A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

Combined or High Dose Immunosuppression in Inflammatory Bowel Disease patients who are NUDT15 Homozygous Harbors Risk of Developing Invasive Fungal Infections: A Case Series.

NUDT15 homozygous mutations predispose patients to severe leucopenia, which invites risk of disseminated fungal infections when high doses or a combination of immunosuppressives are administered in this patient population.

Comparison of conventional diffusion-weighted imaging, diffusion kurtosis imaging and intravoxel incoherent motion in characterization of sonographically indeterminate adnexal masses.

PURPOSE: To evaluate the role of conventional diffusion weighted imaging, diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) in distinguishing benign from malignant adnexal masses. METHODS: 38 patients with 45 adnexal masses were enrolled in this prospective study and assessed with multiparametric MRI, including the IVIM-DKI sequence, on a 3 T MRI system. The mean apparent diffusion coefficient (ADC) from conventional DWI, the apparent diffusion coefficient derived from DKI (Dapp), the apparent kurtosis coefficient (Kapp), true diffusion coefficient (Dt), perfusion fraction (f) and pseudo-diffusion coefficient (Dp) were measured. RESULTS: The mean ADC, Dapp, and Dt were significantly higher in benign adnexal masses than in malignant adnexal masses (p < 0.001). f and Dp were also significantly higher in benign adnexal masses, with p values of 0.026 and 0.002, respectively. Kapp was higher in malignant masses (p < 0.001). Among mean ADC, Dapp, and Dt, mean ADC had the highest area under the curve (AUC) of 0.885. However, no statistically significant differences were observed between the ROCs of various diffusion parameters. CONCLUSION: The mean ADC, Dapp, and Kapp are useful parameters in discriminating between benign and malignant adnexal masses. Dt derived from IVIM also helps in distinguishing benign and malignant adnexal masses; however, no incremental role of IVIM and DKI over ADC could be identified in our study.

The unseen invaders: Tracking phylogeographic dynamics and genetic diversity of cryptic Pomacea canaliculata and P. maculata (Golden apple snails) across Taiwan.

The cryptic invasion of golden apple snails (Pomacea canaliculata and P. maculata) in Taiwan has caused significant ecological and economical damage over the last few decades, however, their management remains difficult due to inadequate taxonomic identification, complex phylogeny, and limited population genetic information. We aim to understand the current distribution, putative population of origin, genetic diversity, and potential path of cryptic invasion of Pomacea canaliculata and P. maculata across Taiwan to aid in improved mitigation approaches. The present investigation conducted a nationwide survey with 254 samples collected from 41 locations in 14 counties or cities across Taiwan. We identified P. canaliculata and P. maculata based on mitochondrial COI and compared their genetic diversity across Taiwan, as well as other introduced and native countries (based on publicly available COI data) to understand the possible paths of invasion to Taiwan. Based on mitochondrial COI barcoding, sympatric and heterogeneous distributions of invasive P. canaliculata and P. maculata were noted. Our haplotype analysis and mismatch distribution results suggested multiple introductions of P. canaliculata in Taiwan was likely originated directly from Argentina, whereas P. maculata was probably introduced from a single, or a few, introduction event(s) from Argentina and Brazil. Our population genetic data further demonstrated a higher haplotype and genetic diversity for P. canaliculata and P. maculata in Taiwan compared to other introduced regions. Based on our current understanding, the establishment of P. canaliculata and P. maculata is alarming and widespread beyond geopolitical borders, requiring a concerted and expedited national and international invasive species mitigation program.

Intravoxel incoherent motion and diffusion kurtosis imaging and their machine-learning-based texture analysis for detection and assessment of prostate cancer severity at 3 T.

OBJECTIVES: To evaluate the role of combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) and their machine-learning-based texture analysis for the detection and assessment of severity in prostate cancer (PCa). MATERIALS AND METHODS: Eighty-eight patients underwent MRI on a 3 T scanner after giving informed consent. IVIM-DKI data were acquired using 13 b values (0-2000 s/mm2) and analyzed using the IVIM-DKI model with the total variation (TV) method. PCa patients were categorized into two groups: clinically insignificant prostate cancer (CISPCa) (Gleason grade ≤ 6) and clinically significant prostate cancer (CSPCa) (Gleason grade ≥ 7). One-way analysis-of-variance, t test, and receiver operating characteristic analysis was performed to measure the discriminative ability to detect PCa using IVIM-DKI parameters. A chi-square test was used to select important texture features of apparent diffusion coefficient (ADC) and IVIM-DKI parameters. These selected texture features were used in an artificial neural network for PCa detection. RESULTS: ADC and diffusion coefficient (D) were significantly lower (p < 0.001), and kurtosis (k) was significantly higher (p < 0.001), in PCa as compared with benign prostatic hyperplasia (BPH) and normal peripheral zone (PZ). ADC, D, and k showed high areas under the curves (AUCs) of 0.92, 0.89, and 0.88, respectively, in PCa detection. ADC and D were significantly lower (p < 0.05) as compared with CISPCa versus CSPCa. D for detecting CSPCa was high, with an AUC of 0.63. A negative correlation of ADC and D with GS (ADC, ρ = -0.33; D, ρ = -0.35, p < 0.05) and a positive correlation of k with GS (ρ = 0.22, p < 0.05) were observed. Combined IVIM-DKI texture showed high AUC of 0.83 for classification of PCa, BPH, and normal PZ. CONCLUSION: D, f, and k computed using the IVIM-DKI model with the TV method were able to differentiate PCa from BPH and normal PZ. Texture features of combined IVIM-DKI parameters showed high accuracy and AUC in PCa detection.

Transformative and sustainable insights of agricultural waste-based adsorbents for water defluoridation: Biosorption dynamics, economic viability, and spent adsorbent management.

With the progression of civilization, the harmony within nature has been disrupted, giving rise to various ecocidal activities that are evident in every spheres of the earth. These activities have had a profound and far-reaching impact on global health. One significant example of this is the presence of fluoride in groundwater exceeding acceptable limits, resulting in the widespread occurrence of "Fluorosis" worldwide. It is imperative to mitigate the concentration of fluoride in drinking water to meet safety standards. While various defluoridation techniques exist, they often have drawbacks. Biosorption, being a simple, affordable and eco-friendly method, has gained preference for defluoridation. However, its limited commercialization underscores the pressing need for further research in this domain. This comprehensive review article offers a thorough examination of the defluoridation potential of agro-based adsorbents, encompassing their specific chemical compositions and preparation methods. The review presents an in-depth discussion of the factors influencing fluoride biosorption and conducts a detailed exploration of adsorption isotherm and adsorption kinetic models to gain a comprehensive understanding of the nature of the adsorption process. Furthermore, it evaluates the commercial viability through an assessment of regeneration potential and a cost analysis of these agro-adsorbents, with the aim of facilitating the scalability of the defluoridation process. The elucidation of the adsorption mechanism and recommendations for overcoming challenges in large-scale implementation offer a comprehensive outlook on this eco-friendly and sustainable approach to fluoride removal. In summary, this review article equips readers with a lucid understanding of agro-adsorbents, elucidates their ideal conditions for improved performance, offers a more profound insight into the fluoride biosorption mechanism, and introduces the concept of effective spent adsorbent management.

Cesium immobilization of high pH and low pH belite-rich cement under varying temperature.

Low-pH cement is being studied in radioactive waste repositories. The belite-rich cement (BRC) recently gained attention due to its higher CO2 sequestration and low pH attainment under carbonation exposure. Therefore, this study evaluated the effects of pH and temperature on cesium immobilization of BRC. High pH (12.6) and low pH (9.9) BRC were produced via air curing and carbonation treatment, respectively. The high and low pH BRC samples were placed in a leaching environment at 25 °C and 45 °C for 90 days. An inverse correlation between pH and cesium mobilization of BRC was observed. The high pH BRC achieved the lowest effective diffusion coefficient (4.05E-09 cm2/s), whereas the highest value (2.64E-07 cm2/s) was achieved in case of low pH BRC. The physicochemical and morphological properties unveiled the decrease in Si/Ca ratio of gel, precipitation of Ca2+ ions in calcite formation, and increment in pore structure connectivity (pore size > 100 nm) in low pH BRC. However, the high pH BRC demonstrated the high Si/Ca ratio in C-S-H gel, hydroxide phases and higher disconnected pores. Thermodynamic modeling revealed the presence of significant carbonated phases beyond 15% CO2 uptake. The findings contributed to the BRC's feasibility in developing nuclear waste storage facility.

Benign paediatric liver tumours: The radiological maze demystified.

The trajectory from the clinical identification of a benign liver mass to establishing a precise diagnosis is perplexing and arduous. Related contributory factors are that such lesions are encountered infrequently and that there is a nonavailability of dedicated paediatric radiologists in the developing world. The objective of this study was to review the spectrum of benign liver lesions in children and their typical imaging features. Cross-sectional imaging of all paediatric patients (< 18 years) with liver lesions (single and multiple) performed in the institute from 01 January 2018 to 01 January 2019 as well as those acquired at outside institutions and referred to the institute for management was included. Ultrasound was done as the first line of investigation in all the cases with suspicious liver masses and retrospectively performed in referral cases in whom CT or MRI was already done. Images were analysed by two senior radiologists. Most of the cases were diagnosed based on clinical, biochemical and imaging findings, and biopsy was only performed in equivocal cases. Most of the benign liver lesions in the paediatric age group were hepatic haemangioma and mesenchymal hamartomas. A simplified clinical-radiologic paradigm should be established for benign liver lesions in children to assist in reaching the correct diagnosis. Contribution: The article demonstrates the salient radiological findings of various benign liver lesions in the paediatric age group and the role of demographic, clinical and biochemical findings, which plays a substantial role in the diagnosis and avoids unnecessary biopsies.

Hepatic and perihepatic PEComas: A study describing a series of five rare cases.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) encompass a group of rare mesenchymal neoplasms, with dual melanocytic and muscular differentiation. Hepatic PEComas are rare and difficult to diagnose, and their behavior is still unclear. MATERIALS AND METHODS: Herein, we report a total of five cases of hepatic and perihepatic PEComas over a period of the last 5 years from our and collaborating center's archive. A detailed histological evaluation was done. A comprehensive panel of immunohistochemical stains was used and fluorescence in-situ hybridization analysis was performed for the TFE3 gene using break-apart probes. RESULT: All these patients were women, with an average age of presentation of 44 years. The lesions were in the right hepatic lobe: three cases, the left hepatic lobe: one case, and gastrohepatic ligament: one case. The preoperative clinicoradiological diagnoses were hepatocellular carcinoma (HCC), focal nodular hyperplasia, hemangioma, metastasis, and gastrointestinal stromal tumor, respectively. Surgical excision was performed in four cases with no further adjuvant therapy. Histopathological examination and subsequent immunophenotyping revealed a diagnosis of PEComa. Fluorescence in-situ hybridization analysis was performed for TFE3 gene rearrangement in four cases. CONCLUSIONS: This series highlights the fact that accurate histological diagnosis of hepatic or perihepatic PEComas is important to prevent unnecessary aggressive treatment, unlike primary hepatocellular carcinomas or hepatoid/epithelioid metastatic tumors.

Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial.

BACKGROUND & AIMS: Coconut water (CW) is anti-inflammatory, can manipulate the gut microbiome, and is a rich source of potassium. Gut microbiome modulation improves outcomes in ulcerative colitis (UC), and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of CW as an adjunct therapy for patients with mild-moderate UC. METHODS: This single-center, double-blind, placebo-controlled trial randomized patients with mild to moderate (Simple Clinical Colitis Activity Index [SCCAI]: 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity [UCEIS] >1) in 1:1 ratio to CW + standard medical therapy (SMT) vs placebo + SMT. Four hundred mL of CW was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤2), and secondary outcome measures were clinical response (SCCAI decline ≥3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. RESULTS: Of 121 patients screened, 95 were included for modified intention to treat analysis (CW, n = 49; placebo, n = 46) (mean age, 37.2 ± 11.2 years; males, 54.1%; disease duration, 48 months [interquartile range (IQR), 24-90 months]; pancolitis, 26.1%; SCCAI, 5 [IQR, 4-6]; UCEIS, 4 [IQR, 3-5]). Clinical response (57.1% vs 28.3%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.4-7.9; P = .01), remission (53.1% vs 28.3%; OR, 2.9; 95% CI, 1.2-6.7; P = .02), and proportion of patients with fecal calprotectin (FCP) <150 µg/g (30.6% vs 6.5%; OR, 6.3; 95% CI, 1.7-23.6; P = .003) were significantly higher in CW. The relative abundance of bacterial taxa that had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP increased at 8 weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable, and no patient developed hyperkalemia. CONCLUSIONS: CW was more effective than placebo for induction of clinical remission in patients with mild to moderate UC. The trial was prospectively registered on Clinical Trials Registry of India (ctri.nic.in, Number: CTRI/2019/03/01827).

