Double longitudinal myotomy in gender-affirming colovaginoplasty: an innovative surgical technique to prevent and treat neovaginal spasms.

BACKGROUND: Gender-affirming colovaginoplasty (GACv) presents excellent postoperative results. However, neovaginal spasms, reported as painful cramps, can affect the sexual life of patients. AIM: The study sought to describe an innovative surgical technique and evaluate its impact on the prevention and treatment of neovaginal spasms. METHODS: This was a single-center prospective observational study with 2 series of patients: (1) patients who underwent GACv with double myotomy (DM) for spasm prevention (series A), in which longitudinal myotomies were performed across the defunctionalized colon, transecting the taenias, and resecting 2 strips of the intestinal muscle layer of approximately 1- to 2-mm wide and tall, leaving intact colonic tissue between strips; and (2) patients who reported neovaginal spasms in whom intravaginal-DM was performed as treatment surgery (series B), in which the posterior wall of the neovagina was dissected from the rectum and transected by longitudinal myotomies, resecting 2 strips of endoluminal mucosa and submucosal muscle of approximately 1- to 2-mm wide and tall, and the colonic mucosa was subsequently closed. OUTCOMES: Patient-reported outcomes and neovaginal examination were performed following standardized protocols. RESULTS: In series A, 177 patients underwent GACv with the DM technique and were prospectively followed for a median time of 18 months (interquartile range, 13-60 months). No patients reported neovaginal spasms. In series B, 18 patients who reported neovaginal spasms after GACv were treated with intravaginal DM. After a median time of 35 months (interquartile range, 26-45 months), 83% (n = 15 of 18) reported remission of symptoms. CLINICAL IMPLICATIONS: Double longitudinal myotomy performed on the derived portion of the colon in colovaginoplasty is an easy-to-perform and safe technique that may prevent and treat postoperative neovaginal spasms. STRENGTHS AND LIMITATIONS: Our results presented certain limitations, mainly associated with a low prevalence of neovaginal spasms, which, being of personal perception, can be underdiagnosed. To the same extent, the fact that it is a monocentric experience limits the possibility of extrapolating it to other centers. Moreover, a more trained surgical team may be the cause of fewer postoperative complications. On the other hand, the fact of being a reference center for gender-affirming surgery, having our procedures protocolized, and the prospective nature of the study allowed us to obtain a certain homogeneity and granularity of the results. CONCLUSION: DM is a safe procedure and appears to be highly effective for the prevention and treatment of neovaginal spasms after GACv. Routine use of this technique does not increase the operating time or postoperative complications. Multicenter, prospective studies are required to validate our results.

Radiomics Analyses to Predict Histopathology in Patients with Metastatic Testicular Germ Cell Tumors before Post-Chemotherapy Retroperitoneal Lymph Node Dissection.

BACKGROUND: The identification of histopathology in metastatic non-seminomatous testicular germ cell tumors (TGCT) before post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) holds significant potential to reduce treatment-related morbidity in young patients, addressing an important survivorship concern. AIM: To explore this possibility, we conducted a study investigating the role of computed tomography (CT) radiomics models that integrate clinical predictors, enabling personalized prediction of histopathology in metastatic non-seminomatous TGCT patients prior to PC-RPLND. In this retrospective study, we included a cohort of 122 patients. METHODS: Using dedicated radiomics software, we segmented the targets and extracted quantitative features from the CT images. Subsequently, we employed feature selection techniques and developed radiomics-based machine learning models to predict histological subtypes. To ensure the robustness of our procedure, we implemented a 5-fold cross-validation approach. When evaluating the models' performance, we measured metrics such as the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F-score. RESULT: Our radiomics model based on the Support Vector Machine achieved an optimal average AUC of 0.945. CONCLUSIONS: The presented CT-based radiomics model can potentially serve as a non-invasive tool to predict histopathological outcomes, differentiating among fibrosis/necrosis, teratoma, and viable tumor in metastatic non-seminomatous TGCT before PC-RPLND. It has the potential to be considered a promising tool to mitigate the risk of over- or under-treatment in young patients, although multi-center validation is critical to confirm the clinical utility of the proposed radiomics workflow.

Deep learning-based dose prediction to improve the plan quality of volumetric modulated arc therapy for gynecologic cancers.

