Alpha-Synuclein Aggregation Mechanism in the Presence of Nanomaterials.

Parkinson's disease (PD) is characterized by the toxic oligomeric and fibrillar phases formed by monomeric alpha-synuclein (α-syn). Certain nanoparticles have been demonstrated to promote protein aggregation, while other nanomaterials have been found to prevent the process. In the current work, we use nuclear magnetic resonance spectroscopy in conjunction with isothermal titration calorimetry to investigate the cause and mechanism of these opposing effects at the amino acid protein level. The interaction of α-syn with two types of nanomaterials was considered: citrate-capped gold nanoparticles (AuNPs) and graphene oxide (GO). In the presence of AuNPs, α-syn aggregation is accelerated, whereas in the presence of GO, aggregation is prevented. The study indicates that GO sequesters the NAC region of α-syn monomers through electrostatic and hydrophobic interactions, leading to a reduced elongation rate, and AuNPs leave the NAC region exposed while binding the N-terminus, leading to higher aggregation. The protein's inclination toward quicker aggregation is explained by the binding of the N-terminus of α-syn with the gold nanoparticles. Conversely, a comparatively stronger interaction with GO causes the nucleation and growth phases to be postponed and inhibits intermolecular interactions. Our finding offers novel experimental insights at the residue level regarding the aggregation of α-syn in the presence of various nanomaterials and creates new opportunities for the development of suitably functionalized nanomaterial-based therapeutic reagents against Parkinson's and other neurodegenerative diseases.

Awareness of Hepatitis C Among the General Population of Riyadh, KSA, in 2023: A Cross-Sectional Study.

Background Hepatitis C, a highly contagious viral infection transmitted through blood-to-blood contact, poses a significant threat to public health owing to its potential to induce extensive liver damage, leading to the development of life-threatening conditions such as liver cirrhosis and hepatocellular carcinoma, commonly known as liver cancer. Objective This cross-sectional study aims to assess the level of awareness of hepatitis C among the general population in Riyadh, Saudi Arabia. Methodology The study was conducted in Riyadh, Saudi Arabia. A national cross-sectional survey was conducted using a predesigned self-administered validated electronic questionnaire. The questionnaire was distributed electronically to the general population from April to September 2023. Results Out of the 800 participants, most were females (472, 59%), and the largest age group was between 23 and 29 years old (305, 38.1%). Saudi Arabians constituted the highest proportion of participants (609, 76.1%), and most participants were single (437, 54.6%). In terms of occupational status, 288 (36%) worked in occupations not listed. The study found that 463 (57.9%) participants had a low level of awareness about the global prevalence of hepatitis C. Additionally, 489 (61.1%) were aware that hepatitis C can cause both acute and chronic hepatitis, and 441 (55.1%) knew that most infected patients may develop chronic hepatitis. A majority (484, 60.5%) were aware of the importance of washing with soap and water after an accidental needle stick injury. Most participants (574, 71.8%) were aware of the common modes of hepatitis C transmission, such as unsterilized instruments, needle stick injuries, and sharing contaminated needles during drug use. Furthermore, 548 (73%) were aware of the transmission risk through unscreened blood transfusion, and 561 (70.1%) were aware of the higher risk of infection for individuals with multiple sexual partners. Conclusion The study highlights a low level of awareness among participants regarding the treatment and prevention of hepatitis C. To address the low level of awareness regarding the treatment and prevention of hepatitis C, targeted strategies and interventions are needed. This includes the development and implementation of public awareness campaigns, creation of informative educational materials, specialized training programs for healthcare professionals, establishment of support groups and counseling services for individuals living with hepatitis C, and continued support for research efforts and knowledge dissemination. By increasing awareness about hepatitis C, its treatment, and prevention, we can improve outcomes for individuals affected by the disease and reduce its overall burden on communities.

Cholangiocarcinoma across England: Temporal changes in incidence, survival and routes to diagnosis by region and level of socioeconomic deprivation.

