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Histotripsy is a noninvasive focused ultrasound therapy that mechanically fractionates tissue to create well-defined lesions. In a previous clinical pilot trial to treat benign prostatic hyperplasia (BPH), histotripsy did not result in consistent objective improvements in symptoms, potentially because of the fibrotic and mechanically tough nature of this tissue. In this study, we aimed to identify the dosage required to homogenize BPH tissue by different histotripsy modalities, including boiling histotripsy (BH) and cavitation histotripsy (CH). A method for histotripsy lesion quantification via entropy (HLQE) analysis was developed and utilized to quantify lesion area of the respective treatments. These data were correlated to changes in mechanical stiffness measured by ultrasound shear-wave elastography before and after treatment with each parameter set and dose. Time points corresponding to histologically observed complete lesions were qualitatively evaluated and quantitatively measured. For the BH treatment, complete lesions occurred with >=30s treatment time, with a corresponding maximum reduction in stiffness of -90.9±7.2(s.d.)%. High pulse repetition frequency (PRF) CH achieved a similar reduction to that of BH at 288s (-91.6±6.0(s.d.)%), and low-PRF CH achieved a (-82.1±5.1(s.d.)%) reduction in stiffness at dose >=144s. Receiver operating characteristic curve analysis showed that a >~75% reduction in stiffness positively correlated with complete lesions observed histologically, and can provide an alternative metric to track treatment progression.
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Objective: To characterize the trends in female representation in the endourology fellowship match compared with the urology residency match. Materials and Methods: Available deidentified match data from 2017 to 2022 was obtained from the American Urological Association and Endourology Society annual census data. We evaluated gender-specific participation in the urology residency and endourology fellowship match and compared differences in the trends over the last 6 years. Results: Between the years 2017 and 2021, there were a total of 313 applicants for a fellowship in endourology, and of those, only 8.6% were women. In that same time period, a significantly larger number of women (27.1%) participated in the urology residency match (p = 0.0002). When specifically examining the endourology applicant trend, there is no significant increase in participation (R = 0.7, p = 0.35) between 2017 and 2021, as compared with the significant increase in total number of applicants (R = 7.1, p = 0.04). However, in the urology match, there has been a constant and significant increase in both female (R = 13.7, p = 0.03) and total applicants (R = 27, p = 0.04) between 2017 and 2022. Conclusions: Although there has been an overall increase in the number of applicants to urology, the number of women in endourology fellowship has not increased at a commensurate rate. In light of these findings, it is the responsibility of the endourology community to identify social and systemic barriers for women in this field and advocate for change.
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INTRODUCTION: With more than 60% of urological procedures performed in ambulatory settings, it is imperative to understand the current trends in postoperative narcotic prescriptions and their adherence to the guidelines. We studied postoperative opioid-prescribing patterns after selected common urology ambulatory procedures. METHODS: A retrospective cohort was derived from a 10% random sample of enrollees within the IQVIA PharMetrics Plus for Academics database from 2015 to 2021. Patient-level baseline characteristics were collected in the year preceding the index date. Descriptive and bivariate analyses were used to compare patient characteristics from opioid and nonopioid cohorts and those who utilized opioids ≤ 7 days and > 7 days postprocedurally. Trends of opioid and nonopioid use were also investigated and compared. RESULTS: Between 2015 to 2021, 17,817 patients underwent urological ambulatory procedures, of which the majority (90.9%) were endoscopic procedures. Of those, 4077 (22%) were prescribed opioids and 978 (5.4%) patients were given prescription nonopioid (ie, ketorolac) medication. From 2015 to 2021, there was an overall decrease in prescription of opioids from 32% to 19%. The acute fulfillment (within 7 days of the procedure) of opioids had notably declined; however, there is a slight increase in the fulfillment of opioids beyond 7 days. CONCLUSIONS: Within the 7-day postsurgical period after ambulatory procedures, narcotic prescribing habits among urologists are congruent with current initiatives to reduce narcotic use in the setting of the opioid pandemic. However, beyond the 7-day postsurgical period, further guidelines are needed to guide narcotic prescribing habits.
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Procedimientos Quirúrgicos Ambulatorios , Analgésicos Opioides , Prescripciones de Medicamentos , Dolor Postoperatorio , Pautas de la Práctica en Medicina , Procedimientos Quirúrgicos Urológicos , Humanos , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Estudios Retrospectivos , Masculino , Femenino , Procedimientos Quirúrgicos Ambulatorios/tendencias , Procedimientos Quirúrgicos Urológicos/tendencias , Procedimientos Quirúrgicos Urológicos/estadística & datos numéricos , Persona de Mediana Edad , Pautas de la Práctica en Medicina/tendencias , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Prescripciones de Medicamentos/estadística & datos numéricos , Anciano , Estados Unidos , Factores de TiempoRESUMEN
BACKGROUND: We recently developed a preliminary predictive model identifying clinical and radiologic factors associated with the need for surgery following blunt abdominal trauma (BAT) in children. Our aim in this study was to further validate the factors in this predictive model in a multi-institutional study. METHODS: A retrospective chart review of pediatric patients from five pediatric trauma centers who experienced BAT between 2011 and 2020 was performed. Patients under 18 years of age who had BAT and computed tomography (CT) abdomen imaging were included. Children with evidence of pneumoperitoneum, and hemodynamic instability were excluded. Fisher's exact test was used for statistical analysis of the association between the following risk factors and need for laparotomy: abdominal wall bruising (AWB), abdominal pain/tenderness (APT), thoracolumbar fracture (TLF), presence of free fluid (FF), presence of solid organ injury (SOI). A predictive logistic regression model was then estimated employing these factors. FINDINGS: Seven hundred thirty-four patients were identified in this multi-institutional dataset with BAT and abdominal CT imaging, and 726 were included. Of those, 59 underwent surgical intervention (8.8%). Univariate analysis of association between the studied factors and need for surgical management showed that the presence of TLF (p < 0.01), APT (p < 0.01), FF (p < 0.01), and SOI (p < 0.01) were significantly associated. A predictive model was created using the 5 factors resulting in an area under the curve (AUC) of 0.80. For the motor vehicle collisions (MVC) group, only FF, SOI, and TLF are significantly associated with the need for surgical intervention. The AUC for the MVC group was 0.87. CONCLUSIONS: A clinical and radiologic prediction rule was validated using a large multi-institutional dataset of pediatric BAT patients, demonstrating a high degree of accuracy in identifying children who underwent surgery. FF, SOI, and TLF are the most important factors associated with the need for surgical intervention. LEVEL OF EVIDENCE: Level III.
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Traumatismos Abdominales , Fracturas Óseas , Heridas no Penetrantes , Humanos , Niño , Adolescente , Estudios Retrospectivos , Traumatismos Abdominales/diagnóstico por imagen , Traumatismos Abdominales/cirugía , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/cirugía , Dolor AbdominalRESUMEN
BACKGROUND: Examine the relationship between exposure to systemic glucocorticoids (steroids) and advanced prostate cancer (PCa) at presentation. Prior work suggested that steroid use may be associated with increased PCa risk. MATERIALS AND METHODS: We queried the linked SEER-Medicare database (2004-2015) to identify PSA screened patients diagnosed with PCa. Criteria for screening included a PSA lab test or DRE exam in both the 12 month and 13 to 36 month periods prior to diagnosis of PCa. Steroid exposure was determined using Medicare Part D and groups were divided based on duration of use in the 3 years prior to diagnosis: controls with no exposure, <30 days, 30 days - 1 year, 1 to 2 years, and >2+ years. Advanced PCa was defined as systemic metastases or regional lymph node metastasis at presentation. Risk estimates for advanced PCa at presentation for steroid exposure groups vs. controls were assessed with univariable and multivariable logistic regression models. RESULTS: We identified 22,920 PSA screened patients diagnosed with PCa of which 29% used glucocorticoids in the exposure period. The mean (SD) duration for glucocorticoid use (in days) among all steroid users was 76.7 days (192.1). On univariable and multivariable analyses, > 2 years of steroid exposure was associated with significantly increased risk for advanced PCa (OR 2.06, 95% CI 1.35-3.14 and OR 1.74, 95% CI 1.12-2.69, respectively). CONCLUSION: In this population-based PSA-screened cohort, prolonged steroid use was associated with increased risk of advanced PCa at diagnosis. With the widespread use of glucocorticoids, it is important to consider the role steroids may play in PCa pathogenesis.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos/epidemiología , Glucocorticoides/efectos adversos , Estudios de Cohortes , Medicare , Neoplasias de la Próstata/patología , EsteroidesRESUMEN
