Best Practices for Measuring the Modulation Transfer Function of Video Endoscopes.

Endoscopes are crucial for assisting in surgery and disease diagnosis, including the early detection of cancer. The effective use of endoscopes relies on their optical performance, which can be characterized with a series of metrics such as resolution, vital for revealing anatomical details. The modulation transfer function (MTF) is a key metric for evaluating endoscope resolution. However, the 2020 version of the ISO 8600-5 standard, while introducing an endoscope MTF measurement method, lacks empirical validation and excludes opto-electronic video endoscopes, the largest family of endoscopes. Measuring the MTF of video endoscopes requires tailored standards that address their unique characteristics. This paper aims to expand the scope of ISO 8600-5:2020 to include video endoscopes, by optimizing the MTF test method and addressing parameters affecting measurement accuracy. We studied the effects of intensity and uniformity of image luminance, chart modulation compensation, linearity of image digital values, auto gain control, image enhancement, image compression and the region of interest dimensions on images of slanted-edge test charts, and thus the MTF based on these images. By analyzing these effects, we provided recommendations for setting and controlling these factors to obtain accurate MTF curves. Our goal is to enhance the standard's relevance and effectiveness for measuring the MTF of a broader range of endoscopic devices, with potential applications in the MTF measurement of other digital imaging devices.

SAGES guidelines for the surgical treatment of hiatal hernias.

BACKGROUND: Hiatal hernia (HH) is a common condition. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of HH. METHODS: Systematic reviews were conducted for four key questions regarding the treatment of HH in adults: surgical treatment of asymptomatic HH versus surveillance; use of mesh versus no mesh; performing a fundoplication versus no fundoplication; and Roux-en-Y gastric bypass (RYGB) versus redo fundoplication for recurrent HH. Evidence-based recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations methodology by subject experts. When the evidence was insufficient to base recommendations on, expert opinion was utilized instead. Recommendations for future research were also proposed. RESULTS: The panel provided one conditional recommendation and two expert opinions for adults with HH. The panel suggested routinely performing a fundoplication in the repair of HH, though this was based on low certainty evidence. There was insufficient evidence to make evidence-based recommendations regarding surgical repair of asymptomatic HH or conversion to RYGB in recurrent HH, and therefore, only expert opinions were offered. The panel suggested that select asymptomatic patients may be offered surgical repair, with criteria outlined. Similarly, it suggested that conversion to RYGB for management of recurrent HH may be appropriate in certain patients and again described criteria. The evidence for the routine use of mesh in HH repair was equivocal and the panel deferred making a recommendation. CONCLUSIONS: These recommendations should provide guidance regarding surgical decision-making in the treatment of HH and highlight the importance of shared decision-making and consideration of patient values to optimize outcomes. Pursuing the identified research needs will improve the evidence base and may allow for stronger recommendations in future evidence-based guidelines for the treatment of HH.

Synthesis, biological evaluation, and molecular modelling of substituted thiazolyl thiourea derivatives: A new class of prolyl oligopeptidase inhibitors.

Prolyl oligopeptidase (POP) is a compelling therapeutic target associated with aging and neurodegenerative disorders due to its pivotal role in neuropeptide processing. Despite initial promise demonstrated by early-stage POP inhibitors, their progress in clinical trials has been halted at Phase I or II. This impediment has prompted the pursuit of novel inhibitors. The current study seeks to contribute to the identification of efficacious POP inhibitors through the design, synthesis, and comprehensive evaluation (both in vitro and in silico) of thiazolyl thiourea derivatives (5a-r). In vitro experimentation exhibited that the compounds displayed significant higher potency as POP inhibitors. Compound 5e demonstrated an IC50 value of 16.47 ± 0.54 µM, representing a remarkable potency. A meticulous examination of the structure-activity relationship indicated that halogen and methoxy substituents were the most efficacious. In silico investigations delved into induced fit docking, pharmacokinetics, and molecular dynamics simulations to elucidate the intricate interactions, orientation, and conformational changes of these compounds within the active site of the enzyme. Moreover, our pharmacokinetic assessments confirmed that the majority of the synthesized compounds possess attributes conducive to potential drug development.

