Nanomaterials for sustainable remediation: efficient removal of Rhodamine B and lead using greenly synthesized novel mesoporous ZnO@CTAB nanocomposite.

This study explores the dual applications of a greenly synthesized ZnO@CTAB nanocomposite for the efficient remediation of Rhodamine B (RhB) and lead (Pb). The synthesis method involves a sustainable approach, emphasizing environmentally friendly practices. FT-IR, XRD, FESEM, zeta potential, and particle size analyzer (PSA), BET, and UV-VIS were used to physically characterize the zinc oxide and CTAB nanocomposite (ZnO@CTAB). The size and crystalline index of ZnO@CTAB are 77.941 nm and 63.56% respectively. The Zeta potential of ZnO@CTAB is about - 22.4 mV. The pore diameter of the ZnO@CTAB was 3.216 nm, and its total surface area was 97.42 m2/g. The mechanism of adsorption was investigated through pHZPC measurements. The nanocomposite's adsorption performance was systematically investigated through batch adsorption experiments. At pH 2, adsorbent dose of 0.025 g, and temperature 50 °C, ZnO@CTAB removed the most RhB, while at pH 6, adsorbent dose of 0.11 g, and temperature 60 °C, ZnO@CTAB removed the most Pb. With an adsorption efficiency of 214.59 mg/g and 128.86 mg/g for RhB and Pb, the Langmuir isotherm model outperforms the Freundlich isotherm model in terms of adsorption. The pseudo-2nd-order model with an R2 of 0.99 for both RhB and Pb offers a more convincing explanation of adsorption than the pseudo-1st-order model. The results demonstrated rapid adsorption kinetics and high adsorption capacities for RhB and Pb. Furthermore, there was minimal deterioration and a high reusability of ZnO@CTAB till 4 cycles were observed.

Wilson's Disease in an Early Adolescent: Classic Magnetic Resonance Imaging Findings.

Wilson's disease (WD), alternatively termed hepatolenticular degeneration, represents a rare autosomal recessive disorder typified by disrupted copper metabolism, culminating in copper accumulation across various organs. WD commonly manifests with early-onset liver cirrhosis, with notable involvement of the central nervous system, particularly impacting the midbrain and basal ganglia. This case report delineates the clinical presentation of an early adolescent female with WD, accentuating classical magnetic resonance imaging (MRI) findings. These MRI findings, which include the "face of a giant panda sign" and the "Face of a miniature panda sign," are pivotal for expeditious diagnosis. Recognition of these classical signs underscores the indispensable role of MRI in elucidating the neurological dimensions of WD.

The Role of Phase-Contrast MRI in Diagnosing Cerebrospinal Fluid Flow Abnormalities.

Background Cerebrospinal fluid (CSF) dynamics play a crucial role in maintaining the homeostasis of the central nervous system (CNS). Any disruption in CSF flow can lead to various congenital and acquired conditions, impacting neurological function and overall health. This study aims to analyze the significance of phase-contrast MRI in evaluating abnormalities in CSF flow and its diagnostic utility in various CSF-related disorders. Phase contrast MRI has emerged as a valuable tool for evaluating CSF dynamics non-invasively by examining CSF flow characteristics such as pulsatile flow patterns, hyperdynamic or hypodynamic flow, and disruptions in CSF circulation. Alterations in CSF pulsatility and stroke volume can indicate changes in intracranial compliance, vascular resistance, or CSF production and absorption rates. The findings of this study will advance our understanding of CSF physiology and its relevance in neurological pathologies, potentially leading to improved patient outcomes and management approaches. Materials and methods The study involved 36 patients and was conducted as an observational, prospective study over 18 months (October 2020 to March 2022) at the Department of Radiology, Saveetha Medical College and Hospital, Chennai. We utilized a 1.5 T Philips Multiva MRI scanner by Philips Healthcare in Amsterdam, Netherlands. The study included patients with suspected CSF flow abnormalities and abnormal MRI findings (normal pressure hydrocephalus (NPH), age-related brain atrophy, aqueduct stenosis (AS), Chiari malformation type 1, syringomyelia, or arachnoid cyst), alongside control exhibiting normal neurological symptoms and MRI results. Exclusions involved individuals with febrile seizures, neurological diseases, cerebrovascular accidents, anti-convulsive medication use, cardiac arrhythmia, or MRI contraindications. Post-processing involved analyzing stroke volume (SV), peak systolic velocity (PSV), end diastolic velocity (EDV), and mean flux. Statistical analysis was conducted using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 24.0, Armonk, NY), employing the χ2-test for categorical variables and nonparametric tests like Mann-Whitney U and Kruskal-Wallis H-tests for quantitative variables. A p-value < 0.05 was considered significant. Results The 36 patients, aged 1 to 80 years, were referred by the neurology department and categorized into four subgroups based on clinical history and conventional MRI findings: NPH, AS, age-related brain atrophy, and a normal control group. MRI CSF flowmetry evaluation focused on PSV, PDV, and SV. We found peak diastolic velocity (PDV), PSV, and average blood velocity (ABV) to be significantly higher in NPH compared to the control group (PSV, EDV, and SV: 9.96 +/- 1.73, 4.72 +/- 0.62, and 63 +/- 12.88 for NPH versus 4.8 +/- 0.39, 3.21 +/- 0.55, and 20.72 +/- 5.7 for control, respectively; p = 0.000). Conversely, patients with age-related brain atrophy and AS exhibited lower values (1.6 +/- 0.44, 1.13 +/- 0.09, and 6.33 +/- 2.08 for AS, and 2.07 +/- 0.09, 1.62 +/- 0.33, and 6.8 +/- 2.16 for age-related brain atrophy versus control; p = 0.002). Conclusion MRI CSF flowmetry emerges as a rapid, accurate, and non-invasive diagnostic tool for various neurological disorders associated with abnormal CSF flow. Additionally, this technique may aid in selecting appropriate treatment strategies.

Magnetic Resonance Imaging-Based Morphometric Analyses of the Bicruciate Injury of the Knee: Is There a Clue in the Distal Femur?

BACKGROUND: The morphology of the distal femur's intercondylar notch has been implicated in the susceptibility to and severity of cruciate ligament injuries. While previous research has primarily focused on isolated anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) injuries, the relationship between notch morphology and combined cruciate injuries remains less understood. OBJECTIVE: This study aimed to explore the association between femoral notch morphology and the severity of combined cruciate ligament injuries in adult males. METHODS: In this retrospective cohort study, MRI scans from 118 adult male participants with and without knee dislocations (60 cases with Schenk classification Type II or higher knee dislocations and 58 controls) were analyzed. The study period ranged from 2015 to 2023. Femoral notch width, notch width index (NWI), and notch shape (U shape, A shape) were assessed using a Philips Multiva 1.5 Tesla system (Philips, Amsterdam, Netherlands). The statistical significance of differences in measurements between cases and controls was evaluated using independent sample t-tests performed with IBM SPSS Statistics, version 26 (IBM Corp., Armonk, NY). RESULTS: The case group exhibited a significantly smaller mean femoral notch width (15.88 mm ± 2.7 mm) and NWI (0.238 ± 0.58) compared to the control group (notch width 18.29 mm ± 3.4 mm, NWI 0.25 ± 0.31), with p-values of 0.004 for both measurements. The notch shape was predominantly A-shaped in the case group (n = 49) as opposed to U-shaped in the control group (n = 41). CONCLUSIONS: The study identifies a significant association between reduced femoral notch dimensions and the severity of complex cruciate ligament injuries. These findings support the notion that specific femoral notch morphologies may predispose individuals to more severe ligamentous injuries.

Occupational and Environmental Exposure Influences the Inflammatory (Pro-and Anti-) Status in Benign Prostate Hyperplasia and Prostate Carcinoma Patients: A Retrospective Analysis.

Multiple diseases and disorders are connected with occupational and environmental exposure risk. It is also well-established that chemicals and chemical mixtures have an influence on the immune cells of humans. This is an important field of research that has been pursued extensively in relation to autoimmune illnesses, allergy/asthma, and lung cancer, but Prostate Carcinoma has received rare reports. Chronic chemical exposure is known to produce inflammation, which is one of the most prominent characteristics of all malignancies. Changes in the ratio of pro-inflammatory to anti-inflammatory molecules are thought to be a key factor in the emergence of inflammation. Prostate gland cells express the pro-inflammatory cytokine interleukin-18 (IL-18), which is a major facilitator of immunological responses. Conversely, interleukin-10 (IL-10) is an anti-inflammatory cytokine that is linked to immune responses and inhibits the development of an inflammatory environment. Our goal is to investigate the inflammatory status of IL-18 (pro-) and IL-10 (anti-) in a variety of occupationally exposed populations in patients with Benign Prostate Hyperplasia (BPH) and patients with Prostate Carcinoma. The present study was conducted with 664 subjects, comprising 285 Prostate Carcinoma patients, 94 BPH patients and 285 controls. The subjects of BPH and Prostate Carcinoma were screened and confirmed on the basis of Prostate Serum Antigen (PSA) and pathological biopsy. All subjects were categorized as per their occupational exposure into various groups. The pro-inflammatory and anti-inflammatory Interleukins (IL-18 and IL-10) and serum PSA levels were analysed by using corresponding quantitative ELISA kits. The results showed that as compared to control participants, the serum PSA levels were higher in the Prostate Carcinoma and BPH groups. When mean levels of IL-18 were compared between various occupational groups, Tanners (tanning industry), Agriculture, and Ordnance workers had significantly higher levels (P < 0.05) of IL-18 than sedentary workers. The pro-inflammatory cytokine (IL-18) levels were also found to be aggravated in Prostate Carcinoma compared to BPH and controls. According to the findings of the current study, the levels of inflammatory cytokines (IL-18 and IL-10) in various occupational groups of BPH, Prostate Carcinoma, and controls were altered. Long-term occupational exposure may have a negative influence on inflammation levels and the immune system; therefore, preventative measures should be explored for improved health.

Circulating miRNA-21 Levels in Breast Cancer Patients Before and After Chemotherapy and Its Association with Clinical Improvement.

Breast cancer is the most frequent type of cancer in women, many patients experience recurrences and metastasis. miR-21 (microRNA-21) as biomarker is under investigation for breast cancer. At present, there is very limited information available regarding effect of chemotherapy on miR-21 expression in breast cancer and its correlation with the clinical improvement. Hence, this study was planned to evaluate the effect of chemotherapy on miR-21 in metastatic breast cancer and its relationship with the clinical outcome. Females, aged-18-90 years diagnosed with Invasive Ductal Carcinoma of breast and candidate of neoadjuvant chemotherapy including Adriamycin (60 mg/m2), Cyclophosphamide (600 mg/m2) with or without Taxane (75-175 mg/m2) were included in the study. Before and after 42 days of staring of chemotherapy sample was collected for circulatory miR-21 and RECIST 1.1 criteria was applied to assess the clinical status. Blood samples for routine clinical biomarkers including liver function test and renal function tests was also collected. miR-21 expression before and after chemotherapy was assessed using standard method based on real time PCR. Expression of miR-21, RECIST criteria and other liver and kidney related biomarkers were compared before and after chemotherapy. After neoadjuvant chemotherapy expression of miR-21 was significantly increased by 5.65-fold. There was significant improvement in clinical scores based on RECIST criteria (0.046). No significant correlation was observed between miR-21 expression and difference in RECIST score (r = - 0.122, p = 0.570). Neoadjuvant chemotherapy causes clinical improvement in breast cancer patients however it is not correlated with the miR-21 expression which significantly increased after chemotherapy.

Traumatic Brachial Plexus Root Avulsion With Pseudomeningocele: A Case Series.

Traumatic avulsion pseudomeningocele of the brachial plexus is an uncommon and challenging condition with particular diagnostic and treatment challenges. This case series intends to investigate the unusual consequences of brachial plexus damage, emphasizing the significance of surgical procedures and rehabilitation strategies. Three cases of traumatic avulsion pseudomeningocele with medical histories, imaging studies, procedures, and recovery plans were carefully examined. The rehabilitation approaches and surgical procedures are outlined in detail. Each case had its own unique set of difficulties and complications. Nerve grafting and pseudomeningocele repair surgery were performed. The outcomes were evaluated based on neurological examination, range of motion, sensory recovery, and patient reports. Only a few patients showed discernible improvements in their quality of life, motor function, and discomfort. In this case series, we highlight the people with traumatic avulsion pseudomeningocele of the brachial plexus and recount their inspiring journeys. Surgical procedures and rehabilitation approaches have produced favorable outcomes regarding recovering functionality and enhancing patients' general well-being. These results highlight the value of interdisciplinary partnerships and individualized strategies in treating this uncommon illness. Further, more profound research and long-term follow-up are required regarding the condition and optimizing the treatment methods for this challenging clinical entity.

Huntington's Disease: A Report of an Interesting Case and Literature Review.

