Clinical outcome analysis of patients with multiple sclerosis - Analysis from the UK Medical Cannabis Registry.

INTRODUCTION: Whilst disease-modifying therapies are the cornerstone for treatment of multiple sclerosis (MS), there is a need to develop novel therapeutics for the symptomatic sequalae of the disease. Cannabis-based medicinal products (CBMPs) have been suggested as a potential therapy for the associated pain, spasticity, and mental health disorders. However, there is a paucity of clinical evidence on CBMPs in MS. The aim of this study is to assess changes in MS-specific and general health-related quality of life (HRQoL) outcomes alongside adverse event incidence in patients prescribed CBMPs for MS from the UK Medical Cannabis Registry (UKMCR). METHOD: Patients prescribed CBMPs for MS symptoms for longer than one month were identified from the UKMCR. The primary outcomes were changes from baseline in MS Quality of Life-54 (MSQoL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scales at one month, three months and six months. p < 0.050 was defined as statistically significant. RESULTS: 141 patients met the inclusion criteria for the study. There was an improvement in the following subscales of the MSQoL-54 at 6 months: change in health scale, cognitive function, mental health composition, physical health, role limitations due to physical limitation and due to emotional problems, as well as social and sexual function (p < 0.050). There were also improvements in the EQ-5D-5L index value, GAD-7 and SQS (p < 0.050). 146 (103.55 %) adverse events were reported in total. Most were considered mild (n = 47; 33.33 %) and moderate (n = 72; 51.06 %). CONCLUSIONS: This preliminary analysis demonstrates a possible association with improved general health-related quality of life in those prescribed CBMPs for MS. Moreover, the results suggest that CBMPs are well-tolerated in the first 6 months of treatment. However, this must be interpreted with caution considering the limitations of the observational study design.

Enrollment Trends Among Patients with Melanoma Brain Metastasis in Active Clinical Trials.

The CNS is a common site for distant metastasis and treatment failure in melanoma patients. This study aimed to evaluate the inclusion rate of patients with melanoma brain metastases (MBM) in prospective clinical trials. 69.3% of trials excluded MBM patients based on their CNS disease. In univariate analysis, trials not employing immunotherapy (p = 0.0174), inclusion of leptomeningeal disease (p < 0.0001) and non-pharmaceutical sponsor trials (p = 0.0461) were more likely to enroll patients with MBM. Thoughtful reconsideration of clinical trial designs is needed to give patients with MBMs access to promising investigational agents and improve outcomes for patients with MBM.

Diagnosis, management, and outcomes of immune checkpoint inhibitor induced acute interstitial nephritis: A single-center experience.

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated acute interstitial nephritis (AIN) is a recognized complication of immunotherapy (IO), but literature on its management and outcomes is limited. METHODS: We retrospectively reviewed patients who received ICIs and developed biopsy-proven or clinically-suspected ICI-associated AIN at the University of Virginia Comprehensive Cancer Center from 2012-2023. We analyzed baseline characteristics and clinical outcomes, including treatment interruption and rechallenge rates. Acute kidney injury (AKI) was defined as a ≥ 1.5-fold increase in baseline creatinine under seven days, a two-fold increase above the upper limit of normal, or an increase by ≥0.3 mg/dL. Kidney function returning to within 0.3 mg/dL or less than twice baseline was considered complete (CRc) and partial (PRc) recovery, respectively. RESULTS: We identified 12 cases of ICI-AIN: four by biopsy (33%) and eight (67%) by clinical suspicion. Two patients received anti-CTLA-4 and anti-PD1, six received anti-PD1 alone, and four received chemo-immunotherapy. The majority (58%) of patients developed AIN within the first 5 cycles. Eight patients developed ≥ Grade 3 AKI, and six developed multiple irAEs. ICI was permanently discontinued in seven patients (58%) and temporarily interrupted in four (30%). The CRc and PRc rates were 67% and 8%, respectively. Upon AIN onset, the best disease response was stable disease in five patients, partial response in three, and progressive disease in three. Median overall survival was 4.87 years, and progression-free survival was 1.5 years. CONCLUSIONS: Rechallenge with IO after kidney irAE may be possible in some patients but requires careful evaluation on an individual basis.

