Prenatal opioid exposure has been associated with developmental problems, including autonomic nervous system dysregulation. However, little is known about the effects of prenatal opioid exposure on ...the autonomic nervous system beyond the first days of life, particularly across both the parasympathetic and sympathetic branches, and when accounting for exposure to other substances. The present study examined the effects of prenatal exposure to opioid agonist therapy (OAT, e.g., methadone) and other opioids on infant autonomic nervous system activity at rest and in response to a social stressor (the Still‐Face Paradigm) at six months among 86 infants varying in prenatal opioid and other substance exposure. Results indicated that OAT and other opioids have unique effects on the developing autonomic nervous system that may further depend on subtype (i.e., methadone versus buprenorphine) and timing in gestation. Results are discussed in the context of theoretical models of the developing stress response system.
Prenatal opioid exposure (POE) is a major public health concern and impacts the fetal and neonatal autonomic nervous system (ANS). However, little is known about POE effects on the ANS beyond the neonatal period and accounting for other substance exposure. The present study describes the effects of POE on infant respiratory sinus arrhythmia and pre‐ejection period at six months of age and the differential effects of type and timing of exposure in the context of polysubstance exposure.
Cancer is one of the major causes of human mortality worldwide. A number of existing antineoplastic medications and treatment regimens are already working in the field, and several new compounds are ...in different phases of clinical trials. An extensive series of anticancer drugs exist in the market, and studies suggest that these molecules are associated with different types of adverse side effects. The reduction of the cytotoxicity of drugs to normal cells is a major problem in anticancer therapy. Therefore, researchers around the globe are involved in the development of more efficient and safer anticancer drugs. The output of extensive research is that the quinazoline scaffold and its various derivatives can be explored further as a novel class of cancer chemotherapeutic agents that has already shown promising activities against different tumours. Quinazoline derivatives have already occupied a crucial place in modern medicinal chemistry. Various research has been performed on quinazoline and their derivatives for anticancer activity and pharmacological importance of this scaffold has been well established.
The aim of this review is to compile and highlight the developments concerning the anticancer activity of quinazoline derivatives as well as to suggest some new aspects of the expansion of anticancer activity of novel quinazoline derivatives as anticancer agents in the near future.
Recent literature related to quinazoline derivatives endowed with encouraging anticancer potential is reviewed. With a special focus on quinazoline moiety, this review offers a detailed account of multiple mechanisms of action of various quinazoline derivatives: inhibition of the DNA repair enzyme system, inhibition of EGFR, thymidylate enzyme inhibition and inhibitory effects for tubulin polymerization by which these derivatives have shown promising anticancer potential.
Exhaustive literature survey indicated that quinazoline derivatives are associated with properties of inhibiting EGFR and thymidylate enzymes. It was also found to be involved in disturbing tubulin assembly. Furthermore, quinazoline derivatives have been found to inhibit critical targets such as DNA repair enzymes. These derivatives have shown significant activity against cancer.
In cancer therapy, Quinazoline derivatives seems to be quite promising and act through various mechanisms that are well established. This review has shown that quinazoline derivatives can further be explored for the betterment of chemotherapy. A lot of potentials are still hidden, which demands to be discovered for upgrading quinazoline derivatives efficacy.
On account of significant biological activities, quinoline derivatives have drawn more attention to the synthesis and biological activities in the search for new therapeutic agents. Several new ...synthetic approaches have been implemented to derive new molecules from quinoline and all the synthesized molecules showed effective anticancer activity.
Some molecules are synthesized using quinolones as precursor reactant, which is another effective product of quinoline, also showing significant activity against malignant tumors. The presence of nitrogen in it and its ability to bind with enzymes like gyrase, topoisomerase II and kinase have also proven it with antitumor activity.
This review encapsulates the recent advances in the synthesis and anticancer activity of Quinoline derivatives.
Diarrhoea is a global health problem. More than a quarter of diarrhoeal deaths occur among children less than five years. Different literatures analyzed presentation and outcomes of less than five ...diarrhoeal children. The world has made remarkable progress in reducing child mortality. So, older children are growing in number. Our aim was to identify clinical differentials and variations of pathogens among younger (less than five) and older (five to nine years) diarrhoeal children.
Data were extracted from the diarrhoeal disease surveillance system (DDSS) of Dhaka Hospital (urban site) and Matlab Hospital (rural site) of the International Centre for Diarrhoeal Disease Research, Bangladesh for the period of January 2012 to December 2021. Out of 28,781 and 12,499 surveillance patients in Dhaka and Matlab Hospital, 614 (2.13%) and 278 (2.22%) children were five to nine-years of age, respectively. Among under five children, 2456 from Dhaka hospital and 1112 from Matlab hospital were selected randomly for analysis (four times of five to nine years age children, 1:4).
