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Journal of Thrombosis and Haemostasis :... Jun 2024Antiphospholipid antibodies (aPL), including lupus anticoagulant (LA), antibodies against β2 glycoprotein I (anti-β2GPI) and anticardiolipin antibodies (aCL) are...
BACKGROUND
Antiphospholipid antibodies (aPL), including lupus anticoagulant (LA), antibodies against β2 glycoprotein I (anti-β2GPI) and anticardiolipin antibodies (aCL) are associated with ischemic stroke (IS). Their prevalence and clinical relevance in atrial fibrillation (AF) remain unclear.
AIM
To assess whether aPL are associated with increased risk of ischemic stroke (IS) in AF patients despite anticoagulation.
MATERIAL AND METHODS
We conducted a post hoc analysis of aPL using blood samples from 243 consecutive AF patients enrolled in the cohort study. Markers of a prothrombotic state, including endogenous thrombin potential (ETP), fibrin clot permeability and lysis time were measured at baseline. During a median follow-up of 52 months, IS/transient ischemic attack (TIA) and major bleeding were recorded.
RESULTS
We observed aPL at a moderate or high titer in 51 (21%) patients, including 17 (7%) with anti-β2GPI, 19 (7.8%) with aCL antibodies, and 37 (15.2%) with LA. aPL-positive patients were more likely to have prior stroke (p=0.01) and be active smokers (p=0.03), along with increased ETP (p=0.02), without any changes in fibrin clot properties. Anti-β2GPI (HR=4.38, 95% CI 1.58-12.19) and aCL (HR=4.70, 95% CI 1.80-12.30) at a moderate or high titer were associated with IS during follow-up (n=20; 1.9%/year). There were 23 major bleedings (2.1% per year) and 20 deaths (1.9% per year), which were not associated with aPL.
CONCLUSION
Our study showed a relatively high prevalence of aPL-positivity in AF patients, which was linked to increased risk of IS/TIA. This suggests that screening for aPL might help optimizing anticoagulant therapy in such patients.
PubMed: 38944242
DOI: 10.1016/j.jtha.2024.05.038 -
Current Problems in Cardiology Jun 2024Public health, personal/community health behaviors, health care delivery, and the scientific community have all been impacted by the COVID-19 pandemic and are... (Review)
Review
Public health, personal/community health behaviors, health care delivery, and the scientific community have all been impacted by the COVID-19 pandemic and are consequently poised to consider substantial paradigm shifts that will enhance disease prevention and public health resilience. The current analysis compares the newly developed Lifestyle Health Index (LHI) to U.S. county-level COVID-19 vaccination, infection, and mortality rates. We linked Centers of Disease Control PLACES, the U.S. Community Profile Report, and Nationhood lab databases through common zip-code identifiers to determine the association between county-level LHI scores and COVID-19 outcomes and vaccination status against the backdrop of U.S. regions with distinct cultural phenotypes. There was a statistically significant relationship between a poor LHI, lower COVID-19 vaccination rates and higher COVID-19 infection and mortality rates. There were clear differences in outcomes across the U.S. regions, suggesting distinct regional cultural characteristics may significantly influence health behaviors and outcomes. In the U.S., a syndemic comprising unhealthy lifestyle, chronic disease, and COVID-19 resulted in unnecessary hospitalizations and deaths. Politicization of the pandemic, socioeconomic inequity and regional cultural values meaningfully contributed to the uneven distribution of poor outcomes during this syndemic. Components of the syndemic were avoidable and should not be repeated. Condensed Abstract: The unhealthy lifestyle - chronic disease - COVID-19 U.S. syndemic resulted in unnecessary hospitalizations and deaths. Politicization of the pandemic, socioeconomic inequity and regional cultural values meaningfully contributed to the uneven distribution of poor outcomes during this syndemic. Components of the syndemic were avoidable and should not be repeated.