Microbial induced carbonate precipitation for remediation of heavy metals, ions and radioactive elements: A comprehensive exploration of prospective applications in water and soil treatment.

Improper disposal practices have caused environmental disruptions, possessing by heavy metal ions and radioactive elements in water and soil, where the innovative and sustainable remediation strategies are significantly imperative in last few decades. Microbially induced carbonate precipitation (MICP) has emerged as a pioneering technology for remediating contaminated soil and water. Generally, MICP employs urease-producing microorganisms to decompose urea (NH2CONH2) into ammonium (NH4+and carbon dioxide (CO2), thereby increasing pH levels and inducing carbonate precipitation (CO32-), and effectively removing remove contaminants. Nonetheless, the intricate mechanism underlying heavy metal mineralization poses a significant challenge, constraining its application in contaminants engineering, particularly in the context of prolonged heavy metal leaching over time and its efficacy in adverse environmental conditions. This review provides a comprehensive idea of recent development of MICP and its application in environmental engineering, examining metabolic pathways, mineral precipitation mechanisms, and environmental factors as well as providing future perspectives for commercial utilization. The use of ureolytic bacteria in MICP demonstrates cost-efficiency, environmental compatibility, and successful pollutant abatement over tradition bioremediation techniques, and bio-synthesis of nanoparticles. limitations such as large-scale application, elevated Ca2+levels in groundwater, and gradual contaminant release need to be overcome. The possible future research directions for MICP technology, emphasizing its potential in conventional remediation, CO2 sequestration, bio-material synthesis, and its role in reducing environmental impact for long-term economic benefits.

Long-term outcomes of laparoscopic Heller's myotomy with angle of His accentuation in patients of achalasia cardia.

BACKGROUND: Laparoscopic Heller's myotomy (LHM) is an established treatment for achalasia cardia. Anti-reflux procedures (ARP) are recommended with LHM to reduce the post-operative reflux though the optimal anti-reflux procedure is still debatable. This study reports on the long-term outcomes of LHM with Angle-of-His accentuation (AOH) in patients of achalasia cardia. METHODS: One hundred thirty-six patients of achalasia cardia undergoing LHM with AOH between January 2010 to October 2021 with a minimum follow-up of one year were evaluated for symptomatic outcomes using Eckardt score (ES), DeMeester heartburn (DMH) score and achalasia disease specific quality of life (A-DsQoL) questionnaire. Upper gastrointestinal endoscopy, high resolution manometry (HRM) and timed barium esophagogram (TBE) were performed when feasible and rates of esophagitis and improvement in HRM and TBE parameters evaluated. Time dependent rates of success were calculated with respect to improvement in ES and dysphagia-, regurgitation- and heartburn-free survival using Kaplan-Meier analysis. RESULTS: At a median follow-up of 65.5 months, the overall success (ES ≤ 3) was 94.1%. There was statistically significant improvement in ES, heartburn score and A-DsQoL score (p < 0.00001, p = 0.002 and p < 0.00001). Significant heartburn (score ≥ 2) was seen in 12.5% subjects with 9.5% patients reporting frequent PPI use (> 3 days per week). LA-B and above esophagitis was seen in 12.7%. HRM and TBE parameters also showed a significant improvement as compared to pre-operative values (IRP: p < 0.0001, column height: p < 0.0001, column width: p = 0.0002). Kaplan-Meier analysis showed dysphagia, regurgitation, and heartburn free survival of 75%, 96.2% and 72.3% respectively at 10 years. CONCLUSIONS: LHM with AOH gives a lasting relief of symptoms in patients of achalasia cardia with heartburn rates similar to that reported in studies using Dor's or Toupet's fundoplication with LHM. Hence, LHM with AOH may be a preferred choice in patients of achalasia cardia given the simplicity of the procedure.

SMARCB1/INI1-Deficient Poorly Differentiated Carcinoma of the Colon With Rhabdoid Features-A Rare Tumor With Serrated Phenotype: Case Report and Review of Literature.

Poorly differentiated colonic carcinoma with rhabdoid features is a rarely described entity. Our knowledge regarding the molecular phenotype of the tumor is evolving. We herein report a similar tumor with rhabdoid differentiation identified in the splenic flexure, which on histological examination showed a poorly differentiated phenotype with epithelioid to spindled morphology, tumor giant cells, and rhabdoid differentiation. The tumor was mismatch repair-proficient, deficient of INI1/SMARCB1, KRAS mutated (A146×), BRAFV600E mutated (c.1799T > A), and NRAS wild-type, indicating serrated differentiation in the tumor. The patient died after 3.5 months post-surgery. INI1-deficient poorly differentiated carcinoma of the colon is a rare, aggressive colonic malignancy showing a serrated phenotype. Routine identification and subtyping are important keeping in mind the distinct tumor phenotype, resistance to conventional chemotherapy, and dismal prognosis.

Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis.

BACKGROUND AND AIMS: Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited. METHOD: We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn's disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up. RESULTS: A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32-51] years, median follow-up: 40 [19-81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45-0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32-6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26-5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27-0.80; p = 0.005] for CD were predictors of thiopurine effectiveness. CONCLUSION: Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.

Radiologists' Rating for Comparative Qualitative Assessment of Intravoxel Incoherent Motion Using Novel Analysis Methods.

OBJECTIVE: The objective was to assess qualitative interpretability and quantitative precision and reproducibility of intravoxel incoherent motion ( IVIM) parametric images evaluated using novel IVIM analysis methods for diagnostic accuracy. METHODS: Intravoxel incoherent motion datasets of 55 patients (male/female = 41:14; age = 17.8 ± 5.5 years) with histopathology-proven osteosarcoma were analyzed. Intravoxel incoherent motion parameters-diffusion coefficient ( D ), perfusion fraction ( f ), and perfusion coefficient ( D* )-were estimated using 5 IVIM analysis methods-(i) biexponential (BE) model, (ii) BE-segmented fitting 2-parameter (BESeg-2), (iii) BE-segmented fitting 1-parameter (BESeg-1), (iv) BE model with total variation penalty function (BE + TV), and (v) BE model with Huber penalty function (BE + HPF). Qualitative scoring in a 5-point Likert scale (uninterpretable: 1; poor: 2; fair: 3; good: 4; excellent: 5) was performed by 2 radiologists for 4 criteria: (a) tumor shape and margin, (b) morphologic correlation, (c) noise suppression, and (d) overall interpretability. Interobserver agreement was evaluated using Spearman rank-order correlation ( rs ). Precision and reproducibility were evaluated using within-subject coefficient of variation (wCV) and between-subject coefficient of variation (bCV). RESULTS: BE + TV and BE + HPF produced significantly ( P < 10 -3 ) higher qualitative scores for D (fair-good [3.3-3.8]) than BE (poor [2.3]) and for D* (poor-fair [2.2-2.7]) and f (fair-good [3.2-3.8]) than BE, BESeg-2, and BESeg-1 ( D* : uninterpretable-poor [1.3-1.9] and f : poor-fair [1.5-3]). Interobserver agreement for qualitative scoring was rs = 0.48-0.59, P < 0.009. BE + TV and BE + HPF showed significantly ( P < 0.05) improved reproducibility in estimating D (wCV: 24%-31%, bCV: 21%-31% improvement) than the BE method and D* (wCV: 4%-19%, bCV: 5%-19% improvement) and f (wCV: 25%-49%, bCV: 25%-47% improvement) than BE, BESeg-2, and BESeg-1 methods. CONCLUSIONS: BE + TV and BE + HPF demonstrated qualitatively and quantitatively improved IVIM parameter estimation and may be considered for clinical use further.

Insight interactions of engineered nanoparticles with aquatic higher plants for phytoaccumulation, phytotoxicity, and phytoremediation applications: A review.

With the growing age of human civilization, industrialization has paced up equally which is followed by the innovation of newer concepts of science and technology. One such example is the invention of engineered nanoparticles and their flagrant use in widespread applications. While ENPs serve their intended purposes, they also disrupt the ecological balance by contaminating pristine aquatic ecosystems. This review encompasses a comprehensive discussion about the potent toxicity of ENPs on aquatic ecosystems, with a particular focus on their impact on aquatic higher plants. The discussion extends to elucidating the fate of ENPs upon release into aquatic environments, covering aspects ranging from morphological and physiological effects to molecular-level phytotoxicity. Furthermore, this level of toxicity has been correlated with the determination of competent plants for the phytoremediation process towards the mitigation of this ecological stress. However, this review further illustrates the path of future research which is yet to be explored. Determination of the genotoxicity level of aquatic higher plants could explain the entire process comprehensively. Moreover, to make it suitable to be used in natural ecosystems phytoremediation potential of co-existing plant species along with the presence of different ENPs need to be evaluated. This literature will undoubtedly offer readers a comprehensive understanding of the stress induced by the irresponsible release of engineered nanoparticles (ENP) into aquatic environments, along with insights into the resilience characteristics of these pristine ecosystems.

Unmasking the great imitators-noninfectious conditions masquerading as spinal tuberculosis in a developing country: A single-center case series analysis.

Background: The diagnosis of spinal tuberculosis often relies on clinical, radiological, and laboratory findings, particularly in resource-constrained settings. However, numerous noninfectious conditions exhibit similar clinical and radiological features to spinal tuberculosis, leading to potential misdiagnosis in the absence of microbiological or histopathological confirmation. This study aims to present a case series from a developing country, highlighting noninfectious conditions that mimic spinal tuberculosis. Methods: A retrospective analysis was conducted on hospital records and imaging of patients diagnosed with spinal tuberculosis, lacking microbiological or histopathological evidence, and unresponsive to empirical antitubercular treatment. Patients displaying noninfectious conditions resembling spinal tuberculosis upon further investigation were included. Clinical and radiological findings of these patients were thoroughly analyzed. Results: Among a total of 23 patients observed over a 6-year period (2015-2020), various noninfectious conditions were identified as mimickers of spinal tuberculosis. These conditions included vertebral body haemangioma, ankylosing spondylitis (with or without Andersson lesion), rheumatoid pannus, osteoid osteoma, cystic hygroma, multiple myeloma, vertebral metastasis, malignant small round-cell tumor, pancreatic pseudocyst, esophageal duplication cyst, Modic changes in degenerative disc disease, Paget's disease, and psoas hematoma. Conclusion: Noninfectious spinal conditions can masquerade as spinal tuberculosis, underscoring the importance of obtaining a definitive tissue diagnosis before initiating antitubercular treatment. Particular attention should be given to features such as central lesions and the absence of soft tissue involvement in suspected cases of spinal tuberculosis, warranting a careful reconsideration of the diagnosis.

ABDA Score: A Non-invasive Model to Identify Subjects with Fibrotic Non-alcoholic Steatohepatitis in the Community.

