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In this second part of the tutorial series, we continue the investigation of Petri net theory as it applies to laboratory automation systems. The focus of this tutorial is the application of theoretical results to the analysis of laboratory automation system models. The mathematical description of a Petri net is introduced. Several analytical methods are reviewed and applied to examples of laboratory automation systems. Analytical results include the identification of deadlock situations, computation of cycle times, optimization of design, and the automatic calculation of system-control schemes. [ABSTRACT FROM AUTHOR]

The Python programming language is reviewed, with an emphasis on features and add-on modules useful for solving problems in the field of laboratory automation. Complexities of multi-instrument automated system control and coordination are discussed, along with the difficulties that arise when multitasking is used to implement system controllers. We introduce Python's generators, a feature not found in other popular languages, and demonstrate how to use them to simplify the development of multi-instrument laboratory automation system controllers. [ABSTRACT FROM AUTHOR]

A move from fixed, statically scheduled laboratory automation systems to more dynamic and adaptive behavior introduces complexities and challenges that have not been thoroughly explored in the field of laboratory automation. Powerful tools are required for the systematic modeling, analysis, simulation, and control of such systems. In this first part of a tutorial series, we introduce and explore Petri nets as a tool that can be used to model dynamically controlled laboratory automation systems. Subsequent contributions to this series will look at formal mathematical techniques for analyzing Petri net models, and methods for simulating and controlling laboratory automation systems using Petri nets. [ABSTRACT FROM AUTHOR]

Tinea capitis is a dermatophytosis, which is more common in children. It is caused by dermatophytes that vary according to the region; the most frequently isolated dermatophyte in our setting is Microsporum canis. Given its anthropophilic nature, its dissemination via interpersonal transmission and through the use of hair care tools is very common. In the course of the past year, an increase has been reported in the incidence of a pathogen that was very rare in our setting: Trichophyton tonsurans. Here we describe a retrospective study of cases of tinea capitis caused by Trichophyton tonsurans identified between September 2021 and March 2023 in the Department of Pediatric Dermatology at a general hospital of the City of Buenos Aires., (Sociedad Argentina de Pediatría.)

(1) Background: There is still disagreement over how sleeve gastrectomy (SG) affects gastroesophageal reflux disease (GERD). The debate regarding the best option for patients undergoing bariatric surgery who are also affected by GERD and/or hiatal hernia continues to divide the community of bariatric surgeons. While concomitant hiatal hernia repair (SG + HHR) has been proposed as a means of reducing the risk of GERD following SG with varying degrees of success, the addition of a fundoplication (SG + FP) has been suggested in recent years as a way to improve the lower esophageal sphincter's competency. The aim of this study is to systematically review and meta-analyze the efficacy of SG + HHR versus SG + FP on GERD remission in patients with obesity. (2) Methods: A systematic review of the literature was conducted, and studies analyzing the effects of SG + HHR versus SG + FP on postoperative GERD were included. The methodological quality of included trials was evaluated. The primary outcome was postoperative GERD rate, erosive esophagitis, and 12-month weight loss. Secondary outcomes included postoperative complications and mortality. The PRISMA guidelines were used to carry out the present systematic review (PROSPERO Registration Number: CRD42023405600). (3) Results: Fifteen articles with a total of 1164 patients were included in the meta-analysis; 554 patients underwent SG + HHR while 610 underwent SG + FP. In the SG + HHR group, 58.5 ± 28.9% of subjects presented clinical GERD symptoms compared to 20.4 ± 17.5% postoperatively ( p < 0.001). In the SG + FP group, 64.8 ± 39.4% were affected by GERD preoperatively compared to only 5 ± 8.1% postoperatively ( p < 0.001). SG + FP patients had a significantly greater GERD remission compared to SG + HHR ( p < 0.001). Weight loss was similar between groups ( p = 0.125). The rate of leaks was 0.18% and 0.33% in the SG + HHR and SG + FP, respectively ( p = 0.657), while perforations were significantly higher after SG + FP compared to the SG + HHR group (3.1% versus 0%, p = 0.002). The mortality rate was significantly greater in the SG + FP group (0.5% versus 0%, p = 0.002). (4) Conclusions: This study revealed that both SG with concomitant HHR and sleeve-fundoplication are effective in terms of reflux resolution and weight outcomes, with superiority of SG + FP in terms of GERD control, despite a greater overall complication rate. Both strategies can therefore be suggested as a suitable alternative variant to a conventional SG in subjects with obesity and concomitant hiatal hernia and/or GERD. Studies with extended follow-up and direct comparisons of these surgical approaches to conventional SG are warranted.

