Effect of diamagnetic Zn(II) ions on the SMM properties of a series of trinuclear ZnDy2 and tetranuclear Zn2Dy2 (LnIII = Dy, Tb, Gd) complexes: combined experimental and theoretical studies.

To study the effect of diamagnetic ions on magnetic interactions, utilizing a compartmental ligand (Z)-2-(hydroxymethyl)-4-methyl-6-((quinolin-8-ylimino)methyl)phenol (LH2), two different series of ZnII-LnIII complexes, namely the trinuclear series of [DyZn2(L)2(µ2-OAc)2(CH3OH)2]·NO3·MeOH (1), [TbZn2(L)2(µ2-OAc)2(CH3OH)2]·NO3·5MeOH·H2O (2), and [GdZn2(L)2(µ2-OAc)2(CH3OH)2]·NO3·MeOH·CHCl3 (3) and the tetranuclear series of [Dy2Zn2(LH)4(NO3)4(µ2OAc)]·NO3·MeOH·H2O (4), [Tb2Zn2(LH)4(NO3)4(µ2-OAc)]·NO3·MeOH·2H2O (5), and [Gd2Zn2(LH)4(NO3)4(µ2-OAc)]·NO3·MeOH·2H2O (6), were synthesized. Trinuclear ZnII-LnIII complexes 1-3 consist of one LnIII ion sandwiched between two peripheral ZnII ions forming a bent type ZnII-DyIII-ZnII array with an angle of 110.64°. Tetranuclear ZnII-LnIII complexes 4-6 are basically a combination of two dinuclear moieties of [LnZn(LH)2(NO3)2]+ connected by one bidentate bridging acetate ion in µ2-OAc coordination mode. The detailed magnetic analysis reveals that complexes 1 and 4 are single molecule magnets having energy barriers of 34.98 K and 46.71 K with relaxation times (τ0) of 5.05 × 10-4 s and 5.24 × 10-4 s, respectively. Ab initio calculations were employed to analyze the magnetic anisotropy and magnetic exchange interaction between the ZnII and LnIII centers with the aim of gaining better insights into the magnetic dynamics of complexes 1-6.

Clarifying the Anatomy of Tetralogy of Fallot with S-shaped Ascending Aorta.

We recently encountered several cases of tetralogy of Fallot with an abnormally oriented S-shaped ascending aorta. In this retrospective study, we sought to clarify morphology of this unusual under-recognized variant. Databases were reviewed to identify all patients with tetralogy of Fallot having an S-shaped ascending aorta. Computed tomographic angiography was used for the assessment of cardiac morphology. Out of the 21 patients, 18 (86%) had a right aortic arch, 2 (9%) had a left aortic arch, and the remaining patient (5%) had a double aortic arch. Patients with a right aortic arch, compared to age and sex-matched patients with a right aortic arch but normally oriented ascending aorta, had lesser aortic override (29.3 ± 14% vs 54.8 ± 13.2%; p = 0.0001) and a wider ascending aorta (25.2 ± 6.9 vs 18.0 ± 3.2 mm; p = 0.0003). The S-shaped ascending aorta was located posteriorly, with a higher sterno-aortic distance (25.5 ± 7.7 vs 9.9 ± 4.5 mm; p = 0.0001). The ascending aorta among patients with tortuosity was longer (4.12 ± 1.7 vs 3.07 ± 0.82, p = 0.03) but with similar tortuosity index (1.22 ± 0.19 vs 1.15 ± 0.17, p = 0.23). Of the cases with right aortic arch and S-shaped ascending aorta, 16 (89%) had extrinsic compression of the right pulmonary artery (p = 0.0001), while 7 (39%) had crossed pulmonary arteries (p = 0.008), with no such findings among those with normally oriented ascending aorta. Tetralogy of Fallot with an S-shaped ascending aorta is a variant with lesser aortic override and a more posteriorly located ascending aorta. Compression of the right pulmonary artery and crossed pulmonary arteries is frequent in the presence of a right-sided aortic arch. These findings have important implications for optimal diagnosis and surgical repair.

