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Mathematical Biosciences and... Mar 2024Hepatitis B is one of the global health issues caused by the hepatitis B virus (HBV), producing 1.1 million deaths yearly. The acute and chronic phases of HBV are...
Hepatitis B is one of the global health issues caused by the hepatitis B virus (HBV), producing 1.1 million deaths yearly. The acute and chronic phases of HBV are significant because worldwide, approximately 250 million people are infected by chronic hepatitis B. The chronic stage is a long-term, persistent infection that can cause liver damage and increase the risk of liver cancer. In the case of multiple phases of infection, a generalized saturated incidence rate model is more reasonable than a simply saturated incidence because it captures the complex dynamics of the different infection phases. In contrast, a simple saturated incidence rate model assumes a fixed shape for the incidence rate curve, which may not accurately reflect the dynamics of multiple infection phases. Considering HBV and its various phases, we constructed a model to present the dynamics and control strategies using the generalized saturated incidence. First, we proved that the model is well-posed. We then found the reproduction quantity and model equilibria to discuss the time dynamics of the model and investigate the conditions for stabilities. We also examined a control mechanism by introducing various controls to the model with the aim to increase the population of those recovered and minimize the infected people. We performed numerical experiments to check the biological significance and control implementation.
Topics: Humans; Incidence; Hepatitis B virus; Hepatitis B; Computer Simulation; Hepatitis B, Chronic; Basic Reproduction Number; Liver Neoplasms; Models, Biological; Algorithms
PubMed: 38872533
DOI: 10.3934/mbe.2024230 -
Open Forum Infectious Diseases Jun 2024Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In...
BACKGROUND
Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration.
METHODS
We retrieved records of adult Mayo Clinic patients (≥18 years) with positive serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti-phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed.
RESULTS
Thirty-one patients were included. Their median age was 58 years (IQR, 50-64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168-414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression.
CONCLUSIONS
Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.
PubMed: 38868311
DOI: 10.1093/ofid/ofae277 -
Clinical Case Reports Jun 2024This case signifies the importance of recognizing DIAIH within the context of antibiotic therapy, especially in older adults and even shortly after common drug exposures...
KEY CLINICAL MESSAGE
This case signifies the importance of recognizing DIAIH within the context of antibiotic therapy, especially in older adults and even shortly after common drug exposures for treating UTI.
ABSTRACT
Various drugs can induce immune-mediated liver damage and in rare instances may lead to autoimmune hepatitis. Here we report an 84-year-old woman who developed autoimmune hepatitis less than 3 weeks after treatment for urinary tract infection with the antibiotic nitrofurantoin. She presented with jaundice, right upper quadrant abdominal pain, nausea, and vomiting. In the absence of a history of an autoimmune disorder or elevated liver enzymes in the past; elevated liver enzymes after a short course of Nitrofurantoin and the presence of smooth muscle antibodies strongly suggested autoimmune hepatitis, which was confirmed through biopsy sample analysis. The patient scored 7 points on the Naranjo adverse reaction probability scale. The patient's rapid recovery within 1 month of prednisone therapy supports the association of liver damage with nitrofurantoin use.
PubMed: 38868111
DOI: 10.1002/ccr3.9050 -
Chemical & Pharmaceutical Bulletin Jun 2024In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases...
In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Topics: Glycosides; Angiotensin-Converting Enzyme 2; Molecular Docking Simulation; Humans; Coumarins; SARS-CoV-2; COVID-19; Rutaceae; COVID-19 Drug Treatment; Antiviral Agents; Plant Roots; Angiotensin-Converting Enzyme Inhibitors
PubMed: 38866495
DOI: 10.1248/cpb.c23-00844 -
Scientific Reports Jun 2024Hepatitis B virus (HBV) infection is highly prevalent in Guangzhou, China. This study aimed to examine the long-term trend of HB incidence from 2008 to 2022 and the...
Hepatitis B virus (HBV) infection is highly prevalent in Guangzhou, China. This study aimed to examine the long-term trend of HB incidence from 2008 to 2022 and the independent impacts of age, period, and cohort on the trends. HBV data were collected from the China Information System for Disease Control and Prevention. Joinpoint regression was utilized to examine temporal trends, and an age-period-cohort model was employed to estimate the effects of age, period, and cohort. A total of 327,585 HBV cases were included in this study. The incidence of chronic and acute HB showed a decreasing trend in Guangzhou over the past 15 years, with an average annual percent change of - 4.31% and - 16.87%, respectively. Age, period, and cohort all exerted significant effects. The incidence of HB was higher in males than in females and non-central areas compared to central areas. Age groups of 0-4 years and 15-24 years were identified as high-risk groups. The period relative risks for chronic HB incidence decreased initially and then stabilized. Cohorts born later had lower risks. Chronic HB incidences remain high in Guangzhou, especially among males, younger individuals, and residents of non-central areas. More efforts are still needed to achieve hepatitis elimination targets.