Background & Aims: While cholangiocarcinoma (CCA) incidence and mortality rates are increasing globally, whether there are regional/temporal variations in these rates for different biliary tract cancer (BTC) subtypes, or whether they differ by sex, socioeconomic status, or route to diagnosis (RtD) remains unknown. In this work, we aimed to perform an in-depth analysis of data on the incidence, mortality, survival and RtD of CCA and other BTCs. Methods: Data on all BTCs diagnosed in England between 2001 and 2018 were extracted from NHS Digital's National Cancer Registration Dataset. Age-standardised incidence rates (ASRs), mortality rates (ASMRs) and net survival rates were calculated, and Kaplan-Meier overall survival estimates and RtD trends were analysed. Analyses were stratified by sex, socioeconomic deprivation, tumour subtype and region. Results: The ASR for CCA rose from 2.9 in 2001-2003 to 4.6 in 2016-2018 and from 1.0 to 1.8 for gallbladder cancers (GBCs). ASMR trends mirror those of incidence, with most deaths due to iCCA. Over 20% of patients with CCA were under 65 years old. The ASRs and ASMRs were consistently higher in the most socioeconomically deprived group for CCA and GBC. The most common RtD was the emergency route (CCA 49.6%, GBC 46.2% and ampulla of Vater cancer 43.0%). The least deprived patients with CCA and ampulla of Vater cancer had better overall survival (p <0.001). Net survival rates rose for all BTCs, with 3-year net survival for CCA increasing from 9.2% in 2001 to 12.6% in 2016-2018. There was notable geographical variation in ASRs, ASMRs and net survival for all BTCs. Conclusions: BTC incidence and mortality rates are increasing, with differences observed between tumour types, socioeconomic deprivation groups, RtDs and geographical regions. This highlights the need for targeted interventions, earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals. Impact and implications: Cholangiocarcinoma (CCA) incidence and mortality rates are rising globally, particularly for intrahepatic CCA. However, it has not previously been reported if, within a single country, there are temporal and regional differences in incidence, mortality and survival rates for different biliary tract subtypes, and whether these differ by sex, socioeconomic status, or route of diagnosis. In this study we show that mortality rates for patients with CCA continue to rise and are almost 40% higher in the most socioeconomically deprived compared to the least; additionally, we observed regional variation within England in incidence, mortality and survival. This study is relevant to researchers and policy makers as it highlights regional variation and inequality, as well as emphasising the need for earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals.

Retraction: Colloid Cyst: A Potentially Life-Threatening Etiology of Severe Headache in a Patient With Migraine.

[This retracts the article DOI: 10.7759/cureus.18424.].

Cohort study to assess geographical variation in cholangiocarcinoma treatment in England.

BACKGROUND: Outcomes for cholangiocarcinoma (CCA) are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types. Beyond curative surgery, which is only an option for a minority of patients diagnosed at an early stage, few systemic therapy options are currently recommended to relieve symptoms and prolong life. Stent insertion to manage disease complications requires highly specialised expertise. Evidence is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA patients. AIM: To assess geographic variation in treatments received amongst CCA patients in England. METHODS: Data used in this cohort study were drawn from the National Cancer Registration Dataset (NCRD), Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset. A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the NCRD. Potentially curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of interest. Linear probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis, and for socio-demographic and clinical characteristics at diagnosis. RESULTS: Of 8853 CCA patients, 1102 (12.4%) received potentially curative surgery. The mean [95% confidence interval (CI)] percentage-point difference from the population average ranged from -3.96 (-6.34 to -1.59)% to 3.77 (0.54 to 6.99)% across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics, showing statistically significant variation. Amongst 7751 who did not receive surgery, 1542 (19.9%) received systemic therapy, with mean [95%CI] percentage-point difference from the population average between -3.84 (-8.04 to 0.35)% to 9.28 (1.76 to 16.80)% across Cancer Alliances after adjustment, again showing the presence of statistically significant variation for some regions. Stent insertion was received by 2156 (27.8%), with mean [95%CI] percentage-point difference from the population average between -10.54 (-12.88 to -8.20)% to 13.64 (9.22 to 18.06)% across Cancer Alliances after adjustment, showing wide and statistically significant variation from the population average. Half of 8853 patients (n = 4468) received no treatment with either surgery, systemic therapy or stent insertion. CONCLUSION: Substantial regional variation in treatments received by CCA patients was observed in England. Such variation could be due to differences in case-mix, clinical practice or access to specialist expertise.

