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Congenital heart defects (CHDs) represent the most common category of congenital malformations and constitute a significant cause of infant morbidity and mortality. Despite advances in prenatal imaging, such as fetal echocardiography, early detection remains challenging, particularly in pregnancies without identified risk factors. Recent studies suggest that maternal circulating non-coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs), may serve as promising non-invasive biomarkers for the prenatal diagnosis of CHDs. Following a review of the most relevant clinical and preclinical studies, it was found that maternal circulating RNA, particularly microRNAs and lncRNAs, shows potential as non-invasive biomarkers for detecting fetal congenital heart defects. Among microRNAs, miR-146a-5p demonstrated the highest diagnostic accuracy for ventricular septal defects (VSDs), while panels of lncRNAs, such as LINC00598, LINC01551, and GATA3-AS1, exhibited high performance for atrial septal defects (ASDs). In addition, miR-19b, miR-29c, and miR-375 were associated with both VSDs and ASDs, suggesting a shared role in septal development. However, the studies displayed variability in biomarker selection and analytical methodologies. The findings indicate that maternal circulating microRNAs and lncRNAs hold significant potential as non-invasive biomarkers for the early detection of CHDs. Nonetheless, methodological heterogeneity and small sample sizes highlight the need for standardized protocols and larger multicenter studies prior to clinical implementation. These observations support the future integration of RNA biomarkers with fetal echocardiography to enhance early CHD screening and to inform prenatal counseling.

Zilebesiran represents an innovative antihypertensive therapy employing small interfering RNA (siRNA) to inhibit hepatic angiotensinogen, a key regulator of the renin–angiotensin–aldosterone system. By directly targeting the source of angiotensin II production, zilebesiran offers a novel mechanism distinct from conventional antihypertensive treatments. In the clinical studies KARDIA-1 and KARDIA-2, zilebesiran demonstrated clinically significant reductions in systolic blood pressure, with effects lasting up to 24 weeks after a single subcutaneous injection. In KARDIA-1, doses of 300 mg and 600 mg administered every 6 months resulted in reductions of over 15 mmHg in systolic blood pressure at 3 months compared with placebo. KARDIA-2 further showed an additional reduction of up to 12.1 mmHg at 3 months when zilebesiran was used as an adjunct to standard antihypertensive therapy. KARDIA-3 is currently evaluating the therapy in a larger global population to assess its impact on major cardiovascular outcomes. Zilebesiran has demonstrated a favorable safety profile with minimal adverse events, offering potential advantages for patients with resistant or uncontrolled hypertension and those at high cardiovascular risk, especially where adherence to daily oral medications is challenging. Beyond blood pressure reduction, zilebesiran may protect target organs, including the heart, kidneys, and retina. In conclusion, zilebesiran represents a promising siRNA-based therapy that may redefine the management of difficult-to-control hypertension, offering durable, targeted, and patient-friendly treatment with broad cardiovascular benefits. Future studies will clarify its long-term safety, efficacy across diverse populations, and integration into personalized hypertension management strategies.

The reason for these delayed diagnoses can be found by looking at the historical, medical, and cultural background of mid-19th century China.8 Despite the presence of public hospitals governed by the Imperial Court's Medical Department, patients preferred to be treated at home, assisted by family members.8 It was only in the late 19th century, when western hospitals were built, that a cultural and social shift began that lead to more patients being treated in hospital. In 2012, the International Association of Cancer Registries estimated that breast cancer was the most common cancer in Chinese women, with an age standardised rate (ASR) of 21·6 cases per 100 000 women.9,10 More specifically, data from the Chinese National Central Cancer Registry showed that breast cancer was the most common tumour among urban women and the fourth most common tumour in rural areas in 2008.8,9 A high incidence of breast cancer was found to occur in socioeconomically developed eastern coastal urban areas. An ASR of 46·6 cases per 100 000 women was reported in Guangzhou in 2012, the same area where Lam Qua's patients once lived.9 The last release of the GLOBOCAN database (International Association of Cancer Registries, September, 2018)10 further confirms that breast cancer in Chinese women (19·2% of total cases) is increasing (breast cancer represents 19·2% of all cancer cases in China), and due to the aging and growing population, and the rise in a westernised lifestyle, the burden is expected to rise in years to come.

The aim of this work is to refer on the death due to crush syndrome in 1277 of Pope John XXI, philosopher, logician, anatomist, physician scientist, university professor of medicine at the university of Siena and author of books adopted for nearly 4 centuries in universities in the Middle Ages. The Pope died crushed by the ceiling of his office which had been built in rush to meet his need for a quiet and warm place, his need of light and nature. There he attended to his duties of governing the church, studied fine theological questions, inspected the stars, made experiments and discussed with the renowned ophthalmologists who in those days made Viterbo the center of the study on vision. Following the fall of the ceiling of his apartment, John XXI was extracted alive from among the pieces of wood and stones. However, a few days after the disaster, he died in bad conditions (miserabiliter). He experienced a typical death due to crush syndrome which was described for the first time by Antonino D’Antona, following the Messina-Reggio Calabria 1908 earthquake. He was born (c. 1210–1220) in Lisbon as Pedro Hispano (Peter of Spain). He had regular trivium and quadrivium courses at the University of Paris under Albertus Magnus, a talented naturalist. He became Master of Arts, then studied medicine out of Paris (probably Montpellier or Salerno). He wrote three treatises (On the eye (De oculo), The Treasury of Medicines for the Poor (Thesaurus Pauperum) and Little Summaries of Logic (Summulae Logicales)) which were used in the European universities from the 13th to the beginning of the 18th century. Pedro Hispano was advisor of King Alphonso III for affairs inherent to the Church, bishop of Braga and then Cardinal Bishop of Tusculum and Pope as John XXI. He was buried in the Cathedral of Viterbo, the city where he had settled the seat of the Pontiff.

Since Antiquity, votive offerings were deposited in temples dedicated to deities in order to fulfil a special request of a supplicant. Later, in Orthodox churches, votive offerings entered in the form of anatomical ex-voto or tamata , metallic effigies that realistically represented the disease-affected portion of the body. In this paper, we show four tamata from eighteenth–nineteenth century identified in the museum of the Orthodox monastery of Floresti (Romania); votive offerings that represent ocular pathologies. Even if the supplicants did not have a medical background and often did not fully understand their diseases, the votive offerings demonstrate their ability to observe pathological changes, at the same time emphasising the importance of their faith in the healing process.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second most common cause of cancer-related death globally. This type of liver cancer is frequently detected at a late stage by current biomarkers because of the high clinical and biological heterogeneity of HCC tumours. From a plethora of molecules and cellular compounds, small nanoparticles with an endosomal origin are valuable cancer biomarkers or cargos for novel treatments. Despite their small sizes, in the range of 40–150 nm, these particles are delimited by a lipid bilayer membrane with a specific lipid composition and carry functional information—RNA, proteins, miRNAs, long non-coding RNAs (lncRNAs), or DNA fragments. This review summarizes the role of exosomal microRNA (miRNA) species as biomarkers in HCC therapy. After we briefly introduce the exosome biogenesis and the methods of isolation and characterization, we discuss miRNA’s correlation with the diagnosis and prognosis of HCC, either as single miRNA species, or as specific panels with greater clinical impact. We also review the role of exosomal miRNAs in the tumourigenic process and in the cell communication pathways through the delivery of cargos, including proteins or specific drugs.