Background: Several methods have been proposed to monitor cerebral perfusion during carotid endarterectomy (CEA), with the purpose of minimizing the risk of perioperative stroke. The INVOS-4100 is able to detect cerebral oxygen saturation providing an intraoperative real-time monitoring system of cerebral oximetry. The aim of this study was to evaluate the performance of the INVOS-4100 in predicting cerebral ischemia during CEA., Methods: Between January 2020 and May 2022, 68 consecutive patients were scheduled for CEA either under general anesthesia or regional anesthesia with deep and superficial cervical block. Vascular oxygen saturation was recorded continually through INVOS before and during clamping of the ICA. Awake testing was performed in the group of patients undergoing CEA under regional anesthesia., Results: Sixty-eight patients were included; 43 were males (63.2%). Severe stenosis of the artery was present in 92%. Forty-one (60.3%) patients were monitored by INVOS, while 22 (39.7%) underwent awake testing. Mean clamping time was 20 ± 6.6 min. Patients undergoing awake testing had a lower hospital stay and ICU stay during admission ( p  = 0.011 and p  = 0.007 respectively). Comorbidities correlated with a higher ICU stay ( p  < 0.05). The INVOS monitoring was able to predict ischemic events with a sensitivity of 98% (AUC = 0.976)., Conclusions: The present study demonstrates that cerebral oximetry monitoring was a strong predictor of cerebral ischemia, although it was not possible to determine the non-inferiority of cerebral oximetry compared to awake testing. Nonetheless, the use of cerebral oximetry evaluates only perfusion in the superficial brain tissue and an absolute rSO2 value corresponding to significant cerebral ischemia has not been established. Therefore, larger prospective studies that correlate cerebral oximetry with neurologic outcomes are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Russo, Gentile, Fenga, Izzo, Denaro, Luka, Frattaroli, Costanzo, Castagneto-Gissey and Salvati.)

Introduction : Despite several perioperative care advancements and innovations in surgical procedures and technologies, the incidence rate of anastomotic leaks (ALs) after colorectal surgery has not substantially decreased. Gut microbiota can play a critical role in the healing process of anastomotic tissue and alterations in its composition may be largely to blame for anastomotic insufficiency. The use of specific antibiotics for preoperative large bowel decontamination could significantly influence the rate of ALs. The aim of this study was to systematically assess the various antibiotic prophylactic regimen strategies for primary prevention of ALs during colorectal surgery, in view of the available evidence. Methods : A systematic review of the literature was conducted, and randomized clinical trials (RCTs) analyzing prophylactic antibiotic bowel preparation in colorectal surgery were included. PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from inception through to 30 November 2022. The methodological quality of the included trials was evaluated. The primary outcome was AL rate; secondary outcomes were superficial/deep surgical site infections (SSIs). The PRISMA guidelines were used to carry out the present systematic review. Results: Thirteen RCTs published between 1977 and 2022, with a total of 4334 patients were included in the meta-analysis. Antibiotic prophylaxis was administered orally in 11/13 studies and intravenously in 2 studies. Patients randomly assigned to antibiotic prophylaxis, regardless of the regimen, had a reduced risk of ALs ( p = 0.003) compared to mechanical bowel preparation (MBP) alone. The use of antibiotic prophylaxis was also more effective in significantly reducing SSIs ( p < 0.001). Conclusions: The evidence points to an advantage of oral antibiotic prophylaxis in terms of AL rate, a significant contributor to perioperative morbidity, mortality, and rising healthcare expenditures. In light of such results, the use of antibiotic prophylaxis should be strongly encouraged prior to colorectal surgery.

