A global view of hepatitis C: physician knowledge, opinions, and perceived barriers to care.

UNLABELLED: Chronic infection with the hepatitis C virus (HCV) is a leading cause of global morbidity and mortality. Although recent advances in antiviral therapy have led to significant improvements in treatment response rates, only a minority of infected patients are treated. Multiple barriers may impede the delivery of HCV therapy. The aim of this study was to identify perceived barriers to care, knowledge, and opinions among a global sample of HCV treatment providers. An international, multidisciplinary survey of HCV treatment providers was conducted. Each physician responded to a series of 214 questions concerning his or her practice characteristics, opinions regarding the state of HCV care, knowledge regarding HCV treatment, and perception of treatment barriers. A total of 697 physicians from 29 countries completed the survey. Overall, physicians viewed patient-level barriers as most significant, including fear of side effects and concerns regarding treatment duration and cost. There were distinct regional variations, with Central and Eastern European physicians citing government barriers as most important. In Latin America, the Middle East, and Africa, payer-level barriers, including lack of treatment coverage, were prominent. Overall, the perception of barriers was strongly associated with physician knowledge, experience, and region of origin, with the fewest barriers reported by Nordic physicians and the most reported by Middle Eastern and African physicians. Globally, physicians demonstrated deficits in basic treatment principles, including the role of viral kinetics and the management of treatment nonresponders. Two thirds of surveyed physicians believed that patients do not have adequate access to providers in their community. CONCLUSION: Barriers to HCV treatment vary globally, though patient-level factors are viewed as most significant by treating physicians. Efforts to improve awareness, education, and specialist availability are needed.

Integrated spectroscopic and MD simulation approach to decipher the effect of pH on the structure function of Staphylococcus aureus thymidine kinase.

Staphylococcus aureus is a major human pathogen responsible for a variety of clinical infections, becoming increasingly resistant to antibiotics. To address this challenge, there is a need to identify new cellular targets and innovative approaches to expand treatment options. One such target is thymidine kinase (TK), a crucial enzyme in the pyrimidine salvage pathway, which plays a key role in the phosphorylation of thymidine, an essential component in DNA synthesis and repair. In this study, we have successfully cloned, expressed, and purified the TK protein. A comprehensive investigation into how different pH levels affect the structure and functional activity of TK, using a combination of spectroscopy, classical molecular dynamics simulations, and enzyme activity assays was conducted. Our study revealed that variation in pH disrupts secondary and tertiary structures of TK with noticeable aggregate formation at pH 5.0. Enzyme activity studies demonstrated that TK exhibited its maximum kinase activity within the physiological pH range. These findings strongly suggest a connection between structural changes and enzymatic activity, which was further supported by the agreement between the spectroscopic features we measured and the results of our MD simulations. Our study provides a deeper insight into the structural features of TK, which could potentially be harnessed for the development of therapeutic strategies aimed at combatting infectious diseases. Conformational dynamics plays an essential role in the design and development of effective inhibitors. Considering the effects of pH on the conformational dynamics of TK, our findings may be implicated in the development of potent and selective inhibitors.Communicated by Ramaswamy H. Sarma.

A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt.

BACKGROUND: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. AIM: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. METHODOLOGY: Data references were identified through indexed journals and non-indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. RESULTS: We estimated that 49.3-64.0 million adults in Asia, Australia and Egypt are anti-HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4 was found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. CONCLUSION: We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection.