Study of Clinicoetiological Spectrum of Bicytopenia and Pancytopenia in Hospitalized Children.

Background The etiological profile of children with bicytopenia and pancytopenia has a very wide spectrum, ranging from transient causes like infections or nutritional deficiencies to bone marrow failure syndromes. Timely diagnosis and treatment impart favorable prognosis to this entity. There is a paucity of data regarding the etiology of cytopenia in hospitalized children at a tertiary center in India. Additionally, only a few studies have discussed the possible association between the severity of cytopenia at presentation and the possible etiology. Methods This is a cross-sectional observational study analyzing bicytopenia and pancytopenia in hospitalized children. Patient details, along with clinical findings and relevant investigations, were recorded on predesigned pro forma and analyzed statistically. Results Out of 202 children, 174 (86.13%) had bicytopenia, and 28 (13.86%) had pancytopenia, with a male predominance resulting in a male-to-female ratio of 1.65:1. The commonest age group affected was pre-adolescent age group (6-12 years). The causes of bicytopenia and pancytopenia in hospitalized children in the decreasing order of frequency were infections (65.84%), benign hematological disorders (18.81%), systemic illness (10.39%), and malignancies (4.95%). The cytopenia was more severe in children with pancytopenia than bicytopenia. Conclusions Infections outweigh the other causes of bicytopenia and pancytopenia. The severity of the cell line affected can help narrow down a diagnosis of cytopenia etiologies. Most of the children with bicytopenia and pancytopenia had treatable etiology and favorable outcomes.

Natural product-loaded lipid-based nanocarriers for skin cancer treatment: An overview.

The skin is essential for body protection and regulating physiological processes. It is the largest organ and serves as the first-line barrier against UV radiation, harmful substances, and infections. Skin cancer is considered the most prevalent type of cancer worldwide, while melanoma skin cancer is having high mortality rates. Skin cancer, including melanoma and non-melanoma forms, is primarily caused by prolonged exposure to UV sunlight and pollution. Currently, treatments for skin cancer include surgery, chemotherapy, and radiotherapy. However, several factors hinder the effectiveness of these treatments, such as low efficacy, the necessity for high concentrations of active components to achieve a therapeutic effect, and poor drug permeation into the stratum corneum or lesions. Additionally, low bioavailability at the target site necessitates high doses, leading to skin irritation and further obstructing drug absorption through the stratum corneum. To overcome these challenges, recent research focuses on developing a medication delivery system based on nanotechnology as an alternative to this traditional approach. Nano-drug delivery systems have demonstrated great promise in treating skin cancer by providing a more effective means of delivering drugs with better stability and drug absorption. An overview of various lipid-based nanocarriers is given in this review article that are utilized to carry natural compounds to treat skin cancer.

Transforming Medicine with Nanobiotechnology: Nanocarriers and Their Biomedical Applications.

Nanobiotechnology, at the intersection of nanotechnology and biology, represents a burgeoning field poised to revolutionize medicine through the use of advanced nanocarriers. These nanocarriers, endowed with distinctive physiobiological attributes, are instrumental in diverse therapeutic domains including drug delivery for microbial infections, cancer treatment, tissue engineering, immunotherapy, and gene therapy. Despite the transformative potential, several challenges hinder their efficacy, such as limited drug capacity, suboptimal targeting, and poor solubility. This review delves into the latest advancements in nanocarrier technologies, examining their properties, associated limitations, and the innovative solutions developed to address these issues. It highlights promising nanocarrier systems like nanocomposites, micelles, hydrogels, microneedles, and artificial cells that employ advanced conjugation techniques, sustained and stimulus-responsive release mechanisms, and enhanced solubility. By exploring these novel structures and their contributions to overcoming existing barriers, the article emphasizes the vital role of interdisciplinary research in advancing nanobiotechnology. This field offers unparalleled opportunities for precise and effective therapeutic delivery, underscoring its potential to reshape healthcare through personalized, targeted treatments and improved drug performance.

Advancing biomedical applications: an in-depth analysis of silver nanoparticles in antimicrobial, anticancer, and wound healing roles.

Introduction: Silver nanoparticles (AgNPs) have gained significant attention in biomedical applications due to their unique physicochemical properties. This review focuses on the roles of AgNPs in antimicrobial activity, anticancer therapy, and wound healing, highlighting their potential to address critical health challenges. Methods: A bibliometric analysis was conducted using publications from the Scopus database, covering research from 2002 to 2024. The study included keyword frequency, citation patterns, and authorship networks. Data was curated with Zotero and analyzed using Bibliometrix R and VOSviewer for network visualizations. Results: The study revealed an increasing trend in research on AgNPs, particularly in antimicrobial applications, leading to 8,668 publications. Anticancer and wound healing applications followed, with significant contributions from India and China. The analysis showed a growing focus on "green synthesis" methods, highlighting a shift towards sustainable production. Key findings indicated the effectiveness of AgNPs in combating multidrug-resistant bacteria, inducing apoptosis in cancer cells, and promoting tissue regeneration in wound healing. Discussion: The widespread research and applications of AgNPs underscore their versatility in medical interventions. The study emphasizes the need for sustainable synthesis methods and highlights the potential risks, such as long-term toxicity and environmental impacts. Future research should focus on optimizing AgNP formulations for clinical use and further understanding their mechanisms of action. Conclusion: AgNPs play a pivotal role in modern medicine, particularly in addressing antimicrobial resistance, cancer treatment, and wound management. Ongoing research and international collaboration are crucial for advancing the safe and effective use of AgNPs in healthcare.

Enhancing Clinical Practice: Creating Dynamic Medical Content in Electronic Medical Records.

The integration of Electronic Medical Records (EMRs) revolutionized healthcare but often retained limitations from paper-based structures. This study proposes a framework for developing dynamic medical content specifically adapted to the clinical context including medical specialty and diseases. Tailoring content to this dynamic context offers several benefits, including improved access to relevant information, streamlined workflows, and potentially better patient outcomes. We applied our framework to develop neurosurgical content, focusing on brain tumors. The method involves defining the medical specialty, outlining user journeys, and iteratively developing artifacts like assessment forms, dashboards, and order sets. Standardized terminologies ensure consistency and interoperability. Our results demonstrate a successful development of content meeting user needs and clinical relevance. While initial implementation focused on neurosurgery, exploring scalability and AI integration offers promising avenues for further advancement. Future studies could quantitatively evaluate the impact of this method on user satisfaction and patient outcomes.

Unexpected Rhythm: Supraventricular Tachycardia Unveiled in a Neonate Diagnosed at Delivery.

Neonatal supraventricular tachycardia (SVT) poses clinical challenges due to its rarity and potential for serious complications. We present a case of a 2.5 kg female neonate delivered at 37.2 weeks of gestation, diagnosed with SVT shortly after birth. Initial management included adenosine administration, which was initially ineffective until a second dose successfully reduced the heart rate. Subsequent episodes required repeated adenosine and the initiation of propranolol therapy. The neonate showed improvement with cessation of SVT episodes, weaning off respiratory support, and successful breastfeeding initiation. Follow-up at one month revealed no recurrent SVT, affirming effective management and favorable outcomes in neonatal SVT cases.

Altered extracellular matrix correlates with an immunosuppressive tumor microenvironment and disease progression in younger adults with oral cavity squamous cell carcinoma.

Introduction: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (<45 years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options. Methods: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults (≥60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ T-cell counts using immunohistochemistry. Results: Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05). Conclusion: Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy.

Bioprospecting of Aspergillus sp. as a promising repository for anti-cancer agents: a comprehensive bibliometric investigation.

Cancer remains a significant global health challenge, claiming nearly 10 million lives in 2020 according to the World Health Organization. In the quest for novel treatments, fungi, especially Aspergillus species, have emerged as a valuable source of bioactive compounds with promising anticancer properties. This study conducts a comprehensive bibliometric analysis to map the research landscape of Aspergillus in oncology, examining publications from 1982 to the present. We observed a marked increase in research activity starting in 2000, with a notable peak from 2005 onwards. The analysis identifies key contributors, including Mohamed GG, who has authored 15 papers with 322 citations, and El-Sayed Asa, with 14 papers and 264 citations. Leading countries in this research field include India, Egypt, and China, with King Saud University and Cairo University as the leading institutions. Prominent research themes identified are "endophyte," "green synthesis," "antimicrobial," "anti-cancer," and "biological activities," indicating a shift towards environmentally sustainable drug development. Our findings highlight the considerable potential of Aspergillus for developing new anticancer therapies and underscore the necessity for further research to harness these natural compounds for clinical use.

Impact of nicotine dependence on self-efficacy and readiness to quit among tobacco consumers in rural areas.

Aim and Objectives: The aim of the present study was to determine the impact or effect of nicotine dependence on self-efficacy and readiness to quit. Materials and Method: The current study was performed using a cross-sectional descriptive questionnaire design among tobacco users visiting primary health care facilities in the rural Jaipur district. Jaipur district is divided into four directions: east, west, north, and south. From each direction, two PHCs were selected randomly based on suitable accessibility to patients. Sample size of study is 465. Out of 465 tobacco consumers, 238 were consuming a smoked form of tobacco, and 227 study participants were consuming a smokeless form of tobacco. Results: It was observed that the majority of study participants (145 (31%)) need smoke/smokeless tobacco within 5 minutes of waking up. With regards to internal stimuli, the majority of study participants (179 (38%)) and (203 (44%)) were not very sure that they would refrain from smoking when they were nervous and depressed. It was determined that quitting tobacco products was not at all important for 159 (34%) study participants. In regards to confidence in tobacco product quitting, only 79 (16%) of tobacco consumers were extremely confident. Conclusion: It was concluded that nicotine dependence impacts both self-efficacy and readiness to quit. It was determined that the higher the nicotine dependence, the less self-efficacy and the less would be the readiness to quit.

Unraveling the Photoionization Dynamics of Indole in Aqueous and Ethanol Solutions.

The photoionization dynamics of indole, the ultraviolet-B chromophore of tryptophan, were explored in water and ethanol using ultrafast transient absorption spectroscopy with 292, 268, and 200 nm excitation. By studying the femtosecond-to-nanosecond dynamics of indole in two different solvents, a new photophysical model has been generated that explains many previously unsolved facets of indole's complex solution phase photochemistry. Photoionization is only an active pathway for indole in aqueous solution, leading to a reduction in the fluorescence quantum yield in water-rich environments, which is frequently used in biophysical experiments as a key signature of the protein-folded state. Photoionization of indole in aqueous solution was observed for all three pump wavelengths but via two different mechanisms. For 200 nm excitation, electrons are ballistically ejected directly into the bulk solvent. Conversely, 292 and 268 nm excitation populates an admixture of two 1ππ* states, which form a dynamic equilibrium with a tightly bound indole cation and electron-ion pair. The ion pair dissociates on a nanosecond time scale, generating separated solvated electrons and indole cations. The charged species serve as important precursors to triplet indole production and greatly enhance the overall intersystem crossing rate. Our proposed photophysical model for indole in aqueous solution is the most appropriate for describing photoinduced dynamics of tryptophan in polypeptide sequences; tryptophan in aqueous pH 7 solution is zwitterionic, unlike in peptides, and resultantly has a competitive excited state proton transfer pathway that quenches the tryptophan fluorescence.

An interventional study evaluating the NTCP (NATIONAL TOBACCO CONTROL PROGRAM) guidelines-based education model in semi-urban school population.

Background: The present study was carried out to assess the awareness of the adverse consequences of tobacco use in the semi-urban school population in Wardha district because tobacco use in schools is a significant concern and is rising at an alarming rate. The purpose of the current study was to assess the prevalence of tobacco use among students and teachers as well as their knowledge of the negative effects of tobacco use. It also aimed to educate students and teachers about these effects and assess the effectiveness of the intervention. Methodology: A total of 350 students from a semi-urban school in the Wardha area participated in this study. Pre-tests were administered to a group of chosen kids and instructors to gauge their familiarity with tobacco. After the pre-test data were analyzed, teachers were offered intervention. PowerPoint presentations, posters, and models were used to educate them about the dangers of tobacco usage for dental health. There were discussions, role plays, and skits done. After the instruction, the students took a post-test to gauge how well they understood what they had learned. Results: The recent study is a significant step toward the semi-urban school population quitting smoking. Overall, the study involves testing participants' knowledge, teaching them about tobacco's negative consequences, and inspiring habitual smokers to completely kick the habit. The majority of the NTCP questionnaire's elements were significant when compared to knowledge of tobacco use and its components (*p0.05; significant). Conclusion: The suggested study is a significant step toward the semi-urban school population quitting smoking. The research will provide a genuine and dependable change and help promote optimal dental health.

Doxorubicin catalyses self-assembly of p53 by phase separation.

Liquid-liquid phase separation plays a crucial role in cellular physiology, as it leads to the formation of membrane-less organelles in response to various internal stimuli, contributing to various cellular functions. However, the influence of exogenous stimuli on this process in the context of disease intervention remains unexplored. In this current investigation, we explore the impact of doxorubicin on the abnormal self-assembly of p53 using a combination of biophysical and imaging techniques. Additionally, we shed light on the potential mechanisms behind chemoresistance in cancer cells carrying mutant p53. Our findings reveal that doxorubicin co-localizes with both wild-type p53 (WTp53) and its mutant variants. Our in vitro experiments indicate that doxorubicin interacts with the N-terminal-deleted form of WTp53 (WTp53ΔNterm), inducing liquid-liquid phase separation, ultimately leading to protein aggregation. Notably, the p53 variants at the R273 position exhibit a propensity for phase separation even in the absence of doxorubicin, highlighting the destabilizing effects of point mutations at this position. The strong interaction between doxorubicin and p53 variants, along with its localization within the protein condensates, provides a potential explanation for the development of chemotherapy resistance. Collectively, our cellular and in vitro studies emphasize the role of exogenous agents in driving phase separation-mediated p53 aggregation.

Early-Onset Takayasu Arteritis in Childhood: A Case Report.

Takayasu arteritis is a chronic, idiopathic, inflammatory disease mainly affecting medium and large vessels with a significant rate of morbidity and mortality. The vessels most frequently affected are the aorta and its branches; branches originating from the aortic arch include right brachiocephalic trunk and its branches, left common carotid artery, left subclavian artery, coronary arteries from the ascending aorta, celiac trunk, right and left renal arteries, superior and inferior mesenteric arteries from the descending aorta, and right and left iliofemoral arteries. Local and systemic inflammation along with end organ ischemia is attributed to severe clinical manifestations associated with this condition. Although Takayasu arteritis is more commonly diagnosed in adults, this study highlights the unusual occurrence of childhood-onset Takayasu arteritis (TAK), presenting a unique set of diagnostic challenges. We present a case of a seven-year-old female patient who manifested atypical symptoms, such as absent pulses and malignant hypertension at an early age, leading to a delayed diagnosis. The patient's clinical course, including diagnostic workup and imaging studies such as CT or MR angiography, is thoroughly discussed. This study emphasizes the importance of recognizing the subtleties of Takayasu arteritis in children. The disease may initially masquerade as other common conditions, such as peripheral arterial disease, coarctation of aorta, renal artery stenosis, chronic renal disease, and increased intracranial pressure, thereby hindering timely diagnosis and appropriate intervention. This case underscores the importance of considering Takayasu arteritis as a differential diagnosis in children, presenting with unexplained constitutional symptoms or signs of systemic vasculitis, emphasizing the need for multidisciplinary collaboration and tailored therapeutic intervention to optimize the outcome in this rare and potentially debilitating condition.