(1) Background: Fluorescence cholangiography has been proposed as a method for improving the visualization and identification of extrahepatic biliary anatomy in order to possibly reduce injuries and related complications. The most common method of indocyanine green (ICG) administration is the intravenous route, whereas evidence on direct ICG injection into the gallbladder is still quite limited. We aimed to compare the two different methods of ICG administration in terms of the visualization of extrahepatic biliary anatomy during laparoscopic cholecystectomy (LC), analyzing differences in the time of visualization, as well as the efficacy, advantages, and disadvantages of both modalities. (2) Methods: A total of 35 consecutive adult patients affected by acute or chronic gallbladder disease were enrolled in this prospective case−control study. Seventeen patients underwent LC with direct gallbladder ICG injection (IC-ICG) and eighteen subjects received intravenous ICG administration (IV-ICG). (3) Results: The groups were comparable with regard to their demographic and perioperative characteristics. The IV-ICG group had a significantly shorter overall operative time compared to the IC-ICG group (p = 0.017). IV-ICG was better at delineating the duodenum and the common hepatic duct compared to the IC-ICG method (p = 0.009 and p = 0.041, respectively). The cystic duct could be delineated pre-dissection in 76.5% and 66.7% of cases in the IC-ICG and IV-ICG group, respectively, and this increased to 88.2% and 83.3% after dissection. The common bile duct could be highlighted in 76.5% and 77.8% of cases in the IC-ICG and IV-ICG group, respectively. Liver fluorescence was present in one case in the IC-ICG group and in all cases after IV-ICG administration (5.8% versus 100%; p < 0.0001). (4) Conclusions: The present study demonstrates how ICG-fluorescence cholangiography can be helpful in identifying the extrahepatic biliary anatomy during dissection of Calot’s triangle in both administration methods. In comparison with intravenous ICG injection, the intracholecystic ICG route could provide a better signal-to-background ratio by avoiding hepatic fluorescence, thus increasing the bile duct-to-liver contrast.

Background: Hyperglycemia and obesity are associated with a worse prognosis in subjects with COVID-19 independently. Their interaction as well as the potential modulating effects of additional confounding factors is poorly known. Therefore, we aimed to identify and evaluate confounding factors affecting the prognostic value of obesity and hyperglycemia in relation to mortality and admission to the intensive care unit (ICU) due to COVID-19., Methods: Consecutive patients admitted in two Hospitals from Italy (Bologna and Rome) and three from Spain (Barcelona and Girona) as well as subjects from Primary Health Care centers. Mortality from COVID-19 and risk for ICU admission were evaluated using logistic regression analyses and machine learning (ML) algorithms., Results: As expected, among 3,065 consecutive patients, both obesity and hyperglycemia were independent predictors of ICU admission. A ML variable selection strategy confirmed these results and identified hyperglycemia, blood hemoglobin and serum bilirubin associated with increased mortality risk. In subjects with blood hemoglobin levels above the median, hyperglycemic and morbidly obese subjects had increased mortality risk than normoglycemic individuals or non-obese subjects. However, no differences were observed among individuals with hemoglobin levels below the median. This was particularly evident in men: those with severe hyperglycemia and hemoglobin concentrations above the median had 30 times increased mortality risk compared with men without hyperglycemia. Importantly, the protective effect of female sex was lost in subjects with increased hemoglobin levels., Conclusions: Blood hemoglobin substantially modulates the influence of hyperglycemia on increased mortality risk in patients with COVID-19. Monitoring hemoglobin concentrations seem of utmost importance in the clinical settings to help clinicians in the identification of patients at increased death risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mayneris-Perxachs, Russo, Ramos, de Hollanda, Arxé, Rottoli, Arnoriaga-Rodríguez, Comas-Cufí, Bartoletti, Verrastro, Gudiol, Fages, Giménez, Gil, Bernante, Tinahones, Carratalà, Pagotto, Hernández-Aguado, Fernández-Aranda, Meira, Castro Guardiola, Mingrone and Fernández-Real.)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver-related mortality. NAFLD is associated with obesity, hepatic fat accumulation, and insulin resistance, all of which contribute to its pathophysiology. Weight-loss is the main therapy for NAFLD, and metabolic surgery is the most effective treatment for morbid obesity and its metabolic comorbidities. Although has been reported that Roux-en-Y gastric bypass can reverse NAFLD, it is unclear whether such effects result from reduced weight, from a lower calorie-intake, or from the direct influence of surgery on mechanisms contributing to NAFLD. We aimed to investigate whether gastrointestinal (GI) bypass surgery could induce direct effects on hepatic fat accumulation and insulin resistance, independently of weight reduction. Twenty Wistar rats on a high-fat diet underwent duodenal-jejunal-bypass (DJB) or sham operation and were pair fed (PF) for 15 wk after surgery to obtain a matched weight. Outcome measures include ectopic fat deposition, expression of genes and proteins involved in fat metabolism, insulin-signaling, and gluconeogenesis in liver and muscle. Despite no differences in body weight and calorie intake, DJB showed lower ectopic fat accumulation, improved peripheral and hepatic insulin sensitivity, and enhanced lipid droplet degradation. In both tissues, DJB increased insulin signaling, whereas hepatic key enzymes involved in gluconeogenesis and de novo lipogenesis were decreased. These findings suggest that DJB can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of NAFLD that share a mutual pathway, in which perilipin-2 (PLIN2) seems to be the main player, supporting further investigation into strategies that target the gut to treat metabolic liver diseases. NEW & NOTEWORTHY Our findings suggest that duodenal-jejunal bypass can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of nonalcoholic fatty liver disease that share a mutual pathway, in which perilipin-2 seems to be the main player. Our study supports further investigation into the role of proximal small intestine exclusion in the pathophysiology of nonalcoholic fatty liver disease to uncover less invasive treatments that mimic the effects of metabolic surgery and aims to prevent and treat metabolic liver disease.