PubMed: 38944225
DOI: 10.1016/j.cpcardiol.2024.102728 -
Microbial Pathogenesis Jun 2024Cervical cancer (CC) is the fourth most common cancer among female patients. The primary cause of all types of cervical cancer is human papillomavirus (HPV), which was...
Cervical cancer (CC) is the fourth most common cancer among female patients. The primary cause of all types of cervical cancer is human papillomavirus (HPV), which was projected to account for 5,70,000 reported cases in 2018. Two HPV strains (16 and 18) account for 70% of cervical abnormalities and precancerous cervical cancers. CC is one of the main causes of the 17% cancer-related death rate among Indian women between the ages of 30 and 69 is CC. The side effects of the currently approved treatments for cervical cancer could endanger the lives of women affected by the illness. Thus, probiotics may be extremely important in the management of CC. Numerous studies on probiotics and their potential for use in cancer diagnosis, prevention, and treatment have been conducted. This review describes the enhancement of the immune system, promotion of a balanced vaginal microbiome, and decreased risk of secondary infections, which have anti-inflammatory effects on the body. Probiotics have the potential to reduce inflammation, thereby adversely affecting cancer cell growth and metastasis. During the course of antibiotic therapy, they support a balanced vaginal microbiome. Oncogenic virus inactivation is possible with probiotic strains. In postmenopausal women, the use of vaginal probiotics helps lessen menopausal symptoms caused by Genitourinary Syndrome of Menopause (GSM). The antitumor effects of other medications can be enhanced by them as potential agents, because they can both promote the growth of beneficial bacteria and reduce the quantity of potentially harmful bacteria. The development of tumors and the proliferation of cancer cells may be indirectly affected by the restoration of the microbial balance. Probiotics may be able to prevent and treat cervical cancer, as they seem to have anticancer properties. To identify probiotics with anticancer qualities that can supplement and possibly even replace traditional cancer treatments, further investigation is required, including carefully planned clinical trials.
PubMed: 38944216
DOI: 10.1016/j.micpath.2024.106764 -
Free Radical Biology & Medicine Jun 2024Phenol red (PR) is a commonly used compound in culture media as a pH indicator. However, it is unknown whether this compound can interfere with the pharmacological...
Phenol red (PR) is a commonly used compound in culture media as a pH indicator. However, it is unknown whether this compound can interfere with the pharmacological induction of ferroptosis. Here, using high-content live-cell imaging death analysis, we determined that the presence of PR in the culture medium preconditioned normal and tumor cells to ferroptosis induced by system x inhibition mediated by imidazole ketone erastin (IKE) or GPX4 blockade in response to RSL-3, but had no significant effects against treatment with the endoperoxide FINO. Mechanistically, we revealed that PR decreases the levels of the antiferroptotic genes Slc7a11, Slc3a2, and Gpx4, while promoting the overexpression de Acls4, a key inducer of ferroptosis. Additionally, through superresolution analysis, we determined that the presence of PR mislocalizes the system x from the plasma membrane. Thus, our results show that the presence of PR in the culture medium can be a problematic artifact for the accurate interpretation of cell sensitivity to IKE or RSL-3-mediated ferroptosis induction.
PubMed: 38944214
DOI: 10.1016/j.freeradbiomed.2024.06.023 -
The American Journal of the Medical... Jun 2024Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD.
PubMed: 38944203
DOI: 10.1016/j.amjms.2024.06.022 -
Drug Discovery Today Jun 2024Cervical cancer (CC) is one of the leading causes of death among women worldwide. The current treatments for this cancer consist of invasive methods such as... (Review)
Review
Cervical cancer (CC) is one of the leading causes of death among women worldwide. The current treatments for this cancer consist of invasive methods such as chemotherapeutic drugs, radiation, immunotherapy and surgery, which could lead to severe side effects and hinder the patient's life quality. Although metal-based therapies, including cisplatin and ruthenium-based compounds, offer promising alternatives, they lack specificity and harm healthy cells. Combining metal nanoparticles with standard approaches has demonstrated remarkable efficacy and safety in the fight against CC. Overall, this review is intended to show the latest advancements and insights into metal-based strategies, creating a promising path for more effective and safer treatments in the battle against CC.
