Revolutionizing Leishmaniasis Treatment with Cutting Edge Drug Delivery Systems and Nanovaccines: An Updated Review.

Leishmaniasis, one of the most overlooked tropical diseases, is a life-threatening illness caused by the parasite Leishmania donovani that is prevalent in underdeveloped nations. Over 350 million individuals in more than 90 different nations worldwide are at risk of contracting the disease, which has a current fatality rate of 50 000 mortalities each year. The administration of liposomal Amp B, pentavalent antimonials, and miltefosine are still considered integral components of the chemotherapy regimen. Antileishmanial medications fail to treat leishmaniasis because of their numerous drawbacks. These include inadequate effectiveness, toxicity, undesired side effects, drug resistance, treatment duration, and cost. Consequently, there is a need to overcome the limitations of conventional therapeutics. Nanotechnology has demonstrated promising outcomes in addressing these issues because of its small size and distinctive characteristics, such as enhanced bioavailability, lower toxicity, biodegradability, and targeted drug delivery. This review is an effort to highlight the recent progress in various nanodrug delivery systems (nDDSs) over the past five years for treating leishmaniasis. Although the preclinical outcomes of nDDSs have shown promising treatment for leishmaniasis, further research is needed for their clinical translation. Advancement in three primary priority domains─molecular diagnostics, clinical investigation, and knowledge dissemination and standardization─is imperative to propel the leishmaniasis field toward translational outcomes.

Mitochondrial Dysfunction, Oxidative Stress and Premature Aging in Children With Nutritional Rickets.

OBJECTIVE: To assess the mitochondrial dysfunction, oxidative stress and premature aging in children with nutritional rickets. METHODS: This cross-sectional study enrolled children between 6 months - 5 years of age with nutritional rickets attending a tertiary care hospital between between January 2021 and August 2022. Mitochondrial dysfunction, oxidative stress and premature aging were assessed by measuring the mitochondrial DNA (mtDNA) content, total antioxidant status (TAOS) and telomere length (TL) in 40 children with nutritional rickets and 40 age- and sex- matched healthy children without rickets (controls). RESULTS: The median (IQR) mtDNA content was significantly higher in children with rickets as compared to controls [152.27 (111.83,218.66) vs 93.7 (72.5,134.14); P < 0.001], implying mitochondrial dysfunction attributed to increased mitochondrial biogenesis in children with rickets. The median (IQR) TAOS was significantly lesser in children with rickets than controls [4.54 (3.93, 5.73) vs 7.86 (5.09, 9.58); P < 0.001)]. The median (IQR) TL in cases was significantly longer in children with rickets compared to controls [417.31 (111.83,218.66) vs 93.7 (72.5,134.14); P < 0.001] implying that children with rickets do not have premature aging. CONCLUSION: Children with rickets have high oxidative stress and mitochondrial dysfunction but no evidence of premature aging.

A comprehensive review of the application of 3D-bioprinting in chronic wound management.

INTRODUCTION: Chronic wounds require more sophisticated care than standard wound care because they are becoming more severe as a result of diseases like diabetes. By resolving shortcomings in existing methods, 3D-bioprinting offers a viable path toward personalized, mechanically strong, and cell-stimulating wound dressings. AREAS COVERED: This review highlights the drawbacks of traditional approaches while navigating the difficulties of managing chronic wounds. The conversation revolves around employing natural biomaterials for customized dressings, with a particular emphasis on 3D-bioprinting. A thorough understanding of the uses of 3D-printed dressings in a range of chronic wound scenarios is provided by insights into recent research and patents. EXPERT OPINION: The expert view recognizes wounds as a historical human ailment and emphasizes the growing difficulties and expenses related to wound treatment. The expert acknowledges that 3D printing is revolutionary, but also points out that it is still in its infancy and has the potential to enhance mass production rather than replace it. The review highlights the benefits of 3D printing for wound dressings by providing instances of smart materials that improve treatment results by stimulating angiogenesis, reducing pain, and targeting particular enzymes. The expert advises taking action to convert the technology's prospective advantages into real benefits for patients, even in the face of resistance to change in the healthcare industry. It is believed that the increasing evidence from in-vivo studies is promising and represents a positive change in the treatment of chronic wounds toward sophisticated 3D-printed dressings.

Fostering human learning in sequential decision-making: Understanding the role of evaluative feedback.