Huntington's disease (HD), referred to as Huntington's chorea, is an infrequent neurodegenerative ailment with an autosomal-dominant inheritance pattern characterized by the progressive deterioration of GABAergic neurons in the basal ganglia. Other ones include subcortical-type dementia, behavioral abnormalities, midlife psychosis, and gradual inadvertent choreoathetosis movements. HD is characterized by atrophy of the dorsal striatum (caudate nucleus and putamen) with concurrent expansion of the frontal horns of the lateral ventricles on imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). A molecular study validates the diagnosis of HD by identifying the disorder's hallmark amplified CAG triplet. Currently, there is no cure for HD, and treatment focuses on providing supportive care and managing the symptoms. Multidisciplinary approaches involving healthcare professionals, neurologists, and psychiatrists are crucial for comprehensive management. Medications are used to alleviate motor symptoms and manage psychiatric manifestations. Physical and occupational therapies help maintain functional abilities and improve quality of life. Genetic counseling and psychosocial support are essential for patients and their families. An additional crucial objective entails advancing more precise and dependable techniques for the timely identification and assessment of HD. Timely interventions and improved symptom management are made possible by early diagnosis. Based on clinical and imaging findings, we present a case of HD in a 62-year-old female.

Retrocaval Ureter as a Rare Cause of Hydroureteronephrosis: A Case Report.

Retrocaval ureter (RCU), also known as pre-ureteral vena cava or circumcaval ureter, is a rare congenital anomaly caused by inferior vena cava (IVC) dysgenesis, leading to the right ureter coursing behind the IVC. RCU results in obstructive proximal hydroureteronephrosis, remaining asymptomatic until the third decade when hydronephrosis develops. Diagnosis relies on imaging modalities like intravenous urography (IVU), ultrasonography, computed tomography urography (CTU), magnetic resonance urography, and nuclear scintigraphy. CTU provides comprehensive 3D evaluation. We report a novel case of a 50-year-old male with RCU complicated by a concurrent distal ureteral calculus. CTU demonstrated the characteristic "S-shaped" proximal ureteral deformity and its aberrant posterior course relative to the IVC, enabling accurate preoperative diagnosis. The co-occurrence of RCU with ureteral calculus is notably rare, underlining the necessity of an exhaustive diagnostic process. The patient successfully underwent a combined surgical intervention, consisting of laparoscopic ureteroureterostomy for RCU correction and ureteroscopic lithotripsy for calculus removal, showcasing a minimally invasive approach to simultaneously address both conditions. This report underscores the significance of advanced cross-sectional imaging in diagnosing RCU and demonstrates the effectiveness of integrated minimally invasive surgical techniques in treating complex urological anomalies. By documenting this case, we contribute to the broader understanding and awareness of RCU among clinicians, potentially guiding more prompt recognition and comprehensive management of this rare condition.

Oleuropein activates autophagy to circumvent anti-plasmodial defense.

Antimalarial drug resistance and unavailability of effective vaccine warrant for newer drugs and drug targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS)-stimulated human THP-1 macrophages (macrophage model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signaling to establish the "immune-homeostasis." Also, OLP treatment influenced the cell death/autophagy axis leading to the modulated inflammation for extended cell survival. The findings with MII prompted us to detect the antimalarial activity of OLP in the wild type (3D7), D10-expressing GFP-Atg18 parasite, and chloroquine-resistant (Dd2) parasite. OLP did not show the parasite inhibition in the routine in vitro culture of P. falciparum whereas OLP increased the antimalarial activity of artesunate. The molecular docking of autophagy-related proteins, investigations with MMI, and parasite inhibition assays indicated that the host activated the autophagy to survive OLP pressure. The challenge model of P. berghei infection showed to induce autophagy for circumventing anti-plasmodial defenses.

Role of Magnetic Resonance Imaging in the Evaluation of Age- and Gender-Related Changes in the Dimensions of the Pituitary Gland in the Indian Population.