We describe a custom Internet of Things (IoT) device used for tracking barcoded containers end to end in a high-throughput analysis and purification laboratory. Our IoT device fills an important gap that previously prevented us from fully tracking barcoded sample containers through manual steps in a multistep workflow, such as when samples are "parked" for temporary storage, or when using instrumentation not otherwise equipped with barcode scanners, a common occurrence found with specific centrifugal evaporation instruments. The custom device reads container barcodes and sends a small amount of data to our back-end data systems. Once data have been received and processed, users are alerted to any system responses via aural and visual feedback. Components of the IoT system include a low-cost headless IoT computer, a barcode reader, and a multicolor LED strip. We believe that the model for our device will facilitate simple and rapid deployment of IoT to the broader laboratory community. All source code and device configurations will be released into the public domain and made freely available.

Objectives: The main purpose of this study was to estimate the incidence rate and prevalence of clinically relevant pituitary adenomas (PAs) within the Hospital Italiano Medical Care Program (HIMCP), a well-defined population of 150,000 members living in the urban and suburban area of the city of Buenos Aires. We defined clinically relevant PAs as those associated with endocrine dysfunction and/or mass effect., Subjects and Methods: A retrospective open cohort study was conducted, including all members of the HIMCP over 18 years old, with active memberships during the period of the study, from January 1st 2003, to January 1, 2014. The incidence rates (IRs) were standardized (SIR) to the World Health Organization (WHO) 2000 standard population and were expressed per 100,000 members/year. Prevalence was estimated at January 1, 2014, and was expressed per 100,000 persons. The clinical records have been electronically managed since 2001. All lab and imaging studies were done in-house., Results: The overall SIR was 7.39/100,000/year (95% CI 4.47-10.31). Female patients had a specific IR significantly higher than male patients (5.85 vs.1.54) and represented 73% of the affected members. Regarding tumor size, 61.4% were microadenomas, and the mean age at diagnosis was 46.4 years. Prolactinomas had the highest SIR (5.41), followed by acromegaly (Acro) and non-functioning adenomas (NFAs) with overlapping 95% CIs (0.44-1.41 and 0.31-0.99, respectively). Microprolactinomas were more frequent in female (72.6%) (p < 0.01) and younger members (38 vs.60 years; p < 0.04). The overall prevalence rate was 97.76/100,000. Prolactinomas had the highest prevalence (56.29), followed by NFAs (21.48), Acro (14.07) and CD (5.93)., Conclusion: Our results demonstrate that clinically relevant PAs are more common than usually suspected, especially prolactinomas and growth-hormone secreting PAs. These data highlight the need to increase the awareness of PAs, thereby enabling early diagnosis and treatment.