INTRODUCTION: We aimed to investigate the clinical utility of quantitative prostatic zonal measurements on multiparametric magnetic resonance imaging (mpMRI) for the predication of clinically significant prostate cancer (csPCa). METHODS: A retrospective, single-institution study included 144 men who underwent mpMRI from 2015-2017. Prostate zone parameters were measured on mpMRI. Correlation and multivariable analysis evaluated the relationship between prostate zone parameters and the presence of csPCa. RESULTS: The mean age was 66.9±7.8 years old. The median (interquartile range [IQR]) prostate volume and prostate-specific antigen (PSA) were 51.6 ml (37.1-74.5) and 6.1 ng/ ml (4.5-8.2), respectively. Men with csPCa had significantly smaller total prostate volume (TPV), transitional zone volume (TZV), and transitional zone thickness (TZT), and larger transitional zone density (TZD) compared to those without PCa; however, on multivariate variable analysis, only TZD maintained significance. TZD had a comparable area under the curve to PSA density (PSAD) and PSA (0.74 vs. 0.73 vs. 0.60, respectively). In a subgroup analysis of men with PCa, PSAD and TZD were significantly higher in men with Gleason grade group (GG) ≥2 compared to those with GG <2 (p=0.002); however, this significance is not maintained on logistic regression in predicting GG. CONCLUSIONS: Quantitative features of prostate zones on MRI may aid in identifying better predictors of csPCa. Zonal-based PSA density (TZD) may be a useful marker in identifying csPCa. Further exploration is needed to understand the clinical application of larger TZV in men with csPCa compared to those with insignificant disease.
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Importance: Postoperative opioid prescriptions are associated with delayed recovery, perioperative complications, opioid use disorder, and diversion of overprescribed opioids, which places the community at risk of opioid misuse or addiction. Objective: To assess a protocol for eliminating postdischarge opioid prescriptions after major urologic cancer surgery. Design, Setting, and Participants: This cohort study of the no opioid prescriptions at discharge after surgery (NOPIOIDS) protocol was conducted between May 2017 and June 2021 at a tertiary referral center. Patients undergoing open or minimally invasive radical cystectomy, radical or partial nephrectomy, and radical prostatectomy were sorted into the control group (usual opioids), the lead-in group (reduced opioids), and the NOPIOIDS group (no opioid prescriptions). Interventions: The NOPIOIDS group received a preadmission educational handout, postdischarge instructions for using nonopioid analgesics, and no routine opioid prescriptions. The lead-in group received a postdischarge instruction sheet and reduced opioid prescriptions at prescribers' discretion. The control group received opioid prescriptions at prescribers' discretion. Main Outcomes and Measures: Primary outcome measures included rate and dose of opioid prescriptions at discharge and for 30 days postdischarge. Additional outcome measures included patient-reported pain and satisfaction level, unplanned health care utilization, and postoperative complications. Results: Of 647 opioid-naive patients (mean [SD] age, 63.6 [10.0] years; 478 [73.9%] male; 586 [90.6%] White), the rate of opioid prescriptions at discharge for the control, the lead-in, and the NOPIOIDS groups was 80.9% (157 of 194), 57.9% (55 of 95), and 2.2% (8 of 358) (Kruskal-Wallis test of medians: P < .001), and the overall median (IQR) tablets prescribed was 14 (10-20), 4 (0-5.3), and 0 (0-0) per patient in the control, lead-in, and NOPIOIDS groups, respectively (Kruskal-Wallis test of medians: P < .001). In the NOPIOIDS group, median and mean opioid dose was 0 tablets for all procedure types, with the exception of kidney procedures (mean [SD], 0.5 [1.7] tablets). Patient-reported pain surveys were received from 358 patients (72.6%) in the NOPIOIDS group, demonstrating low pain scores (mean [SD], 2.5 [0.86]) and high satisfaction scores (mean [SD], 86.6 [3.8]). There was no increase in postoperative complications in the group with no opioid prescriptions. Conclusions and Relevance: This perioperative protocol, with emphasis on nonopioid alternatives and patient instructions, may be safe and effective in nearly eliminating the need for opioid prescriptions after major abdominopelvic cancer surgery without adversely affecting pain control, complications, or recovery.
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Trastornos Relacionados con Opioides , Neoplasias Urológicas , Humanos , Masculino , Persona de Mediana Edad , Femenino , Analgésicos Opioides/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Estudios de Cohortes , Alta del Paciente , Cuidados Posteriores , Prescripciones de Medicamentos , Neoplasias Urológicas/inducido químicamente , Neoplasias Urológicas/complicaciones , Neoplasias Urológicas/tratamiento farmacológico , Pautas de la Práctica en MedicinaRESUMEN
OBJECTIVE: We evaluate the clinical feasibility of a portable, low-field magnetic resonance imaging (MRI) system for prostate cancer (PCa) biopsy. METHODS: A retrospective analysis of men who underwent a 12-core systematic transrectal ultrasound-guided prostate biopsy (SB) and a low-field MRI guided transperineal targeted biopsy (MRI-TB). Comparison of the detection of clinically significant PCa (csPCa) (Gleason Grade [GG] ≥ 2) by SB and low field MRI-TB, stratified by Prostate Imaging Reporting & Data System (PI-RADS) score, prostate volume, and prostate serum antigen (PSA) was performed. RESULTS: A total of 39 men underwent both the MRI-TB and SB biopsy. Median (interquartile range [IQR]) age was 69.0 (61.5-73) years, body mass index (BMI) was 28.9 kg/m2 (25.3-34.3), prostate volume was 46.5 cc (32-72.7), and PSA was 9.5 ng/ml (5.5-13.2). The majority (64.4%) of patients had PI-RADS ≥ 4 lesions and 25% of lesions were anterior on pre-biopsy MRII. Cancer detection rate (CDR) was greatest when combining SB and MRI-TB (64.1%). MRI-TB detected 74.3% (29/39) cancers. Of which, 53.8% (21/39) were csPCa while SB detected 42.5% (17/39) csPCa (p = 0.21). In 32.5% (13/39) of cases, MRI-TB upstaged the final diagnosis, compared to 15% (6/39) of cases in which SB upstaged the final diagnosis (p = 0.11). CONCLUSION: Low-field MRI-TB is clinically feasible. Although future studies on the accuracy of MRI-TB system are needed, the initial CDR is comparable to those seen with fusion-based prostate biopsies. A transperineal and targeted approach may be beneficial in patients with higher BMI and anterior lesions.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Próstata/diagnóstico por imagen , Próstata/patología , Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Estudios Retrospectivos , Estudios de Factibilidad , Estudios Prospectivos , Biopsia Guiada por Imagen/métodosRESUMEN
Tissue-mimicking gels provide a cost-effective medium to optimize histotripsy treatment parameters with immediate feedback. Agarose and polyacrylamide gels are often used to evaluate treatment outcomes as they mimic the acoustic properties and stiffness of a variety of soft tissues, but they do not exhibit high toughness, a characteristic of fibrous connective tissue. To mimic pathologic fibrous tissue found in benign prostate hyperplasia (BPH) and other diseases that are potentially treatable with histotripsy, an optically transparent hydrogel with high toughness was developed that is a hybrid of polyacrylamide and alginate. The stiffness was established using shear wave elastography (SWE) and indentometry techniques and was found to be representative of human BPH ex vivo prostate tissue. Different phantom compositions and excised ex vivo BPH tissue samples were treated with a 700-kHz histotripsy transducer at different pulse repetition frequencies. Post-treatment, the hybrid gels and the tissue samples exhibited differential reduction in stiffness as measured by SWE. On B-mode ultrasound, partially treated areas were present as hyperechoic zones and fully liquified areas as hypoechoic zones. Phase contrast microscopy of the gel samples revealed liquefaction in regions consistent with the target lesion dimensions and correlated to findings identified in tissue samples via histology. The dose required to achieve liquefaction in the hybrid gel was similar to what has been observed in ex vivo tissue and greater than that of agarose of comparable or higher Young's modulus by a factor >10. These results indicate that the developed hydrogels closely mimic elasticities found in BPH prostate ex vivo tissue and have a similar response to histotripsy treatment, thus making them a useful cost-effective alternative for developing and evaluating different treatment protocols.