Recent Advances in Drug Delivery Systems Targeting Insulin Signalling for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of neurofibrillary tangles and amyloid-ß plaques. Recent research has unveiled the pivotal role of insulin signaling dysfunction in the pathogenesis of AD. Insulin, once thought to be unrelated to brain function, has emerged as a crucial factor in neuronal survival, synaptic plasticity, and cognitive processes. Insulin and the downstream insulin signaling molecules are found mainly in the hippocampus and cortex. Some molecules responsible for dysfunction in insulin signaling are GSK-3ß, Akt, PI3K, and IRS. Irregularities in insulin signaling or insulin resistance may arise from changes in the phosphorylation levels of key molecules, which can be influenced by both stimulation and inactivity. This, in turn, is believed to be a crucial factor contributing to the development of AD, which is characterized by oxidative stress, neuroinflammation, and other pathological hallmarks. Furthermore, this route is known to be indirectly influenced by Nrf2, NF-κB, and the caspases. This mini-review delves into the intricate relationship between insulin signaling and AD, exploring how disruptions in this pathway contribute to disease progression. Moreover, we examine recent advances in drug delivery systems designed to target insulin signaling for AD treatment. From oral insulin delivery to innovative nanoparticle approaches and intranasal administration, these strategies hold promise in mitigating the impact of insulin resistance on AD. This review consolidates current knowledge to shed light on the potential of these interventions as targeted therapeutic options for AD.

Support Vector Machine-Based Prediction Models for Drug Repurposing and Designing Novel Drugs for Colorectal Cancer.

Colorectal cancer (CRC) has witnessed a concerning increase in incidence and poses a significant therapeutic challenge due to its poor prognosis. There is a pressing demand to identify novel drug therapies to combat CRC. In this study, we addressed this need by utilizing the pharmacological profiles of anticancer drugs from the Genomics of Drug Sensitivity in Cancer (GDSC) database and developed QSAR models using the Support Vector Machine (SVM) algorithm for prediction of alternative and promiscuous anticancer compounds for CRC treatment. Our QSAR models demonstrated their robustness by achieving a high correlation of determination (R2) after 10-fold cross-validation. For 12 CRC cell lines, R2 ranged from 0.609 to 0.827. The highest performance was achieved for SW1417 and GP5d cell lines with R2 values of 0.827 and 0.786, respectively. Further, we listed the most common chemical descriptors in the drug profiles of the CRC cell lines and we also further reported the correlation of these descriptors with drug activity. The KRFP314 fingerprint was the predominantly occurring descriptor, with the KRFPC314 fingerprint following closely in prevalence within the drug profiles of the CRC cell lines. Beyond predictive modeling, we also confirmed the applicability of our developed QSAR models via in silico methods by conducting descriptor-drug analyses and recapitulating drug-to-oncogene relationships. We also identified two potential anti-CRC FDA-approved drugs, viomycin and diamorphine, using QSAR models. To ensure the easy accessibility and utility of our research findings, we have incorporated these models into a user-friendly prediction Web server named "ColoRecPred", available at https://project.iith.ac.in/cgntlab/colorecpred. We anticipate that this Web server can be used for screening of chemical libraries to identify potential anti-CRC drugs.

Immunomodulation by juglone alleviates acute graft-versus-host disease without compromising the graft-versus-leukaemia activity in mice.