PubMed: 38944184
DOI: 10.1016/j.drudis.2024.104073 -
International Journal of Biological... Jun 2024Diabetes mellitus is a chronic disease leading to the death of millions a year across the world. Insulin is required for Type 1, Type 2, and gestational diabetic... (Review)
Review
Diabetes mellitus is a chronic disease leading to the death of millions a year across the world. Insulin is required for Type 1, Type 2, and gestational diabetic patients, however, there are various modes of insulin delivery out of which oral delivery is noninvasive and convenient. Moreover, factors like insulin degradation and poor intestinal absorption play a crucial role in its bioavailability and effectiveness. This review discusses various types of engineered nanoparticles used in-vitro, in-vivo, and ex-vivo insulin delivery along with their administration routes and physicochemical properties. Injectable insulin formulations, currently in use have certain limitations, leading to invasiveness, low patient compliance, causing inflammation, and side effects. Based on these drawbacks, this review emphasizes more on the non-invasive route, particularly oral delivery. The article is important because it focuses on how engineered nanoparticles can overcome the limitations of free therapeutics (drugs alone), navigate the barriers, and accomplish precision therapeutics in diabetes. In future, more drugs could be delivered with a similar strategy to cure various diseases and resolve challenges in drug delivery. This review significantly describes the role of various engineered nanoparticles in improving the bioavailability of insulin by protecting it from various barriers during non-invasive routes of delivery.
PubMed: 38944087
DOI: 10.1016/j.ijbiomac.2024.133437 -
The Lancet. Child & Adolescent Health Jun 2024Population-based statistics on deaths from child abuse and neglect are only routinely available in countries that have reliable national statistics on child murder. For...
BACKGROUND
Population-based statistics on deaths from child abuse and neglect are only routinely available in countries that have reliable national statistics on child murder. For low-income and middle-income countries, relatively little is known about prevalence trends of child murder. South Africa is an exception, having conducted dedicated national studies on child murders for 2009 and 2017 to provide data on child murders overall and on child abuse and neglect-related murders. We aimed to compare child abuse and neglect-related murders in South Africa across two surveys to determine any change between 2009 and 2017.
METHODS
We conducted two retrospective national mortuary-based surveys on murder of children aged 0-17 years for 2009 and 2017 from a proportionate random sample of medico-legal laboratories in South Africa. A sampling frame of medico-legal laboratories for each study year was prepared with stratification by medico-legal laboratory size. A minimum of 2 years after the crime was allowed before data collection to enable progression of the investigation process. Child abuse and neglect-related murders were identified using both medico-legal laboratory post-mortem autopsy reports and police data. To identify a child abuse and neglect-related murder, we primarily used the framework of abuse happening within the context of responsibility of care arrangements but broadened this to include all perpetrators and abuse identified from the data. We stratified age into 0-4, 5-9, 10-14, and 15-17 years and further stratified children younger than 5 years into early neonates (newborns killed within 6 days of birth), 7 days to 11 months, and 1-4 years. We calculated incidence rate ratios (IRR) with 95% CIs to compare rates between 2009 and 2017.