BACKGROUND: In recent years, deep-learning models have been used to predict entire three-dimensional dose distributions. However, the usability of dose predictions to improve plan quality should be further investigated. PURPOSE: To develop a deep-learning model to predict high-quality dose distributions for volumetric modulated arc therapy (VMAT) plans for patients with gynecologic cancer and to evaluate their usability in driving plan quality improvements. METHODS: A total of 79 VMAT plans for the female pelvis were used to train (47 plans), validate (16 plans), and test (16 plans) 3D dense dilated U-Net models to predict 3D dose distributions. The models received the normalized CT scan, dose prescription, and target and normal tissue contours as inputs. Three models were used to predict the dose distributions for plans in the test set. A radiation oncologist specializing in the treatment of gynecologic cancers scored the test set predictions using a 5-point scale (5, acceptable as-is; 4, prefer minor edits; 3, minor edits needed; 2, major edits needed; and 1, unacceptable). The clinical plans for which the dose predictions indicated that improvements could be made were reoptimized with constraints extracted from the predictions. RESULTS: The predicted dose distributions in the test set were of comparable quality to the clinical plans. The mean voxel-wise dose difference was -0.14 ± 0.46 Gy. The percentage dose differences in the predicted target metrics of D 1 % ${D}_{1{\mathrm{\% }}}$ and D 98 % ${D}_{98{\mathrm{\% }}}$ were -1.05% ± 0.59% and 0.21% ± 0.28%, respectively. The dose differences in the predicted organ at risk mean and maximum doses were -0.30 ± 1.66 Gy and -0.42 ± 2.07 Gy, respectively. A radiation oncologist deemed all of the predicted dose distributions clinically acceptable; 12 received a score of 5, and four received a score of 4. Replanning of flagged plans (five plans) showed that the original plans could be further optimized to give dose distributions close to the predicted dose distributions. CONCLUSIONS: Deep-learning dose prediction can be used to predict high-quality and clinically acceptable dose distributions for VMAT female pelvis plans, which can then be used to identify plans that can be improved with additional optimization.

A deep learning-based approach for statistical robustness evaluation in proton therapy treatment planning: a feasibility study.

Objective. Robustness evaluation is critical in particle radiotherapy due to its susceptibility to uncertainties. However, the customary method for robustness evaluation only considers a few uncertainty scenarios, which are insufficient to provide a consistent statistical interpretation. We propose an artificial intelligence-based approach that overcomes this limitation by predicting a set of percentile dose values at every voxel and allows for the evaluation of planning objectives at specific confidence levels.Approach. We built and trained a deep learning (DL) model to predict the 5th and 95th percentile dose distributions, which corresponds to the lower and upper bounds of a two-tailed 90% confidence interval (CI), respectively. Predictions were made directly from the nominal dose distribution and planning computed tomography scan. The data used to train and test the model consisted of proton plans from 543 prostate cancer patients. The ground truth percentile values were estimated for each patient using 600 dose recalculations representing randomly sampled uncertainty scenarios. For comparison, we also tested whether a common worst-case scenario (WCS) robustness evaluation (voxel-wise minimum and maximum) corresponding to a 90% CI could reproduce the ground truth 5th and 95th percentile doses.Main results. The percentile dose distributions predicted by DL yielded excellent agreements with the ground truth dose distributions, with mean dose errors below 0.15 Gy and average gamma passing rates (GPR) at 1 mm/1% above 93.9, which were substantially better than the WCS dose distributions (mean dose error above 2.2 Gy and GPR at 1 mm/1% below 54). We observed similar outcomes in a dose-volume histogram error analysis, where the DL predictions generally yielded smaller mean errors and standard deviations than the WCS evaluation doses.Significance. The proposed method produces accurate and fast predictions (∼2.5 s for one percentile dose distribution) for a given confidence level. Thus, the method has the potential to improve robustness evaluation.

Deep Learning-Based Dose Prediction for Automated, Individualized Quality Assurance of Head and Neck Radiation Therapy Plans.