Blending polydopamine-derived imprinted polymers with rice straw-based fluorescent carbon dots for selective detection and adsorptive removal of ibuprofen.

Dual-functioning probes capable of detecting and removing hazardous substances have recently received increased attention compared to exclusive sensory probes. Herein, a new composite is synthesized by blending polydopamine imprinted polymers with fluorescent carbon dots (PIP-FCDs) for the selective recognition and adsorption of Ibuprofen (IBF). IBF is a nonsteroidal anti-inflammatory drug and is excessively released in the pharmaceutical wastes. The PIP-FCDs consist of confined pockets for encasing IBF and quenches fluorescence signal when contact with the molecule. PIP-FCDs show high sensitivity (limit of detection = 1.58 × 10-5 µM) and selectivity towards IBF in the presence of other pharmaceutical drugs i.e., aspirin, ketoprofen, norfloxacin, and levofloxacin. The adsorption studies show an adsorption capacity of 209.8 mg g-1 with an extraction efficiency of around 99.9 %. Furthermore, PIP-FCDs are utilized to determine IBF levels in various aqueous pharmaceutical samples. This development provides a simple and dual-functioning probe for the detection and adsorption of IBF from various matrices.

von Willebrand disease: A guide for the internist.

von Willebrand disease (VWD), the most common inherited bleeding disorder, results when patients either do not make enough von Willebrand factor (VWF) or make defective VWF. The pathophysiology of this disorder is complex but needs to be understood to interpret the diagnostic tests. Most patients have mild to moderate symptoms and can be adequately counseled and managed by a general internist, but some need to consult a hematologist. We review the pathophysiology of VWD, its subtypes, common presentations of each subtype, diagnostic testing, and management of mild as well as severe clinical manifestations of VWD.

Sensitising natural wool with green and brown coffee using a facile extraction method to optimise dye process parameters.

Green coffee powder is the raw powder of coffee cherries and all coffee's potential components are held within this green powder. A new natural colourant was extracted from Green Coffee using water as an extractant. To obtain a green-colored solution, a specific amount of green coffee was mixed with distilled water and left for 24 h at room temperature. Furthermore, the colouring performance of extracted colour has been studied using the conventional exhaust dyeing method on wool fabric. Different parameters viz. concentration of Green coffee powder, the temperature of the dye bath, the period for immersion, and solution pH were made to set to obtain a fine tone of green colour. The dyeing parameters (amount of the coffee: 2 g, 100 °C, 70 min & 6.7 pH) were optimised and selected to draw a comparison with the conventional Brown coffee powder. In experiments on wool, this potential solution of Green coffee offered rich green hues with good tonal variation. In addition, the colour fastness to washing was found superior in the case of both Green and Brown coffee and colour fastness to light, rubbing as well as perspiration also showed good performance. In this study, our main focus was to obtain the true and fast green tone of the fabric using Green Coffee and compare it with brown coffee using the same conditions used for dyeing with green coffee. The application of these dyes as natural dyes results in obtaining innovative natural fast colour with remarkable dyeing properties and a new inclusion to the existing commercial spectra of natural dyes.

Targeting aromatase to restrain oestrogen production and developing efficacious interventions against ER-positive cancer.

Being the most frequently diagnosed disease, breast cancer is mainly classified as ER+ cancers due to the detection of estrogen receptor (ER) expression. Irrespetive of the successes achieved in the treatment of ER+ cancers by the use of selective estrogen receptor modulator (SERM) drugs like tamoxifen, resistance to the drug is a major clinical obstacle. Working on alternative treatment approaches, here, on the basis of mode of action of aromatase for the conversion of androstenedione to oestrogen, a series of compounds was developed. Results of all the experiments performed with these compounds led to the identification of three highly potent compounds 5d, 5e and 7d with their IC50 61.0, 83.0 and 54.0 nM for aromatase. Indicating their effectiveness in the treatment of ER+ cancers, appreciable tumor growth inhibitory activities of these compounds were observed against breast cancer cell lines. Further, the physico-chemical experiments including plasma protein binding, HSA binding, kinetic studies, solubility, ADME properties and molecular modelling studies supported the drug like features of the compounds.