Potent, Selective Agonists for the Cannabinoid-like Orphan G Protein-Coupled Receptor GPR18: A Promising Drug Target for Cancer and Immunity.

The human orphan G protein-coupled receptor GPR18, activated by Δ9-tetrahydrocannabinol (THC), constitutes a promising drug target in immunology and cancer. However, studies on GPR18 are hampered by the lack of suitable tool compounds. In the present study, potent and selective GPR18 agonists were developed showing low nanomolar potency at human and mouse GPR18, determined in ß-arrestin recruitment assays. Structure-activity relationships were analyzed, and selectivity versus cannabinoid (CB) and CB-like receptors was assessed. Compound 51 (PSB-KK1415, EC50 19.1 nM) was the most potent GPR18 agonist showing at least 25-fold selectivity versus CB receptors. The most selective GPR18 agonist 50 (PSB-KK1445, EC50 45.4 nM) displayed >200-fold selectivity versus both CB receptor subtypes, GPR55, and GPR183. The new GPR18 agonists showed minimal species differences, while THC acted as a weak partial agonist at the mouse receptor. The newly discovered compounds represent the most potent and selective GPR18 agonists reported to date.

The Safety and Efficacy of Concurrent Laparoscopic Cholecystectomy during Minimally Invasive Roux-en-Y Gastric Bypass: A Systematic Review.

We conducted a systematic review to examine perioperative outcomes for adults undergoing minimally invasive Roux-en-Y gastric bypass (RYGB) with and without concurrent cholecystectomy (CCE). We reviewed the literature using OVID MEDLINE(R), Embase, Cochrane CENTRAL, Web of Science, and medRxiv and identified studies published between 1946 and May 2023. We identified a total of 2402 studies with 11 included in the final analysis (combined 149,356 patients). Studies suggested increased operative time associated with RYGB-CCE, with mixed results regarding length of stay and rates of bile duct injury. Presently available data is not robust enough to conclude whether minimally invasive RYGB with CCE harms or benefits patients compared to RYGB alone.

SAGES guideline for the diagnosis and treatment of appendicitis.

BACKGROUND: Appendicitis is an extremely common disease with a variety of medical and surgical treatment approaches. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians and patients in decisions regarding the diagnosis and treatment of appendicitis. METHODS: A systematic review was conducted from 2010 to 2022 to answer 8 key questions relating to the diagnosis of appendicitis, operative or nonoperative management, and specific technical and post-operative issues for appendectomy. The results of this systematic review were then presented to a panel of adult and pediatric surgeons. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. RESULTS: Conditional recommendations were made in favor of uncomplicated and complicated appendicitis being managed operatively, either delayed (>12h) or immediate operation (<12h), either suction and lavage or suction alone, no routine drain placement, treatment with short-term antibiotics postoperatively for complicated appendicitis, and complicated appendicitis previously treated nonoperatively undergoing interval appendectomy. A conditional recommendation signals that the benefits of adhering to a recommendation probably outweigh the harms although it does also indicate uncertainty. CONCLUSIONS: These recommendations should provide guidance with regard to current controversies in appendicitis. The panel also highlighted future research opportunities where the evidence base can be strengthened.

A novel layered double hydroxide-based ternary nanocomposite for the effective photocatalytic degradation of rhodamine B.

Photocatalytic degradation of organic pollutants is a green and effective route of wastewater treatment. Zinc oxide was initially used for this purpose; however, calcined zinc/chromium layered double hydroxide (ZnCr-LDO) and cadmium sulfide quantum dots (CdSQDs)-based nanocomposites proved as superior alternatives. Herein, we report a green sonochemical method for the sol-gel fabrication of novel CdSQDs@ZnCr-LDO/ZnO ternary nanocomposite that exhibited exceptional photocatalytic activity for the degradation of rhodamine B dye (RhB), in wastewaters, under UV-A-irradiation. The features of the ternary nanocomposite were investigated using various physicochemical techniques, including XRD, SEM, TEM, EDX, XPS, BET, zeta potential, DRS, and PL measurements. The RhB dye % removal was 38.02, 40.2, and 98% using pristine ZnO, ZnCr-LDO and the ternary CdSQDs@ZnCr-LDO/ZnO-based nanomaterials, respectively, reflecting the superior ternary nanocomposite's photocatalytic activity that made it an excellent competitor to commonly reported photocatalysts. Additionally, an investigation was carried out to determine the key reactive species in the photocatalytic degradation of RhB, considering both scavenger's type and concentration. The prevailing mechanism was found to be the reductive photodegradation pathway. Furthermore, several models were utilized to describe the kinetics of photocatalytic performance of the ternary nanocomposite and a typical Z-scheme type-II photocatalytic heterojunction mechanism was inferred.

