Childhood Cancer Incidence and Survival in South Australia and the Northern Territory, 1990-2017, with Emphasis on Indigenous Peoples.

BACKGROUND & AIMS: Reports of a rise in childhood cancer incidence in Australia and globally prompted the investigation of cancer incidence and survival in South Australia (SA) and the Northern Territory (NT) over a 28-year period, with emphasis on Indigenous peoples. METHODS: This cross-sectional analysis of two prospective longitudinal databases, the SA and NT Cancer Registries (1990-2017), included all reported cases of childhood cancers. Poisson regression provided estimates of incidence rate ratios and survival was modelled using Cox proportional hazard models for children aged <5 and ≥5 years. RESULTS: A total of 895 patients across SA (N = 753) and the NT (N = 142) were ascertained. Overall and in the NT, childhood cancer incidence was higher in males compared with females (IRR 1.19 [1.04-1.35] and 1.43 [1.02-2.01], respectively). Lymphocytic leukemia was the most reported cancer type across all locations. With reference to the 1990-1999 era (181.67/100,000), cancer incidence remained unchanged across subsequent eras in the combined cohort (SA and NT) (2000-2009: 190.55/100,000; 1.06 [0.91-1.25]; 2010-2017: 210.00/100,000; 1.15 [0.98-1.35]); similar outcomes were reflected in SA and NT cohorts. Cancer incidence amongst non-Indigenous children significantly decreased from the 1990-1999 era (278.32/100,000) to the 2000-2009 era (162.92/100,000; 0.58 [0.35-0.97]). Amongst 39 Indigenous children in the NT, incidence rates remained unchanged across eras (p > 0.05). With reference to the 1990-1999 era, overall survival improved in subsequent eras in SA (2000-2009: HR 0.53 [0.38-0.73]; 2010-2017: 0.44 [0.28-0.68]); however, remained unchanged in the NT (2000-2009: 0.78 [0.40-1.51]; 2010-2017: 0.50 [0.24-1.05]). In the NT, overall survival of Indigenous patients was significantly lower compared with the non-Indigenous cohort (3.42 [1.92-6.10]). While the survival of Indigenous children with cancer significantly improved in the last two eras (p < 0.05), compared to the 1990-1999 era, no change was noted amongst non-Indigenous children in the NT (p > 0.05). CONCLUSIONS: The incidence of childhood cancers has remained unchanged over 28-years in SA and the NT. Encouragingly, improved survival rates over time were observed in SA and amongst Indigenous children of the NT. Nevertheless, survival rates in Indigenous children remain lower than non-Indigenous children.

Burden of Long COVID-19 in a Cohort of Recovered COVID-19 Patients in Delhi, India.

BACKGROUND: The long COVID phase is characterized by signs and symptoms persisting for at least three months after recovery from acute COVID-19 illness. There is limited data on comprehensive long-term clinical follow-up of COVID-19 patients. AIMS: This study aims to explore the burden and symptomatology of long COVID syndrome and its association with various health parameters. SETTINGS AND DESIGN: This prospective observational study was conducted in Delhi from May 2022 to March 2023. METHODS AND MATERIAL: A total of 553 adult patients who had recovered from COVID-19 were enrolled in the study. A sociodemographic and clinical profile was obtained using validated questionnaires, along with an evaluation of biochemical parameters to assess the associated factors. STATISTICAL ANALYSIS USED: Chi-square test, unpaired t-test, and bivariate regression analysis were applied using Statistical Product and Service Solutions (SPSS, version 28; IBM SPSS Statistics for Windows, Armonk, NY). A p value of <0.05 was considered significant. RESULTS: A total of 252 patients (45.6%) had long COVID syndrome, which was significantly associated with the presence of any pre-existing comorbidity (OR=1.46 (1.02-2.09); p=0.039), previous history of hypertension (OR=1.82 (1.07-3.09); p=0.027), and vaccination against COVID-19 (OR=1.392 (1.171-1.656); p=0.003). The most common symptoms reported were persistent fatigue (33.3%) and persistent dry cough (28.5%). Patients with long COVID syndrome are also reported to have poorer sleep quality. Biochemical findings showed abnormal T lymphocytes (9.3%) and raised HbA1c (11.9%). CONCLUSIONS: Multiple risk factors and symptoms associated with long COVID syndrome were identified in this study. Research efforts and knowledge regarding the pattern of illness will aid in long-term monitoring and development of interventional strategies and guidelines for the care of recovered COVID-19 patients.

Neurogenic and angiogenic poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloyl-glutamate) hydrogel: preconditioning effect under oxidative stress and use in neuroregeneration.

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.

Ocular Tuberculosis Diagnosis Through Biomarkers: Clinical Relevance of Serum C1q and Whole Blood Interferon Gene Signature Score.

PURPOSE: To assess the clinical relevance of pathophysiology-based biomarkers, specifically serum C1q and whole blood interferon gene signature score (IGSS), in ocular tuberculosis (OTB) diagnosis by conducting an integrative analysis of clinical presentations and treatment response. METHODS: This retrospective cohort study analysed data from 70 patients with suspected OTB at a tertiary care uveitis practice in Indonesia. Serum C1q levels and whole blood IGSS were quantified. Patients were categorized into four quadrants based on their biomarker profiles: quadrant 1 (high C1q & low IGSS), quadrant 2 (high C1q & high IGSS), quadrant 3 (low C1q & high IGSS), and quadrant 4 (low C1q & low IGSS). Characteristics of clinical presentations, work-up results, and treatment outcomes were explored according to the predefined quadrants. RESULTS: We identified that the majority of OTB patients diagnosed with concurrent active pulmonary TB were in quadrant 1, 2, or 3 (20/23, 87.0%). Twenty-seven patients (27/47, 57.4%) with clinically undifferentiated uveitis were in quadrant 4 (p < 0.001). Among patients in quadrants 1, 2, and 3, completion of a full course of antitubercular treatment (ATT) was associated with a lower number of patients showing persistence or recurrence of ocular inflammation compared to those who were not fully treated with ATT (14.3% vs 85.7%, p = 0.001). CONCLUSIONS: Based on the analysis of clinical features and treatment outcomes, patients with elevated levels of either or both serum C1q and whole blood IGSS may reflect active TB disease in the eye, necessitating full ATT management.

Intricacies of plants' innate immune responses and their dynamic relationship with fungi: A review.

The role of the plant innate immune system in the defense and symbiosis processes becomes integral in a complex network of interactions between plants and fungi. An understanding of the molecular characterization of the plant innate immune system is crucial because it constitutes plants' self-defense shield against harmful fungi, while creating mutualistic relationships with beneficial fungi. Due to the plant-induced awareness and their complexity of interaction with fungi, sufficient assessment of the participation of the plant innate immune system in ecological balance, agriculture, and maintenance of an infinite ecosystem is mandatory. Given the current global challenge, such as the surge of plant-infectious diseases, and pursuit of sustainable forms of agriculture; it is imperative to understand the molecular language of communication between plants and fungi. That knowledge can be practically used in diverse areas, e.g., in agriculture, new tactics may be sought after to try new methods that boost crop receptiveness against fungal pathogens and reduce the dependence on chemical management. Also, it could boost sustainable agricultural practices via enhancing mycorrhizal interactions that promote nutrient absorption and optimum cropping with limited exposure of environmental contamination. Moreover, this review offers insights that go beyond agriculture and can be manipulated to boost plant conservation, environmental restoration, and quality understanding of host-pathogen interactions. Consequently, this specific review paper has offered a comprehensive view of the complex plant innate immune-based responses with fungi and the mechanisms in which they interact.

Biosynthesized silver nanoparticles prevent bacterial infection in chicken egg model and mitigate biofilm formation on medical catheters.