Cognitive rehabilitation, STEM (science, technology, engineering, and math) skill acquisition, and coaching games such as chess often require tutoring decision-making strategies. The advancement of AI-driven tutoring systems for facilitating human learning requires an understanding of the impact of evaluative feedback on human decision-making and skill development. To this end, we conduct human experiments using Amazon Mechanical Turk to study the influence of evaluative feedback on human decision-making in sequential tasks. In these experiments, participants solve the Tower of Hanoi puzzle and receive AI-generated feedback while solving it. We examine how this feedback affects their learning and skill transfer to related tasks. Additionally, treating humans as noisy optimal agents, we employ maximum entropy inverse reinforcement learning to analyze the effect of feedback on the implicit human reward structure that guides their decision making. Lastly, we explore various computational models to understand how people incorporate evaluative feedback into their decision-making processes. Our findings underscore that humans perceive evaluative feedback as indicative of their long-term strategic success, thus aiding in skill acquisition and transfer in sequential decision-making tasks. Moreover, we demonstrate that evaluative feedback fosters a more structured and organized learning experience compared to learning without feedback. Furthermore, our results indicate that providing intermediate goals alone does not significantly enhance human learning outcomes.

Biofilm Inhibition on Medical Devices and Implants Using Carbon Dots: An Updated Review.

Biofilms are an intricate community of microbes that colonize solid surfaces, communicating via a quorum-sensing mechanism. These microbial aggregates secrete exopolysaccharides facilitating adhesion and conferring resistance to drugs and antimicrobial agents. The escalating global concern over biofilm-related infections on medical devices underscores the severe threat to human health. Carbon dots (CDs) have emerged as a promising substrate to combat microbes and disrupt biofilm matrices. Their numerous advantages such as facile surface functionalization and specific antimicrobial properties, position them as innovative anti-biofilm agents. Due to their minuscule size, CDs can penetrate microbial cells, inhibiting growth via cytoplasmic leakage, reactive oxygen species (ROS) generation, and genetic material fragmentation. Research has demonstrated the efficacy of CDs in inhibiting biofilms formed by key pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Consequently, the development of CD-based coatings and hydrogels holds promise for eradicating biofilm formation, thereby enhancing treatment efficacy, reducing clinical expenses, and minimizing the need for implant revision surgeries. This review provides insights into the mechanisms of biofilm formation on implants, surveys major biofilm-forming pathogens and associated infections, and specifically highlights the anti-biofilm properties of CDs emphasizing their potential as coatings on medical implants.

Diagnostic Accuracy of Waist Circumference and Waist-to-Height Ratio for Moderate and Severe Acute Malnutrition in Under-5 Children.

OBJECTIVE: To determine the most appropriate cut-off values of Waist Circumference (WC) and Waist-to-Height Ratio (WHtR) for diagnosing moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in under-five children. METHODS: This cross-sectional diagnostic accuracy study was conducted between January 2021 and August 2022 in the Department of Pediatrics of a tertiary hospital in Delhi. Children aged 6 months to 5 years attending the outpatient or emergency services were included in the study. Detailed clinical evaluation and anthropometry including measurement of WC were done at enrollment. Body mass index (BMI) and WHtR were calculated. Malnutrition was classified as per the WHO criteria. Receiver operating characteristic curves (sensitivity, specificity) for WC and WHtR (absolute values) were drawn against the standard test of WHO definitions for MAM and SAM to determine the most appropriate cut-offs for diagnosing MAM and SAM. RESULTS: 1500 children with a median (IQR) age of 29 (14, 43) months were enrolled; 21% children had MAM and 11% had SAM as per the WHO criteria. WC < 44.5 cm (sensitivity 74.1%, specificity 71.1%) and WHtR < 0.565 (sensitivity 75.6%, specificity 33.7%) was the best cut-off to identify MAM, whereas WC < 42.3 cm (sensitivity 67.5%, specificity 81.3%) and WHtR < 0.563 (sensitivity 81.3%, specificity 33.4%) was the best cut-off to diagnose SAM. CONCLUSIONS: Waist circumference (< 44.5 cm for MAM; < 42.3 cm for SAM) had a reasonably good sensitivity and specificity for diagnosing MAM and SAM, but the same was not true for WHtR.

Targeting and monitoring ovarian cancer invasion with an RNAi and peptide delivery system.

RNA interference (RNAi) therapeutics are an emerging class of medicines that selectively target mRNA transcripts to silence protein production and combat disease. Despite the recent progress, a generalizable approach for monitoring the efficacy of RNAi therapeutics without invasive biopsy remains a challenge. Here, we describe the development of a self-reporting, theranostic nanoparticle that delivers siRNA to silence a protein that drives cancer progression while also monitoring the functional activity of its downstream targets. Our therapeutic target is the transcription factor SMARCE1, which was previously identified as a key driver of invasion in early-stage breast cancer. Using a doxycycline-inducible shRNA knockdown in OVCAR8 ovarian cancer cells both in vitro and in vivo, we demonstrate that SMARCE1 is a master regulator of genes encoding proinvasive proteases in a model of human ovarian cancer. We additionally map the peptide cleavage profiles of SMARCE1-regulated proteases so as to design a readout for downstream enzymatic activity. To demonstrate the therapeutic and diagnostic potential of our approach, we engineered self-assembled layer-by-layer nanoparticles that can encapsulate nucleic acid cargo and be decorated with peptide substrates that release a urinary reporter upon exposure to SMARCE1-related proteases. In an orthotopic ovarian cancer xenograft model, theranostic nanoparticles were able to knockdown SMARCE1 which was in turn reported through a reduction in protease-activated urinary reporters. These LBL nanoparticles both silence gene products by delivering siRNA and noninvasively report on downstream target activity by delivering synthetic biomarkers to sites of disease, enabling dose-finding studies as well as longitudinal assessments of efficacy.

Skill or Competency: What Should we be Assessing?

India introduced competency-based medical education (CBME) in the year 2019. There is often confusion between terms like ability, skill, and competency. The provided curriculum encourages teaching and assessing skills rather than competencies. Though competency includes skill, it is more than a mere skill, and ignoring the other aspects like communication, ethics, and professionalism can compromise the teaching of competencies as well as their intended benefits to the patient and the society. The focus on skills also undermines the assessment of relevant knowledge. This paper clarifies the differences between ability, skill, and competency, and re-emphasizes the role of relevant knowledge and its assessment throughout clinical training. It is also emphasized that competency assessment is not a one-shot process; rather, it must be a longitudinal process where the assessment should bring out the achievement level of the student. Many of the components of competencies are not assessable by purely objective methods and there is a need to use expert subjective judgments, especially for the formative and classroom assessments. A mentor adds to the success of a competency-based curriculum.

In Vivo Toxicological Analysis of the ZnFe2O4@poly(tBGE-alt-PA) Nanocomposite: A Study on Fruit Fly.

Recently, the use of hybrid nanomaterials (NMs)/nanocomposites has widely increased for the health, energy, and environment sectors due to their improved physicochemical properties and reduced aggregation behavior. However, prior to their use in such sectors, it is mandatory to study their toxicological behavior in detail. In the present study, a ZnFe2O4@poly(tBGE-alt-PA) nanocomposite is tested to study its toxicological effects on a fruit fly model. This nanocomposite was synthesized earlier by our group and physicochemically characterized using different techniques. In this study, various neurological, developmental, genotoxic, and morphological tests were carried out to investigate the toxic effects of nanocomposite on Drosophila melanogaster. As a result, an abnormal crawling speed of third instar larvae and a change in the climbing behavior of treated flies were observed, suggesting a neurological disorder in the fruit flies. DAPI and DCFH-DA dyes analyzed the abnormalities in the larva's gut of fruit flies. Furthermore, the deformities were also seen in the wings and eyes of the treated flies. These obtained results suggested that the ZnFe2O4@poly(tBGE-alt-PA) nanocomposite is toxic to fruit flies. Moreover, this is essential to analyze the toxicity of this hybrid NM again in a rodent model in the future.

Parental Education for Limiting Screen Time in Early Childhood: A Randomized Controlled Trial.

OBJECTIVE: To assess the impact of focused parental education on limiting screen time in early childhood. METHODS: An open label randomized controlled trial was conducted in a tertiary care hospital in Delhi wherein 120 healthy children aged 9-10 months of age, born at term gestation and appropriate for gestational age (birth weight ≥ 2500 g), attending the immunization clinic reporting for measles-rubella (MR) vaccination were enrolled. Primary caregivers were randomized to either receive 30 minutes of in-person active counselling with pre-designed content including a printed pamphlet targeted at reduction of screen time (Educational group, n = 61) or to receive routine in-person counseling on general health measures (Control group, n = 61). All caregivers were followed up. Primary caregivers in both groups were reinforced telephonically every month for 6 months. At the end of six months, we assessed the proportion of children with screen-time > 1 hour/day and the median duration of screen-time (minutes /day). We also compared both groups in terms of changes in pre-post intervention developmental and behavioral scores (measured with Ages and Stages questionnaires). RESULTS: After 6 months of follow-up, 3% (2/61) children in the Educational group had screen time > 1 hour/day as compared to 53% (32/61) (P < 0.001) in the Control group. Median (IQR) for total screen duration in the Educational group was 35 (30,49) minutes/day compared to 75 (50,90) minutes/day in the Control group (P < 0.001). Children in the Educational group were also observed to have a significant change in behavioral score and fine motor and adaptive skills as compared to controls. CONCLUSION: Parental education starting in infancy is a promising intervention to reduce screen exposure in children; it may also have a positive impact on their developmental and behavioral skills.

Anti-cancer Activity of Biogenic Nat-ZnO Nanoparticles Synthesized Using Nyctanthes arbor-tristis (Nat) Flower Extract.

Inorganic nanoparticles (NPs) have played an important role as nano-drug delivery systems during cancer therapy in recent years. These NPs can carry cancer therapeutic agents. Due to this, they are considered a promising ancillary to traditional cancer therapies. Among inorganic NPs, Zinc Oxide (ZnO) NPs have been extensively utilized in cellular imaging, gene/drug delivery, anti-microbial, and anti-cancerous applications. In this study, a rapid and cost-effective method was used to synthesize Nat-ZnO NPs using the floral extract of the Nyctanthes arbor-tristis (Nat) plant. Nat-ZnO NPs were physicochemically characterized and tested further on in vitro cancer models. The average hydrodynamic diameter (Zaverage) and the net surface charge of Nat-ZnO NPs were 372.5 ± 70.38 d.nm and -7.03 ± 0.55 mV, respectively. Nat-ZnO NPs exhibited a crystalline nature. HR-TEM analysis showed the triangular shape of NPs. Furthermore, Nat-ZnO NPs were also found to be biocompatible and hemocompatible when tested on mouse fibroblast cells and RBCs. Later, the anti-cancer activity of Nat-ZnO NPs was tested on lung and cervical cancer cells. These NPs displayed potent anti-cancer activity and induced programmed cell death in cancer cells.

Emerging Trends in Zinc Ferrite Nanoparticles for Biomedical and Environmental Applications.

Over the last few decades, the application of nanoparticles (NPs) gained immense attention towards environmental and biomedical applications. NPs are ultra-small particles having size ranges from 1 to 100 nm. NPs loaded with therapeutic or imaging compounds have proved a versatile approach towards healthcare improvements. Among various inorganic NPs, zinc ferrite (ZnFe2O4) NPs are considered as non-toxic and having an improved drug delivery characteristics . Several studies have reported broader applications of ZnFe2O4 NPs for treating carcinoma and various infectious diseases. Additionally, these NPs are beneficial for reducing organic and inorganic environmental pollutants. This review discusses about various methods to fabricate ZnFe2O4 NPs and their physicochemical properties. Further, their biomedical and environmental applications have also been explored comprehensively.

Anti-cancer Application of Nat-ZnFe2O4 Nanoparticles on 2D Tumor Models.

Metal/Metal Oxide nanoparticles (M/MO NPs) exhibit potential biomedical applications due to their tunable physicochemical properties. Recently, the biogenic synthesis of M/MO NPs has gained massive attention due to their economical and eco-friendly nature. In the present study, Nyctanthes arbor-tristis (Nat) flower extract-derived Zinc Ferrite NPs (Nat-ZnFe2O4 NPs) were synthesized and physicochemically characterized by FTIR, XRD, FE-SEM, DLS, and other instruments to study their crystallinity, size, shape, net charge, presence of phytocompounds on NP's surface and several other features. The average particle size of Nat-ZnFe2O4 NPs was approx. 25.87 ± 5.67 nm. XRD results showed the crystalline nature of Nat-ZnFe2O4 NPs. The net surface charge on NPs was -13.28 ± 7.18 mV. When tested on mouse fibroblasts and human RBCs, these NPs were biocompatible and hemocompatible. Later, these Nat-ZnFe2O4 NPs exhibited potent anti-neoplastic activity against pancreatic, lung, and cervical cancer cells. In addition, NPs induced apoptosis in tested cancer cells through ROS generation. These in vitro studies confirmed that Nat-ZnFe2O4 NPs could be used for cancer therapy. Moreover, further studies are recommended on ex vivo platforms for future clinical applications.

Synthesis of Pectin and Eggshell Biowaste-Mediated Nano-hydroxyapatite (nHAp), Their Physicochemical Characterizations, and Use as Antibacterial Material.

The current study reports the synthesis of sustainable nano-hydroxyapatite (nHAp) using a wet chemical precipitation approach. The materials used in the green synthesis of nHAp were obtained from environmental biowastes such as HAp from eggshells and pectin from banana peels. The physicochemical characterization of obtained nHAp was carried out using different techniques. For instance, X-ray diffractometer (XRD) and FTIR spectroscopy were used to study the crystallinity and synthesis of nHAp respectively. In addition, the morphology and elemental composition of nHAP were studied using FESEM equipped with EDX. HRTEM showed the internal structure of nHAP and calculated its grain size which was 64 nm. Furthermore, the prepared nHAp was explored for its antibacterial and antibiofilm activity which has received less attention previously. The obtained results showed the potential of pectin-bound nHAp as an antibacterial agent for various biomedical and healthcare applications.

Prevalence and Predictors of Vitamin B12 Deficiency in Children with Severe Acute Malnutrition, and its Association with Development.

OBJECTIVES: To determine the proportion of children with severe acute malnutrition (SAM) having vitamin B12 deficiency, its clinical predictors, and its association with development. METHODS: In this cross-sectional study, 100 children between 1 mo to 59 mo [mean (SD) age 17 (12.75) mo; 55 males], with diagnosis of SAM as per WHO criteria, were included. Serum vitamin B12, serum folate, and serum ferritin levels were measured by chemiluminescence immunometric assay method, while serum Homocysteine (Hcy) level was measured by enzymatic cycling method. Development assessment was done by Denver Development Screening Tool (DDST-II). RESULTS: The mean (SD) serum vitamin B12 (cobalamin) levels were 296.52 (246.95) pg/mL; 45% children were vitamin B12 deficient (<203 pg/mL). Hyperhomocysteinemia (>14 µmol/L) was present in 39 (39%), and among these 69% (27/39) children had concomitant low serum vitamin B12 levels. Severe anemia and hypoproteinemia were significantly and independently associated with vitamin B12 deficiency [aOR (95% CI) 3.22 (1.13, 10) and 10 (1.66, 58.82), respectively]. Out of 45 children who were vitamin B12 deficient, 93%, 87%, 62% and 80% had gross motor, fine-motor, language and adaptive-cognitive delay, respectively. Vitamin B12 level was significantly associated (P <0.001) with developmental delay. CONCLUSIONS: There is a high prevalence of vitamin B12 deficiency in children with SAM, which is also associated with development delay across all domains (except language) in these children.

Healthcare provider perspectives on COVID-19 vaccination for children in India.

BACKGROUND: The rapid development and deployment of effective COVID-19 vaccines have been critical to halt the spread of the pandemic. India started vaccinating children in early 2022, however, vaccine uptake has been suboptimal. METHODS: Between September and November 2022, we conducted an online survey that was disseminated to eligible participants via email, text messages and social media platforms across India. The survey aimed to gather the perspectives of Indian healthcare providers regarding key factors related to the rollout of paediatric COVID-19 vaccines. Descriptive statistics were used to analyse participant demographics and responses on knowledge about paediatric COVID-19 vaccines, perceived risks and benefits, and vaccine rollout strategies. RESULTS: The survey yielded 805 respondents from 23 Indian states; 63.5% were men, 97.3% were paediatricians, median age was 44 years (IQR 25-81). Eighty-one per cent and 65.2% respondents had heard about the most common paediatric COVID-19 vaccines in India, Covaxin and Corbevax, but only 52.9%, 53.7% and 62.1% felt adequately informed about their safety, efficacy and vaccination schedules, respectively. Thirty per cent of respondents were unaware of vaccination guidelines. Eighty-five per cent of respondents felt that vaccines would reduce the incidence of severe disease, hospitalisation and deaths, and 60.6% felt children with comorbidities should be prioritised for vaccination. Perceived supply side barriers included lack of enforcement of guidelines (45.2%) and adverse effects following immunisation monitoring systems (37.6%), and on the demand side, parental vaccine hesitancy (64.4%). Eighty-one per cent believed that school-based vaccination strategies would be highly effective in increasing uptake. CONCLUSIONS: Most respondents were in support of the COVID-19 paediatric vaccination, although just over half did not feel adequately informed. Concerns about vaccine hesitancy among caregivers were the leading reported barrier. Targeted interventions are needed to provide adequate knowledge support to healthcare providers and evidence-based public health messaging to reduce vaccine hesitancy among caregivers.

Single Parent Adoption: An Indian Perspective.

Adoption is gaining an increasing acceptance in the society, and is also being researched well globally; yet, the concept of single parent adoption (SPA) is viewed with scepticism. Although, it is legally possible for prospective parents to proceed with adoption, there are several barriers which have made SPA a lengthy and arduous process. We present a strong case for SPA, in the absence of adequate research, by citing a basic flaw when fighting for SPA. Comparing SPA with a "two-parent model" is not only unreasonable but also unfair as it deprives a single parent of the pleasures of parenting and also denies the child an opportunity of living in a home outside the confines of an orphanage.