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Laparoscopic Heller myotomy with Dor fundoplication is the standard surgical treatment for esophageal achalasia. However, there are few reports on the use of this method after gastric surgery. We report a case of a 78‐year‐old man who underwent laparoscopic Heller myotomy with Dor fundoplication for achalasia after distal gastrectomy and Billroth‐II reconstruction. After the intraabdominal adhesion was sharply dissected using an ultrasonic coagulation incision device (UCID), Heller myotomy was performed 5 cm above and 2 cm below the esophagogastric junction using the UCID. To prevent postoperative gastroesophageal reflux (GER), Dor fundoplication was performed without cutting the short gastric artery and vein. The postoperative course was uneventful, and the patient is in good health without symptoms of dysphagia or GER. Although per‐oral endoscopic myotomy is becoming the mainstay of treatment for achalasia after gastric surgery, laparoscopic Heller myotomy with Dor fundoplication is also an effective strategy. [ABSTRACT FROM AUTHOR]

Compared to the more common epiphrenic diverticula, those located at the central section of the esophagus are quite rare. Minimally invasive approaches for mid‐esophageal diverticula have lacked standardization. Certain mid‐esophageal diverticula, like epiphrenic diverticula, have been attributed to esophageal motility disorders. Thus, we believe that surgery for esophageal diverticula requires preoperative evaluation of esophageal function, with additional surgery being performed in case of abnormalities. The laparoscopic trans‐hiatal approach has been a common technique for managing epiphrenic diverticula but can also be used for mid‐esophageal diverticula located far from the esophagogastric junction provided that the port location is carefully considered. Laparoscopic surgery is also preferable given that it is a minimally invasive procedure and allows for diverticulum resection and Heller myotomy and Dor surgery to prevent reflux in the same field of view. Hence, laparoscopic surgery may be a beneficial alternative to the traditional thoracic or thoracoabdominal techniques. [ABSTRACT FROM AUTHOR]

Ischemic cardiomyopathy continues to be a major contributor to congestive heart failure, which places a significant burden on our healthcare system. Improving medications and different coronary revascularization strategies are the mainstays in the management of ischemic cardiomyopathy. Although medications and mechanical circulatory support are playing an ever-increasing role, cardiac transplantation remains the gold standard for treating advanced heart failure. Given the small number of available and suitable donor hearts, transplantation is limited for the majority of patients. Surgical ventricular restoration has repeatedly been suggested as a viable alternative in managing heart failure in select patients, as it is believed that surgically returning the ventricle to its original dimensions is possible and associated with favorable outcomes. The purpose of this manuscript is to comprehensively review the current literature on various surgical strategies for ventricular restoration. We also contextualize the published data with respect to ventricular function, volume, structure, arrhythmias, mitral regurgitation, and clinical outcomes., (© 2021 Wiley Periodicals LLC.)

Background: Achalasia is a primary esophageal motility disorder characterized by aperistalsis and defective relaxation of the lower esophageal sphincter in response to swallowing. Patients' symptoms include dysphagia, regurgitation, weight loss, chest pain and aspiration. The disease is idiopathic, and the goal of treatment is to eliminate the resistance determined by the abnormal lower esophageal sphincter, therefore allowing passage of the ingested food from the esophagus into the stomach. Three effective treatment modalities are available today—pneumatic dilatation, peroral endoscopic myotomy, and laparoscopic Heller myotomy with a partial fundoplication. Methods: We described the technique to perform a laparoscopic Heller myotomy and a Dor fundoplication. Results: Five steps to perform a laparoscopic Heller myotomy and a Dor fundoplication were described. Conclusions: The surgical approach is favored in many centers as it is very effective in relieving symptoms, while avoiding pathologic gastroesophageal reflux in most patients. [ABSTRACT FROM AUTHOR]

