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BACKGROUND: Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS. RESULTS: The imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date, n = 17 patients have received 20 mg kg bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma in situ (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at <1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered. CONCLUSIONS: This study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01837225 (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.).
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OBJECTIVE: To review literature on the impact of stigmatisation and perceived social support on the treatment of substance use disorder patients. METHODS: The systematic review was conducted from March 2020 to June 2021, and comprised literature search through key words on PubMed, Scopus, PsycINFO, Science Direct, Full Free PDF, and Google Scholar databases of studies about stigma, social support and treatment of substance use disorders published in English language between 2010 and 2021. RESULTS: Of the 52 studies found, 8(15.3%) qualified for detailed review. The outcome suggested that the impact of stigma had negative consequences on the treatment of substance use disorders, and negative comments from close relatives was a major cause of relapse. In contrast, perceived social support had a constructive impact on the treatment of substance use disorders. CONCLUSIONS: Further research is required to understand the phenomenon of stigmatisation in the Pakistani population through validated tools.
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Trastornos Relacionados con Sustancias , Humanos , Trastornos Relacionados con Sustancias/terapia , Estereotipo , Estigma Social , Apoyo SocialRESUMEN
Researchers have examined the efficacy of a horticultural stress management program for menopausal women. The quasi-experimental research design was employed by providing stress management and horticulture techniques to the experimental group (n = 55), whereas an informational pamphlet was given to the control group (n = 42). Moreover, this management program was comprised of hands-on training (Herb testing and smelling, Rocky Leaf prints, Grass Doll activity, and Kokedama activity), short lectures, and group discussions (sessions) for two hours, once a week, and continued for four weeks. Data was gathered from public-related activities i.e., camps on women's health and it consisted of three stages; before and after management and one month after completion of the intervention. The primary goal was to increase the stress coping ability, while the secondary goal was to enhance the psychological well-being and decrease menopausal symptoms. The aspects of horticultural attitude, cognitive flexibility, manageability, and knowledge of menopause were measured by using ANCOVA on SPSS 17 v. All the aspects significantly improved in the experimental group. Knowledge of menopause, horticultural attitude, cognitive flexibility, and manageability of stress significantly improved in the experimental group.
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BACKGROUND AND PURPOSE: Contemporary radiotherapy for localized prostate cancer (PCa) is deliverable via stereotactic ablative radiotherapy (SABR) and high dose rate (HDR) brachytherapy. Here we report on a parallel cohort analysis of two prospective, phase II clinical trials of two-fraction prostate SABR versus two-fraction HDR monotherapy. MATERIALS AND METHODS: Enrolled patients had histologically-confirmed PCa (clinical stage T1c-T2b; grade group 1, 2, or 3; and PSA < 20 ng/mL). SABR and HDR doses were 26 Gy and 27 Gy in 2 weekly fractions, respectively. Patient-level data from each cohort was analysed to assess prostate specific antigen (PSA) response kinetics, biochemical failure, toxicity, and quality of life (QOL). RESULTS: Thirty patients receiving SABR and 83 receiving HDR were included. Fifty percent and 30% of patients had unfavourable-intermediate risk disease, respectively. SABR patients had higher mean baseline PSA (8.7 versus 6.8 ng/mL, p = 0.016). Median follow-up was 72.7 and 65.3 months, respectively. Mean dose delivered (Dmean) was 26.6-26.8 Gy for SABR versus 35.5-45.5 Gy for HDR. Both cohorts achieved a median nadir PSA of 0.16 ng/mL at a median of 57 months post-treatment. Cumulative biochemical failure probability (±SE) at 72 months was 3.5% (±3.5%) for SABR versus 12.8% (±4.8%) for HDR (p = 0.19). Low rates of CTCAE grade ≥2 toxicity were observed in both cohorts. No differences in EPIC scores over time were observed between cohorts. CONCLUSIONS: Two-fraction SABR yields similar rates of biochemical failure, acute and late toxicities, and QOL as two-faction HDR brachytherapy. These data support the design of a randomized controlled trial comparing these treatments.
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Braquiterapia , Neoplasias de la Próstata , Radiocirugia , Braquiterapia/efectos adversos , Braquiterapia/métodos , Ensayos Clínicos Fase II como Asunto , Humanos , Masculino , Estudios Prospectivos , Antígeno Prostático Específico , Neoplasias de la Próstata/radioterapia , Calidad de Vida , Radiocirugia/efectos adversos , Radiocirugia/métodos , Dosificación RadioterapéuticaRESUMEN
OBJECTIVE: To adapt, validate and establish psychometric property of the Substance Use Risk Profile scale for Pakistani population. METHODS: The cross-sectional study was conducted from May to September 2021 in Lahore, Pakistan, and comprised clinical and non-clinical adult patients following the International Test Commission guidelines for the adaptation and validation of the Substance Use Risk Profile scale. A The scale's factor structure, internal consistency, content validity, face validity and convergent validity were examined. Confirmatory factor analysis, reliability analysis, and data analysis were done using SPSS 25. RESULTS: Of the 485 subjects, 243(50.1%) were non-clinical and 242(49.9%) were clinical subjects. The overall mean age was 4.68+/-2.3 years (range: 19-58 years). The scale had adequate internal consistency, criterion validity, and construct validity with Cronbach's alphas ranging 0.71-0.95. CONCLUSIONS: The Substance Use Risk Profile was found to be a beneficial tool to be employed in research realted to substance use disorder in Pakistan. .