Inconsistent Methods Used to Set Airway Pressure Release Ventilation in Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Regression Analysis.

Airway pressure release ventilation (APRV) is a protective mechanical ventilation mode for patients with acute respiratory distress syndrome (ARDS) that theoretically may reduce ventilator-induced lung injury (VILI) and ARDS-related mortality. However, there is no standard method to set and adjust the APRV mode shown to be optimal. Therefore, we performed a meta-regression analysis to evaluate how the four individual APRV settings impacted the outcome in these patients. Methods: Studies investigating the use of the APRV mode for ARDS patients were searched from electronic databases. We tested individual settings, including (1) high airway pressure (PHigh); (2) low airway pressure (PLow); (3) time at high airway pressure (THigh); and (4) time at low pressure (TLow) for association with PaO2/FiO2 ratio and ICU length of stay. Results: There was no significant difference in PaO2/FiO2 ratio between the groups in any of the four settings (PHigh difference -12.0 [95% CI -100.4, 86.4]; PLow difference 54.3 [95% CI -52.6, 161.1]; TLow difference -27.19 [95% CI -127.0, 72.6]; THigh difference -51.4 [95% CI -170.3, 67.5]). There was high heterogeneity across all parameters (PhHgh I2 = 99.46%, PLow I2 = 99.16%, TLow I2 = 99.31%, THigh I2 = 99.29%). Conclusions: None of the four individual APRV settings independently were associated with differences in outcome. A holistic approach, analyzing all settings in combination, may improve APRV efficacy since it is known that small differences in ventilator settings can significantly alter mortality. Future clinical trials should set and adjust APRV based on the best current scientific evidence available.

SAGES guideline for the diagnosis and treatment of appendicitis

Appendicitis is an extremely common disease with a variety of medical and surgical treatment approaches. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians and patients in decisions regarding the diagnosis and treatment of appendicitis. A systematic review was conducted from 2010 to 2022 to answer 8 key questions relating to the diagnosis of appendicitis, operative or nonoperative management, and specific technical and post-operative issues for appendectomy. The results of this systematic review were then presented to a panel of adult and pediatric surgeons. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Conditional recommendations were made in favor of uncomplicated and complicated appendicitis being managed operatively, either delayed (>12h) or immediate operation (<12h), either suction and lavage or suction alone, no routine drain placement, treatment with short-term antibiotics postoperatively for complicated appendicitis, and complicated appendicitis previously treated nonoperatively undergoing interval appendectomy. A conditional recommendation signals that the benefits of adhering to a recommendation probably outweigh the harms although it does also indicate uncertainty. These recommendations should provide guidance with regard to current controversies in appendicitis. The panel also highlighted future research opportunities where the evidence base can be strengthened.

Synthesis of the chromone-thiosemicarbazone scaffold as promising α-glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design.

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC50 value of 0.40 ± 0.02 µM, ~2183-fold higher than acarbose having an IC50 of 873.34 ± 1.67 µM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase.

Management of symptomatic, asymptomatic, and recurrent hiatal hernia: a systematic review and meta-analysis.

BACKGROUND: The surgical management of hiatal hernia remains controversial. We aimed to compare outcomes of mesh versus no mesh and fundoplication versus no fundoplication in symptomatic patients; surgery versus observation in asymptomatic patients; and redo hernia repair versus conversion to Roux-en-Y reconstruction in recurrent hiatal hernia. METHODS: We searched PubMed, Embase, CINAHL, Cochrane Library and the ClinicalTrials.gov databases between 2000 and 2022 for randomized controlled trials (RCTs), observational studies, and case series (asymptomatic and recurrent hernias). Screening was performed by two trained independent reviewers. Pooled analyses were performed on comparative data. Risk of bias was assessed using the Cochrane Risk of Bias tool and Newcastle Ottawa Scale for randomized and non-randomized studies, respectively. RESULTS: We included 45 studies from 5152 retrieved records. Only six RCTs had low risk of bias. Mesh was associated with a lower recurrence risk (RR = 0.50, 95%CI 0.28, 0.88; I2 = 57%) in observational studies but not RCTs (RR = 0.98, 95%CI 0.47, 2.02; I2 = 34%), and higher total early dysphagia based on five observational studies (RR = 1.44, 95%CI 1.10, 1.89; I2 = 40%) but was not statistically significant in RCTs (RR = 3.00, 95%CI 0.64, 14.16). There was no difference in complications, reintervention, heartburn, reflux, or quality of life. There were no appropriate studies comparing surgery to observation in asymptomatic patients. Fundoplication resulted in higher early dysphagia in both observational studies and RCTs ([RR = 2.08, 95%CI 1.16, 3.76] and [RR = 20.58, 95%CI 1.34, 316.69]) but lower reflux in RCTs (RR = 0.31, 95%CI 0.17, 0.56, I2 = 0%). Conversion to Roux-en-Y was associated with a lower reintervention risk after 30 days compared to redo surgery. CONCLUSIONS: The evidence for optimal management of symptomatic and recurrent hiatal hernia remains controversial, underpinned by studies with a high risk of bias. Shared decision making between surgeon and patient is essential for optimal outcomes.

Effects of Lung Injury and Abdominal Insufflation on Respiratory Mechanics and Lung Volume During Time-Controlled Adaptive Ventilation.

BACKGROUD: Lung volume measurements are important for monitoring functional aeration and recruitment and may help guide adjustments in ventilator settings. The expiratory phase of airway pressure release ventilation (APRV) may provide physiologic information about lung volume based on the expiratory flow-time slope, angle, and time to approach a no-flow state (expiratory time [TE]). We hypothesized that expiratory flow would correlate with estimated lung volume (ELV) as measured using a modified nitrogen washout/washin technique in a large-animal lung injury model. METHODS: Eight pigs (35.2 ± 1.0 kg) were mechanically ventilated using an Engström Carescape R860 on the APRV mode. All settings were held constant except the expiratory duration, which was adjusted based on the expiratory flow curve. Abdominal pressure was increased to 15 mm Hg in normal and injured lungs to replicate a combination of pulmonary and extrapulmonary lung injury. ELV was estimated using the Carescape FRC INview tool. The expiratory flow-time slope and TE were measured from the expiratory flow profile. RESULTS: Lung elastance increased with induced lung injury from 29.3 ± 7.3 cm H2O/L to 39.9 ± 15.1cm H2O/L, and chest wall elastance increased with increasing intra-abdominal pressures (IAPs) from 15.3 ± 4.1 cm H2O/L to 25.7 ± 10.0 cm H2O/L in the normal lung and 15.8 ± 6.0 cm H2O/L to 33.0 ± 6.2 cm H2O/L in the injured lung (P = .39). ELV decreased from 1.90 ± 0.83 L in the injured lung to 0.67 ± 0.10 L by increasing IAP to 15 mm Hg. This had a significant correlation with a TE decrease from 2.3 ± 0.8 s to 1.0 ± 0.1 s in the injured group with increasing insufflation pressures (ρ = 0.95) and with the expiratory flow-time slope, which increased from 0.29 ± 0.06 L/s2 to 0.63 ± 0.05 L/s2 (ρ = 0.78). CONCLUSIONS: Changes in ELV over time, and the TE and flow-time slope, could be used to demonstrate evolving lung injury during APRV. Using the slope to infer changes in functional lung volume represents a unique, reproducible, real-time, bedside technique that does not interrupt ventilation and may be used for clinical interpretation.

Inactivation of Three Subtypes of Influenza A Virus by a Commercial Device Using Ultraviolet Light and Ozone.

Avian influenza (AI) is a highly contagious disease that can be transmitted to naïve birds through fomites. The survival of AI viruses (AIV) on nonporous and porous fomites also dictates how long the fomite can serve as a vehicle for virus transmission. AIVs are known to be inactivated by ozone and ultraviolet (UV) light. However, the combined effect of UV light and ozone in combating AIV on different fomites has not been investigated. This study was undertaken to determine AIV inactivation by a commercial device called the BioSec shoe sanitizing station. This device generates both ozone and UV light for 8 sec when activated. We evaluated this device against three different subtypes of AIVs applied on seven different fomites. In general, the device inactivated all three AIV subtypes loaded on all fomites but to varying degrees of inactivation. The percentage of virus reduction on nonporous fomites (98.6%-99.9%) was higher than on porous fomites (90.0%-99.5%). In conclusion, this new device has the potential to help reduce the risk of transmission of AIV.

Inactivación de cuatro subtipos del virus de la influenza A mediante un dispositivo comercial usando luz ultravioleta y ozono. La influenza aviar (IA) es una enfermedad altamente contagiosa que puede transmitirse a aves susceptibles a través de fómites. La supervivencia de los virus de la influenza aviar en fómites porosos y no porosos también determina cuánto tiempo el fómite puede servir como vehículo para la transmisión del virus. Se sabe que los virus de influenza aviar son inactivados por el ozono y la luz ultravioleta (UV). Sin embargo, no se ha investigado el efecto combinado de la luz ultravioleta y el ozono para inactivar el virus de la influenza aviar en diferentes fómites. Este estudio se llevó a cabo para determinar la inactivación del virus de la influenza aviar mediante un dispositivo comercial llamado estación de desinfección de calzado BioSec. Este dispositivo genera ozono y luz ultravioleta durante 8 segundos cuando se activa. Se evaluó este dispositivo frente a cuatro subtipos diferentes del virus influenza aviar aplicados en siete fómites diferentes. En general, el dispositivo inactivó los cuatro subtipos de influenza aviar inoculados en todos los fómites, pero con distintos grados de inactivación. El porcentaje de reducción de virus en fómites no porosos (98.6%­99.9%) fue mayor que en fómites porosos (90.0%­99.5%). En conclusión, este nuevo dispositivo tiene el potencial de ayudar a reducir el riesgo de transmisión del virus de la influenza aviar.

Survival of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in the Environment.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine, with losses due to poor reproductive performance and high piglet and growing pig mortality. Transmission of porcine reproductive and respiratory syndrome virus (PRRSV) may occur by both direct and indirect routes; the latter includes exposure to PRRSV-contaminated fomites, aerosols, and arthropod vectors. This review has collected available data on the ex-vivo environmental stability and persistence of PRRSV in an effort to highlight important sources of the virus and to determine the role of environmental conditions on the stability of the virus, especially temperature. The ex-vivo settings include fomites (solid, porous, and liquid fomites), insects, people, and pork meat, as well as the role of environmental conditions on the stability of the virus, especially temperature.

Potential production of Ac-225 at Egyptian second research reactor (ETRR-2) through neutron induced transmutation of Ra-226.

A considerable focus has been paid to the production of 225Ac due to its effective therapeutic action in alpha-targeted radiotherapy. Considering the future global clinical demand, it is necessary to increase the production capacity of 225Ac. A feasibility study was conducted to investigate the production of 225Ac through neutron induced transmutation of 226Ra at the Egyptian Second Research Reactor (ETRR-2) using the MCNPX code. The calculations were carried out for 1 g of 226Ra target exposed to the highest neutron flux in the irradiation grid surrounding the reactor core. The 227Ra, 225Ra, 227Ac, and 225Ac generated activities as a function of irradiation and decay times were estimated. Our study revealed that in this non-linear production process, 39.22 MBq of pure 225Ac could be obtained after three days of irradiation, while 148.74 MBq could be obtained after fifteen days of continuous irradiation.

Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection.