PURPOSE: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. METHODS AND MATERIALS: A total of 245 volumetric modulated arc therapy HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included computed tomography images, target prescriptions, and contours for targets and organs at risk (OARs). The model's performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared with manual flags by 3 HN radiation oncologists. RESULTS: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D1%,D95%, and D99% across the targets were within -2.53% ± 1.34%, -0.42% ± 1.27%, and -0.12% ± 1.97%, respectively, and the OAR mean and maximum doses were within -0.33 ± 1.40 Gy and -0.96 ± 2.08 Gy, respectively. For the plan quality assessment study, radiation oncologists flagged 47 OARs for possible plan improvement. There was high interphysician variability; 83% of physician-flagged OARs were flagged by only one of 3 physicians. The comparative dose prediction model flagged 63 OARs, including 30 of 47 physician-flagged OARs. CONCLUSIONS: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality.

Functional, aesthetic, and sensory postoperative complications of female genital gender affirmation surgery: A prospective study.

BACKGROUND: Female genital gender affirmation surgeries have increased in recent years. Prospective studies with homogeneous standardized techniques and outcomes assessment are scarce in the current literature. This study aims to: 1) report the functional, aesthetic, and sensory postoperative complications (POCs) of primary genital gender confirmation surgeries performed on transgender women and 2) compare functional and aesthetic POCs amongst three vaginoplasty techniques: inverted penile skin, penoscrotal skin graft, and pedicled intestinal flap vaginoplasty. METHODS: All (n = 84) consecutive transfemale individuals who underwent primary genital gender confirmation surgery from January 2015 to December 2016 at IMCLINIC were prospectively followed. Functional, aesthetic, and sensory POCs were registered according to the Clavien-Dindo POC classification. RESULTS: Functional POC rates after vaginoplasty at our centre were 19%, 12%, 13%, and 1% at short (one month), mid-early (three months), mid-late (six months), and long-term (one year) follow-up visits, respectively. None of them were severe complications (grades IV-V), 25% were grade III, and less than 20% were low-grade complications (grades I-II). Overall, aesthetic satisfaction was high (90%). The total number of secondary surgeries needed to satisfy the cosmetic outcome was 20 (aesthetic POC grade IIIb). No differences regarding functional or aesthetic complication rates amongst vaginoplasty techniques were encountered. Twelve months after surgery, 81% of patients had initiated sexual intercourse, and 96% reported clitoral sensitivity. CONCLUSIONS: In our experience, female genital gender affirmation surgery is a feasible, low-complication surgery that offers high satisfaction in the long term. Further multicentric well-designed research is mandatory to improve outcomes.

Ergonomic Factors That Impact Job Satisfaction and Occupational Health during the SARS-CoV-2 Pandemic Based on a Structural Equation Model: A Cross-Sectional Exploratory Analysis of University Workers.

This paper presents a structural equation model to determine the job satisfaction and occupational health impacts concerning organizational and physical ergonomics, using (as a study) objective unionized workers from the University of Sonora, South Campus, as an educational enterprise, during the SARS-CoV-2 pandemic. The above is a key element of an organizational sustainability framework. In fact, there exists a knowledge gap about the relationship between diverse ergonomic factors, job satisfaction, and occupational health, in the educational institution's context. The method used was a stratified sample of workers to which a job satisfaction-occupational health questionnaire was applied, consisting of 31 items with three-dimensional variables. As a result, the overall Cronbach's Alpha coefficient was determined, 0.9028, which is considered adequate to guarantee reliability (i.e., very high magnitude). Therefore, after the structural equation model, only 12 items presented a strong correlation, with a good model fit of 0.036 based on the root mean square error of approximation, 1.09 degrees of freedom for the chi-square, 0.9 for the goodness of fit index, and a confidence level of 95%. Organizational and physical factors have positive impacts on job satisfaction with factor loads of 0.37 and 0.53, respectively, and p-values of 0.016 and 0.000, respectively. The constructs related to occupational health that are considered less important by the workers were also determined, which would imply a mitigation strategy. The results contribute to the body of knowledge concerning the ergonomic dimensions mentioned and support organizational sustainability improvements in educational institutions and other sectors.

Global distribution of IRC7 alleles in Saccharomyces cerevisiae populations: a genomic and phenotypic survey within the wine clade.

The adaptation to the different biotic and abiotic factors of wine fermentation has led to the accumulation of numerous genomic hallmarks in Saccharomyces cerevisiae wine strains. IRC7, a gene encoding a cysteine-S-ß-lyase enzyme related volatile thiols production in wines, has two alleles: a full-length allele (IRC7F ) and a mutated one (IRC7S ), harbouring a 38 bp-deletion. Interestingly, IRC7S -encoding a less active enzyme - appears widespread amongst wine populations. Studying the global distribution of the IRC7S allele in different yeast lineages, we confirmed its high prevalence in the Wine clade and demonstrated a minority presence in other domesticated clades (Wine-PDM, Beer and Bread) while it is completely missing in wild clades. Here, we show that IRC7S -homozygous (HS) strains exhibited both fitness and competitive advantages compared with IRC7F -homozygous (HF) strains. There are some pieces of evidence of the direct contribution of the IRC7S allele to the outstanding behaviour of HS strains (i.e., improved response to oxidative stress conditions and higher tolerance to high copper levels); however, we also identified a set of sequence variants with significant co-occurrence patterns with the IRC7S allele, which can be co-contributing to the fitness and competitive advantages of HS strains in wine fermentations.

Current insight into the functions of microRNAs in common human hair loss disorders: a mini review.

Alopecia areata (AA) and Androgenic alopecia (AGA) are the most common multifactorial hair loss disorders that have a serious psychological impact on the affected individuals, while frontal fibrosing alopecia (FFA) is comparatively less common. However, due to the unknown etiology and the effect of many adverse factors, the prognosis of these conditions is challenging to predict. Moreover, no approved therapy has been available to date to prevent or treat these disorders. MicroRNAs (miRNAs) are a group of evolutionary conserved small non-coding RNA molecules with significant roles in the posttranscriptional gene regulation either through mRNA degradation or translational repression. A number of biological processes are controlled by these molecules, including cell growth and differentiation, proliferation, inflammation, immune responses, and apoptosis. Recently, a handful of studies have demonstrated the impact of miRNAs on common hair loss-related disorders; however, the exhaustive molecular mechanisms are still unclear. In this review, we discussed the functional implications of miRNAs in common hair loss-related disorders and addressed their efficacy to be used for theranostic purposes shortly.

Quantitative phase retrieval with low photon counts using an energy resolving quantum detector.

X-ray phase contrast imaging (PCI) combined with phase retrieval has the potential to improve soft-material visibility and discrimination. This work examined the accuracy, image quality gains, and robustness of a spectral phase retrieval method proposed by our group. Spectroscopic PCI measurements of a physical phantom were obtained using state-of-the-art photon-counting detectors in combination with a polychromatic x-ray source. The phantom consisted of four poorly attenuating materials. Excellent accuracy was demonstrated in simultaneously retrieving the complete refractive properties (photoelectric absorption, attenuation, and phase) of these materials. Approximately 10 times higher SNR was achieved in retrieved images compared to the original PCI intensity image. These gains are also shown to be robust against increasing quantum noise, even for acquisition times as low as 1 s with a low-flux microfocus x-ray tube (average counts of 250 photons/pixels). We expect that this spectral phase retrieval method, adaptable to several PCI geometries, will allow significant dose reduction and improved material discrimination in clinical and industrial x-ray imaging applications.

Ozone structure in Caribbean hurricanes.

Using ozone data from model-assimilated satellite measurements in the eastern Caribbean 15-20N, 60-68W, cases were studied when upper tropospheric O3 values declined below 60 ppb. Secondary criteria on convection and circulation isolated two hurricanes for analysis (Irma and Maria 2017). Winds at 150 hPa (14 km) show divergence over the vortex characterized by ozone <50 ppb. Upper tropospheric O3 concentrations >100 ppb appear west of hurricanes, where sinking motions interact with vortex outflow. Past work suggests that high values are important, but here low ozone concentrations near the core are more conspicuous. The low O3 layer formed over the ocean and lifted by the hurricane circulation and convection, indicates vortex - environment interaction, vertical motion and storm intensity. Upper tropospheric O3 concentrations <50 ppb cover an area about double the radius of heavy rainfall >10 mm/h, appearing as a protective envelope around the core.

The Genus Metschnikowia in Enology.

Over the last decade, several non-Saccharomyces species have been used as an alternative yeast for producing wines with sensorial properties that are distinctive in comparison to those produced using only Saccharomyces cerevisiae as the classical inoculum. Among the non-Saccharomyces wine yeasts, Metschnikowia is one of the most investigated genera due to its widespread occurrence and its impact in winemaking, and it has been found in grapevine phyllospheres, fruit flies, grapes, and wine fermentations as being part of the resident microbiota of wineries and wine-making equipment. The versatility that allows some Metschnikowia species to be used for winemaking relies on an ability to grow in combination with other yeast species, such as S. cerevisiae, during the first stages of wine fermentation, thereby modulating the synthesis of secondary metabolites during fermentation in order to improve the sensory profile of the wine. Metschnikowia exerts a moderate fermentation power, some interesting enzymatic activities involving aromatic and color precursors, and potential antimicrobial activity against spoilage yeasts and fungi, resulting in this yeast being considered an interesting tool for use in the improvement of wine quality. The abovementioned properties have mostly been determined from studies on Metschnikowia pulcherrima wine strains. However, M. fructicola and M. viticola have also recently been studied for winemaking purposes.

Labiaplasty with Clitoropexy.

Supplemental Digital Content is available in the text.

Manejo de perforación esofágica tardía, secundario a cirugía de columna cervical anterior / Management of a late esophageal perforation secondary to an anterior cervical spine surgery

Resumen Introducción: La cirugía anterior de columna cervical es un procedimiento de rutina para la fijación de fracturas vertebrales inestables, las indicaciones para estabilización de las vértebras son osteomielitis, tumores espinales y trauma. Objetivo: Informar sobre una de las complicaciones poco frecuentes y potencialmente peligrosas de la fijación de columna cervical por vía anterior. Pacientes y métodos: CASO 1: Paciente del sexo masculino de 41 años de edad que sufrió un accidente automovilístico. La tomografía reportó fractura del arco anterior de C1 y fractura de apófisis espinosa de C5-C6. Fue intervenido quirúrgicamente, y se le colocó osteosíntesis con placa. Un mes después presentó perforación esofágica, por lo que fue reintervenido, se le retiró la osteosíntesis, se le realizó un drenaje y se le colocó sistema VAC. Fue dado de alta por evolucionar adecuadamente. CASO 2: Paciente mujer de 53 años de edad, que inició su padecimiento un mes antes, con dolor cervicodorsal. Se le realizó una resonancia magnética en la que se encontró hernia discal C4-C5, C5-C6; se realizó artroplastia con prótesis en C4-C5. Cinco meses después, presentó migración del implante protésico; fue intervenida para retirar la prótesis, y presentó perforación esofágica. Fue reintervenida, se realizó el lavado de herida quirúrgica y se le colocó sistema VAC. Evolucionó de forma satisfactoria, por lo que egresó por mejoría. Resultados: La perforación cervical posterior a cirugía anterior de columna cervical es una complicación poco frecuente, y es indispensable su reconocimiento y diagnóstico temprano. Conclusiones: La perforación esofágica posterior a la fijación anterior de columna cervical es una complicación muy rara, con una incidencia de 0.25%, cuya mortalidad es elevada de no ser diagnosticada de manera temprana.

Abstract Introduction: The anterior cervical spine surgery is a routine procedure for the fixation of unstable vertebral fractures; the indications for stabilization of the vertebrae are osteomyelitis, spinal tumors and trauma. Objective: To inform about one of the rare and potentially dangerous complications of the cervical spine fixation by anterior approach. Patients and methods: CASE 1: A 41 year-old male patient who had a car accident. The tomography shows a fracture of the anterior arch of C1 and a spinous process fracture of C5-C6. He underwent surgery, and osteosynthesis with plate fixation was placed. A month later he presented esophageal perforation, and underwent surgery again. Osteosynthesis was removed, drainage was performed and a VAC system was placed. He was discharged by adequate evolution. CASE 2: A 53 year-old female patient, began her condition a month earlier with cervicodorsal pain. A magnetic resonance was performed finding disc herniation C4-C5, C5-C6. An arthroplasty with prosthesis in C4-C5 was performed. Five months later, she presented migration of the prosthetic implant and underwent surgery again to remove the prosthesis, presenting esophageal perforation. The surgical wound was washed and a VAC system was placed with satisfactory evolution. Results: A cervical perforation after an anterior cervical spine surgery is a rare complication; an early diagnosis is crucial.

Aesthetic Refinement in the Creation of the Clitoris, Its Preputial Hood, and Labia Minora in Male-to-Female Transsexual Patients.

BACKGROUND: In male-to-female genital sex reassignment surgery, the clitoris, its prepuce, and the labia minora remain among the most difficult structures to construct. We describe the authors' clitoroplasty and vulvoplasty technique. METHODS: All patients who underwent male-to-female sex reassignment surgery at a single center, between June 2012 and June 2016, were prospectively included. The standard pedicled island neurovascular flap of the glans penis was harvested in a letter M fashion with attached preputial skin. The central triangle of the M was used for the neoclitoris formation. Labia minora and the clitoral prepuce were created with both legs of the M and the preputial skin attached to it. Tactile and erogenous sensitivity was evaluated. RESULTS: Ninety-seven patients were included (mean age, 32 years; range, 17-54 years). All clitoroplasties and vulvoplasties were completed in the same surgical stage as the vaginoplasty. There were no cases of deep or total flap necrosis. Eight patients developed partial and superficial skin necrosis of the flap; one presented an abscess in labia majora, and another patient had urethral hematoma; both required drainage. None of the complications left any sequelae. At 6 months' follow-up all patients maintained tactile and erogenous sensitivity. CONCLUSIONS: The proposed technique represents an aesthetic refinement of the previously described pedicled glans penis flap by allowing the creation of a sensate neoclitoris, its preputial hood, and labia minora with excellent outcomes in the same surgical stage as the sex reassignment.

[Accidental ingestion of dental prostheses; 2 scenarios in the management and outcome. Case reports]. / Ingestión accidental de prótesis dental, 2 panoramas en el manejo y evolución. Reporte de casos.

BACKGROUND: Foreign body ingestion is the second cause of endoscopic emergency in the elderly, and dentures are the most frequent accidently ingested objects. Once in the stomach, their expulsion can be expected in 4 to 6 days. The treatment is wait and see in asymptomatic patients, but preventive endoscopic removal can also be performed. OBJECTIVE: To present 2 scenarios of the outcome and treatment in patients with foreign body ingestion. CASE REPORT: Patient under study due to weight loss, with a denture detected by abdominal x-ray, ingested inadvertently a year ago. A laparotomy was required as extraction by colonoscopy failed, due to excessive inflammation. The second case, of 24-hour onset, was due to the ingestion of a partial denture. As duodenal endoscopy extraction was unsuccessful, the patient was kept under observation. When it did not pass the caecum, it was extracted by colonoscopy, with no further complications and shorter hospital stay. CONCLUSIONS: Follow-up can be by simple abdominal x-ray, with endoscopic management if there is insufficient progress. In one of our cases, the outcome was unfavourable due to time of ingestion, and endoscopic management was not possible, whereas in the second case colonoscopy was performed early with success. Proper diagnostic and timely treatment mark the difference in the progression and outcome of the ingestion of foreign bodies.

Reversible and irreversible inhibitory activity of succinic and maleic acid derivatives on acetylcholinesterase.

Aryl succinic and maleic acid derivatives are potent inhibitors of bovine acetylcholinesterase in vitro. Succinic acid aminophenol derivatives 1b-e and 2b-d act as reversible inhibitors of acetylcholinesterase, while maleic acid aminophenol derivatives 3b-d and 4c-e act as choline subsite-directed irreversible inhibitors, detected by dialysis in the presence of edrophonium. Linear relationships between the logarithm of the velocity of hydrolysis of acetylcholine plotted against the time of incubation at several different inhibitor concentrations were determined. The K(i) for reversible competitive inhibitors was determined. For irreversible inhibitors the K(i) for the dissociation constant of the enzyme-inhibitor complex at the beginning of the recognition process was also determined as well as the inactivation constant of the enzyme-inhibitor adduct formation k(+2) and the bimolecular inhibition constant k(i) for the inhibition of acetylcholinesterase by aminophenol derivatives 3b-d and 4c-e. The conclusions of this study can be summarized as follows for both families: (a) the aromatic moiety played a critical role in the recognition of the active site; (b) in case of the reversible inhibitor, when the ester function took the place of the hydroxyl fragment, there was an important increase in the affinity; and (c) the distance between phenolic hydroxyl and nitrogen was critical because the inhibition is ortho<