Improved survival for stage IV sinonasal small cell neuroendocrine carcinoma treated with chemotherapy and anti-PD-L1 therapy.

Small cell carcinoma neuroendocrine type (SCCNET) is a rare tumour of the head and neck. Due to its infrequency, a paucity of data exists on optimal treatment, and the current paradigm for advanced SCCNET mirrors that of extensive small cell lung cancer. Increasingly, the treatment for extrapulmonary small cell carcinomas like SCCNET has incorporated immune checkpoint inhibitors (ICIs), although the utility of ICIs is not fully understood. We present a case of stage IVC sinonasal SCCNET in a woman in her 90s, who experienced eyelid swelling and unintentional weight loss. After diagnostic work-up, she was treated with etoposide, carboplatin and atezolizumab with a complete response to therapy. The patient had one episode of inflammatory polyarthropathy which resolved with steroids but otherwise tolerated treatment well and is now living with an overall survival of greater than 27 months. This case highlights the long-term efficacy of combination ICIs and chemotherapy in the treatment of SCCNET.

Biomass-Derived Core-Shell Carbon Dots with Embedded Tripodal Receptors for the Selective Recognition of Mefenamic Acid in Pharmaceutical Formulations and Urine.

A tripodal amine (TPA) with -OH, N, and S donors is synthesized to functionalize a core-shell carbon dot composite (FCDs@SiO2-TPA) for sensing application. The TPA is characterized by spectroscopic and spectrometric techniques, and the composite is characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectra (EDS) techniques. The composite has the ability to recognize mefenamic acid (MFA) selectively even in the presence of other drugs like ibuprofen sodium, acetylsalicylic acid, naproxen sodium, diclofenac sodium, and ketoprofen. It can also be used for the quantification of MFA by recording the emission quenching response of the sample at λexc. = 350 nm and λems. = 460 nm (linear range = 1-8 µM and LOD = 197 nM). The density functional theory calculations and 1H NMR titration suggest quenching of the emission signal due to photoinduced electron transfer via hydrogen bonding between the probe and MFA. The composite FCDs@SiO2-TPA has been demonstrated as a reliable and cost-effective sensing probe for the detection of MFA in pharmaceutical formulations, water samples, and cow urine samples.

Systemic Therapy for Melanoma: ASCO Guideline Update.

PURPOSE: To provide guidance to clinicians regarding the use of systemic therapy for melanoma. METHODS: American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature. RESULTS: The updated review identified 21 additional randomized trials. UPDATED RECOMMENDATIONS: Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma. For patients with resected cutaneous melanoma, adjuvant nivolumab or pembrolizumab was newly recommended for stage IIB-C disease and adjuvant nivolumab plus ipilimumab was added as a potential option for stage IV disease. For patients with unresectable or metastatic cutaneous melanoma, nivolumab plus relatlimab was added as a potential option regardless of BRAF mutation status and nivolumab plus ipilimumab followed by nivolumab was preferred over BRAF/MEK inhibitor therapy. Talimogene laherparepvec is no longer recommended as an option for patients with BRAF wild-type disease who have progressed on anti-PD-1 therapy. Ipilimumab- and ipilimumab-containing regimens are no longer recommended for patients with BRAF-mutated disease after progression on other therapies.This full update incorporates the new recommendations for uveal melanoma published in the 2022 Rapid Recommendation Update.Additional information is available at www.asco.org/melanoma-guidelines.

Diagnosis and management of gastrointestinal SMARCA4-deficient undifferentiated tumors.

SMARCA4-deficient undifferentiated tumors are a rare clinical entity with an aggressive clinical course, poor prognosis, and no standard-of-care therapeutic approach. These have most frequently been documented in the lung and thoracic cavity. There is a growing body of evidence for the role of immunotherapy in SMARCA4-deficient lung cancer, a disease process that historically does very poorly with cytotoxic chemotherapy alone. We present three cases where the primary tumors were instead found within the gastrointestinal system: two originating from the small bowel and one from the esophagus. In all three cases, clinical response was seen with pembrolizumab therapy, with two of the three patients receiving long-term benefit. Our series suggests that anti-PD1 immunotherapy may have promising efficacy for undifferentiated carcinomas of the gastrointestinal tract with SMARCA4 deficiency.