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Ultrasonido Enfocado de Alta Intensidad de Ablación , Hiperplasia Prostática , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Humanos , Hidrogeles , Masculino , Fantasmas de Imagen , SefarosaRESUMEN
IMPORTANCE: Clinical data on the use of overactive bladder (OAB) medications are limited by the physician interpretation of adverse effects rather than those that are patient reported. OBJECTIVE: The aim of the study was to evaluate the association between OAB medications and adverse drug events (ADEs) through the self-reporting U.S. Food and Drug Administration Adverse Event Report System database. STUDY DESIGN: The U.S. Food and Drug Administration Adverse Event Report System (FAERS) database was queried from 2004 to 2019. Adverse drug events were recategorized. Disproportionality analysis was used to detect the risk signals for each OAB medication and ADEs. χ 2 values were calculated to assess the association between ADEs and dosage. RESULTS: A total number of 14,102 reports were identified. The most frequently reported OAB medications were mirabegron (35%), transdermal oxybutynin (27%), and solifenacin (25%). Neuropsychiatric (NP) ADEs were highest with tolterodine and fesoterodine usage (16% and 15.6%, respectively) and transdermal oxybutynin had the lowest (6.5%). Increasing the dose of tolterodine or fesoterodine was not associated with increased NP ADEs. Oxybutynin had the highest risk of affect/mood disorder, agitation, and balance/movement disorder; however, it had the lowest risk of headache/migraine compared with all OAB medications. Mirabegron compared with all other OAB medications had the lowest risk of affect/mood disorder and agitation; however, it had the highest risk of headache and migraines. CONCLUSIONS: The FAERS database not only is a repository of ADEs but also may represent evolving prescribing habits for OAB medications. Transdermal oxybutynin had the lowest NP ADEs and may be appropriate for selected individuals.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Vejiga Urinaria Hiperactiva , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Cefalea/inducido químicamente , Cefalea/tratamiento farmacológico , Humanos , Antagonistas Muscarínicos , Tartrato de Tolterodina , Vejiga Urinaria Hiperactiva/diagnóstico , Vejiga Urinaria Hiperactiva/tratamiento farmacológicoRESUMEN
Solid organ transplant (SOT) candidates and recipients are often subject to intense screening regimens that can potentially delay transplantation and cause unnecessary harm. Although initial studies suggested that SOT recipients had elevated risk of prostate cancer (PCa), contemporary studies have shown that transplant recipients with low- or intermediate-risk PCa have similar outcomes to their counterparts without a transplant. However, there are limited data on the relationship between prior transplant exposure and the risk of clinically significant aggressive PCa at presentation. To provide additional insight, we queried the Surveillance, Epidemiology and End Results-Medicare database to establish a cohort of prostate-specific antigen (PSA)-screened transplant patients who then went on to develop PCa. Procedure and diagnosis codes were then used to identify patients with a history of SOT. Aggressive PCa phenotype was defined as death from PCa or de novo metastasis, regional lymph node metastasis, PSA >20 ng/l, or Gleason score 8-10 at presentation. On univariable and multivariable (adjusted for age and race) analyses, transplant patients (n = 292) were not at significantly higher risk of an aggressive prostate cancer phenotype with odds ratios of 0.95 (95% confidence interval 0.72-1.25) and 1.18, (95% confidence interval 0.90-1.57), respectively. The results suggest that transplant recipients can have similar screening protocols to those for the general population. Patient summary: Using database results for transplant recipients, we investigated their risk of developing aggressive prostate cancer after transplantation. We found that having a transplant did not increase the risk of aggressive prostate cancer. This work suggests that transplant recipients are unlikely to benefit from more rigorous screening protocols than those for the general population.