Investigating the application of innovative antimicrobial surface coatings on medical devices is an important field of research. Many of these coatings have significant drawbacks, including biocompatibility, coating stability and the inability to effectively combat multiple drug-resistant bacteria. In this research, we developed an antibiofilm surface coating for medical catheters using biosynthesized silver nanoparticles (b-Cs-AgNPs) developed using leaves extract of Calliandra surinamensis. Various characterization techniques were employed to thoroughly characterize the synthesized b-Cs-AgNPs and c-AgNPs. b-Cs-AgNPs were compatible with human normal kidney cells and chicken embryos. It did not trigger any skin inflammatory response in in vivo rat model. b-Cs-AgNPs demonstrated potent zone of inhibition of 19.09 mm when subjected to the disc diffusion method in E. coli confirming strong antibacterial property. Different anti-bacterial assays including liquid growth curve, colony counting assay, biofilm formation assay supported the potent antimicrobial efficacy of b-Cs-AgNPs alone and when coated to medical grade catheters. Mechanistic studies reveal the presence of ferulic acid, that was important for the synthesis of b-AgNPs along with enhanced antibacterial effects of b-Cs-AgNPs compared to c-AgNPs, supported by molecular docking analysis. These results together demonstrated the effective role b-Cs-AgNPs in combating infections and mitigating biofilm formations, highlighting their need for further study in the field of biomedical applications.

Long-term outcomes comparison of mitral valve repair or replacement for secondary mitral valve regurgitation. An updated systematic review and reconstructed time-to-event study-level meta-analysis.

BACKGROUND AND AIM: The ideal surgical intervention for secondary mitral regurgitation (SMR), a disease of the left ventricle not the mitral valve itself, is still debated. We performed an updated systematic review and study-level meta-analysis investigating mitral valve repair (MVr) versus mitral valve replacement (MVR) for adult patients with SMR, with or without coronary artery disease (CAD). METHODS: PubMed, CENTRAL and EMBASE were searched for studies comparing MVr versus MVR. Randomized trial or observational studies were considered eligible. Primary endpoint was long-term mortality for any cause. Kaplan-Meier survival curves were reconstructed and compared with Cox linear regression. Landmark analysis and time-varying hazard ratio (HR) were analyzed. Sensitivity analyses included meta-regression and separate sub-analysis. A random effects model was used. RESULTS: Twenty-three studies (MVr=3,727 and MVR=2,839) were included. One study was a randomized trial, and 19 studies were adjusted. The mean weighted follow-up was 3.7±2.8 years. MVR was associated with significative greater late mortality (HR=1.26; 95 % CI, 1.14-1.39; P<0.0001) at 10-year follow-up. There was a time-varying trend showing an increased risk of mortality in the first 2 years after MVR (HR=1.38; 95 % CI, 1.21-1.56; P<0.0001), after which this difference dissipated (HR=0.94; 95 % CI, 0.81-1.09; P=0.41). Separate sub-analyses showed comparable long-term mortality in patients with concomitant coronary surgery ≥90 %, left ventricle ejection fraction ≤40 %, and sub-valvular apparatus preservation rate of 100 %. CONCLUSIONS: Compared to repair, MVR is associated with higher probability of mortality in the first 2 years following surgery, after which the two procedures showed comparable late mortality rate.

The Association between Anemia and Mortality of Severe Pneumonia COVID-19 Patients in the High Care Unit of a Tertiary Hospital in Jakarta.

BACKGROUND: Numerous studies explored the association between anemia and mortality in patients with severe pneumonia due to COVID-19. However, the findings were inconsistent. Therefore, this study was conducted to investigate the association between anemia at HCU admission and in-hospital mortality in severe pneumonia COVID-19 patients. METHODS: This retrospective cohort study obtained data on 110 COVID-19 patients with severe pneumonia who were admitted to the HCU between January, 1st 2021, and May 31st, 2021. Patients were categorized as anemic and non-anemic based on the World Health Organization (WHO) guidelines. The demographic and clinical characteristics of the subjects were described. The Chi-squared test was carried out followed by a logistic regression test to determine the association of anemia and mortality. RESULTS: Anemia was observed in 31% of 110 patients with severe pneumonia COVID-19. The source population consisted of 60.9% men and 39.1% women with a median age of 58 years. The most prevalent comorbidity was hypertension (38.2%), followed by diabetes mellitus (27.2%), renal diseases (19.1%) and heart diseases (10%). TAnemia on HCU admission was associated with in-hospital mortality in patients with severe pneumonia COVID-19 (RR: 2.794, 95% CI 1.470-5.312). After adjusting comorbidities as confounding factors, anemia was independently associated with mortality (RR: 2.204, 95% CI: 1.124-4.323, P < 0.021). The result also showed anemic patients had longer lengths of stay and higher levels of D-dimer than non-anemic patients. The median duration length of stay among the anemic and non-anemic was 16 (11-22) and 13 (9-17) days, respectively. The median D-dimer among the anemic and non-anemic was 2220 µg/ml and 1010 µg/ml, respectively. CONCLUSION: There is a significant association between anemia at HCU admission and mortality in patients with severe pneumonia COVID-19 during hospitalization.

Polymeric micelle gel with luliconazole: in vivo efficacy against cutaneous candidiasis in Wistar rats.

The objective of this research was focused on the design and development of luliconazole-loaded polymeric micelle hydrogel (LUL-PM-CHG) using quality by design (QbD) principle to improve the penetration and retention of LUL in the skin. The optimization of the formulation involved the utilization of a Box-Behnken design with three factors and three levels. The impact of specific formulation variables, namely the ratio of poloxamer P123 and F127, sonication time, and the quantity of drug, was investigated in terms of particle size, micellar incorporation efficiency, and polydispersity index. The LUL-loaded P123/F127 mixed micelles involved the thin film hydration method for thin preparation. The characteristics of optimized formulation include a particle size of 226 ± 8.52 nm, a polydispersity index (PDI) of 0.153 ± 0.002, a zeta potential (ZP) of 30.15 ± 2.32 mV, and a micellar incorporation efficiency (MIE) of 88.38 ± 3.84%. In vitro release studies indicated a sustained release of LUL-PM-CHG for a duration of up to 8 h. The MIC, GI50, and GI90 of different formulations on Candida albicans were determined using both the microtiter broth dilution method and the plate method and showed that LUL-PM-CHG exhibited the highest antifungal activity compared to the other formulations, with MIC values of 3.25 ± 0.19 ng/mL, GI50 values of 37.11 ± 2.89, and GI90 values of 94.98 ± 3.41 The study also measured the % of inhibition activity and the generation of intracellular reactive oxygen species (ROS) using flow cytometry. LUL-PM-CHG showed the highest percentage of inhibition (75.5%) and ROS production (MFI-140951), indicating its enhanced activity compared to LUL-CHG and LUL. Fungal infection was induced in Wistar rats using immunosuppressant's treatment followed by exposure to C. albicans. Finally, in vivo fungal scaling and histopathological studies indicated a reduction in fungal infection in Wistar rat skin after treatment. The obtained results suggested that LUL-PM can serve as a promising formulation to enhance luliconazole antifungal activity and increase patient compliance.

Prevalence of metabolic disorders among women in reproductive age group in hilly rural area of North India.

Background: Metabolic syndrome consists of cardiometabolic risk factors that promote the development of atherosclerotic cardiovascular disease, type 2 'DM' and obesity. These are associated with increased cardiovascular mortality and morbidity. Metabolic disorders (MD) are becoming more prevalent both in developing countries and developed countries and are now considered as lifestyle diseases. In women of reproductive age group, especially pregnancy, the blood glucose level is increasing which adversely affects the health of mother and child. Similarly, high blood pressure also precipitates the problems. This study was carried out to find the prevalence of hypertension, diabetes mellitus, obesity and 'MD' among the women living in remote rural set-up. Materials and Methods: This cross-sectional study was done among women of reproductive age group in 15 villages from 5 panchayats of field practice area of Maharishi Markandeshwar Medical College and Hospital, Kumarhatti, Solan. They were screened for 'MD' through investigative procedures (weight, height, BMR, abdominal girth, blood pressure through sphygmomanometer, blood glucose through the glucometer method), serum HDL and triglycerides. Respondents from the family were asked about the common/general information of house. The tool used for collecting general and relevant information from the respondent was a questionnaire, which was pretested for validity before being used in the field. Results: Four-hundred and sixty-seven women of reproductive age group participated in the study. Half of the participants were with qualification of matriculate and 9.2% participants were illiterate. Three-fourths of the participants were married women and 89% were vegetarian. Sixty-four per cent of participants were housewives. Half of the participants had a normal BMI, whereas 28.9% were overweight and 10% were obese. The prevalence of hypertension and diabetes among the participants were 12.5% and 9.8%, respectively. Forty-seven per cent participants had a waist circumference above 80 cm. Conclusion: The level of non-communicable diseases is related with the MD which has the adverse effect on the various systems and organs of the subjects. The MD can be controlled with the certain changes in the life style pattern. The GOI is also concerned with such scenarios in the country. It is recommended that women of reproductive age group undergo regular blood pressure and blood sugar screenings to detect hypertension and diabetes early and take appropriate measures to manage them.

Medical thoracoscopy with cryobiopsy as diagnostic tool for pleural metastatic in cutaneous squamous cell carcinoma: a rare case report.

Introduction: Distance metastasis of cutaneous squamous cell carcinoma (cSCC) to pleural is rarely reported, and meets difficulties in diagnosing due to quality of pleural biopsy sample. This case presented a novel technique by using cryobiopsy to obtain adequate sample and was first conducted in our hospital. Case presentation: A 62-years-old man admitted to hospital with dyspnoea due to massive right pleural effusion. Lung multi-sliced computed tomography showed right lung pleural effusion with compression atelectasis as well as collapse of medial lobe and upper lobe, multiple solitary nodules on mediastinal, costal antero-posterior and right diaphragm pleural part. Medical thoracoscopy was performed to obtain pleural samples by using cryobiopsy and forceps biopsy. Pathological analysis with Immunohistochemistry (IHC) revealed metastatic squamous cell carcinoma. Discussion: Recurrence rate of cSCC remains high even after treatment, with worse prognosis. Distant metastasis to pleural is rarely reported. Clinical approach for malignant pleural effusion by using medical thoracoscopy has 80% sensitivity with minimal complication. Pleural cryobiopsy is a novel technique used for obtaining sample from pleural biopsy with significant larger size of the specimen, less crush artefacts, fragmented and better tissue integrity, although the diagnostic yield and bleeding severity between cryobiopsy and conventional forceps biopsy are not significant. Conclusion: Medical thoracoscopy with cryobiopsy should be considered as a preferrable diagnostic tool for obtaining better sample specimen, especially for pleural metastatic.

Small for gestational age and anthropometric body composition from early childhood to adulthood: the Aboriginal Birth Cohort study.

Background: In Australia the estimated rate of small for gestational age (SGA) births is 9% among non-Indigenous births compared to 14% among Aboriginal and Torres Strait Islanders. There is limited research investigating the effect of being born SGA on body composition later in life in Indigenous Australians. Methods: Using data from the Aboriginal Birth Cohort longitudinal study, we compared the body composition of those born SGA to non-SGA by analysing anthropometric measures (height, weight, waist circumference, fat percentage [FAT%], body mass index [BMI], waist-to-height ratio, and A body shape index [ABSI]) collected at four follow-up periods (from childhood to adult). For cross-sectional analyses, linear regression models were employed to assess factors associated with anthropometric measures. For longitudinal analyses linear mixed models were employed to assess differences in anthropometric measures among SGA versus non-SGA individuals while adjusting for repeated measures. Results: The analytic baseline cohort were those who participated in Wave 2 (n = 570). In cross-sectional analyses, across all waves those born SGA had smaller anthropometric z-scores compared to non-SGA individuals (ß ranging from -0.50 to -0.25). Participants residing in urban environments were significantly larger in Waves 2 to 4 (ß ranged 0.26 to 0.65). Those born SGA had higher ABSI scores in Waves 2 and 4 (ß 0.26 and 0.37, respectively). In longitudinal analyses, those born SGA had smaller measures of body composition across the life course; these differences were larger in urban communities. In remote communities those born SGA had significantly higher ABSI scores during adolescence and young adulthood, and this difference was not observed in urban communities. Conclusion: Indigenous Australians born SGA are smaller anthropometrically later in life compared to their non-SGA counterparts. In remote communities, those born SGA had higher levels of central adiposity compared to non-SGA.