BACKGROUND AND PURPOSE: Acute graft-versus-host disease (GVHD) remains a major barrier to successful transplantation outcomes. Recent studies have shown that pharmacotherapy for GVHD should target both the innate and adaptive inflammatory immune responses. Juglone, a redox-active phytochemical found in walnuts, has shown potent anti-inflammatory effects in models of colitis and inflammatory bowel disease. However, its effects on T-cell-mediated immune responses remain largely unknown. Considering the overlapping mediators of inflammation in GVHD and the aforementioned conditions, we investigated the use of juglone as a prophylactic agent for GVHD. EXPERIMENTAL APPROACH: Immunomodulatory activity and mechanism of action of juglone were studied using murine splenic leukocytes in vitro. The GVHD prophylactic efficacy of orally administered juglone was evaluated using a murine model of allogeneic haematopoietic stem cell transplantation based on an MHC mismatch. KEY RESULTS: Juglone exhibited immunomodulatory activity by (i) inhibiting the activation of dendritic cells and CD4+ T-cells, (ii) inhibiting cytokine secretion and lymphocyte proliferation, and (iii) inducing exhaustion of CD4+ T-cells, as shown by increased expression of CTLA-4 (CD152) and Fas (CD95). Oral administration of juglone significantly reduced mortality and morbidity associated with GVHD while maintaining graft-versus-leukaemia activity. This was accompanied by a decrease in the number of naïve CD4+ cells, and an increase in the number of CD4+ and CD8+ central memory T-cells. CONCLUSION AND IMPLICATIONS: Juglone is a potent immunomodulator for GVHD prophylaxis. Our study is the first to provide a dosage framework for the oral administration of juglone that can be used for clinical development.

Electric-Field-Tunable Edge Transport in Bernal-Stacked Trilayer Graphene.

This Letter presents a nonlocal study on the electric-field-tunable edge transport in h-BN-encapsulated dual-gated Bernal-stacked (ABA) trilayer graphene across various displacement fields (D) and temperatures (T). Our measurements revealed that the nonlocal resistance (R_{NL}) surpassed the expected classical Ohmic contribution by a factor of at least 2 orders of magnitude. Through scaling analysis, we found that the nonlocal resistance scales linearly with the local resistance (R_{L}) only when the D exceeds a critical value of ∼0.2 V/nm. Additionally, we observed that the scaling exponent remains constant at unity for temperatures below the bulk-band gap energy threshold (T<25 K). Further, the value of R_{NL} decreases in a linear fashion as the channel length (L) increases. These experimental findings provide evidence for edge-mediated charge transport in ABA trilayer graphene under the influence of a finite displacement field. Furthermore, our theoretical calculations support these results by demonstrating the emergence of dispersive edge modes within the bulk-band gap energy range when a sufficient displacement field is applied.

The correlation between obesity and prostate volume in patients with benign prostatic hyperplasia: A prospective cohort study.

OBJECTIVE/BACKGROUND: Benign prostatic hyperplasia (BPH) is increasing substantial burden on health care systems. Men with high body mass index (BMI) have bigger prostate volumes (PV) with subsequent increase in lower urinary tract symptoms (LUTS) than men with normal BMI. The purpose of this research was to investigate the correlation between Obesity and PV in patients with BPH. METHOD: The study included 560 patients (50-80 years) with BPH. Weight and height measured to calculate BMI. TRUS was used to measure PV. Patient demographics such as IPSS score and prostate specific antigen (PSA) were also noted. RESULTS: Patients in the study had a mean age of 65.3 ± 9.45 years and the mean BMI was 23.97 ± 4.89 kg/m2. The mean PV of each BMI group were 37.45 ± 0.81, 57.89 ± 1.52 and 77.94 ± 2.17 (ml) for normal, overweight and obese groups, respectively, and the average PV score was 57.76 ± 1.50 ml. The mean PSA score was 3.26 ± 0.94 (ng/dl) with a range of 0.6-10.4. There was significant correlation between BMI and PV (p = 0.001) as well as between BMI with PSA and IPSS (p = 0.02, 0.001, respectively). CONCLUSION: The results showing strong correlation between BMI and PV also BMI with PSA and IPSS. Therefore reducing weight may lead to a lower prostate volume in the elderly stage, making LUTS less noticeable and improving quality of life.

Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Mechanistic insights into the potential role of dietary polyphenols and their nanoformulation in the management of Alzheimer's disease.

Alzheimer's disease (AD) is a very common neurodegenerative disorder associated with memory loss and a progressive decline in cognitive activity. The two major pathophysiological factors responsible for AD are amyloid plaques (comprising amyloid-beta aggregates) and neurofibrillary tangles (consisting of hyperphosphorylated tau protein). Polyphenols, a class of naturally occurring compounds, are immensely beneficial for the treatment or management of various disorders and illnesses. Naturally occurring sources of polyphenols include plants and plant-based foods, such as fruits, herbs, tea, vegetables, coffee, red wine, and dark chocolate. Polyphenols have unique properties, such as being the major source of anti-oxidants and possessing anti-aging and anti-cancerous properties. Currently, dietary polyphenols have become a potential therapeutic approach for the management of AD, depending on various research findings. Dietary polyphenols can be an effective strategy to tackle multifactorial events that occur with AD. For instance, naturally occurring polyphenols have been reported to exhibit neuroprotection by modulating the Aß biogenesis pathway in AD. Many nanoformulations have been established to enhance the bioavailability of polyphenols, with nanonization being the most promising. This review comprehensively provides mechanistic insights into the neuroprotective potential of dietary polyphenols in treating AD. It also reviews the usability of dietary polyphenol as nanoformulation for AD treatment.

A Cross-Sectional Survey to Assess the Preparedness of Healthcare Workers of Isolation Intensive Care Units for Anticipated Another Wave of the COVID-19 Pandemic in a Tertiary Care Center.

BACKGROUND: Our fight against coronavirus disease 2019 (COVID-19) has not ended yet. Another wave, possibly due to another variant, can put the healthcare system on its toes again. The outcome of the intensive care unit (ICU) depends on the teamwork of doctors, nursing staff, and care assistants (CAs). AIM: This survey was conducted to assess the level of preparedness of healthcare workers (HCWs) in isolation ICUs by recording and calculating the score of their responses, using a validated pre-formed questionnaire. METHODS: A cross-sectional survey was conducted on 200 HCWs in isolation ICUs by using a pre-validated questionnaire form as an assessment tool. HCWs in isolation ICUs included doctors, nurses, and CAs who have worked in ICUs dedicated to COVID-19 patients. The response was documented and scores as per the response were assessed by analog scale. RESULTS: Most of the HCWs were anxious (53%) and 96.5% were either bothered or scared. HCWs with adequate knowledge have higher generalized anxiety disorder scores (χ2 = 15.287, p = 0.015). Despite having adequate/average knowledge, most of the HCWs have insufficient knowledge of the correct steps of donning and doffing. CONCLUSION: HCWs were aware of the COVID-19 pandemic but were not prepared for the anticipated second wave.

Computational identification of candidate inhibitors for Dihydrofolate reductase in Acinetobacter baumannii.

Acinetobacter baumannii is one of the emerging causes of hospital acquired infections and this bacterium, due to multi-drug resistant and Extensive Drug resistant has been able to develop resistance against the antimicrobial agents that are being used to eliminate it. A.baumannii has been the cause of death in immune compromised patients in hospitals. Hence it is the urgent need of time to find potential inhibitors for this bacterium to cease its virulence and affect its survival inside host organisms. The Dihydrofolate reductase enzyme, which is an important biocatalyst in the conversion of Dihydrofolate to Tetrahydrofolate, is an important drug target protein. In the present study high throughput screening is used to identify the inhibitors of this enzyme. The prioritized ligand molecular candidates identified through virtual screening for the substrate binding site of the predicted model are Z1447621107, Z2604448220 and Z1830442365. The Molecular Dynamics Simulation study suggests that potential inhibitor of the Dihydrofolate reductase enzyme would prevent bacteria from completing its life cycle, affecting its survival. Finally the complexes were analysed for binding free energy of the Dihydrofolate reductase enzyme complexes with the ligands.

Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.

Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.

Corrigendum: Cytokinin and abiotic stress tolerance -What has been accomplished and the way forward?

[This corrects the article DOI: 10.3389/fgene.2022.943025.].

A Spin-Frustrated Azide- and Alkoxide-Bridged Heterobimetallic Mixed-Valence MnIIMnIII2NiII4 Disc with S = 17/2 or 19/2.

Seven-membered homometallic FeIII7, MnIII3MnII4 coordination clusters were previously reported to be spin-frustrated molecular discs. Herein, a mixed bimetallic and mixed-valence dicationic [MnIIMnIII2NiII4(N3)4(hmp)10](NO3)2 (12+(NO3)2) was isolated in pure form without scrambling of Ni/Mn ions. It was structurally characterized by single-crystal X-ray single-crystal diffraction. The presence of MnII ions at the center of the disc has been confirmed by EPR measurements. The magnetic studies suggest that complex 12+(NO3)2 possesses spin frustration with spin ground states S = 17/2 and 19/2, which has been studied and supported by DFT calculation. The purity of 12+(NO3)2 was confirmed by powder XRD measurements, and the ratio of Ni:Mn = 4:3 was further determined by SEM-EDX analysis.

Powders to Thin Films: Advances in Conjugated Microporous Polymer Chemical Sensors.

Chemical sensing of harmful species released either from natural or anthropogenic activities is critical to ensuring human safety and health. Over the last decade, conjugated microporous polymers (CMPs) have been proven to be potential sensor materials with the possibility of realizing sensing devices for practical applications. CMPs found to be unique among other porous materials such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) due to their high chemical/thermal stability, high surface area, microporosity, efficient host-guest interactions with the analyte, efficient exciton migration along the π-conjugated chains, and tailorable structure to target specific analytes. Several CMP-based optical, electrochemical, colorimetric, and ratiometric sensors with excellent selectivity and sensing performance were reported. This review comprehensively discusses the advances in CMP chemical sensors (powders and thin films) in the detection of nitroaromatic explosives, chemical warfare agents, anions, metal ions, biomolecules, iodine, and volatile organic compounds (VOCs), with simultaneous delineation of design strategy principles guiding the selectivity and sensitivity of CMP. Preceding this, various photophysical mechanisms responsible for chemical sensing are discussed in detail for convenience. Finally, future challenges to be addressed in the field of CMP chemical sensors are discussed.

Preclinical evaluation of engineered L-asparaginase variants to improve the treatment of Acute Lymphoblastic Leukemia.

INTRODUCTION: Escherichia coli l-asparaginase (EcA), an integral part of multi-agent chemotherapy protocols of acute lymphoblastic leukemia (ALL), is constrained by safety concerns and the development of anti-asparaginase antibodies. Novel variants with better pharmacological properties are desirable. METHODS: Thousands of novel EcA variants were constructed using protein engineering approach. After preliminary screening, two mutants, KHY-17 and KHYW-17 were selected for further development. The variants were characterized for asparaginase activity, glutaminase activity, cytotoxicity and antigenicity in vitro. Immunogenicity, pharmacokinetics, safety and efficacy were tested in vivo. Binding of the variants to pre-existing antibodies in primary and relapsed ALL patients' samples was evaluated. RESULTS: Both variants showed similar asparaginase activity but approximately 24-fold reduced glutaminase activity compared to wild-type EcA (WT). Cytotoxicity against Reh cells was significantly higher with the mutants, although not toxic to human PBMCs than WT. The mutants showed approximately 3-fold lower IgG and IgM production compared to WT. Pharmacokinetic study in BALB/c mice showed longer half-life of the mutants (KHY-17- 267.28±9.74; KHYW-17- 167.41±14.4) compared to WT (103.24±18). Single and repeat-doses showed no toxicity up to 2000 IU/kg and 1600 IU/kg respectively. Efficacy in ALL xenograft mouse model showed 80-90 % reduction of leukemic cells with mutants compared to 40 % with WT. Consequently, survival was 90 % in each mutant group compared to 10 % with WT. KHYW-17 showed over 2-fold lower binding to pre-existing anti-asparaginase antibodies from ALL patients treated with l-asparaginase. CONCLUSION: EcA variants demonstrated better pharmacological properties compared to WT that makes them good candidates for further development.