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PURPOSE: Opioid prescriptions after surgery are major contributors to the opioid abuse epidemic. Several measures designed to limit opioid prescriptions at discharge have been evaluated. We conducted a comprehensive review and meta-analysis of the effectiveness of various types of interventions in reducing opioid prescriptions after urological surgery. MATERIALS AND METHODS: A systematic review including MEDLINE®, Web of Science™ and Cochrane databases was conducted to identify studies on opioid prescriptions and urological surgery. Twenty-two studies met the inclusion criteria, of which 19 were used for quantitative analysis for reduction in opioid prescriptions. Additional outcomes included opioid consumption and satisfaction with analgesia. RESULTS: Of the 8,318 patients, 53% were in the pre- and 47% in the post-intervention cohort. Overall mean reduction/patient in prescribed opioids was -67.59 (95% CI 54.23 to 80.94) morphine milligram equivalents (MME). Direct interventions, implemented by providers within their local department or hospital, were more effective in reducing prescribed opioids compared to indirect, or systemic, interventions, at -76.68 MME (95% CI 60.04 to -93.31) vs -46.72 MME (95% CI 24.20 to -69.23; p=0.04). Opioid consumption significantly decreased post-intervention with a mean reduction of -18.31 MME (95% CI 7.89 to 28.72). Patient satisfaction with analgesia remained unchanged between the pre- and post-intervention groups. CONCLUSIONS: Successful reduction in opioid prescriptions, without compromising pain control, can be achieved through a variety of interventions. Direct interventions appear to have a greater impact than indirect interventions in reducing opioid prescriptions. Despite the reduction, unused, excess prescription opioids were still noted, which provides an opportunity for further control on opioid prescriptions.
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Analgésicos Opioides , Dolor Postoperatorio , Analgésicos Opioides/uso terapéutico , Humanos , Manejo del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Pautas de la Práctica en Medicina , PrescripcionesRESUMEN
Toxicity of synthesized nanoparticles is the area of concern to all the researchers due to their possible health implications. Here we synthesized copper oxide nanoparticles (CuO NPs) without surfactant at pH value of 2, 7, 10 and with cetyletrimethylammoniumbromide (CTAB) surfactant at pH 7. Synthesized nanoparticles were characterized for various structural parameters including crystallite size, lattice parameters, strain, phase analysis using X-ray diffraction analysis, and morphological aspects have been analyzed using FESEM and HRTEM imaging. All the four nano-formulations were analyzed for their toxic potential using Allium cepa L. at three different concentrations (0.1, 0.01 and 0.001 g/100 ml). Cytological and genetic parameters including mitotic index, mitotic inhibition, aberrant cells, binucleated cells, micronucleated cells, chromosomal bridges, fragmentation, stickiness, laggards, vagrants, c-mitosis and disturbed spindle were analyzed. Our results revealed a dose dependent increase in cytotoxic parameters including decreased total dividing cells, mitotic index, and increased mitotic inhibition. Genotoxic parameters also increased at higher treatment concentrations including chromosomal aberrations and percent aberrant cells. The pH value at the time of particle synthesis has significant influence on the crystallite size and agglomeration as assessed by XRD, FESEM and HRTEM analysis. The NPs synthesized at pH 2 and 10 were found to be of smaller size and posed more toxic effects as compared to particles synthesized at neutral pH. On the other hand, CTAB assisted CuO NPs synthesized at pH 7 revealed even smaller crystallite sizes and thus boost the toxicity in all the parameters as compared to NPs synthesized without CTAB. The present study suggested an increase in toxic parameters of synthesized CuO NPs with respect to crystallite size which is pH dependent. Addition of CTAB at pH 7 decreased the crystallite as well as particle size and enhanced the toxic potential. Further studies are recommended to analyze the effect of surfactant addition in toxicological studies on CuO NPs.
