Comprehensive Case Analysis of Tuberculous Meningitis in an Immunocompetent Patient: Diagnostic Challenges and Therapeutic Strategies.

Tuberculosis (TB) continues to be a significant global health concern, with India contributing substantially to the global burden. The management of TB is further complicated by HIV-associated immunodeficiency and the emergence of drug-resistant TB strains. Early diagnosis and treatment are critical, particularly for tubercular meningitis (TBM), which is among the most severe forms of extrapulmonary TB. We present the case of a 55-year-old male who arrived at our emergency department with a one-week history of fever, headache, incoherent speech, and slurred speech. The patient had no relevant medical history or known contact with TB patients. Neurological examination revealed ptosis of the right eye and a left extensor plantar response. Laboratory investigations revealed a miliary pattern on chest radiography, and cerebrospinal fluid analysis showed an adenosine deaminase (ADA) level of 14.4 U/L, a total cell count of 110/mm³, glucose of 6 mg/dL, and protein of 228.4 mg/dL, supporting the diagnosis of TBM. Magnetic resonance imaging (MRI) indicated brain lesions consistent with TBM. TBM represents the most devastating form of extrapulmonary TB if left untreated. Therefore, prompt initiation of antitubercular therapy and continued vigilance in endemic regions are essential for addressing this complex global health issue.

Magnetic engineering nanoparticles: Versatile tools revolutionizing biomedical applications.

The use of nanoparticles has increased significantly over the past few years in a number of fields, including diagnostics, biomedicine, environmental remediation, and water treatment, generating public interest. Among various types of nanoparticles, magnetic nanoparticles (MNPs) have emerged as an essential tool for biomedical applications due to their distinct physicochemical properties compared to other nanoparticles. This review article focuses on the recent growth of MNPs and comprehensively reviews the advantages, multifunctional approaches, biomedical applications, and latest research on MNPs employed in various biomedical techniques. Biomedical applications of MNPs hold on to their ability to rapidly switch magnetic states under an external field at room temperature. Ideally, these MNPs should be highly susceptible to magnetization when the field is applied and then lose that magnetization just as quickly once the field is removed. This unique property allows MNPs to generate heat when exposed to high-frequency magnetic fields, making them valuable tools in developing treatments for hyperthermia and other heat-related illnesses. This review underscores the role of MNPs as tools that hold immense promise in transforming various aspects of healthcare, from diagnostics and imaging to therapeutic treatments, with discussion on a wide range of peer-reviewed articles published on the subject. At the conclusion of this work, challenges and potential future advances of MNPs in the biomedical field are highlighted.

Development of Antifouling Thin-Film Composite/Nanocomposite Membranes for Removal of Phosphate and Malachite Green Dye.

Nowadays polymer-based thin film nanocomposite (TFN) membrane technologies are showing key interest to improve the separation properties. TFN membranes are well known in diverse fields but developing highly improved TFN membranes for the removal of low concentration solutions is the main challenge for the researchers. Application of functional nanomaterials, incorporated in TFN membranes provides better performance as permeance and selectivity. The polymer membrane-based separation process plays an important role in the chemical industry for the isolation of products and recovery of different important types of reactants. Due to the reduction in investment, less operating costs and safety issues membrane methods are mainly used for the separation process. Membranes do good separation of dyes and ions, yet their separation efficiency is challenged when the impurity is in low concentration. Herewith, we have developed, UiO-66-NH2 incorporated TFN membranes through interfacial polymerization between piperazine (PIP) and trimesoyl chloride (TMC) for separating malachite green dye and phosphate from water in their low concentration. A comparative study between thin-film composite (TFC) and TFN has been carried out to comprehend the benefit of loading nanoparticles. To provide mechanical strength to the polyamide layer ultra-porous polysulfone support was made through phase inversion. As a result, outstanding separation values of malachite green (MG) 91.90 ± 3% rejection with 13.32 ± 0.6 Lm-2h-1 flux and phosphate 78.36 ± 3% rejection with 22.22 ± 1.1 Lm-2h-1 flux by TFN membrane were obtained. The antifouling tendency of the membranes was examined by using bovine serum albumin (BSA)-mixed feed and deionized water, the study showed a good ~84% antifouling tendency of TFN membrane with a small ~14% irreversible fouling. Membrane's antibacterial test against E. coli. and S. aureus. also revealed that the TFN membrane possesses antibacterial activity as well. We believe that the present work is an approach to obtaining good results from the membranes under tricky conditions.

A Novel Approach for the Development of Low-Cost Polymeric Thin-Film Nanocomposite Membranes for the Biomacromolecule Separation.

The separation of biomacromolecules, mainly proteins, plays a significant role in the pharmaceutical and food industries. Among the membranes' techniques, thin-film nanocomposite nanofiltration membranes are the best choice due to their high energy efficiency, excellent productivity, cost-effective and tuneable properties that have captured the attention of the efficient separation of biomacromolecules, especially from the industrial perspective. The present work directs the efficient separation study of proteins, namely, lysozyme, trypsin, pepsin, bovine serum albumin (BSA), and cephalexin, using a thin-film nanocomposite membrane integrated with Arg-MMT (arginine-montmorillonite) clay nanoparticles. The surface morphology and cross-section images of the TFN membranes were studied using a field emission scanning electron microscope (FE-SEM) and a high-resolution transmission electron microscope (HR-TEM). The thermal stability and hydrophilicity of the membranes were examined using thermogravimetric analysis (TGA) and contact angle, respectively. The surface chemistry of the selective layer has different functional groups that were analyzed using FTIR spectroscopy. The performance of the membranes was studied at different trans-membrane pressures and permeation times. The effect of monomer concentration on the separation performance of the membranes was also studied at different permeation times. The membranes' antibacterial activity was evaluated using the Muller-Hinton disk diffusion method using gram-negative Escherichia coli (E. coli) and gram-positive Staphylococcus aureus (S. aureus) bacteria. The highest rejection was achieved for BSA up to 98.92 ± 1%, and the highest permeation was obtained against lysozyme feed solution up to 26 L m-2 h-1 at 5 bar pressure. The membrane also illustrated excellent rejection of cephalexin antibiotics with a rejection of 98.17 ± 1.75% and a permeation flux of 26.14 L m-2 h-1. The antifouling study performed for the membranes exhibited a flux recovery ratio of 86.48%. The fabricated thin-film nanocomposite membrane demonstrated a good alternative for the separation of biomacromolecules and has the potential to be used in different sectors of industry, especially the pharmaceutical and food industry.

Nanocomposite and bio-nanocomposite polymeric materials/membranes development in energy and medical sector: A review.

Nanocomposite and bio-nanocomposite polymer materials/membranes have fascinated prominent attention in the energy as well as the medical sector. Their composites make them appropriate choices for various applications in the medical, energy and industrial sectors. Composite materials are subject of interest in the polymer industry. Different kinds of fillers, such as cellulose-based fillers, carbon black, clay nanomaterials, glass fibers, ceramic nanomaterial, carbon quantum dots, talc and many others have been incorporated into polymers to improve the quality of the final product. These results are dependent on a variety of factors; however, nanoparticle dispersion and distribution are major obstacles to fully using nanocomposites/bio-nanocomposites materials/membranes in various applications. This review examines the various nanocomposite and bio-nanocomposite materials applications in the energy and medical sector. The review also covers the variety of ways for increasing nanocomposite and bio-nanocomposite materials features, each with its own set of applications. Recent researches on composite materials have shown that polymeric nanocomposites and bio-nanocomposites are promising materials that have been intensively explored for many applications that include electronics, environmental remediation, energy, sensing (biosensor) and energy storage devices among other applications. In this review, we studied various nanocomposite and bio-nanocomposite materials, their controlling parameters to develop the product and examine their features and applications in the fields of energy and the medical sector.

