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1.
Blood Cancer J ; 14(1): 99, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890297

ABSTRACT

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 rate was 25.6% (50/195). We additionally identified several pre-therapy factors predictive of inferior CR1 including male gender (P = 0.026), ≥2 autosomal monosomies (P < 0.001), -17/17p (P = 0.011), multi-hit TP53 allelic state (P < 0.001) and CUX1 co-alterations (P = 0.010). In univariable analysis of the entire cohort, inferior OS24 was predicated by ≥2 monosomies (P = 0.004), TP53 VAF > 25% (P = 0.002), TP53 splice junction mutations (P = 0.007) and antecedent treated myeloid neoplasm (P = 0.001). In addition, mutations/deletions in CUX1, U2AF1, EZH2, TET2, CBL, or KRAS ('EPI6' signature) predicted inferior OS24 (HR = 2.0 [1.5-2.8]; P < 0.0001). In a subgroup analysis of HMA +/-Ven treated individuals (N = 144), TP53 VAF and monosomies did not impact OS24. A risk score for HMA +/-Ven treated individuals incorporating three pre-therapy predictors including TP53 splice junction mutations, EPI6 and antecedent treated myeloid neoplasm stratified 3 prognostic distinct groups: intermediate, intermediate-poor, and poor with significantly different median (12.8, 6.0, 4.3 months) and 24-month (20.9%, 5.7%, 0.5%) survival (P < 0.0001). For the first time, in a seemingly monolithic high-risk cohort, our data identifies several baseline factors that predict response and 24-month survival.


Subject(s)
Mutation , Tumor Suppressor Protein p53 , Humans , Male , Female , Aged , Tumor Suppressor Protein p53/genetics , Middle Aged , Aged, 80 and over , Adult , Prognosis , Treatment Outcome
2.
Front Plant Sci ; 15: 1393305, 2024.
Article in English | MEDLINE | ID: mdl-38841280

ABSTRACT

Pecan (Carya illinoensis), an economically important deciduous tree, bears commercially valuable nutritional nuts. Spring freezes in April can severely injure pecan buds, decreasing bloom, and fruit set. This study determined how low temperatures affect pecan buds/flowers at different growth stages in several pecan scion/rootstock combinations. This study focused on three pecan scion/rootstock combinations: Pawnee/Peruque (PP), Kanza/Giles (KG), and Maramec/Colby (MC), grown at the Cimarron Valley Research Station, Perkins, Oklahoma. Branches at three different growth stages, i.e., outer bud scale shed, one week after bud break, and early bloom stages were collected from PP, MC, and KG. Branches were held in a Conviron E8 freezing unit at 4 temperatures (-2, 0, 2, and 4°C) for 4 and 8 hours; A total of 8 treatments. One sample set was kept as an untreated control. After 2-3 weeks, branch samples from all the temperature treatments were observed and categorized into two groups. Group one with number of branches had healthy buds/formation of healthy leaves/flowers and group two with number of dead branches. The carbohydrate content reserved from dormant was analyzed using an Anthrone reagent. Visual observations and carbohydrate analyses revealed differences in damage and carbohydrate content among the scion/rootstock combinations, low-temperature treatments, and growth stages. The MC combination had minimum visual damage to leaves, buds, and flowers and significantly lower soluble sugars and starch in bark phloem as well as significantly lower soluble sugars in woody tissue xylem. The KG combination had maximum visual damage and significantly higher soluble sugars and starches in the bark, and soluble sugars in the woody tissues. These results indicate the MC combination is more tolerant to spring freeze damage at all three growth stages compared to the other two pecan scion/rootstock combinations. The results also demonstrate the MC combination is using more non-structural carbohydrates, soluble sugars and starches, suggesting this is a possible mechanism in its freeze tolerance.