Systemic therapy for melanoma: ASCO guideline update

To provide guidance to clinicians regarding the use of systemic therapy for melanoma. American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature. The updated review identified 21 additional randomized trials. Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma. For patients with resected cutaneous melanoma, adjuvant nivolumab or pembrolizumab was newly recommended for stage IIB-C disease and adjuvant nivolumab plus ipilimumab was added as a potential option for stage IV disease. For patients with unresectable or metastatic cutaneous melanoma, nivolumab plus relatlimab was added as a potential option regardless of BRAF mutation status and nivolumab plus ipilimumab followed by nivolumab was preferred over BRAF/MEK inhibitor therapy. Talimogene laherparepvec is no longer recommended as an option for patients with BRAF wild-type disease who have progressed on anti­PD-1 therapy. Ipilimumab- and ipilimumab-containing regimens are no longer recommended for patients with BRAF-mutated disease after progression on other therapies. This full update incorporates the new recommendations for uveal melanoma published in the 2022 Rapid Recommendation Update. Additional information is available at www.asco.org/melanoma-guidelines

A Review of Sensing Applications of Molecularly Imprinted Fluorescent Carbon Dots for Food and Biological Sample Analysis.

Molecularly imprinted fluorescent carbon dots (MI-FCDs) find numerous applications in analytical chemistry due to their outstanding photoluminescent properties and having specific pockets for the recognition of target molecules. Despite significant advances, practical applications of MI-FCDs-based fluorescent sensors are still in their initial stages. Therefore, the topical developments in the synthesis, working, and application of MI-FCDs for sensing various target species (e.g., pharmaceuticals, biomolecules, pesticides, food additives, and miscellaneous species) in food and biological media have been highlighted. Moreover, a careful evaluation has been made to select the best methods based on their performance in terms of analytical parameters. To expand the horizons of this field, important challenges and future directions for developing MI-FCDs for practical use are also presented. This review will highlight important aspects of MI-FCDs-based fluorescent sensors for their applicability in food science, material science, environmental science, nanoscience, and biotechnology.

Synthesis of a trinuclear zinc(II) cluster composed of [4.4.3.01,5]tridecane cages: a rapid detection and degradation probe for the chemical warfare agent simulant diethyl cyanophosphonate in protein-rich food products.

Diethyl cyanophosphonate (DCNP), a simulant of Tabun, is a common pollutant in pharmaceutical waste and poses a high risk to living organisms. Herein, we demonstrate a compartmental ligand-derived trinuclear zinc(II) cluster [Zn3(LH)2(CH3COO)2] as a probe for the selective detection and degradation of DCNP. It consists of two pentacoordinated Zn(II) [4.4.3.01,5]tridecane cages bridged through a hexacoordinated Zn(II) acetate unit. The structure of the cluster has been elucidated by spectrometric, spectroscopic, and single-crystal X-ray diffraction studies. The cluster shows a two-fold increased emission as compared to the compartmental ligand (at λexc = 370 nm and λem = 463 nm) due to the chelation-enhanced fluorescence effect and acts as a turn-off signal in the presence of DCNP. It can detect DCNP at nano levels up to 186 nM (LOD). The direct bond formation between DCNP and Zn(II) via the -CN group degrades it to inorganic phosphates. The mechanism of the interaction and degradation is supported by spectrofluorimetric experiments, NMR titration (1H and 31P), time of flight mass spectrometry and density functional theory calculations. The applicability of the probe has been further tested by the bio-imaging of zebrafish larvae, analysis of high-protein food products (meat and fish) and vapour phase detection by paper strips.

Selective quantification of diclofenac from groundwater and pharmaceutical samples by magnetic molecularly imprinted polymer-based sorbent coupled with the HPLC-PDA detection.