Background MRI is the standard tool for imaging the pituitary gland. MRI is useful in detecting pathological conditions in the pituitary. Changes in the size and shape of the pituitary among different age groups are seen in MRI. Linear growth is seen in the pituitary during puberty except for growth spurts at the 1st, 10th, and 15th years, followed by a decline in pituitary height and cross-sectional area with increasing age. A convex upper margin was seen in females more than in males. There is a shortage of information about pituitary dimensions and volume in various age groups and among both genders in the Indian population. Hence, a study is needed to assess these parameters. Materials and methods A retrospective cross-sectional study was done in the MRI unit of Radiology, Saveetha Medical College and Hospital, Chennai. A total of 200 patients in the age group of 11-80 years who underwent MRI free from neuroendocrine, neurological, and psychiatric disorders were included in this study. Statistical analysis Measurements were made of the pituitary gland's height, volume, and anteroposterior and transverse dimensions. Using SPSS Statistics software (IBM Corp. IBM SPSS Statistics for Windows. Armonk, NY: IBM Corp.), the data was input and examined. The ANOVA test revealed the relationship between anteroposterior dimension, transverse dimension, height, and volume with age. In contrast, an independent t-test determined the association of the same parameters with sex. The Chi-square test was used to assess the association of the shape of the pituitary gland with age and sex. Results Anteroposterior dimension, height, and volume of the pituitary gland were found to be statistically significant with age (p<0.05), but the transverse dimension was not significant with age (p>0.05). However, the independent t-test showed highly significant differences between the anteroposterior dimension in males and females. The shape of the pituitary gland was found to be statistically significant with age and gender. In contrast, the pituitary gland's transverse diameter, height, and volume showed no significance. Conclusion The study helps identify the substantial changes in the pituitary gland during a person's lifespan, which are affected by age and gender. The pituitary height and volume will reflect physiological neuroendocrine differences between younger and older male and female subjects.

Unilateral Hyperlucent Lung in Adulthood: A Case Report of Swyer-James-Macleod Syndrome.

Swyer-James-Macleod syndrome (SJMS) or Bret syndrome presents as unilateral hyperlucent lung, an uncommon pulmonary condition. The accurate diagnosis of SJMS requires high-resolution CT (HRCT), as conventional chest radiographs may underestimate this condition. We present a case of SJMS in a 54-year-old male who was managed with bronchodilators and intravenous antibiotics. This case report underscores the rarity of SJMS in adulthood, with only a limited number of cases reported globally so far. Comprehensive use of HRCT is crucial for precise diagnosis, and early intervention with appropriate medical management is imperative for favorable outcomes.

Parry-Romberg syndrome: A case report and literature review.

Parry-Romberg syndrome (PRS) is a rare neurocutaneous and craniofacial disorder characterized by progressive hemifacial wasting and atrophy that predominantly affects children and young adults, with an estimated prevalence of 1 in 700,000 individuals. Despite its rarity, PRS poses significant challenges for patients, their families, and healthcare providers due to its unpredictable course and potential functional and aesthetic impairments. The main aim is to provide a comprehensive overview of PRS, encompassing its clinical features, pathogenesis, and management techniques. We present a case of PRS in a 9-year-old female with pronounced facial asymmetry, with marked wasting and atrophy involving the entire right side of the face. CT scan revealed right sided hypoplasia of maxilla, mandible, and zygomatic arch with enophthalmos of right eye. MRI showed right temporalis, medial and lateral pterygoid, masseter, risorius, buccinator, zygomaticus major and minor, levator labii superioris, levatorangulioris and orbicularis oris muscles atrophy. The clinical presentation of PRS typically involves progressive facial atrophy, predominantly affecting the subcutaneous tissues, muscles and bones. Patients may experience various symptoms as the condition advances, including facial asymmetry, hemifacial pain, dental and ocular abnormalities and neurological manifestations. The exact etiology of PRS remains unknown, although autoimmune, genetic and vascular factors are likely contributors. Treatment of PRS needs a multidisciplinary approach involving dermatologists, plastic surgeons, neurologists, ophthalmologists, and dental specialists. Treatment options aim to alleviate symptoms, improve function and address cosmetic concerns. Surgical interventions such as autologous fat grafting, facial reconstructive procedures and orthognathic surgery have restored facial symmetry and function. Additionally, nonsurgical modalities, including botulinum toxin injections, prosthetic devices and dental interventions, may offer symptomatic relief and enhance overall quality of life.

Dyke-Davidoff-Masson Syndrome as a Rare Cause of Cerebral Hemiatrophy: Insights From a Case Series.

Dyke-Davidoff-Masson syndrome (DDMS) is an uncommon neurological condition marked by changes in the skeletal structure, cerebral hemiatrophy, and ventriculomegaly. Manifesting primarily in early life, DDMS presents with seizures, hemiplegia, facial asymmetry, and intellectual disabilities. There are congenital and acquired types of DDMS, with ischemia being the most common cause of the latter. Three cases are presented here to highlight the radiological and clinical characteristics of DDMS. The first case involves a 27-year-old male with generalized seizures and right-sided hemiparesis since childhood, along with developmental delays and facial asymmetry. The second case features a 20-year-old male with recurrent seizures and developmental delays. The third case involves a 25-year-old female with uncontrolled seizures and learning difficulties since childhood. The clinical and radiological characteristics of DDMS are demonstrated in all three cases, emphasizing the significance of early detection and differential diagnosis. Imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), which demonstrate ipsilateral ventriculomegaly, brain atrophy, and associated bone abnormalities, are highly helpful in the diagnosis. Differential diagnoses include Sturge-Weber syndrome, linear nevus sebaceous syndrome (LNSS), Silver-Russell syndrome, Fishman syndrome, and Rasmussen encephalitis. Treatment aims at managing seizures and associated disabilities, with hemispherectomy considered for eligible cases. This case series underscores the significance of prompt diagnosis and multidisciplinary management in improving outcomes for individuals with DDMS.

Neuroimaging Abnormalities in Patients with Subacute Sclerosing Panencephalitis : Prospective Follow-up Study.

OBJECTIVE: This study aimed to assess the neuroimaging abnormalities and their progression in patients with Subacute sclerosing panencephalitis (SSPE) and identify clinical predictors of these imaging findings. METHODS: This prospective observational study evaluated clinical and neuroimaging features in patients with SSPE. Patients were categorized using Dyken's criteria, Jabbour's staging system, and the definition of fulminant SSPE. They underwent comprehensive clinical assessments, cerebrospinal fluid examination, Electroencephalogram (EEG), and Magnetic Resonance Imaging (MRI) scans. Treatment involved intrathecal interferon­α and antiepileptic medications. Functional disability was assessed using the modified Barthel index. Follow-ups were performed at 6 months, including reassessment of Modified Barthel Index (MBI) and Jabbour's staging and EEG and MRI scans. RESULTS: The mean age was 13.9 ± 6.7 years, with males comprising 81.5% (44/54) of the cohort. Fulminant SSPE was noted in 33% (18/54) of cases. Disease duration before presentation varied significantly between fulminant and non-fulminant forms (p = 0.001). Neuroimaging abnormalities were more prevalent in JS III stage patients, with diffuse cerebral atrophy being a significant finding (p = 0.011). Basal ganglia involvement correlated with movement disorders. The 6­month follow-up showed increased cerebral atrophy (p = 0.004). Increasing disease duration was an independent predictor of cerebral atrophy. An Intercomplex interval (ICI) of more than 10 minutes correlated with normal neuroimaging, 10 patients died within the study period, 8 of whom had fulminant SSPE. CONCLUSION: Parieto-occipital White matter hyperintensity (WMH) is the most prevalent and sensitive neuroimaging finding for the diagnosis of SSPE. Despite interferon treatment, cerebral atrophy progressed in both aggressive and fulminant SSPE. Increasing disease duration is an independent predictor of cerebral atrophy.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

The frequency and clinical outcome of mono-hit and multi-hit TP53 aberrations in newly diagnosed multiple myeloma.

We investigated the frequency and outcome of mono-hit and multi-hit TP53 aberrations [biallelic or ≥1 TP53 mutations (TP53mut) or TP53mut with variant allele frequency (VAF) ≥55%] in an Indian cohort of newly diagnosed multiple myeloma (NDMM) patients. We employed fluorescence insitu hybridisation (FISH; n=457) and targeted next-generation sequencing (NGS; n=244) on plasma cell-enriched samples. We also studied the impact of TP53mut in cases with and without TP53 deletions (TP53del). In our cohort with a median age of 60 years, TP53del and TP53mut were seen in 12.9% (n=59/457; 14-95% cells) and 10.2% (n=25/244; 30 variants; VAF 3.4-98.2%; median 38.2%) respectively. Mono-hit and multi-hit-TP53 aberrations were observed in 10.2% and 7.8%, respectively. Compared to TP53-wild-type (TP53wt), mono-hit and multi-hit TP53 aberrations were associated with significantly poorer progression-free survival (PFS) (22.6 vs 12.1 vs 9.5 months; p=0.004) and overall survival (OS) [not reached (NR) vs 13.1 vs 15.6 months respectively; p=0.024]. However, multi-hit TP53 did not significantly differ in OS/PFS compared to mono-hit cases. Compared to TP53wt, PFS and OS were significantly poorer in patients with TP53mut only (9.5 vs 22.6 months and 12.1 months vs NR, respectively; p=0.020/0.004). TP53mut retained its significance even in the presence of any Revised International Staging System (HR 2.1; 95% CI 1.1-3.8; p=0.015) for OS. The detection of additional cases with TP53 aberrations, as well as poor survival associated with the presence of mutation alone, supports TP53mut testing in NDMM at least in patients without TP53del and other high-risk cytogenetic abnormalities.