3.
BMJ Open ; 14(4): e080303, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38626969

ABSTRACT

INTRODUCTION: Anaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high in this age group. Hepcidin remains high in ACD, preventing utilisation of iron for heme synthesis. Vitamin D3 has shown hepcidin suppression activity in both in vitro and in vivo studies. As there is no study assessing the effect of iron-folic acid (IFA) with vitamin D3 on haemoglobin levels in the elderly in India, we want to conduct this study to estimate the impact of supplementation of a therapeutic package of IFA and vitamin D3 on haemoglobin levels in the elderly with mild-to-moderate anaemia in comparison with IFA only. The study will also assess the impact of the proposed intervention on ferritin, hepcidin, 25-hydroxyvitamin D, C reactive protein (CRP) and parathyroid hormone (PTH) levels. METHODS AND ANALYSIS: This study is a community-based, double-blind, placebo-controlled, randomised trial. The study will be done in the Kalyani municipality area. Individuals aged ≥60 years with mild-to-moderate anaemia and normal vitamin D3 levels will be randomised into the intervention (IFA and vitamin D3 supplementation) group or the control group (IFA and olive oil as placebo). All medications will be self-administered. Follow-up will be done on a weekly basis for 12 weeks. The calculated sample size is 150 in each arm. Block randomisation will be done. The primary outcome is change in haemoglobin levels from baseline to 12 weeks. Secondary outcome is change in serum ferritin, 25-hydroxyvitamin D, hepcidin, CRP and PTH levels from baseline to 12 weeks. ETHICS AND DISSEMINATION: Ethical approval from the Institutional Ethics Committee of All India Institute of Medical Sciences Kalyani has been obtained (IEC/AIIMS/Kalyani/Meeting/2022/03). Written informed consent will be obtained from each study participant. The trial results will be reported through publication in a reputable journal and disseminated through health talks within the communities. TRIAL REGISTRATION NUMBER: CTRI/2022/05/042775. PROTOCOL VERSION: Version 1.0.


Subject(s)
Anemia, Iron-Deficiency , Anemia , Humans , Aged , Iron , Cholecalciferol/therapeutic use , Hepcidins , Dietary Supplements , Folic Acid , Anemia/drug therapy , Anemia/epidemiology , Vitamin D , Vitamins/therapeutic use , Ferritins , C-Reactive Protein/metabolism , Double-Blind Method , Calcifediol , Hemoglobins/metabolism , Randomized Controlled Trials as Topic
4.
Int J Cancer ; 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642029

ABSTRACT

In low- and middle-income countries most of the cancer patients attend the hospital at a late stage and treatment completion of these cases is challenging. The early detection program (EDP), in rural areas of Punjab state, India was initiated to identify breast, cervical, and oral cancer at an early stage by raising awareness and providing easy access to diagnosis and treatment. A total of 361 health education programs and 99 early detection clinics were organized. The symptomatic and self-interested (non-symptomatic individuals who opted for screening) cases visited the detection clinic. They were screened for breast, cervical, and/or oral cancer. Further diagnosis and treatment of screen-positive cases were carried out at Homi Bhabha Cancer Hospital (HBCH), Sangrur. Community leaders and healthcare workers were involved in all the activities. The EDP, Sangrur removed barriers between cancer diagnosis and treatment with the help of project staff. From 2019 to 2023, a total of 221,317 populations were covered. Symptomatic and self-interested individuals attended the breast (1627), cervical (1601), and oral (1111) examinations. 46 breast (in situ-4.3%; localized-52.2%), 9 cervical (localized-77.8%), and 12 oral (localized-66.7%) cancer cases were detected, and treatment completion was 82.6%, 77.8%, and 50.0%, respectively. We compared cancer staging and treatment completion of cases detected through EDP with the cases attended HBCH from Sangrur district in 2018; the difference between two groups is statistically significant. Due to the early detection approach, there is disease down-staging and improvement in treatment completion. This approach is feasible and can be implemented to control these cancers in low- and middle-income countries.

5.
Phytopathology ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38648116

ABSTRACT

In this review, we highlight studies where whole genome sequencing, comparative genomics and population genomics have provided unprecedented insights into past and ongoing pathogen evolution. These include new understanding of adaptive evolution of secretion systems and their effectors. We focus on Xanthomonas pathosystems that have seen intensive study and improved our understanding of pathogen emergence and evolution, particularly in the context of host specialization: citrus canker, bacterial blight of rice, and bacterial spot of tomato and pepper. Across pathosystems, pathogens appear to follow a pattern of bursts of evolution and diversification that impact host adaptation. There remains a need for studies on the mechanisms of host range evolution and genetic exchange among closely related but differentially host-specialized species, and to start moving beyond the study of specific strain and host cultivar pairwise interactions to thinking about these pathosystems in a community context.

6.
ISME Commun ; 4(1): ycae037, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38645272

ABSTRACT

Structurally complex corn bran arabinoxylan (CAX) was used as a model glycan to investigate gut bacteria growth and competition on different AX-based fine structures. Nine hydrolyzate segments of the CAX polymer varying in chemical structure (sugars and linkages), CAX, five less complex non-corn arabinoxylans, and xylose and glucose were ranked from structurally complex to simple. The substrate panel promoted different overall growth and rates of growth of eight Bacteroides xylan-degrading strains. For example, Bacteroides cellulosilyticus DSM 14838 (Bacteroides cellulosilyticus) grew well on an array of complex and simple structures, while Bacteroides ovatus 3-1-23 grew well only on the simple structures. In a competition experiment, B. cellulosilyticus growth was favored over B. ovatus on the complex AX-based structure. On the other hand, on the simple structure, B. ovatus strongly outcompeted B. cellulosilyticus, which was eliminated from the competitive environment by Day 11. This adaptation to fine structure and resulting competition dynamics indicate that dietary fiber chemical structures, whether complex or simple, favor certain gut bacteria. Overall, this work supports a concept that fiber degraders diversify their competitive abilities to access substrates across the spectrum of heterogeneity of fine structural features of dietary fibers.

7.
J Pharm Bioallied Sci ; 16(Suppl 1): S118-S121, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595606

ABSTRACT

Background: Knowledge and awareness studies reveal the basic information of the community and the misconceptions in relation to practices of a disease. The identification of such factors is important as they directly influence the health care-related interventions. Hypertension is one of the emerging noncommunicable diseases (NCDs) globally. So, we conducted this study to assess the status of our community regarding hypertension. Materials and Methods: The study was conducted on 300 hypertensive patients to assess the knowledge and awareness by a hypertension fact questionnaire. Medication adherence was assessed in the same group of patients by Hill-Bone scale-a uniform scale used worldwide. Results: Our study revealed a greater number of females with hypertension as compared to males and a maximum number of patients being in the age-group of 61-70 years and belonging to rural areas. Most of the patients had a secondary education as a highest educational qualification with only 10% of patients being postgraduates. A fair number of patients had a good knowledge and awareness about their disease, and most of the respondents accounted forgetfulness as a main reason for nonadherence to therapy over other reasons. Conclusion: Our population has good knowledge and awareness about their disease despite not having very good educational qualifications, and we need to strengthen our healthcare programs for even more greater dissemination of information.

8.
Cureus ; 16(2): e53692, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38455788

ABSTRACT

Introduction Lip prints are the characteristic pattern of wrinkles and grooves on the labial mucosa. Lip prints can be classified into various patterns and can be used for personal identification as they are unique and do not change during the life of a person. Cheiloscopy is a forensic investigation technique that deals with the identification of humans based on lip traces. Objectives This study aimed to investigate the distribution of lip print patterns, to assess gender differences, and to calculate the lip score using a weighted value scoring system. Material and methods A cross-sectional study was carried out in the Department of Anatomy, All India Institute of Medical Sciences (AIIMS), Guwahati, India, from May to October 2023, after getting approval from the Institutional Ethics Committee (IEC). A total of 200 individuals (100 males and 100 females) were included in the study. Each lip print was divided into four quadrants. In each quadrant, up to 14 grooves were marked from the midline, and the pattern of each groove was observed. Each pattern was given an Arabic numeral score. Weighted values were given for the grooves in descending order from 15 to 1 with reference to their position from the midline of the lip print. The product of the Arabic numeral score of the groove and the weighted value of the groove is the lip line score. The sum of the lip line scores was calculated. Results The most common pattern observed in the present study is type II, with 3,816/12,000 (31.8%), followed by type I' with 3,146/12,000 (26.21%), type I with 1,865/12000 (15.54%), type III with 1,491/12,000 (12.42%), type IV with 1,133/12,000 (9.44%), and type V with 549/12,000 (4.5%). The mean total lip score is 1,467.68 (1,486.41 in males and 1448.96 in females). Conclusion Lip prints are unique and useful for personal identification, as the lip score in various quadrants and the total lip score are different for different individuals.

9.
Heliyon ; 10(6): e27814, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38533012

ABSTRACT

Two-pore K+ (TPK) channels are voltage-independent and involved in stress response in plants. Herein, we identified 12 TaTPK genes located on nine chromosomes in the Triticum aestivum genome. The majority of TaTPK genes comprised two exons. Each TaTPK channel comprised four transmembrane (TM) helices, N- and C-terminal ion-channel domains, two EF-hand domains and one 14-3-3 binding site. Additionally, highly conserved 'GYGD' motif responsible for K+ ion specificity, was found in between the TMs in both the ion-channel domains. Nine TaTPK channels were predicted to be localised at the plasma membrane, while three were vacuolar. The protein-protein and protein-chemical interactions indicated the coordinated functioning of the TaTPK channels with the other K+ transporters and their possible interaction with the Ca2+-signaling pathway. Expression studies suggested their importance in both vegetative and reproductive tissues development. Significantly modulated expression of various TaTPK genes during heat, drought, combined heat and drought and salt stresses, and after fungal infestation, depicted their function in stress responses. The miRNAs and transcription factors interaction analyses suggested their role in the hormone, light, growth and development-related, and stress-responsive signaling cascades. The current study suggested vital functions of various TaTPK genes, especially in stress response, and would provide an opportunity for their detailed characterization in future studies.

10.
Indian J Otolaryngol Head Neck Surg ; 76(1): 262-267, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38440660

ABSTRACT

The metabolic syndrome (MS) is a cluster of conditions that occur. togehther, increase risk of heart disease, storke, type 2 diabetes mellitus and hypertension as a possible outcome. The previous research has shown a link between hearing loss and being overweight, diabetic, or suffering from heart disease. However, research on the possible link between hearing loss and metabolic syndrome is limited. Hearing loss due to metabolic syndrome was evaluated in the present investigation. Two hundred individuals with metabolic syndrome were included. All the patients were evaluated on three types of audiometry (pure tone, impedence, and DPOAE).Anthropometric data, blood pressure, blood sugar, and lipid profiles, were all collected from each patient. We also asked about their smoking and drinking habits in the past. SPSS v. 22.0 was used to conduct the statistical analysis. Overall, SNHL affected 58.5% of patients. Patients having moderate hearing loss were the largest demographic group (40%), followed by those with mild hearing loss (15% ). Severe hearing loss only occurred in 3.5% of patients. Hearing loss was shown to be more prevalent in patients with more than three components of metabolic syndrome. Significant associations were found between hearing impairment and metabolic risk factors as waist circumference, fasting blood sugar, serum high-density lipoprotein, serum triglycerides, and systolic and diastolic blood pressure. Hearing loss was only marginally connected to smoking and excessive drinking.

11.
ACS Sens ; 9(2): 615-621, 2024 02 23.
Article in English | MEDLINE | ID: mdl-38315454

ABSTRACT

Self-assembly of misfolded proteins can lead to the formation of amyloids, which are implicated in the onset of many pathologies including Alzheimer's disease and Parkinson's disease. The facile detection and discrimination of different amyloids are crucial for early diagnosis of amyloid-related pathologies. Here, we report the development of a fluorescent coumarin-based two-sensor array that is able to correctly discriminate between four different amyloids implicated in amyloid-related pathologies with 100% classification. The array was also applied to mouse models of Alzheimer's disease and was able to discriminate between samples from mice corresponding to early (6 months) and advanced (12 months) stages of Alzheimer's disease. Finally, the flexibility of the array was assessed by expanding the analytes to include functional amyloids. The same two-sensor array was able to correctly discriminate between eight different disease-associated and functional amyloids with 100% classification.


Subject(s)
Alzheimer Disease , Parkinson Disease , Animals , Mice , Alzheimer Disease/pathology , Amyloid/metabolism , Amyloidogenic Proteins/metabolism , Coumarins
13.
Sensors (Basel) ; 24(4)2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38400486

ABSTRACT

The Zero Trust safety architecture emerged as an intriguing approach for overcoming the shortcomings of standard network security solutions. This extensive survey study provides a meticulous explanation of the underlying principles of Zero Trust, as well as an assessment of the many strategies and possibilities for effective implementation. The survey begins by examining the role of authentication and access control within Zero Trust Architectures, and subsequently investigates innovative authentication, as well as access control solutions across different scenarios. It more deeply explores traditional techniques for encryption, micro-segmentation, and security automation, emphasizing their importance in achieving a secure Zero Trust environment. Zero Trust Architecture is explained in brief, along with the Taxonomy of Zero Trust Network Features. This review article provides useful insights into the Zero Trust paradigm, its approaches, problems, and future research objectives for scholars, practitioners, and policymakers. This survey contributes to the growth and implementation of secure network architectures in critical infrastructures by developing a deeper knowledge of Zero Trust.

14.
J Conserv Dent Endod ; 27(1): 42-45, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38389735

ABSTRACT

Background: Endodontic infections have been clearly described as biofilm-mediated infections. Bacteria and their by-products have been known to cause these infections. With the introduction of new drugs and the use of nanoparticles in recent times, there has been a significant reduction in the bacterial load in endodontic infections. Aims and Objectives: The in vitro study focuses on checking the antibacterial efficacy of silver nanoparticles and its combination with other medicaments against the root canal pathogen - Enterococcus faecalis (E. faecalis). Methodology: In the present study, 140 extracted human teeth were used. The teeth were sectioned, and biomechanical preparation was done. The root canals of the extracted teeth were inoculated with the culture of E. faecalis. The teeth were divided into six groups based on the intracanal medicament used: Group 1 - Silver nanocure gelGroup 2 - Silver nanocure gel + Cavisept gel (1:1)Group 3 - Silver nanocure gel + Aveu-Cal gel (1:1)Group 4 - Silver nanocure gel + Cavisept gel + Aveu-Cal gel (1:1:1)Group 5 - Positive control (specimens were inoculated with Enterococcus faecalis and left untreated to confirm the presence of infection)Group 6 - Negative control (no bacterial contamination of specimens). The colony-forming units were recorded after 48 h of incubation. Results: The statistical analysis of the colony-forming units was done using the Kruskal-Wallis tests. Silver nanocure gel + Cavisept gel + Aveu-Cal gel (1:1:1) showed the least colony-forming units. Conclusion: The present study is an in vitro study, in which we concluded that the combination of all the intracanal medicaments is the best for the elimination of E. faecalis biofilm from the root canal. The above findings need to be tested in vivo also.

15.
Curr Diabetes Rev ; 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38351690

ABSTRACT

Diseases that are caused by a person's everyday habits are known as lifestyle diseases. Habits that devoid people of their daily activities and direct them towards a sedentary lifestyle cause numerous health problems that can lead to non-communicable diseases. Noncommunicable diseases, or NCDs, kill more than 41 million individuals per year, accounting for 74% of all deaths worldwide. In India, 63% of all fatalities were attributed to NCDs in 2016, with 23% of those deaths being early. Compared to the current state of various lifestyle diseases, the prevalence of adult obesity, hypertension, and other lifestyle disorders in Punjab was determined by the National Family Healthcare Surveys (NFHS-4 and NFHS-5). NFHS-5 survey conducted in Punjab was used to examine the general distribution of these disorders. The National Family Health Survey 2019-21 (NFHS-5), the fifth survey in the NFHS series, provides information on the population, health, and nutritional status of all states and union territories (UT) in India. NFHS-5 also gives district-level estimates for several crucial variables, similar to the NFHS-4 survey 2015-16.

16.
Curr Diabetes Rev ; 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38275038

ABSTRACT

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes that damages the retina, leading to blindness. People with type 1 diabetes are at greater risk of developing DR than people with type 2 diabetes. Diabetic retinopathy may be divided into two primary categories: proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (NPDR). There are multiple risk factors for the onset and progression of diabetic retinopathy, such as hypertension, obesity, smoking, duration of diabetes, and genetics. Numerous investigations have evaluated the levels of a wide range of inflammatory chemokines within DR patients' serum, vitreous, and aqueous fluids. In diabetic retinopathy, the vitreous fluid exhibited rises in angiogenic factors like platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) or declines in antiangiogenic factors like pigment epithelium-derived factor (PEDF). For prevention of diabetic retinopathy, more physical activity as well as less sedentary behavior were linked to a reduced likelihood of DR. Supplementing with nutraceuticals containing vitamins (B1, B2, B6, B12, C, D, E, and l-methyl folate) and mineral (zinc) can help decrease or avoid an outbreak of DR. Only laser photocoagulation and Anti-vascular endothelial growth factor (Anti-VEGF) injections are advised as favorable therapies in severe retinopathy. When it comes to treating DR's VEGF levels, inflammation, oxidative stress, apoptosis, and angiogenesis, traditional Chinese medicine (TCM) has an excellent future.

17.
Trials ; 25(1): 34, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38195605

ABSTRACT

BACKGROUND: Stroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery. METHODS: This randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale. DISCUSSION: We hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT05479006 . Registered on 26 July 2022.


Subject(s)
Motor Disorders , Stroke , Transcranial Direct Current Stimulation , Adult , Humans , Cross-Over Studies , Stroke/diagnosis , Stroke/therapy , Upper Extremity , Randomized Controlled Trials as Topic
18.
Mol Divers ; 28(1): 97-110, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36853528

ABSTRACT

Pro-inflammation, which is developed due to the increased production of cytokines, mainly interleukin-6 (IL-6), during the working of immune system pathways, becomes a major concern these days for many researchers. So, it is desired to design, screen, and synthesize new molecules with multi-parametric features showing their efficacy for Toll-like receptors (TLRs) and inhibiting the disease-causing receptor sites like viral infections, cancers, etc. along with controlling inflammation, fever, and other side effects during such pathways. Further, looking at the literature, curcumin a multi-targeted agent is showing its efficiency toward various receptor sites involved in many diseases as mentioned above. This fascinated us to build up new molecules which behave like curcumin with minimum side effects. In silico studies, involving ADMET studies, toxicological data, and docking analyses, of newly synthesized compounds (3-5) along with tautomers of curcumin i.e., (1-2), and some reported compounds like 9 and 10 have been studied in detail. Great emphasis has been made on analyzing binding energies, protein-ligand structural interactions, stabilization of newly synthesized molecules against various selected receptor sites using such computational tools. Compound 3 is the most efficient multifunctional agent, which has shown its potential toward most of the receptor sites in docking analysis. It has also responded well in Molecular dynamics (MD) simulation toward 5ZLN, 4RJ3, 4YO9, 4YOJ, and 1I1R sites. Finally, studies were extended to understand in vitro anti-inflammatory activity for particularly compound 3 in comparison to diclofenac and curcumin, which signifies the efficiency of compound 3.


Subject(s)
Antineoplastic Agents , Curcumin , Humans , Curcumin/pharmacology , Curcumin/chemistry , Molecular Docking Simulation , Antineoplastic Agents/pharmacology , Pyrimidines , Immune System , Inflammation , Purines
19.
AIDS Care ; 36(1): 17-25, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37666211

ABSTRACT

Findings on the association between childhood sexual abuse (CSA) and antiretroviral therapy (ART) adherence have been varied, with some studies showing a relationship, or a lack thereof. However, to our knowledge, no study has examined this association among older adults living with HIV (OALH). Therefore, the purpose of this study was to examine the association between CSA and ART adherence among OALH using a mixed methods approach. This study, which involved a concurrent design, had two phases. The first phase comprised in-depth, semi-structured interviews of 24 adults aged 50 and older living with HIV in South Carolina. The second phase included data from 91 OALH. Thematic analysis and multivariable regression models, adjusting for age, gender, race, and income, were used to determine the association between CSA and ART adherence. The main theme emerging from the qualitative data was that CSA was not linked with ART adherence. However, contrastingly, quantitative analyses revealed a negative statistically significant association between CSA and ART adherence (adjusted ß: -3.35; 95% CI: -5.37, -1.34). This difference in findings could be due to the hidden impact of trauma and/or the use of different study populations. Future research should assess mediating pathways between CSA and ART adherence.


Subject(s)
HIV Infections , Sex Offenses , Humans , Child , Middle Aged , Aged , HIV Infections/drug therapy , Anti-Retroviral Agents/therapeutic use , Gender Identity , Medication Adherence
20.
AIDS Care ; 36(3): 291-295, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37288795

ABSTRACT

HIV disproportionately affects the South compared to other regions of the US. Some people living with HIV (PLWH) may acquire HIV-associated neurocognitive disorders (HAND), of which HIV-associated dementia (HAD) is the most severe form. This study aimed to examine the disparities in mortality among individuals with HAD. Data were obtained from the South Carolina Alzheimer's Disease and Related Dementias Registry from 2010 to 2016 (HAD: n = 505; N = 164,982). Logistic regression and Cox proportional hazards models were used to determine mortality related to HIV-associated dementia and potential sociodemographic differences. Adjusted models controlled for age, gender, race, rurality, and place of diagnosis. Individuals diagnosed in a nursing facility were three times more likely to die with HAD compared to those diagnosed in the community (OR: 3.25; 95% CI: 2.08-5.08). Black populations were more likely to die with HAD compared to White populations (OR: 1.52; 95% CI: 0.953-2.42). Disparities in mortality among patients with HAD were found in place of diagnosis and by race. Future research should determine if mortality among individuals with HAD were as a result of HAD or non-HIV related decline.


Subject(s)
AIDS Dementia Complex , HIV Infections , Humans , South Carolina/epidemiology , HIV Infections/complications , HIV Infections/psychology , Population Groups , Health Inequities
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