Secreted IgM modulates IL-10 expression in B cells.

IL-10+ B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10+ B cell differentiation are ill-defined. Here we find that IL-10+ B cells expand in mice lacking secreted IgM ((s)IgM-/-) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10+ B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10+ B cells. Lack of the high affinity receptor for sIgM, FcµR, in B cells translates into an intermediate IL-10+ B cell phenotype relative to WT or sIgM-/- mice. Our study thus shows that sIgM regulates IL-10 programming in B cells in part via B cell-expressed FcµR, thereby revealing a function of sIgM in regulating immune homeostasis.

Absent Superior Vena Cava: An Uncommon Cause of Anomalous Systemic Venous Return.

We report a case of a one-year-old boy with tetralogy of Fallot, who was preoperatively diagnosed to have an associated systemic venous anomaly. Computed tomography confirmed the absent superior vena cava, and the case was managed with an appropriate cannulation strategy. Preoperative diagnosis and thorough planning of this rather benign anomaly were imperative for the successful outcome of this case. Clinical and surgical implications of this anomaly are discussed in this report.

Limb Salvage Surgery in a Rare Case of Recurrent Parosteal Osteosarcoma with Vascular Graft Thrombosis.

Recurrent parosteal sarcomas with vascular involvement are rare and present unique challenges in their diagnosis and management. We report the case of a 21-year-old woman with parosteal osteosarcoma of the left distal femur, encasing the popliteal vessels. En bloc transarticular resection of the distal femur and popliteal vessels was performed, followed by reconstruction using a modular prosthesis and a saphenous vein autograft for both the artery and vein. On the 1st postoperative day, the patient developed an arterial thrombus requiring reintervention with a jump polytetrafluoroethylene (PTFE) graft. Histopathology confirmed parosteal osteosarcoma. After a disease-free survival of 41 months, the patient experienced local recurrence involving the PTFE graft, leading to graft compression, erosion, and subsequent thrombosis. Despite these complications, limb salvage was possible due to adequate collateral blood supply. This case highlights the feasibility of limb salvage surgery in select cases of parosteal osteosarcoma with vascular involvement.

Alterations of the expression of TET2 and DNA 5-hmC predict poor prognosis in Myelodysplastic Neoplasms.

BACKGROUND: Myelodysplastic Neoplasms (MDS) are clonal stem cell disorders characterized by ineffective hematopoiesis and progression to acute myeloid leukemia, myelodysplasia-related (AML-MR). A major mechanism of pathogenesis of MDS is the aberration of the epigenetic landscape of the hematopoietic stem cells and/or progenitor cells, especially DNA cytosine methylation, and demethylation. Data on TET2, the predominant DNA demethylator of the hematopoietic system, is limited, particularly in the MDS patients from India, whose biology may differ since these patients present at a relatively younger age. We studied the expression and the variants of TET2 in Indian MDS and AML-MR patients and their effects on 5-hydroxymethyl cytosine (5-hmC, a product of TET2 catalysis) and on the prognosis of MDS patients. RESULTS: Of the 42 MDS patients, cytogenetics was available for 31 sub-categorized according to the Revised International Prognostic Scoring System (IPSS-R). Their age resembled that of the previous studies from India. Bone marrow nucleated cells (BMNCs) were also obtained from 13 patients with AML-MR, 26 patients with de-novo AML, and 11 subjects with morphologically normal bone marrow. The patients had a significantly lower TET2 expression which was more pronounced in AML-MR and the IPSS-R higher-risk MDS categories. The 5-hmC levels in higher-risk MDS and AML-MR correlated with TET2 expression, suggesting a possible mechanistic role in the loss of TET2 expression. The findings on TET2 and 5-hmC were also confirmed at the tissue level using immunohistochemistry. Pathogenic variants of TET2 were found in 7 of 24 patient samples (29%), spanning across the IPSS-R prognostic categories. One of the variants - H1778R - was found to affect local and global TET2 structure when studied using structural predictions and molecular dynamics simulations. Thus, it is plausible that some pathogenic variants in TET2 can compromise the structure of TET2 and hence in the formation of 5-hmC. CONCLUSIONS: IPSS-R higher-risk MDS categories and AML-MR showed a reduction in TET2 expression, which was not apparent in lower-risk MDS. DNA 5-hmC levels followed a similar pattern. Overall, a decreased TET2 expression and a low DNA 5-hmC level are predictors of advanced disease and adverse outcome in MDS in the population studied, i.e., MDS patients from India.

Aortic Uncrossing for Circumflex Aorta.

Circumflex aorta is described as a retroesophageal aortic arch, with opposite-sided descending aorta forming a true vascular ring with ligamentum arteriosum. We report two cases of right-sided circumflex aorta with varied clinical presentation. Computed tomography diagnosed this vascular ring anomaly. The patients were managed with the aortic uncrossing procedure as a primary surgical strategy. Preoperative diagnosis and thorough planning were essential for the successful outcome. The patients did not have any residual symptoms of tracheal and esophageal compression on follow up.

Comparison of home-based palliative care delivered by community health workers versus usual care: research protocol for a pilot randomized controlled trial.

BACKGROUND: Research studies demonstrate that palliative care can improve patient outcomes such as quality of life, symptom burden and patient satisfaction with care (Gomes B, et al. Effectiveness and cost-effectiveness of home palliative care services for adults with advanced illness and their caregivers. Cochrane Database Syst Rev. 2013(6):CD00776) (World Health Organization. Palliative Care. Published 2020.). While 76% of patients who need palliative care live in limited-resource countries, access to high quality palliative services in these countries is minimal (Worldwide Hospice and Palliative Care Association and World Health Organization. Global Atlas of Palliative Care (2nd ed). 2020.). In 2014 the Worldwide Hospice Palliative Care Alliance, with strong endorsement by the WHO, released the Palliative Care Toolkit to provide a training and implementation toolkit for empowering community members to deliver palliative care in resource poor settings (Worldwide Hospice and Palliative Care Association and World Health Organization. Global Atlas of Palliative Care at the End of Life. Geneva, Switzerland 2014.). They encouraged researchers and public health practitioners to conduct rigorous evaluation of the toolkit in diverse settings and contexts. To address this need, we will conduct a pilot randomized controlled trial (RCT) to examine implementation and explore potential effect of an intervention based upon the Palliative Care Toolkit, as adapted and used by community health workers (CHWs) working with a cancer center in Kolkata, India to deliver home-based palliative care for rural patients. METHODS: Utilizing a randomized controlled trial design, intervention patients (n = 45) receive home-based palliative services (Pal-Care) delivered by community health workers (CHWs), with comparison against a control group of patients (n = 45) who receive usual cancer-center-based palliative services. Primary outcome measures include evaluation of CHW training outcomes, roles and responsibilities of the CHWS and how they assist patients, trial recruitment, stakeholder perceptions of the intervention, and fidelity to study protocol. Secondary outcomes measure patient self-report of health-related quality of life, symptom burden, palliative needs and patient care experience, outcomes The RE-AIM framework guides our evaluation plan to measure the reach, effectiveness, adoption, implementation and maintenance of the Pal-Care intervention (Gaglio B, et al. The RE-AIM framework: a systematic review of use over time. Am J Public Health. 2013;103(6):e38?46.). Data will be analyzed in SAS. All measures will be evaluated overall and by patient age, gender and cancer type and by CHW caseload. DISCUSSION: Pal-Care is a RCT funded by the NCI to explore utilization of CHWs to deliver a home-based palliative care intervention built upon the WHO Palliative Care toolkit (PCT), as compared to a usual care control group. The long-term goal of this research is to develop an effective and sustainable model for delivering home-based palliative care for cancer patients in underserved areas. TRIAL REGISTRATION (TRN): ClinicalTrials.gov ID# NCT04972630.