HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus-Based In Vivo Prediction in Humans: Part I.

Tolterodine tartrate (TOTA) is associated with adverse effect, high hepatic access, varied bioavailability, slight aqueous solubility, and short half-life after oral delivery. Hansen solubility parameters (HSP, HSPiP program), experimental solubility (T = 298.2 to 318.2 K and p = 0.1 MPa), computational (van't Hoff and Apelblat models), and thermodynamic models were used to the select solvent(s). HSPiP predicted PEG400 as the most suitable co-solvent based on HSP values (δd = 17.88, δp = 4.0, and δh = 8.8 of PEG400) and comparable to the drug (δd = 17.6, δp = 2.4, and δh = 4.6 of TOTA). The experimental mole fraction solubility of TOTA was maximum (xe = 0.0852) in PEG400 confirming the best fit of the prediction. The observed highest solubility was attributed to the δp and δh interacting forces. The activity coefficient (ϒi) was found to be increased with temperature. The higher values of r2 (linear regression coefficient) and low RMSD (root mean square deviation) indicated a good correlation between the generated "xe" data for crystalline TOTA and the explored models (modified Apelblat and van't Hoff models). TOTA solubility in "PEG400 + water mixture" was endothermic and entropy-driven. IR (immediate release product) formulation can be tailored using 60% PEG400 in buffer solution for 2 mg of TOTA in 0.25 mL (dosing volume). The isotonic binary solution was associated with a pH of 7.2 suitable for sub-Q delivery. The approach would be a promising alternative with ease of delivery to children and aged patients.

Harnessing the Power of Stimuli-Responsive Nanoparticles as an Effective Therapeutic Drug Delivery System.

The quest for effective and reliable methods of delivering medications, with the aim of improving delivery of therapeutic agent to the intended location, has presented a demanding yet captivating field in biomedical research. The concept of smart drug delivery systems is an evolving therapeutic approach, serving as a model for directing drugs to specific targets or sites. These systems have been developed to specifically target and regulate the administration of therapeutic substances in a diverse array of chronic conditions, including periodontitis, diabetes, cardiac diseases, inflammatory bowel diseases, rheumatoid arthritis, and different cancers. Nevertheless, numerous comprehensive clinical trials are still required to ascertain both the immediate and enduring impacts of such nanosystems on human subjects. This review delves into the benefits of different drug delivery vehicles, aiming to enhance comprehension of their applicability in addressing present medical requirements. Additionally, it touches upon the current applications of these stimuli-reactive nanosystems in biomedicine and outlines future development prospects.

Overprescribing of potentially harmful medication: an observational study in England's general practice.

BACKGROUND: Overprescribing of potentially harmful medication in UK general practice has a complex association with socioeconomic deprivation. AIM: To assess trends in general practice prescribing of five high-risk medications and their relationship to deprivation. DESIGN & SETTING: We conducted an observational study using general practice data from three English regions with varied socio-demographic factors: West Yorkshire and Harrogate (WY), Black Country and West Birmingham (BC), and Surrey and East Sussex (SE). METHOD: Practice-level prescribing data was obtained from 2016-2021 for five drug classes: opioids, hypnotics, gabapentinoids, non-steroidal anti-inflammatory drugs (NSAIDs) and antibacterials. Prescribing trends were demonstrated using a linear model. RESULTS: Reduction in NSAID, Opioid, Hypnotic and Antibacterial prescriptions, and the increase in gabapentinoid prescriptions, were significant at each financial-year time period. Index of Multiple Deprivation (IMD) was positively associated with all drug classes except antibacterials, which showed a positive association when incorporating the interaction term between IMD and age.When adjusting for IMD and population, region was independently associated with prescribing rate. Compared to WY, IMD had a smaller association with prescribing in BC for NSAIDs (Coefficient -0.01578, P=0.004) and antibacterials (Coefficient -0.02769, P=0.007), whereas IMD had a greater association with prescribing in SE for NSAIDs (Coefficient 0.02443, P<.001), opioids (Coefficient 0.08919 p<.001), hypnotics (Coefficient 0.09038 p<.001), gabapentinoids (Coefficient 0.1095, P<.001) and antibacterials (Coefficient 0.01601, P=0.19). CONCLUSION: The association of socioeconomic deprivation with overprescribing of high-risk medication in general practice varies by region and drug type. Geographical location is associated with overprescribing, independent of socioeconomic status.

It Is All about Probiotics to Control Cervical Cancer.

Cervical cancer (CC) is the fourth most common malignancy in female patients. "Human papillomavirus" (HPV) contamination is a leading cause of all forms of cervical cancer, accounting for an expected 570,000 reported incidents in 2018. Two HPV strains (16 and 18) are responsible for 70% of CC and pre-cancerous cervical abnormalities. CC is one of the foremost reasons for the malignancy death rate in India among women ranging from 30 to 69 years of age in India, responsible for 17% of all cancer deaths. Currently approved cervical cancer treatments are associated with adverse reactions that might harm the lives of women affected by this disease. Consequently, probiotics can play a vital role in the treatment of CC. It is reflected from various studies regarding the role of probiotics in the diagnosis, prevention or treatment of cancer. In this review article, we have discussed the rationale of probiotics for treatment of CC, the role of probiotics as effective adjuvants in anti-cancer therapy and the combined effect of the anti-cancer drug along with probiotics to minimize the side effects due to chemotherapy.

A correlation between oxidative stress and diabetic retinopathy: An updated review.

Oxidative stress (OS) is a cytopathic outcome of excessively generated reactive oxygen species (ROS), down regulated antioxidant defense signaling pathways, and the imbalance between the produced radicals and their clearance. It plays a role in the genesis of several illnesses, especially hyperglycemia and its effects. Diabetic retinal illness, a micro vascular side effect of the condition, is the prime reason of diabetic related blindness. The OS (directly or indirectly) is associated with diabetic retinopathy (DR) and related consequences. The OS is responsible to induce and interfere the metabolic signaling pathways to enhance influx of the polyol cascades and hexosamine pathways, stimulate Protein Kinase-C (PKC) variants, and accumulate advanced glycation end products (AGEs). Additionally, the inequity between the scavenging and generation of ROS is caused by the epigenetic alteration caused by hyperglycemia that suppresses the antioxidant defense system. Induced by an excessive buildup of ROS, retinal changes in structure and function include mitochondrial damage, cellular death, inflammation, and lipid peroxidation. Therefore, it is crucial to comprehend and clarify the mechanisms connected to oxidative stress that underlie the development of DR.

A panel cointegration analysis of linkages between international trade and tourism: case of India and South Asian Association for Regional Cooperation (SAARC) countries.

The study is undertaken to examine international trade and tourism nexus in case of India and SAARC countries. To achieve the objective, panel cointegration is employed over the period of 22 years (1997 to 2018). The results from both first and second generation cointegration tests indicated the existence of long run equilibrium among tourism, export, and import. Albeit there are differences between short-term and long-term associations, the findings from autoregressive distributed lag approach indicates strong long-term linkages between trade and tourism. A possible channel of exports exerting a positive influence on tourist arrival is that the products in foreign markets increase the recognition and image of a country eventually leading to more tourists. Moreover, increased exports are expected to increase business trips further increasing the leisure trips and hence a strong linkage between export and tourism. On the other hand, a possible explanation of positive effect of imports on tourism could be that the destination countries which provide tourists with products according to their home taste encourage tourists to travel to these countries. The findings provided in the paper have strong implications for expanding India's tourism footprint in the region.

Using Machine Learning to Predict and Understand Complex Self-Assembly Behaviors of a Multicomponent Nanocomposite.

Blends of nanoparticles, polymers, and small molecules can self-assemble into optical, magnetic, and electronic devices with structure-dependent properties. However, the relationship between a multicomponent nanocomposite's formulation and its assembled structure is complex and cannot be predicted by theory. The blends can be strongly influenced by processing conditions, which can introduce non-equilibrium states. Currently, nanocomposite devices are designed through cycles of experimental trial and error. Machine learning (ML) methods are a compelling alternative because they can use existing datasets to map high-dimensional spaces. These methods do not rely on known relationships between parameters, so they are suited to complex systems without a solid theoretical foundation. Here, a dataset of 595 microscopy images of nanocomposite thin films is used to train a series of ML models. Correlations between the input and output parameters are examined, providing new insights into the system. Finally, the most successful ML model is used to predict the structures of new nanocomposite compositions. The results confirm that ML techniques can be used to improve the efficiency of nanocomposite device design. More broadly, the current study suggests some of the advantages and challenges associated with applying ML to complex systems.

Repeated analyses of national clinical audit reports demonstrate improvements in feedback methods.

BACKGROUND: There is growing interest in the impact of national clinical audit programmes on the quality of healthcare. There is also an evolving evidence-base for enhancing the design and delivery of audit and feedback. We assessed the extent to which a sample of UK national clinical audit feedback reports met a set of good practice criteria over three time points. METHODS: We undertook three cross-sectional content analyses. We developed good practice criteria for the content and delivery of feedback based upon evidence, behavioural theory and expert opinion. We applied these to a feedback reports from 23 national audits listed on the Healthcare Quality Improvement Partnership (HQIP) website in November 2015. We repeated our assessments in January 2017 for 20 repeat feedback reports, after HQIP had published reporting guidance for national audits, and in August 2019 for a further 14 repeat feedback reports. We verified our assessments, where possible, with audit leads. RESULTS: Feedback reports consistently included strengths at baseline, including past or planned repeated audit cycles (21; 91%), stating the importance of the topic in relation to patient care (22; 93%), using multi-modal data presentation (23; 100%), and summarising key findings (23; 100%). We observed improvements over subsequent assessments, so that by 2019, at least 13 out of 14 (93%) feedback reports presented easily identifiable key findings and recommendations, linked recommendations to audit standards, and proposed easily identifiable action plans. Whilst the use of regional comparators did not improve, audit leads highlighted that programmes now provide local data via additional means. The main shortcoming was the time lag between data collection and feedback; none of the 14 reports assessed in 2019 presented performance data less than 6 months old. Audit leads highlighted that some of these data might be available via programme websites. CONCLUSION: We identified increased adherence to good practice in feedback by national clinical audit programmes that may enhance their impact on service delivery and outcomes. There is scope for improvement, especially in the recency of performance data. With further refinements, a criterion-based assessment offers an efficient means of monitoring the quality of national clinical audit feedback reports.

Promising Role of Nano-Encapsulated Drugs for Spinal Cord Injury.

Nanomaterials have been utilized for the drug delivery in the central nervous system (CNS), and many research investigators are currently focussing on this specified area. There has been a lot of advancement in the nanoparticle-mediated drug delivery to the brain. Neuronal injuries including spinal cord injury (SCI) and their targeted therapies are still in its infancy on this planet. SCI has been known to cause axonal damage followed by the loss of communication between CNS and other non-neuronal systems. SCI has been critically associated with prolonged inflammation, sensory dysfunction, and motor impairment in SCI patients. There has been a critical crosstalk in SCI and blood brain barriers (BBBs) for drug absorption and distribution in patients. There is a paucity of possible therapies for proper intervention of SCI due to selective permeability of the drugs across BBB. Nanomaterials are contemplated in the drug delivery system for SCI. In addition, self-assembled nanomicelles, lipid nanoparticles, and other co-polymers have now been explored for neuronal injuries. This review focuses on the promising approach and/or role of nanodrug delivery to target SCI in both in vitro and in vivo models.

The current status of culturally adapted mental health interventions: a practice-focused review of meta-analyses.

In recent years, there has been a steadily increasing recognition of the need to improve the cultural competence of services and cultural adaptation of interventions so that every individual can benefit from evidence-based care. There have been attempts at culturally adapting evidence-based interventions for mental health problems, and a few meta-analyses have been published in this area. This is, however, a much debated subject. Furthermore, there is a lack of a comprehensive review of meta-analyses and literature reviews that provide guidance to policy makers and clinicians. This review summarizes the current meta-analysis literature on culturally adapted interventions for mental health disorders to provide a succinct account of the current state of knowledge in this area, limitations, and guidance for the future research.

Physical activity and the risk for gestational diabetes mellitus amongst pregnant women living in Soweto: a study protocol.

BACKGROUND: Over the past decade the prevalence of gestational diabetes mellitus (GDM) has increased rapidly in both developed and developing countries and has become a growing health concern worldwide. A recent systematic review highlighted the paucity of data available on the prevalence and potential burden of GDM in Africa, which was emphasised by the fact that only 11 % of African countries were represented in the review. In South Africa, the prevalence of GDM remains unknown, although one would estimate it to be high due to urbanisation and the growing obesity epidemic. In addition, the association between physical activity (PA), sedentary behaviour (SB) and GDM is not well understood in this population. The aim of the proposed research is to determine whether there is an association between physical activity, sedentary behaviour and risk for GDM in pregnant black women living in urban Soweto in South Africa. METHODS/DESIGN: This prospective cohort study of 80 participants will include pregnant women from Soweto enrolled into the Soweto First 1000 Days Study (S1000) at the MRC/Wits Departmental Pathways for Health Research Unit (DPHRU) based at the Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. Women will be enrolled into the S1000 Study at <14 weeks gestation, and baseline demographic and anthropometric measures will be taken at 14-18 weeks gestation (visit 1). In addition, participants will complete the Global Physical Activity Questionnaire (GPAQ) to measure self-reported physical activity and will be given an ActiGraph accelerometer to wear for seven days to measure habitual physical activity at 14-18 weeks gestation (visit 1), and at 28-33 weeks gestation (visit 3). At visit 2 (24-28 weeks gestation) an oral glucose tolerance test (OGTT) will be conducted. DISCUSSION: Physical activity during pregnancy has been associated with minimum risk to a pregnancy and may play a role in improving glucose metabolism and therefore decreasing risk for GDM. This is particularly pertinent to assess amongst black South African women who are a potentially high risk population due to the high prevalence of obesity and type 2 diabetes (T2D). The findings of the study will assist in developing targeted interventions as well as feasible healthcare strategies.

Epilepsy and the subsequent risk of cerebral tumour: record linkage retrospective cohort study.

BACKGROUND: Studies suggest that seizures may precede the detection of cerebral tumour by several years. Aim To quantify the risk of cerebral tumour after new onset seizures, with particular interest in long term risk. METHODS: Using the Oxford Record Linkage Study (ORLS, 1963-1998) and English national linked Hospital Episode Statistics (1999-2005), cohorts of people with a first admission for epilepsy were constructed. Subsequent admissions with cerebral tumour were identified. The rate of occurrence of subsequent cerebral tumour in each epilepsy cohort was compared with that in a comparison cohort and expressed as a rate ratio (RR). RESULTS: The RR for cerebral tumour after epilepsy, relative to the rate of cerebral tumour in the comparison cohort, was 19.9 (95% CI 17.2 to 22.9) in the ORLS cohort and 19.7 (18.3-21.1) in the England cohort. The RR for malignant tumours were, respectively, 25.6 (21.7 to 30.0) and 27.3 (25.2 to 29.6). The RR for benign tumours were 10.1 (7.38 to 13.6) and 10.4 (9.07 to 11.8), respectively. The risk was highest for those aged 15-44 years at initial admission for epilepsy both in Oxford (24.2, 18.5 to 31.5) and England (38.1, 32.8 to 44.2). The risk of cerebral tumour was still raised several years after initial admission for epilepsy: in the ORLS cohort at 15 years or more, the RR was 3.29 (1.39 to 6.66) and, in the England cohort 5-7 years after initial admission, the RR was 5.27 (3.87 to 7.06). CONCLUSIONS: Seizures may herald the development of cerebral tumour, remote in time as well as soon after onset, with implications for guidelines on continued surveillance of those with new onset seizures.