Nitric oxide releasing novel amino acid-derived polymeric nanotherapeutic with anti-inflammatory properties for rapid wound tissue regeneration.

Endogenous gasotransmitter nitric oxide (NO) is a central signalling molecule that modulates wound healing by maintaining homeostasis, collagen formation, wound contraction, anti-microbial action and accelerating tissue regeneration. The optimum delivery of NO using nanoparticles (NPs) is clinically challenging; hence, it is drawing significant attention in wound healing. Herein, a novel polymeric nanoplatform loaded with sodium nitroprusside (SP) NPs was prepared and used for wound healing to obtain the sustained release of NO in therapeutic quantities. SP NPs-induced excellent proliferation (∼300%) of mouse fibroblast (L929) cells was observed. With an increase in the SP NPs dose at 200 µg mL-1 concentration, a 200% upsurge in proliferation was observed along with enhanced migration, and only 17.09 h were required to fill the 50% gap compared to 37.85 h required by the control group. Further, SP NPs showed an insignificant impact on the coagulation cascade, revealing safe wound-healing treatment when tested in isolated rat RBCs. Additionally, SP NPs exhibited excellent angiogenic activity at a 10 µg mL-1 dose. Moreover, the formulated SP nanoformulation is non-irritant, non-toxic, and does not produce any skin sensitivity reaction on the rat's skin. Further, an in vivo wound healing study revealed that within 11 days of treatment with SP nanoformulation, 99.2 ± 1.0% of the wound was closed, while in the control group, only 45.5 ± 3.8% was repaired. These results indicate that owing to sustained NO release, the SP NP and SP nanoformulations are paramount with enormous clinical potential for the regeneration of wound tissues.

Progress in Treatment and Diagnostics of Infectious Disease with Polymers.

In this era of advanced technology and innovation, infectious diseases still cause significant morbidity and mortality, which need to be addressed. Despite overwhelming success in the development of vaccines, transmittable diseases such as tuberculosis and AIDS remain unprotected, and the treatment is challenging due to frequent mutations of the pathogens. Formulations of new or existing drugs with polymeric materials have been explored as a promising new approach. Variations in shape, size, surface charge, internal morphology, and functionalization position polymer particles as a revolutionary material in healthcare. Here, an overview is provided of major diseases along with statistics on infection and death rates, focusing on polymer-based treatments and modes of action. Key issues are discussed in this review pertaining to current challenges and future perspectives.

Health benefits of ghee: Review of Ayurveda and modern science perspectives.

The scientific view on dairy fats is undergoing a change. While at one time they were associated with negative health effects, recent scientific research has provided new insights into the functional benefits of dairy fats and their fatty acids. This changing scientific view on dairy fats is also resulting in a scientific interest in Ghee, the clarified butter obtained from milk. Ghee, besides being a traditional milk product of cultural importance in India and finding extensive use in its cuisines, is also one of the most important ingredients of the materia medica of Ayurveda, the traditional system of medicine that originated in India. While modern scientific literature has limited studies on functional benefits of ghee, Ayurveda literature extensively catalogues the therapeutic potential of ghee and details different types of ghee based on source of milk, manufacturing method, maturation and physical phase. This work reviewed the Ayurveda literature on health benefits of ghee and examined the complementarity and gaps between Ayurveda literature and modern scientific literature to identify research questions and hypotheses for further exploring the therapeutic potential of ghee. The Ayurveda literature review involved curation of references to ghee in eleven important Ayurvedic texts spanning over 3000 years. 4000 references to milk and milk products were curated from these texts, of which 2913 mentions were in the context of therapeutic benefits of milk products. Of these, ghee had 774 mentions, the highest amongst milk-based products. These mentions were grouped into 15 benefit clusters. A review of ghee in modern literature published between 1990 and 2023 was also conducted. A comparison of this with the Ayurveda literature showed that there were major differences in the focus areas of health between the two. While recent research primarily focused on ghee's connection with cardiovascular health, wound healing and skin health, Ayurveda prioritized cognitive benefits, gastrointestinal health, and nourishing. These later areas are of growing importance to human health as global population ages, and chronic and brain related diseases start dominating public health concerns. As scientists search for solutions to these, ghee, its usage and formulations in Ayurveda and the detailed associations between ghee's animal source, processing, maturation, phases and health benefits, may have scientific insights to offer that can guide future research.

Association between perinatal and early life exposures and lung function in Australian Indigenous young adults: The Aboriginal Birth Cohort study.

BACKGROUND AND OBJECTIVE: Despite the high burden of respiratory disease amongst Indigenous populations, prevalence data on spirometric deficits and its determinants are limited. We estimated the prevalence of abnormal spirometry in young Indigenous adults and determined its relationship with perinatal and early life factors. METHODS: We used prospectively collected data from the Australian Aboriginal Birth Cohort, a birth cohort of 686 Indigenous Australian singletons. We calculated the proportion with abnormal spirometry (z-score <-1.64) and FEV1 below the population mean (FEV1 % predicted 0 to -2SD) measured in young adulthood. We evaluated the association between perinatal and early life exposures with spirometry indices using linear regression. RESULTS: Fifty-nine people (39.9%, 95%CI 31.9, 48.2) had abnormal spirometry; 72 (49.3%, 95%CI 40.9, 57.7) had a FEV1 below the population mean. Pre-school hospitalisations for respiratory infections, younger maternal age, being overweight in early childhood and being born remotely were associated with reduced FEV1 and FVC (absolute, %predicted and z-score). The association between maternal age and FEV1 and FVC were stronger in women, as was hospitalization for respiratory infections before age 5. Being born remotely had a stronger association with reduced FEV1 and FVC in men. Participants born in a remote community were over 6 times more likely to have a FEV1 below the population mean (odds ratio [OR] 6.30, 95%CI 1.93, 20.59). CONCLUSION: Young Indigenous adults have a high prevalence of impaired lung function associated with several perinatal and early life factors, some of which are modifiable with feasible interventions.

Quality by Design Assisted Development of Luliconazole Transethosomes in Gel for the Management of Candida albicans Infection.

The objective of this study was to develop and evaluate a novel vesicular formulation of luliconazole (LUL) for the management of Candida albicans infection through a topical route. LUL-loaded transethosomes (LUL-TE) were prepared by the film hydration method and various independent and dependent variables were optimized using the Box-Behnken design. Selected critical material attributes were the content of phospholipids (X1), concentration of ethanol (X2), and amount of sodium cholate (X3). Formulated LUL-TE were characterized for percent entrapment efficiency, percent drug loading, vesicle size, and polydispersity index (PDI) and were incorporated into the carbomer gel base and further evaluated for gel characterizations. The prepared transethosomal gel (LUL-TE-CHG) was evaluated for pH, spreadability, viscosity, antifungal activity, and in vitro study. From the observed results, it was evident that the prepared LUL-TE-CHG was in the desired pH (6.2 ± 0.45), spreadability [8.3 ± 0.42 g/(cm·s)], viscosity (236.1-19.2.26 mPa·s), nanovesicle size (252 ± 9.82), entrapment efficiency (85% ± 5.24%), zeta potential (-34.05 ± 3.52 mV), and PDI (0.233 ± 0.002). The zone of inhibition results suggested that the LUL-TE-CHG formulation has the highest antifungal activity, that is, 5.83 ± 0.15 mm3. The in vitro results showed that drug release within 2 h was 18.1% ± 2.0% and after that sustained release action, 83.2% ± 1.7% within 8 h. Finally, to confirm the therapeutic efficacy of the developed formulation, fungal infection was induced by using C. albicans in Wistar rats. In vivo, skin irritation study and histopathology studies were performed in the disease-induced model. Animal experiments revealed that LUL-TE-CHG has significantly improved the diseased condition in Wistar rats. The results observed from the skin permeation and skin deposition profile ensure that the prepared novel LUL-loaded TE system had a higher permeation rate and increased retention time compared with LUL-CHG. The hydrogel incorporated with LUL could be a novel approach with safe and effective fungal treatment.