A scheduler has been developed for an integrated laboratory robot system that operates in an always-on mode. The integrated system is designed for imaging plates containing protein crystallization experiments, and it allows crystallographers to enter plates at any time and request that they be imaged at multiple time points in the future. The scheduler must rearrange tasks within the time it takes to image one plate, trading off the quality of the schedule for the speed of the computation. For this reason, the scheduler was based on a simulated annealing algorithm with an objective function that makes use of a linear programming solver. To optimize the scheduler, extensive computational simulations were performed involving a difficult but representative scheduling problem. The simulations explore multiple configurations of the simulated annealing algorithm, including both geometric and adaptive annealing schedules, 3 neighborhood functions, and 20 neighborhood diameters. An optimal configuration was found that produced the best results in less than 60 seconds, well within the window necessary to dynamically reschedule imaging tasks as new plates are entered into the system., (© 2014 Society for Laboratory Automation and Screening.)

A systematic method for assembling and solving complex compound distribution problems is presented in detail. The method is based on a model problem that enumerates the mathematical equations and constraints describing a source container, liquid handler, and three types of destination containers involved in a set of compound distributions. One source container and one liquid handler are permitted in any given problem formulation, although any number of compound distributions may be specified. The relative importance of all distributions is expressed by assigning weights, which are factored into the final mathematical problem specification. A computer program was created that automatically assembles and solves a complete compound distribution problem given the parameters that describe the source container, liquid handler, and any number and type of compound distributions. Business rules are accommodated by adjusting weighting factors assigned to each distribution. An example problem, presented and explored in detail, demonstrates complex and nonintuitive solution behavior.

In this study we have examined the combustion dynamics of 1,5-dinitrobiuret (DNB) and nitric acid using reactive molecular dynamics simulations. Simulations were performed using the ReaxFF force field with parameters that were fitted against quantum mechanical calculations on model compounds/clusters relevant for this particular chemical system. Several different compositions were investigated, at densities of 0.5 and 1.0 g/mL, to examine the reaction kinetics in a dense vapor and liquid phase of these mixtures. Our simulations show that at certain compositions of the mixture reaction kinetics result in a very sharp release of thermal energy, which we associate with spontaneous ignition or hypergolicity. Analysis of key reaction mechanisms responsible for this process is discussed.

Computational chemistry simulations were performed to determine the effect that the addition of a single formic acid molecule has on the structure and stability of protonated water clusters. Previous experimental studies showed that addition of formic acid to protonated pure water results in higher intensities of large-sized clusters when compared to pure water and methanol-water mixed clusters. For larger, protonated clusters, molecular dynamics simulations were performed on H(+)(H(2)O)(n), H(+)(H(2)O)(n)CH(3)OH, and H(+)(H(2)O)(n)CHOOH clusters, 19-28 molecules in size, using a reactive force field (ReaxFF). Based on these computations, formic acid-water clusters were found to have significantly higher binding energies per molecule. Addition of formic acid to a water cluster was found to alter the structure of the hydrogen-bonding network, creating selective sites within the cluster, enabling the formation of new hydrogen bonds, and increasing both the stability of the cluster and its rate of growth.

Purpose: To assess the comparative therapeutic value of valproate (VPA), lamotrigine (LTG), and their combination in patients with complex partial seizures resistant to other established antiepileptic drugs (AEDs)., Methods: After a 3-month prospective baseline, 20 adults with refractory complex partial seizures not exposed previously to VPA and LTG were scheduled to receive three consecutive add-on treatments with VPA, LTG, or their combination, according to an open, response-conditional, crossover design. Each period consisted of a 6- to 12-week dose optimization followed by 3-month evaluation at stabilized serum drug levels. Only patients not responding to one phase proceeded to the next., Results: A >50% reduction in seizure frequency was observed in three of 20 patients given VPA and in four of 17 patients given LTG. Of the remaining 13 patients, four became seizure free, and an additional four experienced seizure reductions of 62-78% when VPA and LTG were given in combination. Mild tremor was observed in three patients receiving VPA and in all patients taking the VPA--LTG combination. In patients responding to combination therapy, optimized dosages and peak serum levels of both VPA and LTG were lower than those during separate administration., Conclusions: A considerable proportion of patients who failed to respond to VPA and LTG separately improved when the two drugs were combined, although serum levels of both agents were lower during combination therapy. Despite methodologic limitations in the nonrandomized treatment sequence, these findings suggest that VPA and LTG exhibit a favorable pharmacodynamic interaction in patients with refractory partial epilepsy. The dosage of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects.