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OBJECTIVE: To conduct a systematic review on the current state of T1 bladder tumor substaging. These neoplasms display significant heterogeneity in oncological behavior and prognosis, leading to the proposal of various substaging methods. Our aim was to investigate the potential diagnostic and prognostic value of substaging in stage T1 bladder cancer for better oncologic outcomes. METHODS: A literature search using MEDLINE, EMBASE and Cochrane Library databases was conducted in March 2024 to identify relevant studies on T1 urothelial bladder cancer staging. A systematic review of included articles was performed following the PRISMA guideline statement. Literature search was conducted in English. RESULTS: Overall, 63 studies published between 1990 and 2024 were included for final review including a total number of 8328 bladder tumor patients subject to T1 substaging. Various substaging methods have been developed, broadly classified into histometric (anatomy-based) and micrometric (semiquantitative) techniques. Advanced stages have been consistently associated with worse prognosis and need for a more radical therapeutic approach. A standardized, validated, unified substaging report system is lacking. CONCLUSION: T1 substaging is a strong predictor of oncologic outcomes. Micrometric methods seem to be more reproducible and precise than histometric techniques in terms of feasibility and prognostic value. Standardization and validation of the technique could potentially enhance the bladder cancer treatment algorithm.
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INTRODUCTION: HPV vaccination prevents most HPV-related cancers, yet uptake remains low. HPV is linked to an estimated 70% of oropharyngeal cancers (OPCs) in the US and outnumber cases of HPV-related cervical cancers. Not all OPCs can be detected through routine screening, making HPV vaccination a more effective primary prevention strategy. However, bridging primary and oral healthcare faces challenges due to a lack of referral networks between practices. The purpose of this study is to identify key infrastructure elements and policies, as well as HPV prevention strategies, among an academic practice network of dental clinics and partnering community health clinics in a southeastern state. METHODS: Researchers held interviews with directors and focus groups with staff at six dental clinics and eight associated community clinics in a southeastern state. Interviews and focus groups at dental and community clinics were analyzed by two study team members using thematic analysis with Nvivo software. RESULTS: A total of 90 participants participated in all focus groups and interviews (N = 14 interviews, 10 focus groups (5-13 participants per focus group). Most participants identified as white (58.9%) and female (70%), with an average age of 38.5 years. Researchers identified nine key study themes: three specific to the dental clinics' HPV conversations with patients, two related to community clinics' vaccine provision, and four involving the relationship between the dental and co-located community clinics. Dental clinic staff do not currently discuss HPV with patients. They are open to discussing HPV with patients but anticipate barriers that require preparation to overcome them. Community clinics have demonstrated previous success with HPV vaccination, but patients over the age of 18 face financial barriers to vaccination. Community clinics and dental clinics report that they do not currently have existing referral networks but are open to a referral system between practices if infrastructure is put into place to support it. CONCLUSIONS: Our findings indicate that there is interest in, and potential for, increased discussion of HPV with dental patients and collaboration between dental and community clinics for HPV vaccination referral. The results of this investigation can be used to develop intervention strategies to increase HPV vaccination through referrals between dental clinics and nearby community clinics. Ultimately, this work can reduce health inequities in HPV-related cancers, serve as a model for US dental practices, and possibly influence public health policy.
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The l-asparaginase (l-ASNase) enzyme catalyzes the conversion of the non-essential amino acid l-asparagine into l-aspartic acid and ammonia. Importantly, the l-ASNases are used as a key part of the treatment of acute lymphoblastic leukemia (ALL); however, despite their benefits, they trigger severe side effects because they have their origin in bacterial species (Escherichia coli and Erwinia chrysanthemi). Therefore, one way to solve these side effects is the use of l-ASNases with characteristics similar to those of bacterial types, but from different sources. In this sense, Cavia porcellus l-ASNase (CpA) of mammalian origin is a promising enzyme because it possesses similarities with bacterial species. In this work, the hydrolysis reaction for C. porcellus l-asparaginase was studied from an atomistic point of view. The QM/MM methodology was employed to describe the reaction, from which it was found that the conversion mechanism of l-asparagine into l-aspartic acid occurs in four steps. It was identified that the nucleophilic attack and release of the ammonia group is the rate-limiting step of the reaction. In this step, the nucleophile (Thr19) attacks the substrate (ASN) leading to the formation of a covalent intermediate and release of the leaving group (ammonia). The calculated energy barrier is 18.9 kcal mol-1, at the M06-2X+D3(0)/6-311+G(2d,2p)//CHARMM36 level of theory, which is in agreement with the kinetic data available in the literature, 15.9 kcal mol-1 (derived from the kcat value of 38.6 s-1). These catalytic aspects will hopefully pave the way toward enhanced forms of CpA. Finally, our work emphasizes that computational calculations may enhance the rational design of mutations to improve the catalytic properties of the CpA enzyme.
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Asparaginase , Asparagina , Animais , Cobaias/metabolismo , Amônia/química , Asparaginase/genética , Asparaginase/metabolismo , Asparaginase/uso terapêutico , Asparagina/química , Asparagina/genética , Asparagina/metabolismo , Ácido Aspártico , Mamíferos/metabolismo , MutaçãoRESUMO
Mainly due to their great antioxidant, anti-inflammatory and anticancer capacities, natural polyphenolic compounds have many properties with important applications in the food, cosmetic and pharmaceutical industries. Unfortunately, these molecules have very low water solubility and bioavailability. Glucosylation of polyphenols is an excellent alternative to overcome these drawbacks. Specifically, for the natural polyphenol resveratrol this process is very inefficiently performed by the native enzyme sucrose phosphorylase (BaSP) from the organism Bifidobacterium adolescentis (4%). However, the Q345F point mutation of the sucrose phosphorylase (BaSP Q345F) has been shown to achieve 97% monoglucosylation for the same substrate and the mechanism is still unknown. This report presents an analysis of MD simulations performed with the BaSP Q345F and BaSP systems in complex with resveratrol monoglucoside, followed by a study of the transglucosylation reaction of the mutant enzyme BaSP Q345F with resveratrol through the QM/MM hybrid method. With respect to the MD simulations, both protein structures showed greater similarity to the phosphate-binding conformation, and a larger active site and conformational changes in certain structures were found for the mutant system compared with the native enzyme; all this is in agreement with experimental data. With regard to the QM/MM calculations, the structure of an oxocarbenium ion-like transition state and the minimum energy adiabatic path (MEP) that connects the reactants with the products were obtained with a 20.3 kcal mol-1 energy barrier, which fits within the known experimental range for this type of enzyme. Finally, the analyses performed along the MEP suggest a concerted but asynchronous mechanism. In particular, they show that the interactions involving the residues of the catalytic triad (Asp192, Glu232, and Asp290) together with two water molecules at the active site strongly contribute to the stabilization of the transition state. The understanding of this glucosylation mechanism of the polyphenol resveratrol carried out by the mutant sucrose phosphorylase enzyme presented in this work could serve as the basis for subsequent studies on related carbohydrate-active enzymes.
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Bifidobacterium adolescentis , Domínio Catalítico , Glucosiltransferases , Polifenóis , Resveratrol , ÁguaRESUMO
Purpose: This study investigated the effect of perioperative intravenous (IV) acetaminophen on opioid requirements in pediatric patients undergoing tonsillectomy at a single center. Methods: This retrospective chart review included patients who were less than 18 years old and underwent an outpatient tonsillectomy procedure. Patients who received non-Food and Drug Administration (FDA)-approved dosing of IV acetaminophen, without documented weights, and on chronic pain medications at the time of the procedure were excluded. The primary outcome was opioid requirements postoperatively prior to discharge measured as morphine equivalents per kilogram. Descriptive statistics were used to compare differences between groups. A multivariate analysis was performed, accounting for differences between groups in baseline and procedural characteristics. Results: In total, 157 patients were included in this study, of whom 55 had received IV acetaminophen and 102 had not. The average IV acetaminophen dose for was 14.5 mg/kg for patients weighing less than 50 kg (n = 22); the remaining patients received the maximum 1 g dose. Patients who received IV acetaminophen were less likely to be administered postoperative opiates as compared with those did not (45.5% vs 63.7%, odds ratio = 0.48, P = .036). There was a trend toward a decrease in total amount of opiates administered with IV acetaminophen (0 vs 0.033 µg/kg, P = .61). After adjusting for age and documented pain assessment, IV acetaminophen administration remained a significant factor for postoperative opiate administration. Conclusions: Perioperative administration of IV acetaminophen was associated with less frequent administration of symptom-directed opiates in pediatric tonsillectomies. This finding indicates that the agent may have an opioid-sparing effect in this patient population.
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INTRODUCTION: The treatment of ureteropelvic junction has evolved considerably over the past 20 years, resulting in new surgical techniques, but traditional open surgery remains the gold standard treatment. Currently, less invasive techniques are used for the treatment of ureteropelvic junction obstruction. The purpose of our study is to compare the surgical and functional results between laparoscopic and open pyeloplasty performed at our department during the last 12 years. MATERIAL AND METHODS: This is a retrospective review of 92 cases performed in a period of 12 years. Two groups were compared: 30 patients were treated with open surgery (OP) and 62 with a laparoscopic approach (LP). Demographics, clinical presentation, functionality of the affected kidney, presence of polar vessels, kidney stones, hospital stay, complications and functional results were statistically analyzed. RESULTS: The mean age was 42 years. The most common clinical presentation was kidney or ureteral pain: 60% (OP) vs. 52% (LP). The right side was affected in 59%; presence of crossing vessels was 47% (OP) vs. 58% (LP); presence of kidney stones was 20% (OP) vs. 19% (LP), with an average hospital stay of 5.86 days (OP) vs. 3.36 days (LP) p <0.05. Post-operative complications were observed in 3 (OP) vs. 5 (LP) patients, with a success rate comparable between groups. CONCLUSIONS: In our department, we recommend LP as the standard treatment for ureteropelvic junction obstruction because of the equal success rate compared to OP and the benefits of a minimally invasive surgery.
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INTRODUCTION: Radical cystectomy in elderly patients is a controversial issue that has noticed an increase in importance overtime because of the lengthening average life span. Our objective was to determine if there were significant differences in the perioperative outcomes of patients over 70 years with bladder cancer treated with laparoscopic radical cystectomy (LRC) compared to those of younger patients. MATERIAL AND METHODS: We selected 180 patients who underwent LRC in our department in the period between 2005-2012. We divided them into 2 groups: 57% <70 years and 43% >70 years, and we compared the different parameters such as: comorbidities, intraoperative and post-operative complications, TNM stage and overall survival. RESULTS: The group <70 years had less comorbidities when compared with the group >70 years. Heterotopic urinary diversion was the diversion of choice in the elderly patients (97.4%). Paralytic ileus and the worsening of renal function were the only complications with statistical differences between the groups. Mean hospital length of stay was not significantly different between the groups. Younger and older patients had similar pathological staging : pT1 or less: 26,2 vs. 18.2%, pT2: 19.4 vs. 16.9%, pT3 38.8 vs. 37.7% and pT4 15.6 vs. 17.2%. Kaplan-Meier curves did not show significant differences in survival. CONCLUSIONS: Laparoscopic radical cystectomy in the elderly patient has similar rates of perioperative morbidity when compared with the younger patient and may be offered as a treatment option in selected elderly patients.
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INTRODUCTION: We have performed laparoscopic pyeloplasty (LP) in our department since 2004. Our goal is to describe, step by step, the approach of kidney stones during transperitoneal laparoscopic pyeloplasty and the outcomes after the procedure. MATERIAL AND METHODS: Twelve patients with kidney stones treated by transperitoneal laparoscopic pyeloplasty were found. The hospital records with clinical features, supplementary tests, and imaging studies were reviewed for demographic, procedural, and efficacy data. RESULTS: Kidney stones were found in 12 of 62 patients (19%) who had undergone transperitoneal laparoscopic pyeloplasty. Eight cases were treated using a flexible cystoscope and a nitinol N-Circle basket; in the remaining four cases the stones were extracted using laparoscopic grasping instruments. We want to emphasize a case of horseshoe kidney associated with ureteropelvic junction (UPJ) obstruction and a kidney stone in which the procedure was performed successfully. CONCLUSIONS: Laparoscopic pyeloplasty has now emerged as a standard approach to UPJ obstruction. Associated renal abnormalities or kidney stones add complexity to the procedure, however, as shown in our results, centers with experience in the laparoscopic approach of reconstructive urology make this technique feasible.
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We present what is to our knowledge, the first case of laparoscopic ureteral reimplantation reported in the renal transplant. The ureteral stenosis is one of the most difficult renal transplant complications to deal with. With the development of the endourological approach, this treatment has become the first treatment option for these patients. The patient is a 28-year-old female who received a renal allograft from a cadaver donor in 2008. Ureteral stenosis was diagnosed. The laparoscopic approach seems to be a good option over the open approach, with the benefits related with laparoscopic surgery.
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Se analizaron los resultados de 248 histerosalpingografías practicadas en la evalución de igual número de mujeres que consultaron por esterilidad e infertilidad. La patología tubaria fue el hallazgo más frecuente, siendo la exclusión tubárica (18,2%) la anormalidad de mayor incidencia. Las anomalías congénitas del útero representan el 5,2%, mientras que el pólipo mucoso (11,3%) y la hiperplasia endometrial fueron los hallazgos que más se observaron en la patología corporal. Por la alta incidencia de imágenes patológicas *82,5%), su fácil y segura ejecución, la HSG debe ser exploración rutinaria en pacientes infértiles