Comparative study of the outcomes of newly developed polypropylene-based modified trabeculectomy and glaucoma shunt surgery in neovascular glaucoma.

BACKGROUND: Neovascular glaucoma (NVG) is a secondary glaucoma with a poor visual prognosis. Trabeculectomy with antifibrotic agents, glaucoma drainage devices (GDDs), and cyclo-destructive procedures are recommended in patients who are refractory to medical management. However, due to the poor success rate of conventional trabeculectomy and the higher cost of GDDs, alternative procedures need to be looked at. PURPOSE: To compare the surgical outcomes and economic aspects of a newly developed polypropylene suture bed-based modified trabeculectomy to Ahmed glaucoma valve (AGV) implantation for NVG. METHODS: It was a prospective interventional study conducted at a tertiary care center between 2018 and 2020. Consecutive patients with NVG with a minimum follow-up of 18 months were included. Surgical outcomes are mainly based on intraocular pressure (IOP) control and the cost of surgery. RESULTS: Sixty eyes were included out of which 40 (60.6%) underwent modified trabeculectomy and 20 (33.7%) underwent AGV. At the final follow-up, no significant difference (P < 0.05) was found between the surgical outcomes of both groups. The complete success rate (IOP < 21 mm Hg without antiglaucoma medications) was 60 and 65% while the qualified success rate (IOP < 21 mm Hg with antiglaucoma medications) was 30 and 25% in modified trabeculectomy and AGV groups, respectively, at final follow-up. The cost of surgery was significantly higher in the AGV group (P < 0.0001). CONCLUSION: Modified trabeculectomy as described might be a better alternative for NVG eyes.

Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble ß-amyloid peptide (Aß) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD.

Understanding the diabetes self-care behaviour in rural areas: Perspective of patients with type 2 diabetes mellitus and healthcare professionals.

BACKGROUND: Diabetes self-care behaviour plays a crucial role in managing the diabetes effectively and preventing complications. Patients with type 2 diabetes mellitus (T2DM) and health care professionals (HCPs) of rural areas often face unique challenges when it comes to diabetes self-care practices (SCPs). Therefore, this study aim to explore the perspectives of patients with T2DM and HCPs on diabetes SCPs. METHODS: Eight focus group discussions (FGDs) among individuals with T2DM and In-depth interviews (IDIs) with 15 HCPs were conducted in rural areas of Punjab, North India. Capability, Opportunity, Motivation, and Behaviour model (COM-B) was employed for thematic framework analyses. RESULTS: The study participants perceived that a limited understanding of diabetes mellitus (DM), beliefs in alternative therapies, drug side effects, attitudes towards DM (psychological capability), comorbidities (physical capability), family support (social opportunity), financial and time constraints, and weather conditions (physical opportunity) contributed to lack of DM SCPs. Physicians' guidance and support were motivating them to adhere to SCPs, especially when aligned with their sense of self-efficacy (reflective motivation). HCPs constraints in providing patient-centred care are due to training limitations (psychological capability) and a lack of essential resources (physical opportunities). Participants expressed need for comprehensive diabetes care (automatic motivation) through structured diabetes education intervention to improve diabetes SCPs. CONCLUSIONS: The study findings indicate that various factors influence diabetes SCPs from the perspectives of both patients with T2DM and HCPs and emphasizes the need for a multi-faceted approach to improve diabetes SCPs in rural areas. Implementing a structured diabetes self-care intervention strategy in rural areas may help for preventing and mitigating the impact of diabetes-related complications in rural areas.