Acute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LVT) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA). The LVT approach attempts to protect already open lung tissue from overdistension, while simultaneously resting collapsed tissue by excluding it from the cycle of mechanical ventilation. By contrast, the OLA attempts to reinflate potentially recruitable lung, usually over a period of seconds to minutes using higher PEEP used to prevent progressive loss of end-expiratory lung volume (EELV) and RACE. However, even with these protective strategies, clinical studies have shown that ARDS-related mortality remains unacceptably high with a scarcity of effective interventions over the last two decades. One of the main limitations these varied interventions demonstrate to benefit is the observed clinical and pathologic heterogeneity in ARDS. We have developed an alternative ventilation strategy known as the Time Controlled Adaptive Ventilation (TCAV) method of applying the Airway Pressure Release Ventilation (APRV) mode, which takes advantage of the heterogeneous time- and pressure-dependent collapse and reopening of lung units. The TCAV method is a closed-loop system where the expiratory duration personalizes VT and EELV. Personalization of TCAV is informed and tuned with changes in respiratory system compliance (CRS) measured by the slope of the expiratory flow curve during passive exhalation. Two potentially beneficial features of TCAV are: (i) the expiratory duration is personalized to a given patient's lung physiology, which promotes alveolar stabilization by halting the progressive collapse of alveoli, thereby minimizing the time for the reopened lung to collapse again in the next expiration, and (ii) an extended inspiratory phase at a fixed inflation pressure after alveolar stabilization gradually reopens a small amount of tissue with each breath. Subsequently, densely collapsed regions are slowly ratcheted open over a period of hours, or even days. Thus, TCAV has the potential to minimize VILI, reducing ARDS-related morbidity and mortality.

SAGES peritoneal dialysis access guideline update 2023.

BACKGROUND: Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed. RESULTS: After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction. CONCLUSIONS: In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.

Airway pressure release ventilation for lung protection in acute respiratory distress syndrome: an alternative way to recruit the lungs.

PURPOSE OF REVIEW: Airway pressure release ventilation (APRV) is a modality of ventilation in which high inspiratory continuous positive airway pressure (CPAP) alternates with brief releases. In this review, we will discuss the rationale for APRV as a lung protective strategy and then provide a practical introduction to initiating APRV using the time-controlled adaptive ventilation (TCAV) method. RECENT FINDINGS: APRV using the TCAV method uses an extended inspiratory time and brief expiratory release to first stabilize and then gradually recruit collapsed lung (over hours/days), by progressively 'ratcheting' open a small volume of collapsed tissue with each breath. The brief expiratory release acts as a 'brake' preventing newly recruited units from re-collapsing, reversing the main drivers of ventilator-induced lung injury (VILI). The precise timing of each release is based on analysis of expiratory flow and is set to achieve termination of expiratory flow at 75% of the peak expiratory flow. Optimization of the release time reflects the changes in elastance and, therefore, is personalized (i.e. conforms to individual patient pathophysiology), and adaptive (i.e. responds to changes in elastance over time). SUMMARY: APRV using the TCAV method is a paradigm shift in protective lung ventilation, which primarily aims to stabilize the lung and gradually reopen collapsed tissue to achieve lung homogeneity eliminating the main mechanistic drivers of VILI.

Design, synthesis, molecular docking and biological evaluation of 1,3,5-trisubstituted-1H-pyrazole derivatives as anticancer agents with cell cycle arrest, ERK and RIPK3- kinase activities.

The need for new ERK and RIPK3 kinase modulators arises from their central roles in cellular processes, especially in diseases like cancer. This research focused on a ligand-based strategy, incorporating previously documented 1,3,5-trisubstituted-1H-pyrazole derivatives, to craft innovative inhibitors specifically targeting ERK and RIPK3 kinases. Compounds 6, 7, 10a, 10c, and 10d exhibited significant cytotoxicity against PC-3 and MCF-7 cancer cell lines, with IC50 values ranging from 21.9 to 28.6 µM and 3.90-35.5 µM, respectively values surpassing those of the reference compound Doxorubicin. Additionally, cell cycle analysis revealed intriguing results, particularly with 10d inducing cell cycle arrest at the S phase in treated PC-3 cells, indicating potential DNA replication phase inhibition. Moreover, compounds 6, 10a, and 10d exhibited promising results in the in vitro kinase assay supported by molecular docking studies. The core scaffold of these compounds established interactions with vital amino acids within the active pockets of ERK and RIPK3 kinases, thereby securely anchoring them in place. These findings underscore the development of promising modulators for ERK and RIPK3 kinases, suggesting their potential for future contributions to cancer treatments.