Clinicopathological and immunophenotypic features of early T cell precursor acute lymphoblastic leukaemia: A flow cytometry score for the initial diagnosis.

OBJECTIVE: To assess the prevalence of early T precursor-acute lymphoblastic leukaemia (ETP-ALL), study its clinicopathological features and devise a 'flow score' based on immunophenotypic profiles. MATERIAL METHODS: This was a retrospective study where clinical and laboratory data of all consecutive T-ALL cases were analysed to identify features differentiating ETP from non-ETP-ALL. The utility of a flow score based on the five commonly used markers in leukaemia panels for T-ALL (CD34, CD8, CD5, CD13 and CD33) was evaluated to differentiate ETP from non-ETP-ALL. RESULTS: Early T precursor-acute lymphoblastic leukaemia constituted 24.2% (n = 29) of all T-ALL cases. It was significantly more common in adults (30.2%) as compared to paediatric (17.5%) patients (P = .046). The median age of presentation was significantly higher than the non-ETP group. (24 vs 19 years; P = .01). Patients with ETP-ALL usually presented with organomegaly, lymphadenopathy, lower levels of haemoglobin, total leucocyte count, peripheral blood blast proportion and LDH levels as compared to non-ETP-ALL. The majority of ETP-ALL cases had L2 morphology with a moderate amount of cytoplasm showing frequent blebbing. A flow score cut-off value of ≥3 on ROC curve analysis had a sensitivity and specificity of 100% and 94.6% respectively. CONCLUSION: Early T precursor-acute lymphoblastic leukaemia had unique clinical and laboratory features. The prevalence of this entity is more common in the adult population. A flow score based on a minimum of five widely used markers can confidently identify ETP-ALL and should be included in the primary panel of markers used for flow cytometric analysis.

Hematological characteristics, cytogenetic features, and post-induction measurable residual disease in thymic stromal lymphopoietin receptor (TSLPR) overexpressed B-cell acute lymphoblastic leukemia in an Indian cohort.

The overexpression of cytokine receptor-like factor-2 (CRLF2) identified by anti-thymic stromal lymphopoietin receptor/TSLPR flow cytometry (FCM) has been reported as a screening tool for the identification of BCR-ABL1-like B-cell acute lymphoblastic leukemia/B-ALL with CRLF2 re-arrangement. TSLPR expression was studied prospectively in consecutive 478 B-ALLs (≤ 12 years (n = 244); 13-25 years (n = 129); > 25 years (n = 105)) and correlated with various hematological parameters and end-of-induction measurable residual disease (day 29; MRD ≥ 0.01% by 10-color FCM). TSLPR positivity in ≥ 10% leukemic cells was detected in 14.6% (n = 70) of B-ALLs. CRLF2 re-arrangement was detected in eight cases (11.4%) including P2RY8-CRLF2 (n = 6), and IgH-CRLF2 (n = 2) with a median TSLPR positivity of 48.8% and 99% leukemic cells, respectively. Recurrent gene fusions/RGF (BCR-ABL1 (17.1%); ETV6-RUNX1 (4.2%), TCF3-PBX1 (1.4%)), other BCR-ABL1-like chimeric gene fusions/CGFs (PDGFRB-rearrangement (2.9%), IgH-EPOR (1.4%)), CRLF2 extra-copies/hyperdiploidy (17.1%), and IgH translocation without a known partner (10%) were also detected in TSLPR-positive patients. CD20 positivity (52.9% vs 38.5%; p = 0.02) as well as iAMP21 (4.3% vs 0.5%; p = 0.004) was significantly more frequent in TSLPR-positive cases. TSLPR-positive patients did not show a significantly higher MRD, compared to TSLPR-negative cases (37% vs 33%). Increasing the threshold cut-off (from ≥ 10 to > 50% or > 74%) increased the specificity to 88% and 100% respectively in identifying CRLF2 translocation. TSLPR expression is not exclusive for CRLF2 translocations and can be seen with various other RGFs, necessitating their testing before its application in diagnostic algorithms. In patients with high TSLPR positivity (> 50%), the testing may be restricted to CRLF2 aberrancies, while patients with 10-50% TSLPR positivity need to be tested for both CRLF2- and non-CRLF2 BCR-ABL1-like CGFs.

Hb Mizuho (HBB: c.206T>C): Pitfalls of Screening Tests in an Unstable Hemoglobin Variant Diagnosed after Targeted Next-Generation Sequencing.

Hyperunstable hemoglobins (Hbs) are challenging to diagnose and may be missed on conventional hemolytic anemia work-up. Here, we report the case of a 2-year-old Indian boy with infancy-onset severe hemolytic anemia. Its etiology was revealed by targeted next-generation sequencing (NGS) to be the rare Hb Mizuho (HBB: c.206T>C). This variant had been missed on the initial routine laboratory investigations (heat and isopropanol tests for unstable Hbs) owing to its hyperunstable nature.

Subcategorisation of AUS/FLUS thyroid lesions as per the 2017 Bethesda System for Reporting Thyroid Cytopathology: a retrospective study from a tertiary care centre analysing risk of malignancy (ROM) of the different subcategories.

AIMS: The 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommends subclassification of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) into six subcategories. The present study evaluates the risk of malignancy (ROM) and risk of neoplasm (RON) among these. METHODS: All thyroid aspirates reported as AUS/FLUS over a 4.5-year period, with available histology, were reviewed and subclassified as per TBSRTC. ROM and RON were calculated and compared. RESULTS: Of 2554 thyroid aspirates, 281 (11.0%) were AUS/FLUS. Eighty-one with available histology were evaluated. ROM was 51.8%. Cytologic and architectural atypia (AUS-C&A) was the most prevalent (62.9%), followed by Hürthle cell type (19.6%), AUS-A (11.1%), AUS-not otherwise specified (NOS) (7.4%), cytologic atypia (AUS-C) (4.9%) and atypical lymphoid cells (1.2%). Papillary thyroid carcinoma (PTC) and adenomatous goitre (AG) were the most common histological diagnoses (27% each). On histology, AUS-C had 2/4 PTC and 2/4 AG on histology. AUS-A had 4/9 follicular neoplasm (FN) and 2/9 non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) while AUS C&A had 18/51 PTC, 13/51 AG, 11/51 NIFTP and 5/51 FN. ROM and RON were similar across subcategories, ROM was the highest for AUS-C&A (58.8%), AUS-C (50%) and AUS-NOS (50%). NIFTP reclassification as non-malignant reduced ROM to 35.8% (absolute reduction of 16% and a relative decrease of 31%) with the greatest relative decrease seen in AUS-A (50%), followed by AUS-C&A (37%), and none in others. CONCLUSIONS: AUS/FLUS subcategorisation helped to indicate risk for the more likely neoplasm, whether PTC or FN. ROM was the highest for cases with cytological atypia but did not differ significantly across different subcategories. NIFTP changed the ROM of AUS-A and AUS-C&A, since both NIFTP and FN have microfollicles.

Acquired Platelet Dysfunction with Eosinophilia (APDE) Syndrome: A Case Report.

Acquired platelet dysfunction with eosinophilia (APDE) is a syndrome which has transient state of platelet dysfunction in the presence of marked eosinophilia. This bleeding disorder, otherwise known as "non-thrombocytopenic purpura with eosinophilia", occurs commonly in children from South-East Asia. We report an 11 years old male child, who presented with ecchymotic patches over lower limbs, of recent onset. His hemogram revealed increased eosinophils with a normal platelet count. Coagulation screen revealed normal parameters except increase in bleeding time. Platelet aggregation studies showed normal platelet aggregation with ristocetin, reduced aggregation with ADP and no aggregation was seen with collagen.