Background: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are prevalent in the community, especially among those with metabolic syndrome. Patients with fibrotic NASH are at increased risk of liver-related-events. Currently available non-invasive tests have not been utilized for screening for fibrotic NASH among the community. We aimed to develop a screening tool for fibrotic NASH among community members. Methods: We included two large cohorts aimed at assessing cardiovascular disease among community members. Fibrotic NASH was defined using the FibroScan-aspartate aminotransferase score of ≥0.67 that identifies ≥F2 fibrosis and a non-alcoholic fatty liver disease activity score ≥4 with a specificity of 90%. Metabolic parameters, biochemical tests and anthropometry were used to develop a multivariate model. Results: The derivation cohort (n = 1660) included a population with a median age 45 years, 42.5% males, metabolic syndrome in 66% and 2.7% (n = 45) with fibrotic NASH. Multivariate analysis identified the four significant variables (Age, body mass index , Diabetes and alanine aminotransferas levels) used to derive an ABDA score. The score had high diagnostic accuracy (the area under receiver-operating characteristic curve, 0.952) with adequate internal validity. An ABDA score ≥-3.52 identified fibrotic NASH in the derivation cohort with a sensitivity and specificity of 88.9% and 88.3%. The score was validated in a second cohort (n = 357) that included 21 patients (5.9%) with fibrotic NASH, where it demonstrated a high area under receiver-operating characteristic curve (0.948), sensitivity (81%) and specificity (89.3%). Conclusions: ABDA score utilizes four easily available parameters to identify fibrotic NASH with high accuracy in the community.

Development of a Physiologically Based Pharmacokinetic Model for Nitrofurantoin in Rabbits, Rats, and Humans.

Nitrofurantoin (NFT) is a commonly used antibiotic for the treatment of urinary tract infections that can cause liver toxicity. Despite reports of hepatic adverse events associated with NFT exposure, there is still limited understanding of the interplay between NFT exposure, its disposition, and the risk of developing liver toxicity. In this study, we aim to develop a physiologically based pharmacokinetic (PBPK) model for NFT in three different species (rabbits, rats, and humans) that can be used as a standard tool for predicting drug-induced liver injury (DILI). We created several versions of the PBPK model using previously published kinetics data from rabbits, and integrated enterohepatic recirculation (EHR) using rat data. Our model showed that active tubular secretion and reabsorption in the kidney are critical in explaining the non-linear renal clearance and urine kinetics of NFT. We subsequently extrapolated the PBPK model to humans. Adapting the physiology to humans led to predictions consistent with human kinetics data, considering a low amount of NFT to be excreted into bile. Model simulations predicted that the liver of individuals with a moderate-to-severe glomerular filtration rate (GFR) is exposed to two-to-three-fold higher concentrations of NFT than individuals with a normal GFR, which coincided with a substantial reduction in the NFT urinary concentration. In conclusion, people with renal insufficiency may be at a higher risk of developing DILI due to NFT exposure, while at the same time having a suboptimal therapeutic effect with a high risk of drug resistance. Our PBPK model can in the future be used to predict NFT kinetics in individual patients on the basis of characteristics like age and GFR.

The role of bacterial exopolysaccharides (EPS) in the synthesis of antimicrobial silver nanomaterials: A state-of-the-art review.

The emergence of multi-drug resistant (MDR) pathogens poses a significant global health concern due to the failure of conventional medical treatment. As a result, the development of several metallic (Ag, Au, Zn, Ti, etc.) nanoparticles, has gained prominence as an alternative to conventional antimicrobial therapies. Among these, green-synthesized silver nanoparticles (AgNPs) have gained significant attention due to their notable efficiency and broad spectrum of antimicrobial activity. Bacterial exopolysaccharides (EPS) have recently emerged as a promising biological substrate for the green synthesis of AgNPs. EPS possess polyanionic functional groups (hydroxyl, carboxylic, sulfate, and phosphate) that effectively reduce and stabilize AgNPs. EPS-mediated AgNPs exhibit a wide range of antimicrobial activity against various pathogenic microbes, including Gram-positive and Gram-negative bacteria, as well as fungi. The extraction and purification of bacterial EPS play a vital role in obtaining high-quality and -quantity EPS for industrial applications. This study focuses on the comprehensive methodology of EPS extraction and purification, encompassing screening, fermentation optimization, pretreatment, protein elimination, precipitation, and purification. The review specifically highlights the utilization of bacterial EPS-mediated AgNPs, covering EPS extraction, the synthesis mechanism of green EPS-mediated AgNPs, their characterization, and their potential applications as antimicrobial agents against pathogens. These EPS-mediated AgNPs offer numerous advantages, including biocompatibility, biodegradability, non-toxicity, and eco-friendliness, making them a promising alternative to traditional antimicrobials and opening new avenues in nanotechnology-based approaches to combat microbial infections.