Introduction: Achalasia is an esophageal motility disorder characterized by disordered esophageal peristalsis with failed relaxation of the lower esophageal sphincter resulting in a functional obstruction.Treatment can include medical, endoscopic, or surgical interventions. Although none of these are curative, they each offer methods to create esophageal outflow. Materials and Methods: This article discusses our preferred surgical technique used for laparoscopic Heller myotomy with Dor fundoplication. This technique has been developed over the author's career. Conclusion: The technique discussed provides a safe and effective strategy to manage achalasia. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate intracytoplasmic sperm injection (ICSI) outcomes in young patients with diminished ovarian reserve (DOR) plus severe male factor (SMF) compared with age‐matched controls with DOR. Study design: A total of 189 infertile women under 35 years with DOR undergoing ICSI procedures were included retrospectively. Participants whose partners' sperm analysis was normal considered as the DOR group (n = 154) and whose partners' had SMF considered as the DOR + SMF group (n = 35). The two groups were compared regarding cycle characteristics and pregnancy outcomes. Results: Demographic features except infertility duration were similar between two groups. The duration of infertility was significantly longer in the DOR + SMF group compared to the DOR group (p = 0.02). Ovarian stimulation characteristics, oocyte retrieval parameters, fertilization rate, quality of embryos, embryo cancellation rate, and development up to blastocyst stage were found similar between two groups. Implantation, clinical pregnancy, abortion, and live birth rate, multiple pregnancy rate per cycle were distributed homogenously between the DOR and DOR + SMF groups. Regarding perinatal and neonatal outcomes of groups, fetal height and weight were significantly lower in DOR + SMF group than in DOR group (p = 0.001 and 0.01, respectively). Gestational week at delivery was lower in the DOR + SMF group compared to the DOR group (p < 0.0001). Conclusion: Fetal anthropometric measures were lower regarding to preterm delivery in the DOR + SMF group than the DOR group. Large sample‐sized studies should be performed to explain the decreased gestational week at the time of delivery in the DOR + SMF group. [ABSTRACT FROM AUTHOR]

An on‐land frequency domain electromagnetic geophysical survey was conducted across a tombolo delimiting the southern bay of Tel Dor (northern Israel) to the south. It was accompanied by a marine archaeological survey adjacent to its northern edge. Results indicate a deep channel connecting the bay and the Tantura Lagoon to the south. At its northern exit, an NW–SE trending square anomaly is visible in the geophysical data, buried underneath centuries of sand accumulation. It is parallel and similar in shape and scale to a Hellenistic feature observed in satellite data and excavated during the underwater archaeological survey. It seems that during the beginning/Middle Bronze Age, a natural or manmade channel was utilized as an entrance to the bay. As sea levels rose and sand began to accumulate, the channel was periodically filled in and would have needed to have been cleared. Eventually, it became too expensive or inconvenient to maintain, probably during the Byzantine period. The southern anchorage was abandoned for more favorable conditions to the north of the Tel. The sequence of events shows how ancient builders first utilized a natural channel, maintained it as sea levels rose, and abandoned it when it became too problematic to maintain. [ABSTRACT FROM AUTHOR]

The regulation of autophagy in metazoans is only partly understood, and there is a need to identify the proteins that control this process. The diabetes- and obesity-regulated gene (DOR), a recently reported nuclear cofactor of thyroid hormone receptors, is expressed abundantly in metabolically active tissues such as muscle. Here, we show that DOR shuttles between the nucleus and the cytoplasm, depending on cellular stress conditions, and re-localizes to autophagosomes on autophagy activation. We demonstrate that DOR interacts physically with autophagic proteins Golgi-associated ATPase enhancer of 16 kDa (GATE16) and microtubule-associated protein 1A/1B-light chain 3. Gain-of-function and loss-of-function studies indicate that DOR stimulates autophagosome formation and accelerates the degradation of stable proteins. CG11347, the DOR Drosophila homologue, has been predicted to interact with the Drosophila Atg8 homologues, which suggests functional conservation in autophagy. Flies lacking CG11347 show reduced autophagy in the fat body during pupal development. All together, our data indicate that DOR regulates autophagosome formation and protein degradation in mammalian and Drosophila cells. [ABSTRACT FROM AUTHOR]

Two studies were conducted to explore the effects of differential observing responses (DORs) on vocal tact acquisition in preschool‐age children of typical development. In Study 1 with three participants, an identity‐matching DOR was incorporated into tact instruction trials with novel visual stimuli. Acquisition rates were similar in the DOR condition and in a non‐DOR condition. In Study 2 with five new participants, the identity‐matching DOR was implemented as an intervention when standard discrete‐trial instruction failed to produce acquisition of tacts of compound stimuli. Two participants reached mastery after the identity‐matching DOR was introduced, whereas three participants' progress was unaffected. For those three, the identity‐matching DOR was replaced with a verbal DOR (tacting of stimulus components), but although one participant's correct responding increased, none reached mastery. Two participants ultimately reached mastery after a non‐DOR intervention. Conditions under which DORs facilitate stimulus control outside of MTS tasks remain to be identified. [ABSTRACT FROM AUTHOR]

Doravirine (DOR) is a non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV‐1. Its use in combination with rifapentine (RPT), an antituberculosis (TB) antibiotic, may reduce the exposure of DOR compromising viral suppression in those living with HIV‐1 co‐infected with TB. We conducted a prospective, phase I, open label, two‐period, fixed sequence, drug interaction study to evaluate the effect of once‐weekly RPT and isoniazid (INH) on the pharmacokinetics (PKs) of DOR in healthy volunteers. DOR 100 mg was administered alone twice‐daily for 4 days in period 1. In period 2, once‐weekly RPT + INH were co‐administered with multiple doses of DOR 100 mg twice‐daily for study days 7, 14, and 21. Plasma was obtained for DOR PKs when given alone and co‐administered with RPT + INH. Eleven healthy volunteers enrolled and completed the study. The geometric mean ratios and 90% confidence intervals for DOR area under the concentration‐time curve from zero to 12 hours (AUC0–12) and C12 in the presence of RPT + INH compared with DOR alone were 0.71 (0.60–0.85) and 0.69 (0.54–0.89), respectively. Although exposures were moderately reduced in the presence of RPT + INH, trough DOR values were within the concentration range associated with virological suppression. These results demonstrate that a modest decrease in DOR exposure would unlikely be clinically relevant in a virally suppressed patient co‐administered once‐weekly RPT + INH. [ABSTRACT FROM AUTHOR]

Background and Aims: Partial fundoplication is commonly performed in conjunction with Heller Myotomy. It is, however, controversial whether anterior Dor or posterior Toupet partial fundoplication is the antireflux procedure of choice. The aim was to perform a systematic review and meta-analysis of studies comparing these two procedures. Material and Methods: A search of PubMed, Cochrane database, Medline, Embase, Science Citation Index, Google scholar and current contents for English language articles comparing Dor and Toupet fundoplication following HM between 1991 and 2018 was performed. The outcome variables analyzed included operating time, length of hospital stay (LOHS), overall complication rate, quality of life (QOL), postoperative reflux, residual postoperative dysphagia, treatment failure and reoperations. The meta-analysis was prepared in accordance with the PRISMA-P statement. Results: Seven studies totaling 486 patients (Dor = 245, Toupet = 241) were analyzed. LOHS was significantly shorter for Toupet repair compared to Dor procedure (WMD 0.73, 95% CI 0.47 to 0.99; P < 0.0001). Furthermore, patients after Toupet experienced significantly better QOL than those after Dor (WMD 1.68, 95% CI 0.68 to 2.73, P < 0.001). All other variables showed comparable effects for these two procedures. Conclusion: Our systematic review and meta-analysis revealed that Toupet fundoplication is superior to Dor in terms of LOHS and QOL following HM. For other variables such as postoperative reflux, postoperative dysphagia, complication rates and treatment failure, both Dor and Toupet fundoplication produced effective and equivalent results. [ABSTRACT FROM AUTHOR]

