Multilocular cystic nephroma in an adult: a diagnostic quandary.

Multilocular cystic nephroma (MLCN) is an unusual, benign slow-growing renal cystic neoplasm which mimics other cystic renal lesions and has such clinical, radiological, and morphological features that causes diagnostic dilemma. MLCN lies in the spectrum of mixed epithelial and stromal tumor (MEST) family of kidney. According to World Health Organization (WHO 2016 classification), MEST encompasses spectrum of tumors ranging from predominantly cystic tumors, adult cystic nephroma (ACN) to tumors that are variably solid (MEST), thus creating diagnostic dilemma. Moreover, it has several benign and malignant differentials due to its several overlapping histomorphological features which when not cautiously dealt with may result in misdiagnosing it as malignant lesion. We hereby present a case of a woman in late twenties who presented with left flank swelling and pain since 6 months which was misdiagnosed as renal cell carcinoma on radiology which turned out to be ACN on histology and further verified on immunohistochemistry.

Twelve tips to leverage AI for efficient and effective medical question generation: A guide for educators using Chat GPT.

BACKGROUND: Crafting quality assessment questions in medical education is a crucial yet time-consuming, expertise-driven undertaking that calls for innovative solutions. Large language models (LLMs), such as ChatGPT (Chat Generative Pre-Trained Transformer), present a promising yet underexplored avenue for such innovations. AIMS: This study explores the utility of ChatGPT to generate diverse, high-quality medical questions, focusing on multiple-choice questions (MCQs) as an illustrative example, to increase educator's productivity and enable self-directed learning for students. DESCRIPTION: Leveraging 12 strategies, we demonstrate how ChatGPT can be effectively used to generate assessment questions aligned with Bloom's taxonomy and core knowledge domains while promoting best practices in assessment design. CONCLUSION: Integrating LLM tools like ChatGPT into generating medical assessment questions like MCQs augments but does not replace human expertise. With continual instruction refinement, AI can produce high-standard questions. Yet, the onus of ensuring ultimate quality and accuracy remains with subject matter experts, affirming the irreplaceable value of human involvement in the artificial intelligence-driven education paradigm.

Withaferin-A attenuates diabetes mellitus induced male reproductive dysfunction mediated by ERα in brain and testes of Swiss albino mice.

Diabetes mellitus (DM) is a chronic metabolic disease, characterized by persistent hyperglycemia resulting from diminished insulin secretion or insulin resistance. The present study evaluated the ameliorative effects of Withaferin-A (WA) on DM-induced reproductive dysfunction in mice. For the same, mice were intraperitoneally injected with Streptozotocin (STZ), (40 mg/kg/day) for 5 consecutive days to induce DM. Mice were then treated with WA (8 mg/kg/day) in normal and diabetic conditions (STZ + WA). Next, blood glucose levels, oral glucose tolerance, intraperitoneal insulin tolerance, oxidative stress and reproductive parameters were estimated. For reproductive performance, immunofluorescent localization of gonadotropin-releasing hormone (GnRH-I) and estrogen receptor alpha (ERα) in the preoptic area and paraventricular nucleus region of hypothalamus and ERα in testes was performed. STZ-induced diabetes triggered reproductive dysfunctions as mediated by low GnRH-I and ERα in the brain and ERα in the testes along with declined testosterone and estradiol levels. Treatment with WA significantly reduced the blood glucose levels and enhanced glucose clearance accompanied by reduced oxidative stress in the brain, pancreas and testes as indicated by the low levels of H2O2 and MDA in diabetic mice treated with WA (STZ + WA). This study reports, for the first time, that WA can efficiently ameliorate DM-induced reproductive dysfunctions by enhancing endogenous testosterone, estrogen and increased GnRH-I and ERα in the brain and ERα in the testes of DM-induced male mice.

Gold nanoparticles and gold nanorods in the landscape of cancer therapy.

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

Targeted therapy of breast tumor by PLGA-based nanostructures: The versatile function in doxorubicin delivery.

Breast carcinoma is a molecularly diverse illness, and it is among the most prominent and often reported malignancies in female across the globe. Surgical intervention, chemotherapy, immunotherapy, gene therapy, and endocrine treatment are among the currently viable treatment options for the carcinoma of breast. Chemotherapy is among the most prevalent cancer management strategy. Doxorubicin (DOX) widely employed as a cytostatic medication for the treatment of a variety of malignancies. Despite its widespread acceptance and excellent efficacy against an extensive line up of neoplasia, it has a variety of shortcomings that limit its therapeutic potential in the previously mentioned indications. Employment of nanoparticulate systems has come up as a unique chemo medication delivery strategy and are being considerably explored for the amelioration of breast carcinoma. Polylactic-co-glycolic acid (PLGA)-based nano systems are being utilized in a number of areas within the medical research and medication delivery constitutes one of the primary functions for PLGA given their inherent physiochemical attributes, including their aqueous solubility, biocompatibility, biodegradability, versatility in formulation, and limited toxicity. Herein along with the different application of PLGA-based nano formulations in cancer therapy, the present review intends to describe the various research investigations that have been conducted to enumerate the effectiveness of DOX-encapsulated PLGA nanoparticles (DOX-PLGA NPs) as a feasible treatment option for breast cancer.

Hearing outcomes in pediatric tympanoplasty and factors affecting surgical outcomes in the current era.

OBJECTIVES: Type-1 tympanoplasty continues to be the treatment of choice for tympanic membrane perforations resulting from chronic suppurative otitis media (CSOM) in children, which is a principal cause of correctable hearing loss in the pediatric population. There is an ongoing debate about the surgical success rate, the factors affecting success as well as the best intervention time for this population group. This study assessed the outcome of Type-1 tympanoplasty in children in terms of 1) graft uptake and 2) hearing improvement as assessed by audiology. METHODS: The study involved 40 patients aged 6 to ≤14 years suffering from tubotympanic chronic suppurative otitis media. The patients in the study had a central perforation of the pars tensa of the tympanic membrane. Pre-op investigations included Pure tone audiometry, Eustachian tube function test and nasopharyngeal x-ray. Type-1 tympanoplasty was performed on all patients. They were followed up at end of two months, six months, and one year postoperatively to assess surgical success and hearing outcomes. RESULTS: Overall graft uptake and the surgical success rate was 80%. Postoperatively air-bone gap closure up to 5 dB was achieved in 62.5% of patients at the end of one year. A normal type A tympanometry curve was achieved in 75% of patients. There was a significant reduction in hearing handicap. The best results were obtained in the 9-10 years age group. CONCLUSION: Tympanoplasty has a high success rate in children. There is a significant improvement in hearing post-surgery. There is a minimal impact of traditionally believed confounding factors. Considering the positive impact of improved hearing and reduced hearing disability, the authors suggest that surgeons should take young children up for tympanoplasty.

New opportunities for RGD-engineered metal nanoparticles in cancer.

The advent of nanotechnology has opened new possibilities for bioimaging. Metal nanoparticles (such as gold, silver, iron, copper, etc.) hold tremendous potential and offer enormous opportunities for imaging and diagnostics due to their broad optical characteristics, ease of manufacturing technique, and simple surface modification. The arginine-glycine-aspartate (RGD) peptide is a three-amino acid sequence that seems to have a considerably greater ability to adhere to integrin adhesion molecules that exclusively express on tumour cells. RGD peptides act as the efficient tailoring ligand with a variety of benefits including non-toxicity, greater precision, rapid clearance, etc. This review focuses on the possibility of non-invasive cancer imaging using metal nanoparticles with RGD assistance.

Heavy metal contamination in river water, sediment, groundwater and human blood, from Kanpur, Uttar Pradesh, India.

Exponential industrialization and anthropogenic activities have resulted in water contamination by various heavy metals in Kanpur city, India. Heavy metal pollution, an issue of great concern, is not only affecting river water, but contamination of groundwater is creating health issues and worries. In the present investigation, blood samples were collected from selected volunteers, water and sediment samples from four sites of river Ganga and drinking groundwater samples from 23 locations of Kanpur city. Heavy metals analysis in river water, sediment, and human blood, was done by inductively coupled plasma optical emission spectroscopy (ICP-OES) and atomic absorption spectroscopy (AAS) was used for groundwater samples. Human blood showed a high concentration of arsenic (As) (66.6 ± 0.00 and 76.9 ± 0.01 µg L-1 in males and female subjects, respectively) and thallium (Tl) (13.4 ± 0.004 and 16.6 ± 0.005 µg L-1 in males and female subjects, respectively) with higher concentrations in females than males. Other heavy metals (Nickle, Beryllium, Cadmium, Cobalt, Chromium, Lithium, Molybdenum, Lead) were not observed in any of the tested human blood samples. However, in groundwater sampling, iron (Fe), copper (Cu), and arsenic (As) were detected, one sample had the presence of chromium (Cr), and two samples showed lead (Pb) contamination. River water [Cu (32-125 µg L-1), Cr (19-725 µg L-1), Cd (1-59 µg L-1), Pb (37-163 µg L-1), As (32-153 µg L-1), Th (26.75 µg L-1)] showed a high level of the heavy metals, as compared to reference values of BIS, CPCB (2016a), WHO, EPA and USEPA. River sediment [Cu (4168-34,470 µg Kg-1), Cr (4040-145,650 µg Kg-1), Cd (326-5340 µg Kg-1), Pb (1840-19,350 µg Kg-1), As (103-188 µg Kg-1)] also showed high concentration when compared to reference values of USEPA and PASS. River site 4, with high Cr (725 µg L-1), also showed Cr levels (19.8 µg L-1) in the groundwater samples, indicating Cr contamination in groundwater while Pb was observed at groundwater samples close to two industrial sites. Drinking water might be the primary exposure pathway for As and Tl to enter the human body. The study recommends periodic monitoring of river water, sediment, groundwater, and human blood samples for contamination of heavy metals.

Implications of CD45RA and CD45RO T cell subsets in patients of chronic rhinosinusitis with nasal polyposis infected with Aspergillus flavus.

T cell subsets (CD4 and CD8) play a prominent role in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). Colonization with Aspergillus flavus is recognized as a trigger for the growth of nasal polyps. The fungal proteins initiate the recruitment of T cells into the nasal mucosa, which contributes to the progression of nasal polyps. The study included 50 cases of CRSwNP and 50 healthy controls. Biopsies were subjected to KOH and culture for mycological investigation. We examined the changes in T helper (CD4+) and T cytotoxic (CD8+) in total T cells (CD3+) and expression of naive (CD45RA) and memory (CD45RO) cell markers in T cell subsets in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens in cases before and after treatment and in healthy controls by flow cytometry. Predominantly, A. flavus (86%) identified in nasal polyp biopsies of patients. An increased percentage of CD3+CD4+ T cells observed after A. flavus stimulation in patients when compared with healthy controls. The expression of CD4+CD45RA+ cells was significantly (P < .05) reduced in patients and increased CD4+CD45RO+ was observed upon stimulation with A. flavus in patients when compared with healthy control. Continuous exposure to inhaled fungal spores may induce aberrant immune responses to A. flavus spores, causing an allergic immunological reaction with high CD4+T cell responses, resulting in an unfavourable outcome. Elevated CD4+CD45RO+ T cells may transform the pathogenic response and highlight the chances of A. flavus reactive T cells involvement in prompting inflammation in CRSwNP.

A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome.

Cervical cancer is a dreaded form of cancer in women, the fourth most common cancer, with around 0.3 million females suffering from this disease worldwide. Over the past several decades, global researches have focused on the mitigation of cervical lesions and cancers and have explored the impact of physiological and psychological stress and insomnia on cervical pathogenesis. Furthermore, disruption of the cervicovaginal microbiome profiles is identified as an added high-risk factor for the occurrence of cervical cancer. The physiological regulation of stress has an underlying mechanism controlled via hypothalamic pituitary adrenal (HPA) and sympatho-adrenal medullary (SAM) axes. Disruptions in these axes have been identified as the factors responsible for maintaining the homeostasis balance. Recent studies on microbiomes have offered novel ways to combat cervical cancer and cervix infection by exploring the interplay of the cervicovaginal microbiome. Moreover, the integration of various immune cells and microbiome diversity is known to act as an effective strategy to decipher the cervix biological activity. Cytokine profiling and the related immune competence, and physiological stress and insomnia impart to the regulatory networks underlying the mechanism which may be helpful in designing mitigation strategies. This review addressed the current progress in the research on cervical cancer, HPV infection, immune cell interaction, and physiological stress and insomnia with the cervicovaginal microbiome to decipher the disease occurrence and therapeutic management.

Thermodynamic and structural profiles of multi-target binding of vinblastine in solution.

Structural information about drug-receptor interactions is paramount in drug discovery and subsequent optimization processes. Drugs can bind to multiple potential targets as they contain common chemical entities in their structures. Understanding the details of such interactions offer possibilities for repurposing and developing potent inhibitors of disease pathways. Vinblastine (VLB) is a potent anticancer molecule showing multiple receptor interactions with different affinities and degrees of structural perturbations. We have investigated the multi-target binding profile of VLB with DNA and human serum albumin (HSA) in a dynamic physiological environment using spectroscopic, molecular dynamics simulations, and quantum mechanical calculations to evaluate the structural features, mode, ligand and receptor flexibility, and energetics of complexation. These results confirm that VLB prefers to bind in the major groove of DNA with some inclination toward Thymidine residue and the TR-5 binding site in HSA with its catharanthine half making important contacts with both the receptors. Spectroscopic investigation at multiple temperatures has also proved that VLB binding is entropy driven indicating the major groove and TR-5 binding site of interaction. Finally, the overall binding is facilitated by van der Waals contacts and a few conventional H-bonds. VLB portrays reasonable conformational diversity on binding with multiple receptors.

Novel Use of Platelet Rich Fibrin Membrane in Transcanal Myringoplasty: A Prospective Study-Letter to Editor.

This is a letter to the editor enlisting a few concerns and points of view which arose on reading a recently published article on the novel use of platelet rich fibrin membrane in transcanal myringoplasty.

Post Viral Olfactory Dysfunction After SARS-CoV-2 Infection: Anticipated Post-pandemic Clinical Challenge.

Persistent olfactory dysfunction (OD) is the second most common symptom of post coronavirus disease-19 (COVID-19) now being termed long-COVID. Its prevalence after recovery from COVID-19 is estimated to be 12% after nearly 6 months of follow-up. It thus becomes imperative for the treating clinicians to update themselves with the pathophysiology of this post COVID disability as well as the tools for diagnosis and the available treatment options. A systematic literature search was performed as per PRISMA guidelines in MEDLINE, Cochrane Library, LILACS, Google Scholar, ClinicalTrials.gov, and medRxiv databases. The keywords used were covid-19, Olfactory Disorders, Smell, Anosmia, PVOD, Post Viral Olfactory Disorders, post-covid and post haul. All articles were studied for definition, mechanism, diagnostic tests and treatment options for post COVID OD. 33 published articles and 8 ongoing trials were found relevant and included after full-text review. SARS-CoV-2 can cause conductive, neural and central OD. Olfactory evaluation can be done both subjectively (visual analogue scale) and objectively (Sniffin' sticks, Sinonasal Outcome Test, University of Pennsylvania Smell Identification Test and modified Davidson's alcohol sniff test). They can be used to detect and follow-up patients. Despite several on-going clinical trials, the most reliable and advisable treatment option available till date is olfactory training.

EHMT1/EHMT2 in EMT, cancer stemness and drug resistance: emerging evidence and mechanisms.

Metastasis, therapy failure and tumour recurrence are major clinical challenges in cancer. The interplay between tumour-initiating cells (TICs) and epithelial-mesenchymal transition (EMT) drives tumour progression and spread. Recent advances have highlighted the involvement of epigenetic deregulation in these processes. The euchromatin histone lysine methyltransferase 1 (EHMT1) and euchromatin histone lysine methyltransferase 2 (EHMT2) that primarily mediate histone 3 lysine 9 di-methylation (H3K9me2), as well as methylation of non-histone proteins, are now recognised to be aberrantly expressed in many cancers. Their deregulated expression is associated with EMT, cellular plasticity and therapy resistance. In this review, we summarise evidence of their myriad roles in cancer metastasis, stemness and drug resistance. We discuss cancer-type specific molecular targets, context-dependent mechanisms and future directions of research in targeting EHMT1/EHMT2 for the treatment of cancer.