Vomiting, abdominal pain, and dehydrating diarrhoea were significantly higher in older children in comparison to children of less than five years age (p-value <0.05) after adjusting study site, gender, antibiotic use before hospitalization, diarrhoeal duration < 24 hours, intake of oral rehydration fluid at home, parental education, WASH practice and history of cough. Vibrio. cholerae, Salmonella, and Shigella were the common fecal pathogen observed among older children compared to under five after adjusting for age, gender and study site.
Although percentage of admitted diarrhoeal children with five to nine years is less than under five years children but they presented with critical illness with different diarrhoeal pathogens. These observations may help clinicians to formulate better case management strategies for children of five to nine years that may reduce morbidity.
Future targets are a promising prospect to overcome the limitation of conventional and current approaches by providing secure and effective treatment without compromising patient compliance. Diabetes ...mellitus is a fast-growing problem that has been raised worldwide, from 4% to 6.4% (around 285 million people) in past 30 years. This number may increase to 430 million people in the coming years if there is no better treatment or cure is available. Ageing, obesity and sedentary lifestyle are the key reasons for the worsening of this disease. It always had been a vital challenge, to explore new treatment which could safely and effectively manage diabetes mellitus without compromising patient compliance. Researchers are regularly trying to find out the permanent treatment of this chronic and life threatening disease. In this journey, there are various treatments available in market to manage diabetes mellitus such as insulin, GLP-1 agonist, biguanides, sulphonyl ureas, glinides, thiazolidinediones targeting the receptors which are discovered decade before. PPAR, GIP, FFA1, melatonin are the recent targets that already in the focus for developing new therapies in the treatment of diabetes. Inspite of numerous preclinical studies very few clinical data available due to which this process is in its initial phase. The review also focuses on the receptors like GPCR 119, GPER, Vaspin, Metrnl, Fetuin-A that have role in insulin regulation and have potential to become future targets in treatment for diabetes that may be effective and safer as compared to the conventional and current treatment approaches.
Antimicrobial resistance against shigellosis is increasingly alarming. However, evidence-based knowledge gaps regarding the changing trends of shigellosis in Bangladesh exist due to the scarcity of ...longitudinal data on antimicrobial resistance. Our study evaluated the last 20 years antimicrobial resistance patterns against shigellosis among under-5 children in the urban and rural sites of Bangladesh. Data were extracted from the Diarrheal Disease Surveillance System (DDSS) of Dhaka Hospital (urban site) and Matlab Hospital (rural site) of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between January 2001 and December 2020. We studied culture-confirmed shigellosis cases from urban Dhaka Hospital (n = 883) and rural Matlab Hospital (n = 1263). Since 2001, a declining percentage of shigellosis in children observed in urban and rural sites. Moreover, higher isolation rates of Shigella were found in the rural site 1263/15684 (8.1%) compared to the urban site 883/26804 (3.3%) in the last 20 years. In both areas, S. flexneri was the predominant species. The upward trend of S. sonnei in both the study sites was statistically significant after adjusting for age and sex. WHO-recommended 1st line antibiotic ciprofloxacin resistance gradually reached more than 70% in both the urban and rural site by 2020. In multiple logistic regression after adjusting for age and sex, ciprofloxacin, azithromycin, mecillinam, ceftriaxone, and multidrug resistance (resistance to any two of these four drugs) among under-5 children were found to be increasing significantly (p<0.01) in the last 20 years in both sites. The study results underscore the importance of therapeutic interventions for shigellosis by appropriate drugs based on their current antibiogram for under-5 children. These observations may help policymakers in formulating better case management strategies for shigellosis.
Antimicrobial resistance against shigellosis is increasingly alarming. However, evidence-based knowledge gaps regarding the changing trends of shigellosis in Bangladesh exist due to the scarcity of ...longitudinal data on antimicrobial resistance. Our study evaluated the last 20 years antimicrobial resistance patterns against shigellosis among under-5 children in the urban and rural sites of Bangladesh. Data were extracted from the Diarrheal Disease Surveillance System (DDSS) of Dhaka Hospital (urban site) and Matlab Hospital (rural site) of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between January 2001 and December 2020. We studied culture-confirmed shigellosis cases from urban Dhaka Hospital (n = 883) and rural Matlab Hospital (n = 1263). Since 2001, a declining percentage of shigellosis in children observed in urban and rural sites. Moreover, higher isolation rates of Shigella were found in the rural site 1263/15684 (8.1%) compared to the urban site 883/26804 (3.3%) in the last 20 years. In both areas, S. flexneri was the predominant species. The upward trend of S. sonnei in both the study sites was statistically significant after adjusting for age and sex. WHO-recommended 1st line antibiotic ciprofloxacin resistance gradually reached more than 70% in both the urban and rural site by 2020. In multiple logistic regression after adjusting for age and sex, ciprofloxacin, azithromycin, mecillinam, ceftriaxone, and multidrug resistance (resistance to any two of these four drugs) among under-5 children were found to be increasing significantly (p<0.01) in the last 20 years in both sites. The study results underscore the importance of therapeutic interventions for shigellosis by appropriate drugs based on their current antibiogram for under-5 children. These observations may help policymakers in formulating better case management strategies for shigellosis.
•Hepatic biomarkers can be used to identify the presence of liver damage, its severity, prognosis, pharmacologic source, or the type of hepatotoxicity.•Different hepatic biomarkers are explored as ...noninvasive identifiers for hepatic damage, as well as clinical variables linked with it.•These biomarkers will assist us in evaluating signals as potential indicators of liver injury, which serve as bridge markers for tracking hepatic disease and hepatotoxicity.
Hepatotoxicity is the foremost issue for clinicians and the primary reason for pharmaceutical product recalls. A biomarker is a measurable and quantifiable attribute used to evaluate the efficacy of a treatment or to diagnose a disease. There are various biomarkers which are used for the detection of liver disease and the intent of liver damage.
This review aims to investigate the current state of hepatotoxicity biomarkers and their utility in clinical settings. Using hepatic biomarkers, the presence of liver injury, its severity, prognosis, causative agent, and type of hepatotoxicity can all be determined.
Relevant published articles up to 2022 were systematically retrieved from MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as drug toxicity, hepatotoxicity biomarkers, biochemical parameters, and nonalcoholic fatty liver disease.
In clinical trials and everyday practice, biomarkers of drug-induced liver injury are essential for spotting the most severe cases of hepatotoxicity. Hence, developing novel biomarker approaches to enhance hepatotoxicity diagnosis will increase specificity and/or identify the person at risk. Importantly, early clinical studies on patients with liver illness have proved that some biomarkers such as aminotransferase, bilirubin, albumin, and bile acids are even therapeutically beneficial.
By assessing the unique signs of liver injury, health care professionals can rapidly and accurately detect liver damage and evaluate its severity. These measures contribute to ensuring prompt and effective medical intervention, hence reducing the risk of long-term liver damage and other major health concerns.
The graphical abstract depicts major aspects of hepatotoxicity including: its biochemical parameters, drug factors responsible for liver toxicity, heavy metal toxicity, epidemiology, clinical signs of hepatotoxicity, and stages of liver damage. Display omitted
To identify dietary patterns in US infants at age 6 and 12 months, sociodemographic differences in these patterns, and their associations with infant growth from age 6 to 12 months.
We analyzed a ...subsample (760 boys and 795 girls) of the Infant Feeding Practices Study II (2005-2007). Mothers reported their infants' intakes of 18 types of foods in the past 7 days, which were used to derive dietary patterns at ages 6 and 12 months by principal component analysis.
Similar dietary patterns were identified at ages 6 and 12 months. At 12 months, infants of mothers who had low education or non-Hispanic African American mothers (vs non-Hispanic white) had a higher score on "High sugar/fat/protein" dietary pattern. Both "High sugar/fat/protein" and "High dairy/regular cereal" patterns at 6 months were associated with a smaller increase in length-for-age z score (adjusted β per 1 unit dietary pattern score, -1.36 95% confidence interval (CI), -2.35 to -0.37 and -0.30 -0.54 to -0.06, respectively), while with greater increase in BMI z score (1.00 0.11 to 1.89 and 0.32 0.10 to 0.53, respectively) from age 6 to 12 months. The "Formula" pattern was associated with greater increase in BMI z score (0.25 0.09 to 0.40). The "Infant guideline solids" pattern (vegetables, fruits, baby cereal, and meat) was not associated with change in length-for-age or BMI z score.
Distinct dietary patterns exist among US infants, vary by maternal race/ethnicity and education, and have differential influences on infant growth. Use of "Infant guideline solids" with prolonged breastfeeding is a promising healthy diet for infants after age 6 months.