Several lines of evidence support that food overconsumption may be related to the role of the endogenous opioid system in the control of food palatability. The opioid system, and particularly the delta opioid receptor (DOR), plays a crucial role in the regulation of food rewarding properties. In our study, we used operant conditioning maintained by chocolate-flavoured pellets to investigate the role of DOR in the motivation for palatable food and the structural plasticity changes promoted by this behaviour. For this purpose, we evaluated the specific role of this receptor in the behavioural and neuroplastic changes induced by palatable food in the prefrontal cortex (PFC), hippocampus (HCP) and nucleus accumbens (NAc) in constitutive knockout (KO) mice deficient in DOR. Mutant mice and their wild-type littermates were trained to obtain chocolate-flavoured pellets on fixed ratio 1 (FR1), FR5 and progressive ratio (PR) schedule of reinforcement. No significant differences between genotypes were revealed on operant behaviour acquisition in FR1. DOR knockout mice displayed lower number of active lever-presses than wild-type mice on FR5, and a similar decrease was revealed in DOR KO mice in the breaking point during the PR. This operant training to obtain palatable food increased dendritic spine density in the PFC, HCP and NAc shell of wild-type, but these plasticity changes were abolished in DOR KO mice. Our results support the hypothesis that DOR regulates the reinforcing effects and motivation for palatable food through neuroplastic changes in specific brain reward areas. [ABSTRACT FROM AUTHOR]

Abstract: DOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress–response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption. [Copyright &y& Elsevier]

Transgender women may have concerns of drug interactions between feminizing hormone therapy (FHT) and antiretrovirals, leading to nonadherence. This randomized, three‐period crossover, open‐label, phase I trial assessed the effects of doravirine (DOR) and tenofovir disoproxil fumarate (TDF) on the pharmacokinetics (PKs) of estradiol, spironolactone, and total testosterone and vice versa in healthy transgender women. Volunteers were randomized 1:1 into two sequences containing three treatment groups (DOR, lamivudine [3TC], and TDF alone; estradiol, spironolactone, and placebo; and DOR/3TC/TDF, estradiol, and spironolactone). Eight subjects enrolled in the study and six had completed all study periods. The geometric mean ratios for DOR area under the concentration‐time curve from zero to last measured concentration (AUC0‐last), maximum concentration (Cmax), and concentration at 24 h (C24) were similar. However, tenofovir (TFV) AUC0‐last, Cmax, and C24 moderately increased by 14%–38%. Last, estradiol AUC0‐last, Cmax, and C24 were increased by 10%–13%. Whereas most 90% confidence intervals did not meet the bioequivalence bounds of 80%–125%, the point estimates fell within the intervals. Log‐transformed DOR, TFV, and estradiol PK parameters computed with and without co‐administration were not statistically different (p > 0.05). There were no serious adverse events. There is not a clinically significant impact of FHT on DOR/TFV PKs. Similarly, there is no observed impact on estradiol PKs and total testosterone following use of DOR/3TC/TDF. [ABSTRACT FROM AUTHOR]

Problem: Diminished ovarian reserve (DOR) is a daunting obstacle in in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI), leading to poor reproductive outcomes. We aim to characterize the T cell and cytokine profiles in follicular fluid (FF) and elucidate its contribution to the development of DOR. Method of study: A total of 92 infertile women were enrolled in the study. We assessed the ultrastructure, proliferation, and apoptosis of granulosa cells (GCs). The levels of CCL5 and cytokines in FF was measured. Additionally, we classified the T cells and analyzed cytokines production in T cell. We further verified whether CCL5 can recruit specific T cell subcytes to the follicles. Results: Cytoplasmic vacuolization, nucleolar dissociation, partial shortening, swelling, and fusion of mitochondrial cristae were obvious in GCs with DOR. The proliferation of GCs decreased and the proportion of apoptosis increased in DOR. The down‐regulation of Bcl‐2 and up‐regulation of caspase3 were seen in GCs with DOR. The number of CD8+ T cells and proportion of CD8+ /CD4+ T cells in DOR exceeded the control. Higher positive percentage of CD69, CCR5, and IFN‐γ in CD8+ T cells, lower positive percentage of IL‐10 in CD4+ T cells and PD‐1 in CD8+ T cells were detected in DOR. CCL5 accumulated promoting the recruitment of CD8+ T cells to the follicles on interaction with CCR5. Conclusion: The abnormal proportion of CD8+ T cells and elevated CCL5 and IFN‐γ may change the immune balance in FF and impair the growth of GCs, which in turn fuel the progression of DOR. [ABSTRACT FROM AUTHOR]