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Cobre/química , Nanopartículas del Metal/toxicidad , Compuestos de Amonio Cuaternario/química , Daño del ADN/efectos de los fármacos , Concentración de Iones de Hidrógeno , Nanopartículas del Metal/química , Mitosis/efectos de los fármacos , Cebollas/efectos de los fármacos , Cebollas/fisiología , Tamaño de la Partícula , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/fisiología , Tensoactivos/químicaRESUMEN
Naively one might have expected an early division between phosphate monoesterases and diesterases of the alkaline phosphatase (AP) superfamily. On the contrary, prior results and our structural and biochemical analyses of phosphate monoesterase PafA, from Chryseobacterium meningosepticum, indicate similarities to a superfamily phosphate diesterase [Xanthomonas citri nucleotide pyrophosphatase/phosphodiesterase (NPP)] and distinct differences from the three metal ion AP superfamily monoesterase, from Escherichia coli AP (EcAP). We carried out a series of experiments to map out and learn from the differences and similarities between these enzymes. First, we asked why there would be independent instances of monoesterases in the AP superfamily? PafA has a much weaker product inhibition and slightly higher activity relative to EcAP, suggesting that different metabolic evolutionary pressures favored distinct active-site architectures. Next, we addressed the preferential phosphate monoester and diester catalysis of PafA and NPP, respectively. We asked whether the >80% sequence differences throughout these scaffolds provide functional specialization for each enzyme's cognate reaction. In contrast to expectations from this model, PafA and NPP mutants with the common subset of active-site groups embedded in each native scaffold had the same monoesterase:diesterase specificities; thus, the >107-fold difference in native specificities appears to arise from distinct interactions at a single phosphoryl substituent. We also uncovered striking mechanistic similarities between the PafA and EcAP monoesterases, including evidence for ground-state destabilization and functional active-site networks that involve different active-site groups but may play analogous catalytic roles. Discovering common network functions may reveal active-site architectural connections that are critical for function, and identifying regions of functional modularity may facilitate the design of new enzymes from existing promiscuous templates. More generally, comparative enzymology and analysis of catalytic promiscuity can provide mechanistic and evolutionary insights.
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Evolución Molecular , Hidrolasas Diéster Fosfóricas/química , Hidrolasas Diéster Fosfóricas/metabolismo , Monoéster Fosfórico Hidrolasas/química , Monoéster Fosfórico Hidrolasas/metabolismo , Biocatálisis , Dominio Catalítico , Chryseobacterium/enzimología , Hidrólisis , Modelos Moleculares , Mutación , Hidrolasas Diéster Fosfóricas/genética , Monoéster Fosfórico Hidrolasas/genética , Especificidad por Sustrato , Xanthomonas/enzimologíaRESUMEN
BACKGROUND AND SUMMARY: Thousands of workers are engaged in textile industry worldwide. Textile industry involves the use of different kinds of dyes which are known to possess carcinogenic properties. Solvents used in these industries are also associated with different health related hazards including cancer. In previous studies on textile and iron industries, the authors have reported genotoxicity among them and observed occurrence of cancer deaths among textile industry workers. Thus, an attempt has been made to compile the studies on the prevalence of different types of cancers among textile industry workers. LITERATURE SEARCH: A wide literature search has been done for compiling the present paper. Papers on cancer occurrence among textile industry workers have been taken from 1976 to 2015. A variety of textile dyes and solvents, many of them being carcinogenic, are being used worldwide in the textile industry. The textile industry workers are therefore, in continuous exposure to these dyes, solvents, fibre dusts and various other toxic chemicals. The present study evaluates the potential of different chemicals and physical factors to be carcinogenic agents among occupationally exposed workers by going through various available reports and researches. Papers were collected using different databases and a number of studies report the association of textile industry and different types of cancer including lung, bladder, colorectal and breast cancer. After going through the available reports, it can be concluded that workers under varied job categories in textile industries are at a higher risk of developing cancer as various chemicals used in the textile industry are toxic and can act as potential health risk in inducing cancer among them. Assessing the cancer risk at different job levels in textile industries may be found useful in assessing the overall risk to the workers and formulating the future cancer preventive strategies.
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Graphene has attracted much attention of scientific community due to its enormous potential in different fields, including medical sciences, agriculture, food safety, cancer research, and tissue engineering. The potential for widespread human exposure raises safety concerns about graphene and its derivatives, referred to as graphene family nanomaterials (GFNs). Due to their unique chemical and physical properties, graphene and its derivatives have found important places in their respective application fields, yet they are being found to have cytotoxic and genotoxic effects too. Since the discovery of graphene, a number of researches are being conducted to find out the toxic potential of GFNs to different cell and animal models, finding their suitability for being used in new and varied innovative fields. This paper presents a systematic review of the research done on GFNs and gives an insight into the mode and action of these nanosized moieties. The paper also emphasizes on the recent and up-to-date developments in research on GFNs and their nanocomposites for their toxic effects.