Topics: Humans; China; Female; Male; Incidence; Adolescent; Adult; Middle Aged; Infant; Child; Child, Preschool; Young Adult; Hepatitis B; Infant, Newborn; Aged; Age Factors; Cohort Effect; Hepatitis B virus; Risk Factors
PubMed: 38862511
DOI: 10.1038/s41598-024-63796-0 -
BMJ Case Reports Jun 2024Rarer causes of acute pancreatitis may be considered in certain settings, such as parasitism in endemic regions. This report describes a pregnant female (second...
Rarer causes of acute pancreatitis may be considered in certain settings, such as parasitism in endemic regions. This report describes a pregnant female (second trimester) in her 20s who presented with 3-day steady epigastric pain radiating to the back and passage of worm from the mouth. She was diagnosed with mild acute pancreatitis, given a significantly elevated serum lipase and absence of organ failures. Fecalysis showed ova; hence, she was treated with mebendazole. Plain MR cholangiopancreatography showed an 842 mL necrotic pancreatic fluid collection and tubular flow void foci within the gallbladder and duodenum consistent with helminthiasis. The patient was managed conservatively in the absence of indications for drainage. The abdominal pain remarkably improved, and she underwent eventual vacuum-assisted delivery to a healthy term baby 4 months after the bout of acute pancreatitis.
Topics: Humans; Female; Ascariasis; Pregnancy; Pancreatitis, Acute Necrotizing; Animals; Ascaris lumbricoides; Pregnancy Complications, Parasitic; Adult; Mebendazole; Abdominal Pain; Cholangiopancreatography, Magnetic Resonance
PubMed: 38862191
DOI: 10.1136/bcr-2024-260316 -
The International Journal on Drug Policy Jun 2024Women who inject drugs are significantly less likely to initiate hepatitis C virus (HCV) treatment than men. Concerted efforts are needed to minimise gender-based...
BACKGROUND
Women who inject drugs are significantly less likely to initiate hepatitis C virus (HCV) treatment than men. Concerted efforts are needed to minimise gender-based inequalities in care. The study aim was to use a stigma and time framework to investigate how women who inject drugs experienced HCV care in healthcare settings.
METHODS
Semi-structured, in-depth interviews were conducted with 34 participants from the ETHOS Engage Cohort (n = 1,443) in Australia. Inclusion criteria were aged ≥18 years, history of injection drug use, and persons who injected in the prior six months or were currently receiving opioid agonist treatment. Drawing on the original qualitative dataset (n = 34), we conducted a secondary analysis focused on women participants' experiences of receiving HCV related care (n = 21/34). Utilising thematic analysis, we applied Earnshaw's theoretical framework, which incorporates time into stigma and health research via three "timescales" - historical context, human development, and status course.
RESULTS
Among the 21 women interviewed (mean age 42 years, 5 are Aboriginal, 11 received HCV treatment), the majority were currently receiving opioid agonist treatment and over half injected drugs in the past month. For historical context, most participants were diagnosed with HCV during the interferon era (1990s-2014). Participants had to navigate a sociomedical landscape not only largely bereft of adequate HCV medical knowledge, appropriate support, and adequate treatments, but were also generally assessed as "unsuitable" for treatment based on their perceived personhood as people who inject drugs. For human development, many participants reported encountering overlapping stigmatizing experiences (layered stigma) while receiving their HCV diagnosis in prenatal care and early postpartum. Under status course, participants acutely recognised the intersection of HCV infection, injection drug use, and gender, and reported concerns about being judged more harshly from healthcare providers as a result.
CONCLUSION
A stigma and time framework illuminated multiple overlapping stigmatizing experiences for women who inject drugs in HCV care and in turn, can help to inform tools and interventions to counter their impact.
PubMed: 38861842
DOI: 10.1016/j.drugpo.2024.104477 -
American Journal of Physiology. Lung... Jun 2024COVID-19 syndrome is characterized by acute lung injury, hypoxemic respiratory failure, and high mortality. Alveolar Type 2 (AT2) cells are essential for gas exchange,...
COVID-19 syndrome is characterized by acute lung injury, hypoxemic respiratory failure, and high mortality. Alveolar Type 2 (AT2) cells are essential for gas exchange, repair, and regeneration of distal lung epithelium. We have shown that the causative agent, SARS-CoV-2 and other β-coronavirus genus members induce an ER stress response , however the consequences for host AT2 function are less understood. To study this, two murine models of coronavirus infection were employed- mouse hepatitis virus-1 (MHV-1) in A/J mice and a mouse adapted SARS-CoV-2 strain. MHV-1 infected mice exhibited dose-dependent weight loss with histological evidence of distal lung injury accompanied by elevated bronchoalveolar lavage fluid (BALF) cell counts and total protein. AT2 cells showed evidence of both viral infection and increased BIP/GRP78 expression, consistent with activation of the unfolded protein response (UPR). The AT2 UPR included increased IRE1α signaling and a biphasic response in PERK signaling accompanied marked reductions in AT2 and BALF surfactant protein (SP-B, SP-C) content, increases in surfactant surface tension, and emergence of a re-programmed epithelial cell population (, ). The loss of a homeostatic AT2 endophenotype was attenuated by treatment with the IRE1α inhibitor OPK711. As proof-of-concept, C57BL6 mice infected with mouse-adapted SARS-CoV-2 demonstrated similar lung injury and evidence of disrupted surfactant homeostasis. We conclude that lung injury from β-coronavirus infection results from an aberrant host response activating multiple AT2 UPR pathways, altering surfactant metabolism/function, and changing AT2 endophenotypes offering a mechanistic link between SARS-CoV-2 infection, AT2 cell biology, and acute respiratory failure.