Diclofenac (DCF) is a pharmaceutical contaminant of water bodies and therefore, improvement of analytical techniques for its removal and quantitation is one of the current interests of analysts. Herein, DCF selective magnetic molecularly imprinted polymer (MMIP) has been fabricated and characterized by Fourier transform-infrared spectroscopy, thermogravimetric analysis, vibrating scanning magnetometer, scanning electron microscopy, high-resolution transmission electron microscope, energy-dispersive X-ray spectroscopy, and Brunauer-Emmett-Teller analyzer. Furthermore, the protocol for the quantification of DCF using MMIP-HPLC-PDA combo has been optimized by investigating the effect of the amount of MMIP, type and volume of eluent, and variation of pH. The optimized protocol suggested a method detection limit of 0.042 ng mL-1 and linearity of results in the range 0.1-100 ng mL-1 (R2 = 0.99). The fabricated material offered recovery of DCF up to 96.38-99.46% from groundwater and pharmaceutical samples with a relative standard deviation of <4%. In addition, the material was found selective and sensitive for DCF among its analogous drugs like mefenamic acid, ketoprofen, fenofibrate, aspirin, ibuprofen, and naproxen.

Prognostic significance of extra-nodal extension and positive surgical margins in HPV positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Whether extra-nodal extension (ENE+) and surgical margin positivity (margin+) are poor prognostic factors in HPV-associated (HPV+) oropharyngeal carcinoma (OPC) remains uncertain. RESULTS: Our study evaluated if microscopic ENE+ and/or margin+ are associated poorer recurrence free survival (RFS) and overall survival (OS) in HPV+ OPC. Patients were classified as high risk (ENE+ and/or margin+) or low risk (ENE- and margins-). Of a total of 176 patients HPV+ OPC, 81 underwent primary surgery and dad data on ENE and margin status. There was no statistically significant difference in RFS (p = 0.35) or OS (p = 0.13) for high-risk versus low-risk groups. Ongoing smoking (p = 0.023), alcohol use (p = 0.044) and advanced stage (p = 0.019) were associated with higher risk of recurrence. Only advanced stage (p-value <0.0001) was associated poorer overall survival. CONCLUSIONS: The presence of ENE+ and/or margin+ was not an independent predictor of poor RFS or OS in HPV+ OPC.

Engineered organotin(IV) and vanadium(V) derivatives with distinct coordination modes and luminescent properties for the efficient detection and quantification of permanganate ions.

The distinction in coordination modes of metal complexes leads to their versatile structural features and unique properties. Here, we report two tetradentate Schiff base ligands (H2L1 and H2L2) bearing N2O2 donor sets, tactically selected to provide distinct coordination modes with different metal ions. The ligands were utilized to synthesize their organotin(IV) (1-4) and vanadium(V) (5) derivatives. The synthesized compounds were characterized using elemental analysis, FT-IR spectroscopy, multi-nuclei NMR (1H, 13C, and 119Sn) spectroscopy, mass spectrometry, and single-crystal X-ray diffraction. The organotin(IV) derivatives (1-4) displayed hepta-coordination around both the Sn centres as they were achieved in their dimeric form. Contrariwise, the vanadium(V) compound (5) was isolated as a mononuclear entity exhibiting penta-coordinated geometry around the vanadium centre. The variation in the coordination modes was evident in their UV-vis and fluorescence spectra. The organotin(IV) compounds (1-4) exhibited a strong emission band centred at 468 nm when excited at a wavelength of 360 nm whereas the vanadium(V) (5) derivative displayed poor fluorogenic response. Compound 1 was further explored for the fluorogenic chemo-sensing of permanganate ions (MnO4-) amongst various anions by quenching response. A detailed investigation of the recognition of permanganate ions was accomplished by spectrofluorometric, spectroscopic (119Sn NMR), mass spectrometric, and computational studies.

Exploring risks of investor claims brought forth after the TRIPS waiver for COVID-19.

This research plans to explore the risks of the investment claims involved in the ongoing technology transfers to COVID-19 vaccine manufacturers based on the recently approved 'Agreement on Trade-Related Aspects of Intellectual Property Rights' (TRIPS) waiver. These investment claims are based on the various intellectual property rights protected under international investment laws. The recently approved TRIPS waiver only deals with the patent rights involved in producing the COVID-19 vaccine but does not deal with the other related intellectual property rights such as trade secrets. This work sounds the alarm of investment dispute for the mass-production of vaccines based on the TRIPS waiver. The research suggests a plan by which the Indian government can address the global issue of COVID-19 technology transfer in India.

Phase I/II clinical trial of a helper peptide vaccine plus PD-1 blockade in PD-1 antibody-naïve and PD-1 antibody-experienced patients with melanoma (MEL64).