Environmental enrichment improves cognitive function, learning, memory and anxiety-related behaviours in rodent models of dementia: Implications for future study.

Environmental enrichment (EE) is a process of brain stimulation by modifying the surroundings, for example, by changing the sensory, social, or physical conditions. Rodents have been used in such experimental strategies through exposure to diverse physical, social, and exploration conditions. The present study conducted an extensive analysis of the existing literature surrounding the impact of EE on dementia rodent models. The review emphasised the two principal aspects that are very closely related to dementia: cognitive function (learning and memory) as well as psychological factors (anxiety-related behaviours such as phobias and unrealistic worries). Also highlighted were the mechanisms involved in the rodent models of dementia showing EE effects. Two search engines, PubMed and Science Direct, were used for data collection using the following keywords: environmental enrichment, dementia, rodent model, cognitive performance, and anxiety-related behaviour. Fifty-five articles were chosen depending on the criteria for inclusion and exclusion. The rodent models with dementia demonstrated improved learning and memory in the form of hampered inflammatory responses, enhanced neuronal plasticity, and sustained neuronal activity. EE housing also prevented memory impairment through the prevention of amyloid beta (Aß) seeding formation, an early stage of Aß plaque formation. The rodents subjected to EE were observed to present increased exploratory activity and exert less anxiety-related behaviour, compared to those in standard housing. However, some studies have proposed that EE intervention through exercise would be too mild to counteract the anxiety-related behaviour and risk assessment behaviour deficits in the Alzheimer's disease rodent model. Future studies should be conducted on old-aged rodents and the duration of EE exposure that would elicit the greatest benefits since the existing studies have been conducted on a range of ages and EE durations. In summary, EE had a considerable effect on dementia rodent models, with the most evident being improved cognitive function.

Very Long-term Outcome of Bilateral Internal Thoracic Artery in Diabetic Patients: A Systematic Review and Reconstructed Time-To-Event Meta-analysis.

The benefits of single (SITA) and bilateral internal thoracic arteries (BITA) in diabetics undergoing coronary bypass grafting (CABG) are conflicting. We undertook a study-level meta-analysis to compare early and long-term outcomes of both CABG configurations. PubMed, CENTRAL, and EMBASE were searched for studies comparing BITA versus SITA for isolated CABG surgery in diabetics. Randomized trials or observational studies were considered eligible for the analysis. Kaplan-Meier curves of long-term survival were reconstructed and compared with Cox linear regression; incidence rate ratios (IRR) with 95% confidence intervals (CI) for long-term survival were calculated. Landmark analysis and time-varying hazard ratio (HR) were analyzed. Odds ratios (OR) were extracted for early mortality, postoperative stroke, deep sternal wound infection (DSWI), and myocardial infarction (MI). A random effects meta-analysis was performed. Sensitivity analyses included leave-one-out-analyses and meta-regression. Thirteen studies (7332 patients) were included. Overall, at 20-year follow-up, BITA was associated with higher survival (HR = 0.77; 95% CI, 0.71-0.84; P < 0.0001). Time-varying HR and landmark analysis reported BITA was associated with a higher rate of 10-year survival (HR = 0.75, 95% CI 0.68-0.82, P < 0.0001), while from 10 to 20-year follow-up no difference was revealed (HR = 0.99, 95% CI 0.82-1.19, P = 0.93). There was no increase in early mortality, postoperative MI, stroke, or DSWI between the groups. At meta-regression, the higher the age, the higher the long-term overall survival in patients with BITA. In diabetics, the BITA approach is associated with improved 10-year survival with no increase in early mortality, MI, stroke, or DSWI. In the 10-20-year timeframe, BITA and SITA showed comparable survival.