PubMed: 38860845
DOI: 10.1152/ajplung.00324.2023 -
Immunity, Inflammation and Disease Jun 2024The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response is crucial for disease management, although diminishing immunity raises the possibility...
BACKGROUND
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response is crucial for disease management, although diminishing immunity raises the possibility of reinfection.
METHODS
We examined the immunological response to SARS-CoV-2 in a cohort of convalescent COVID-19 patients in matched samples collected at 1 and 6-8 months after infection. The peripheral blood mononuclear cells were isolated from enrolled study participants and flow cytometry analysis was done to assess the lymphocyte subsets of naive, effector, central memory, and effector memory CD4+ or CD8+ T cells in COVID-19 patients at 1 and 6-8 months after infection. Immunophenotypic characterization of immune cell subsets was performed on individuals who were followed longitudinally for 1 month (n = 44) and 6-8 months (n = 25) after recovery from COVID infection.
RESULTS
We observed that CD4 +T cells in hospitalized SARS-CoV-2 patients tended to decrease, whereas CD8+ T cells steadily recovered after 1 month, while there was a sustained increase in the population of effector T cells and effector memory T cells. Furthermore, COVID-19 patients showed persistently low B cells and a small increase in the NK cell population.
CONCLUSION
Our findings show that T cell responses were maintained at 6-8 months after infection. This opens new pathways for further research into the long-term effects in COVID-19 immunopathogenesis.
Topics: Humans; COVID-19; Longitudinal Studies; Male; Female; SARS-CoV-2; Middle Aged; Adult; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Survivors; Immunologic Memory; Cohort Studies; Aged; Killer Cells, Natural
PubMed: 38860770
DOI: 10.1002/iid3.1238 -
Cureus May 2024Background Kyasanur Forest Disease (KFD) has emerged as an important differential diagnosis of febrile illness for physicians caring for patients in the Western Ghats of...
Background Kyasanur Forest Disease (KFD) has emerged as an important differential diagnosis of febrile illness for physicians caring for patients in the Western Ghats of South India over the last decade. Aim This study seeks to familiarize physicians with the clinical presentation and the clinical, laboratory and imaging findings of the various complications of KFD. It also seeks to review the literature on the complications of KFD described. Material and methods This was a records-based retrospective study of the patients with KFD referred for tertiary care management to Government Medical College Kozhikode, Kerala over 11 years, from January 2013 to December 2023. Results A total of 12 case records were obtained and analysed. All the patients in this case series belonged to tribal ethnic groups enhancing its social significance. The complications of KFD (as calculated in the 11 patients for whom all the records were available) were altered sensorium (nine, 82%), persistent shock (seven, 64%), Acute Respiratory Distress Syndrome (ARDS)/pneumonitis (six, 55%), encephalitis (six, 55%), myocarditis (six, 55%), bleeding manifestations (six, 55%), hepatitis (six, 55%), acute kidney injury (four, 36%), rhabdomyolysis (three. 27%), hemophagocytic lymphohistiocytosis (HLH) (two, 18%), stress hyperglycaemia (two, 18%), pancreatitis (one, 9%), peritonitis (one, 9%). The case fatality rate in this series was 42%( n=5/12). An autopsy was done on one patient which showed congested and oedematous lungs with subpleural haemorrhage. Petechial haemorrhages were noted in the liver, spleen and kidney. The total leucocyte count was lower than 2500 c/mm3 in 10 (90%) patients. Out of the four patients in whom serum ferritin was tested, it was elevated (above 500 ng/ml) in all patients; and was above 1000 ng/ml in three patients. Hemophagocytic lymphohistiocytosis was diagnosed in two patients. This is a unique finding of our series. Both of these patients succumbed to the illness. A cerebrospinal fluid study was done in six patients and revealed normal values except in one patient. Troponin assays were done in seven patients and were positive in five patients indicating that myocarditis is a major contributor to shock, which is one of the commonest complications in KFD. Serum creatinine phosphokinase ranged from 656 to 23,000 U/L. Conclusions Altered sensorium was the most common alarming symptom that warrants referral to a higher centre. The major organ involvements that dominated the clinical presentation and course of illness were neurological complications, hypotension, significantly contributed by myocarditis and acute respiratory distress syndrome/pneumonitis. Encephalitis, myocarditis, ARDS and HLH were the major complications that caused mortality in our series. The elevated serum ferritin and the mortality associated with HLH described need further research to investigate the role of the macrophage system in the pathogenesis of severe KFD.
PubMed: 38854314
DOI: 10.7759/cureus.59971