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Welding is used extensively in different industries. Welders are always at a risk of exposure to a number of gases and metal-containing fumes in their respective microenvironments in which they work. Welding fumes consist of a wide range of complex metal oxide particles which can deposit in different parts of their bodies causing serious health problems. In the present study, 35 welders (age: 33.80 ± 1.04 years) from two iron-based industries have been assessed for DNA damage in peripheral blood lymphocytes using single-cell gel electrophoresis. An equal number of subjects (N = 35; age: 30.40 ± 1.51 years) matched to exposed subjects with respect to sex, age, socioeconomic status, smoking, and alcoholic habits were taken as controls. The results revealed that the damaged cell frequency (DCF) and mean comet tail length (CTL) in welders were significantly higher as compared to the controls (DCF: 69.74 ± 1.68 vs. 31.14 ± 1.67 and CTL: 29.21 ± 1.48 vs. 1.47 ± 0.08; p < 0.05). The effect of confounding factors such as age, duration of exposure, smoking, and drinking habits was also studied. Blood lead levels also showed a positive correlation with duration of exposure and CTL, and the overall results indicated an increased genetic damage as an index of genotoxicity in workers occupationally engaged in welding microenvironments.
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Contaminantes Ocupacionales del Aire/toxicidad , Daño del ADN/efectos de los fármacos , Mutágenos/toxicidad , Exposición Profesional/análisis , Soldadura , Adulto , Estudios de Casos y Controles , Humanos , Leucocitos Mononucleares/efectos de los fármacosRESUMEN
Myiasis, the infestation of tissues of live humans and other vertebrate animals with dipteran larvae (maggots), is a phenomenon of widespread occurrence throughout the tropical regions of the world. It is commonly seen in domestic and wild animals but occurs rarely in man also. The tissue invasion in man by maggots is generally a well-recognized complication of neglected wounds. The condition may be asymptomatic but occasionally results in more or less severe problems and even death when larvae invade body cavities or areas that forbid their direct visual examination. Many cases of myiasis, however, usually do not reach the attention of medical practitioners because of the tendency of the mature larvae to migrate out of the lesion for pupation. In the present study, the authors reviewed the past literature describing the cases of human myiasis, causative fly species and predisposing factors for the onset of the same. The aim of the present manuscript is to provide a database for the future reference of medical entomologists, medical practitioners and veterinarians. Review of literature revealed that 37 fly species belonging to ten families were responsible worldwide for the onset of human myiasis. The incidence of myiasis among humans can be correlated to increasing fly populations, poor hygienic conditions and presence of domestic animals in the close vicinity. Other factors responsible for myiasis include neglected open wounds and foul-smelling discharge from natural body openings. Moreover, ignorance plays a key role in its occurrence since people are generally unaware about the actual cause and often correlate the condition to their superstitious beliefs. It is emphasized that the patients should not neglect their wounds and should take proper medical care; otherwise, myiasis may supervene.
Asunto(s)
Miasis/parasitología , Animales , Dípteros/clasificación , Humanos , Miasis/epidemiología , Miasis/etiología , Factores de Riesgo , Especificidad de la EspecieRESUMEN
Moyamoya disease (MMD) primarily causes constriction of internal carotid artery, but it is known to extend to the middle and anterior cerebral arteries. Some of the symptoms caused by MMD include transient ischemic attack (TIA) and seizures. The etiology of MMD from Graves' disease (GD) is mostly caused by thyrotoxicosis, but our finding of leukocytosis indicates a new finding that may help physicians prepare for the pending outcome of MMD from GD with leukocytosis. A 26-year-old Hispanic woman with a significant past medical history of GD and hypertension presented to the emergency department complaining of cough and shortness of breath for the past 5 days. During the patient's stay in the hospital, the patient suddenly developed numbness of the right arm with subsequent right arm weakness 10 minutes later. The head CT showed no acute intercranial hemorrhage, but MRA showed right intracranial internal carotid artery stenosis, with marked focal stenosis along the proximal supraclinoid segment, moderate stenosis along its distal supraclinoid segment with marked stenosis along the origin of the right A1 segment. It was therefore believed to be moyamoya-like phenomena. We discuss an atypical presentation that led to moyamoya-like phenomena which we believe has not been described before. We believe that presentation of idiopathic leukocytosis may have triggered the cerebral stenosis.