BACKGROUND: A vaccine containing 6 melanoma-associated peptides to stimulate helper T cells (6MHP) is safe, immunogenic, and clinically active. A phase I/II trial was designed to evaluate safety and immunogenicity of 6MHP vaccines plus programmed death 1 (PD-1) blockade. PARTICIPANTS AND METHODS: Participants with advanced melanoma received 6MHP vaccines in an incomplete Freund's adjuvant (6 vaccines over 12 weeks). Pembrolizumab was administered intravenously every 3 weeks. Tumor biopsies at baseline and day 22 were analyzed by multiplex immunohistochemistry. Primary end points were safety (Common Terminology Criteria for Adverse Events V.4.03) and immunogenicity (ex vivo interferon-γ ELISpot assay). Additional end points included changes in the tumor microenvironment (TME) and clinical outcomes. RESULTS: Twenty-two eligible participants were treated: 6 naïve to PD-1 antibody (Ab) and 16 PD-1 Ab-experienced. Median follow-up was 24.4 months. Most common treatment-related adverse events (any grade) included injection site reactions, fatigue, anemia, lymphopenia, fever, elevated aspartate aminotransferase, pruritus, and rash. Treatment-related dose-limiting toxicities were observed in 3 (14%) participants, which did not cross the study safety bound. A high durable T cell response (Rsp) to 6MHP was detected in only one participant, but twofold T cell Rsps to 6MHP were detected in 7/22 (32%; 90% CI (16% to 52%)) by week 13. Objective clinical responses were observed in 23% (1 complete response, 4 partial responses), including 4/6 PD-1 Ab-naïve (67%) and 1/16 PD-1 Ab-experienced (6%). Overall survival (OS) was longer for PD-1 Ab-naïve than Ab-experienced participants (HR 6.3 (90% CI (2.1 to 28.7)). In landmark analyses at 13 weeks, OS was also longer for those with T cell Rsps (HR 6.5 (90% CI (2.1 to 29.2)) and for those with objective clinical responses. TME evaluation revealed increased densities of CD8+ T cells, CD20+ B cells, and Tbet+ cells by day 22. CONCLUSIONS: Treatment with the 6MHP vaccine plus pembrolizumab was safe, increased intratumoral lymphocytes, and induced T cell Rsps associated with prolonged OS. The low T cell Rsp rate in PD-1 Ab-experienced participants corroborates prior murine studies that caution against delaying cancer vaccines until after PD-1 blockade. The promising objective response rate and OS in PD-1 Ab-naïve participants support consideration of a larger study in that setting.

In-situ generation of fluorescent silica nano-aggregates of silatranyl appended furfural Schiff base and its application to the spectrofluorimetric analysis of phenolic brominated flame retardants in aqueous medium.

A silatranyl appended furfural Schiff base (Silt-FUR) has been synthesized and characterized by spectroscopic techniques, elemental analysis and mass spectrometry. The dissolution of Silt-FUR in methanol-water (90:10 v/v) results in the formation of fluorescent nano-aggregates due to the hydrolysis of the silatranyl ring. The formation of nano-aggregates has been confirmed by dynamic light scattering, scanning electron microscopy and transmission electron microscopy. The nano-aggregates exhibit quenching of fluorescence in the presence of phenolic brominated flame retardants such as 3,3',5,5'-tetrabromobisphenol A, 2,4-dibromophenol, 2,4,6-tribromophenol, and pentabromophenol. Density-Functional Theory and NMR titration suggest that acid-base pair formation between azomethinic functionality and flame retardants is the main cause of quenching of fluorescent signal as it causes photoinduced electron transfer. Due to the excellent spectrofluorimetric response of Silt-FUR nano-aggregates to detect brominated phenols, a spectrofluorimetric method has been standardized for the quantification of brominated flame retardants. The detection limit for pentabromophenol obtained is 0.432 µM under optimal experimental conditions, and the linear range of the determination is 0.0495-1.35 µM. Thus, the in-situ generation of nano-aggregates offers a user-friendly method for the detection, quantification and extraction of the brominated phenols with exceptionally high sensitivity and selectivity for pentabromophenol.