Light and scanning electron microscopy of an ischnoceran louse, Felicola rohani, and an amblyceran louse, Heterodoxus spiniger (Phthiraptera: Insecta) from the Indian grey mongoose, Herpestes edwardsii.

The ischnoceran louse, Felicola rohani Werneck, 1956 is reported for the first time from India on the Indian grey mongoose - Herpestes edwardsii (Geoffroy Saint-Hilaire, 1818) and the amblyceran louse, Heterodoxus spiniger (Enderlein, 1909) is recorded for the first time from that host species. The lice were collected from freshly accidentally killed specimen of the host, preserved and kept at the Museum of Estuarine Biology Regional Centre, Zoological Survey of India, Gopalpur-on-sea, Ganjam Odisha. Detailed morphological descriptions of the lice, based on light and scanning electron microscopy, are presented in this paper.

Scanning electron microscopy of Cysticercus fasciolaris (larval Taenia taeniaeformis Batsch, 1786) from the wild rat, Rattus rattus Linnaeus, 1758, morpho-physiology and risk to human health.

Autopsy of Rattus rattus (n=65) revealed 1-7 creamish to white cysts, 2-7 mm in diameter embedded in the liver parenchyma of 12 rats. Dissection yielded 45-65 mm×5 mm sized segmented strobilocercii of Cysticercus fasciolaris (larval Taenia taeniaeformis) coiled inside. Light microscopy indicated large scolices, the rostellum armed with four suckers and one row of taenoid type hooks having long blunt handle with sharp pointed blade, other row of hooks was in the developing stage. The strobila lacked genital organs and ended in a tail-bulb suggesting it was juvenile. SEM showed anterior crown of 19 hooks and poorly developed posterior crown. A collar (66.0-86.0 µm in width) armed with papillae (30.2-35.4 µm base and 12.5-14.5 µm tip) and pores (17.0-22.4 µm in diameter) surrounded the hooks. The body segments were 125-145 µm in diameter, at the tail bud, 380-410 µm in diameter. The segments were armed with pores, 11.5-14.5 µm in diameter. Netted (2.5-4.5 µm wide and of varying lengths) body segments provide flexibility to the worm during attachment. The tail bud was 2.4-2.7 mm in length and 1.5-1.71 mm in width. The SEM data presents a significant advancement over light microscopy and the morphological features generated herein can safely be utilized to correlate with the parasite's physiological functions. This is the first report of R. rattus as a natural intermediate host of T. taeniaeformis, and may pose serious risk to human health in urban areas of Bareilly, India and merits attention.

TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis.

BACKGROUND: T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus. RESULTS: The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-ß levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls. CONCLUSIONS: Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.

Global study of variability in olfactory sensitivity.

Variability in human olfactory sensitivity has been attributed to individual-level factors such as genetics, age, sex, medical history of infections and trauma, neurogenerative diseases, and emotional disorders. Scarce evidence exists on the cross-cultural variation in olfactory sensitivity. Hence, we performed 2 studies to estimate the variability in olfactory threshold as a function of location and environment. Study 1 involved 11 laboratories from 4 continents (N = 802). In each location, in a designated laboratory, approximately 80 subjects underwent olfactory sensitivity testing with custom-made tests with eucalyptol and phenylethanol (PEA) odors. Tests were based on the Threshold subtest of the Sniffin' Sticks battery. In Study 2, we compared olfactory sensitivity and suprathreshold perception of PEA and eucalyptol in 2 Chinese (N = 160) and 2 Indian (N = 92) populations-one based in their native country and the other in Germany. Both studies present large-scale evidence that olfactory sensitivity varies as a function of geographical location and suggest that environmental factors play an important role in shaping olfactory sensitivity and suprathreshold olfactory perception. We delineate further steps necessary to identify specific factors underlying uncovered variability and the relationship between olfactory sensitivity and suprathreshold odor perception. (PsycInfo Database Record (c) 2020 APA, all rights reserved).