FINDINGS
An estimated 458 (95% CI 377-539) children in 2009 and 213 (179-247) children in 2017 were murdered in circumstances of child abuse and neglect. The percentage of all child murders that were child abuse and neglect-related declined from 2009 to 2017 (458 [45·0%] of 1018 in 2009 vs 213 [25·0%] of 851 in 2017), with the overall age-standardised rate decreasing from 2·6 to 1·1 per 100 000 children aged 0-17 years (IRR 0·43 [95% CI 0·35-0·54]). Girls represented 276 (60·3%) of 458 murders in 2009, which declined to 96 (45·1%) of 213 murders in 2017, and boys represented 178 (38·9%) of 458 murders in 2009 and 109 (51·4%) of 213 murders in 2017. The decrease was statistically significant for girls in the 0-4 year (IRR 0·33 [0·22-0·49]) and 5-9 year (0·33 [0·15-0·73]) age groups and for boys in the 0-4 year age group (0·49 [0·33-0·71]). Among early neonates (within 6 days of birth), the decrease in child abuse and neglect-related murders was more pronounced among girls than among boys (IRR 0·33 [95% CI 0·19-0·56] vs 0·46 [0·28-0·77]).
INTERPRETATION
Child abuse and neglect-related murders are common in South Africa but our study shows that they can be reduced. The high rate of these murders points to the need to continue research and monitoring to inform priority targeted interventions and to better understand the impact of child support policies.
FUNDING
Ford Foundation and South African Medical Research Council.
PubMed: 38944051
DOI: 10.1016/S2352-4642(24)00110-X -
Lancet (London, England) Jun 2024Neonatal sepsis remains one of the key challenges of neonatal medicine, and together with preterm birth, causes almost 50% of all deaths globally for children younger... (Review)
Review
Neonatal sepsis remains one of the key challenges of neonatal medicine, and together with preterm birth, causes almost 50% of all deaths globally for children younger than 5 years. Compared with advances achieved for other serious neonatal and early childhood conditions globally, progress in reducing neonatal sepsis has been much slower, especially in low-resource settings that have the highest burden of neonatal sepsis morbidity and mortality. By contrast to sepsis in older patients, there is no universally accepted neonatal sepsis definition. This poses substantial challenges in clinical practice, research, and health-care management, and has direct practical implications, such as diagnostic inconsistency, heterogeneous data collection and surveillance, and inappropriate treatment, health-resource allocation, and education. As the clinical manifestation of neonatal sepsis is frequently non-specific and the current diagnostic standard blood culture has performance limitations, new improved diagnostic techniques are required to guide appropriate and warranted antimicrobial treatment. Although antimicrobial therapy and supportive care continue as principal components of neonatal sepsis therapy, refining basic neonatal care to prevent sepsis through education and quality improvement initiatives remains paramount.
PubMed: 38944044
DOI: 10.1016/S0140-6736(24)00495-1 -
Epilepsy & Behavior : E&B Jun 2024Status epilepticus (SE) is a medical and neurologic emergency that may lead to permanent brain damage, morbidity, or death. Animal models of SE are particularly...
Status epilepticus (SE) is a medical and neurologic emergency that may lead to permanent brain damage, morbidity, or death. Animal models of SE are particularly important to study the pathophysiology of SE and mechanisms of SE resistance to antiseizure medications with the aim to develop new, more effective treatments. In addition to rodents (rats or mice), larger mammalian species such as dogs, pigs, and nonhuman primates are used. This short review describes and discusses the value and limitations of the most frequently used mammalian models of SE. Issues that are discussed include (1) differences between chemical and electrical SE models; (2) the role of genetic background and environment on SE in rodents; (3) the use of rodent models (a) to study the pathophysiology of SE and mechanisms of SE resistance; (b) to study developmental aspects of SE; (c) to study the efficacy of new treatments, including drug combinations, for refractory SE; (d) to study the long-term consequences of SE and identify biomarkers; (e) to develop treatments that prevent or modify epilepsy; (e) to study the pharmacology of spontaneous seizures; (4) the limitations of animal models of induced SE; and (5) the advantages (and limitations) of naturally (spontaneously) occurring SE in epileptic dogs and nonhuman primates. Overall, mammalian models of SE have significantly increased our understanding of the pathophysiology and drug resistance of SE and identified potential targets for new, more effective treatments. This paper was presented at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in April 2024.
PubMed: 38944026
DOI: 10.1016/j.yebeh.2024.109923