Bioresorbable scaffolds: current concepts and future technology / "Scaffolds" bioabsorbibles: conceptos actuales y tecnología futura

The introduction of the drug-eluting (DES) stent to percutaneous coronary intervention (PCI) had a significant impact on patient management of coronary artery disease and has been called the "third revolution" in interventional cardiology after the first 2 revolutions of balloon angioplasty and bare-metal stents. The promise of adaptive remodeling, restoration of vasomotion, late luminal enlargement, and retained potential for future coronary artery bypass grafting at the site of previous PCI has been the driving force behind bioresorbable stent/scaffold (BRS) technology development. Moreover, because of the inherent risk of late and very late stent thrombosis, BRS potentially offers a solution and recent years have seen heightened interest, hype, and hope. In this current review, we are aiming to shed light on strength and weakness of various BRS including the future perspective. (AU)

La introducción del stent liberador de fármacos (DES) en la intervención coronaria percutánea (ICP) tuvo un impacto significativo en el tratamiento de los pacientes con enfermedad de las arterias coronarias y se ha denominado la "tercera revolución" en cardiología intervencionista después de las dos primeras revoluciones de la angioplastia con balón y stents de metal desnudo. La promesa de remodelación adaptativa, restauración de la vasomoción, agrandamiento luminal tardío y potencial retenido para futuros injertos de derivación de la arteria coronaria en el sitio de la PCI anterior ha sido la fuerza impulsora detrás del desarrollo de la tecnología de stent/armazón biorreabsorbible (BRS). Además, debido al riesgo inherente de trombosis del stent tardía y muy tardía, la BRS ofrece potencialmente una solución y en los últimos años se ha visto un mayor interés, entusiasmo y esperanza. En esta revisión actual, nuestro objetivo es arrojar luz sobre la fortaleza y la debilidad de varios BRS, incluida la perspectiva futura. (AU)

Family history of diabetes and parental consanguinity: important risk for impaired fasting glucose in South East Asians / Historia familiar de diabetes y consanguinidad de los padres: riesgo importante para la glucosa en ayunas alterada en Asiáticos Sudorientales

OBJECTIVE: Offsprings of Type 2 diabetics have increased risk of metabolic disturbances. The aim of the study is to assess the potential effect of family history of Type 2 diabetes (FHD) and parental consanguinity on fasting plasma glucose (FPG) levels. SUBJECTS AND METHODS: Non-diabetic offsprings of one or both parents with Type 2 diabetes and healthy controls of comparable age, without a FHD were the subjects of this study. Family history of Type 2 diabetes was defined by the presence of Type 2 diabetes in one or both parents of the subject. Consanguinity was defined as history of marriage with a first cousin. Fasting plasma glucose levels were determined in cases and controls. RESULTS: Impaired fasting glucose (IFG) was identified in 42% ofsubjects with FHD and in 14% without FHD. We found a strong independent association of FHD with impaired fasting glucose in both males and females by logistic regression analysis after adjusting the data for age, gender and body mass index (BMI). Parental consanguinity modifies the effect of FHD on IFG. CONCLUSION: We concluded that family history of diabetes and parental history of consanguinity determine the risk for impaired fasting glucose in this study population.

OBJETIVO: Los hijos con diabetes de Tipo 2 tienen un riesgo mayor de trastornos metabólicos. El objetivo de este estudio es evaluar el efecto potencial de la historia familiar en la diabetes Tipo 2 (HFD) y la consanguinidad de los padres en los niveles de glucosa plasmática en ayunas (GPA). SUJETOS Y MÉTODOS: Los hijos no diabéticos de uno o ambos padres con diabetes de Tipo 2 y controles sanos de edad comparable, sin HFD, constituyeron los sujetos de este estudio. La historia familiar de diabetes de Tipo 2 se definió por la presencia de la diabetes de Tipo 2 en uno o ambos padres del sujeto. La consanguinidad se definió como la historia del matrimonio con un primer primo o prima. Los niveles de glucosa plasmática fueron determinados en los casos y los controles. RESULTADOS: La glucosa en ayunas alterada (GAA) fue identificada en el 42% de los sujetos con HFD y en 14% sin HFD. Se halló una fuerte asociación independiente fuerte de HFD con la glucosa en ayunas alterada tanto en varones como en hembras, mediante el análisis de regresión logística después de ajustar los datos de edad, género e índice de masa corporal (IMC). La consanguinidad de los padres modifica el efecto de HFD sobre la GAA. CONCLUSIÓN: Se llegó a la conclusión de que la historia familiar de diabetes y la historia de consanguinidad de padre y madre determina el riesgo de glucosa en ayunas alternada en la población bajo estudio.