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Reproducibilidad de los Resultados , Adulto , Humanos , Preescolar , Niño , Pakistán/epidemiología , Estudios Transversales , Encuestas y Cuestionarios , PsicometríaRESUMEN
BACKGROUND: Re-excision due to positive margins following breast-conserving surgery (BCS) negatively affects patient outcomes and healthcare costs. The inability to visualize margin involvement is a significant challenge in BCS. 5-Aminolevulinic acid hydrochloride (5-ALA HCl), a non-fluorescent oral prodrug, causes intracellular accumulation of fluorescent porphyrins in cancer cells. This single-center Phase II randomized controlled trial evaluated the safety, feasibility, and diagnostic accuracy of a prototype handheld fluorescence imaging device plus 5-ALA for intraoperative visualization of invasive breast carcinomas during BCS. METHODS: Fifty-four patients were enrolled and randomized to receive no 5-ALA or oral 5-ALA HCl (15 or 30 mg/kg). Forty-five patients (n = 15/group) were included in the analysis. Fluorescence imaging of the excised surgical specimen was performed, and biopsies were collected from within and outside the clinically demarcated tumor border of the gross specimen for blinded histopathology. RESULTS: In the absence of 5-ALA, tissue autofluorescence imaging lacked tumor-specific fluorescent contrast. Both 5-ALA doses caused bright red tumor fluorescence, with improved visualization of tumor contrasted against normal tissue autofluorescence. In the 15 mg/kg 5-ALA group, the positive predictive value (PPV) for detecting breast cancer inside and outside the grossly demarcated tumor border was 100.0% and 55.6%, respectively. In the 30 mg/kg 5-ALA group, the PPV was 100.0% and 50.0% inside and outside the demarcated tumor border, respectively. No adverse events were observed, and clinical feasibility of this imaging device-5-ALA combination approach was confirmed. CONCLUSIONS: This is the first known clinical report of visualization of 5-ALA-induced fluorescence in invasive breast carcinoma using a real-time handheld intraoperative fluorescence imaging device. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01837225 . Registered 23 April 2013.
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Ácido Aminolevulínico/uso terapéutico , Neoplasias de la Mama/diagnóstico por imagen , Imagen Óptica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Medios de Contraste/uso terapéutico , Femenino , Fluorescencia , Humanos , Cuidados Intraoperatorios , Márgenes de Escisión , Mastectomía Segmentaria , Persona de Mediana Edad , Imagen Óptica/instrumentación , Valor Predictivo de las Pruebas , Cirugía Asistida por ComputadorRESUMEN
Top-Down Proteomics (TDP) is an emerging proteomics protocol that involves identification, characterization, and quantitation of intact proteins using high-resolution mass spectrometry. TDP has an edge over other proteomics protocols in that it allows for: (i) accurate measurement of intact protein mass, (ii) high sequence coverage, and (iii) enhanced identification of post-translational modifications (PTMs). However, the complexity of TDP spectra poses a significant impediment to protein search and PTM characterization. Furthermore, limited software support is currently available in the form of search algorithms and pipelines. To address this need, we propose 'SPECTRUM', an open-architecture and open-source toolbox for TDP data analysis. Its salient features include: (i) MS2-based intact protein mass tuning, (ii) de novo peptide sequence tag analysis, (iii) propensity-driven PTM characterization, (iv) blind PTM search, (v) spectral comparison, (vi) identification of truncated proteins, (vii) multifactorial coefficient-weighted scoring, and (viii) intuitive graphical user interfaces to access the aforementioned functionalities and visualization of results. We have validated SPECTRUM using published datasets and benchmarked it against salient TDP tools. SPECTRUM provides significantly enhanced protein identification rates (91% to 177%) over its contemporaries. SPECTRUM has been implemented in MATLAB, and is freely available along with its source code and documentation at https://github.com/BIRL/SPECTRUM/.
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Algoritmos , Proteómica/métodos , Programas Informáticos , Bases de Datos de Proteínas , Conjuntos de Datos como Asunto , Células HeLa , Humanos , Peso Molecular , Isoformas de Proteínas/química , Isoformas de Proteínas/aislamiento & purificación , Isoformas de Proteínas/metabolismo , Procesamiento Proteico-Postraduccional , Proteoma/química , Proteoma/aislamiento & purificación , Proteoma/metabolismo , Análisis de Secuencia de Proteína/métodosRESUMEN
The xylanase gene (xynA) of Bacillus licheniformis 9945A was cloned and expressed in Escherichia coli BL21(DE3) using pET-22b(+) as an expression vector. The recombinant xylanase enzyme was purified by ammonium sulfate precipitation, followed by single-step immobilized metal ion affinity chromatography with a 57.58-fold purification having 138.2 U/mg specific activity and recovery of 70.08 %. Molecular weight of the purified xylanase, 23 kDa, was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme was stable for up to 70 °C with a broad pH range of 4-9 pH units. The enzyme activity was increased in the presence of metal ions especially Ca(+2) and decreased in the presence of EDTA, indicating that the xylanase was a metalloenzyme. However, an addition of 1-4 % Tween 80, ß-mercaptoethanol, and DTT resulted in the increase of enzyme activity by 51, 52, and 5 %, respectively. Organic solvents with a concentration of 10-40 % slightly decreased the enzyme activity. The xylanase enzyme possesses the ability of bioconversion of plant biomasses like wheat straw, rice straw, and sugarcane bagasse. Among the different tested biomasses, the highest saccharification percentage was observed with 1 % sugarcane bagasse after 72 h of incubation at 50 °C with 20 units of enzyme. The results suggest that recombinant xylanase can be used in the bioconversion of natural biomasses into simple sugars which could be further used for the production of biofuel.