haemodialysis (HD), 11% started with peritoneal dialysis (PD), and 6% underwent pre-emptive kidney transplantation. On 31 December 2023, the prevalence of KRT was 1101 pmp. Among prevalent patients, 24% were aged ≥75 years, 62% were male, and the most common PRD was of miscellaneous origin (18%). Moreover, 56% of prevalent patients received HD, 5% received PD, and 39% were living with a functioning graft. In 2023, the kidney transplantation rate was 43 pmp, with 69% of kidneys coming from deceased donors. For patients starting KRT between 2014 and 2018, 5-year survival probability was 51%. The proportions of incident and prevalent patients aged ≥75 varied considerably across European countries. In addition, incident patients aged ≥75 were more often male, and had more often hypertension as PRD compared with younger patients. Only 1% of incident patients aged ≥75 received a pre-emptive kidney transplant, while among prevalent patients of the same age, 22% was living with a functioning graft.

Background The systems for paying health care providers consist of a complex set of arrangements, including payment methods and supporting elements. A diversity of payment methods exists, and for each of them the administrative process of setting prices (tariffs) plays a pivotal role. It defines the exact amount of money that a purchaser pays a health care provider for delivering a given service, unit of activity, or specific outcome. This study aimed to provide a structured comparison of the systems for setting prices for hospital care services in the public health insurance systems of seven Central and Eastern European countries (Bulgaria, Estonia, Czechia, Hungary, Lithuania, Poland, and Slovakia), as well as identify major challenges. Methods The methods involved three consecutive steps: (1) a conceptual framework and data collection form were developed based on existing literature; (2) national experts identified through purposive, snow-ball sampling were asked to complete the data collection form; and (3) a comparative analysis was performed. Results All analysed CEE countries use mixed payment methods, with a dominant role of diagnose-related groups, in paying for hospital care provision. The price-setting process follows similar general steps: collecting costing data; calculating tariff weights; setting the price by using a dedicated base rate; conducting negotiations with providers; and applying price adjustments. However, the scope and details of each element may vary significantly between the countries. In Hungary and Bulgaria, there is no structured costs data collection process (historical weights are adjusted). The analysed countries face similar challenges in building effective price-setting systems: (1) incomplete and/or low quality hospital cost data, (2) insufficient institutional capacity; (3) methodological challenges of the costing model; and (4) barriers driven by the overall health system context. These challenges can lead to both under- and over-pricing of hospital services and generate system-level inefficiencies. Conclusions There is a strong need to support investments in data infrastructure and improvements in system governance across all analysed countries. Digital solutions could enhance the efficiency of the process by limiting the potential trade-off between the timeliness (and accuracy) of reporting cost data and the feasibility constraints.

INTRODUCTION:Small intestinal atresia (SIA) consists of a congenital obstruction of the lumen of the duodenum, jejunum, or ileum with varying severity. The aim of the investigation was to analyze the prevalence and mortality of SIA, using data from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). METHODS:Data on SIA cases were collected from 25 ICBDSR members' surveillance programs in 17 countries over 1974-2015. All pregnancy outcomes were included, but terminations of pregnancy were not available for 11 programs. Statistical analysis is descriptive, and the prevalence is established by the total of SIA cases divided by the total of births. The survival time was calculated, and mortality was analyzed individually using the Kaplan-Meier method for comparison. RESULTS:The total prevalence of SIA was 2.1 per 10,000 births. Iran had the highest prevalence with 11.5 per 10,000 total births (95% CI: 9-14.1); on the other hand, the lowest prevalence of SIA was in Mexico-Nuevo Leon with 0.5 per 10,000 births (95% CI: 0.3-0.8), and Cali-Colombia had zero cases. In South America, a higher prevalence of SIA was estimated compared to what was reported in 2000. Most deaths occurred between Day 2 and 6, except in Bogotá-Colombia, Spain, UK-Wales, and Mexico, where the deaths occurred on Day 1. The mortality in the first year was 4.3%, but the specific causes of death were not determined in this study. CONCLUSION:The prevalence of SIA was about 2.1 per 10,000 births during a 41-year period in 25 centers, with variations in prevalence according to geographical locations. Future research is suggested to analyze changes in trends and the impact of early diagnosis and treatment in mortality.