Renal fibrosis is a common pathological feature of progressive chronic kidney disease (CKD). It is indicated that transforming growth factor‐β1 (TGF‐β1) plays as a central mediator in renal fibrosis. The present study aimed to investigate the role of δ‐opioid receptor (DOR) on renal fibrosis of the rat renal proximal tubular epithelial cell line (NRK‐52E) induced by TGF‐β1 and to elucidate its underlying mechanism, as well as its involvement in signaling pathways. Cells were treated with TGF‐β1 (10 ng·mL−1), along with a specific DOR agonist (UFP‐512) or naltrindole (a DOR antagonist). Cell viability and morphology, as well as cell migration, were measured after drug administration. Western blotting was employed to examine the extracellular matrix (ECM) protein Fibronectin, and the tubular epithelial–mesenchymal transition (EMT) markers (E‐cadherin and α‐smooth muscle actin (α‐SMA)), signal transducer (p‐Smad3), and EMT‐regulatory gene (Snail). The expression level of phosphorylated Akt and p38 was also examined. Our results showed that TGF‐β1 induced fibroblastic appearance and increased the expression of Fibronectin, α‐SMA, P‐Smad3, and Snail, while it decreased the expression of E‐cadherin in NRK‐52E cells. Moreover, TGF‐β1 induced the activation of Akt and p38 MAPK signaling pathways. DOR activation was found to efficiently block morphological changes and cell migration, as long as the expression changes of Fibronectin, E‐cadherin, α‐SMA, P‐Smad3, Snail, P‐Akt, and P‐p38 were induced by TGF‐β1. These findings suggest that DOR may serve as an antifibrotic factor for renal proximal tubule cells by inhibiting the fibrosis process via TGF‐β/Smad, Akt, and p38 MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

We construct an investor‐based measure of differences of opinion (DO) to investigate the different implications of DO between retail investors (DOR), institutional investors (DOI), and analysts (DOA) on asset pricing. Using Chinese stock data, we find that three DO measures (DOR, DOI, and DOI) are negatively related to future returns; DOI's ability to predict returns can be partly explained by DOR and DOA, whereas DOR contains incremental information not available from DOI and DOA. DOR is more strongly associated with the severe overvaluation caused by retail investors' optimism than DOI or DOA, emphasising the specific role of retail investors in China's market. We further show that DOI and DOA are the results of the differences in their information sets, whereas DOR are the results of different interpretations of public information. [ABSTRACT FROM AUTHOR]

R2776 --> 833.3 --> Alzheimer's disease (AD) is the most common form of dementia, which affects 47 million people worldwide. There are over five million AD patients over the age of 65 in the U.S. which is predicted to increase to 16 million by 2050. There are currently no approved disease‐modifying therapies for AD and attempts to prevent or slow the progression of the formation of beta‐amyloid plaques by targeting both the beta‐secretase 1 (BACE1) and gamma‐secretase enzymes have not yet achieved clinical success. Studies suggest that indirect modulation of the function of these enzymes via G‐protein coupled receptors (GPCRs) may provide a novel strategy to reduce A‐beta peptide production with potentially less side effects. Among GPCRs that influence amyloidogenesis, the delta opioid receptor (DOR), in particular, has been shown to play an important role in the trafficking and function of BACE1 and gamma‐secretase and in the production of A‐beta peptide. DOR activation increases BACE1 and gamma‐secretase activity in vitro and in a mouse model of AD, and antagonism of DOR specifically blocks the amyloidogenic pathway and efficaciously prevents AD progression in mice. These effects were demonstrated using a known DOR antagonist, naltrindole. However, the potential of DOR antagonists as therapeutic agents for AD has yet to be explored. The aim of this project is to create novel DOR antagonists via medicinal chemistry and identify the most promising lead compound based on binding, selectivity, and functional profile in vitro. Further, select a small set of the most promising compounds and evaluate the compound's ability to mitigate AD‐like pathology in vivo using APP/PS double‐transgenic mice. We report here the identification of several selective DOR antagonists with low nanomolar affinity/potency that have been shown to block BACE1 activity in vitro. Lead compound SRI‐22136, showed systemic stability and blood brain barrier penetration using the in vivo tail flick assay in CD‐1 mice. SRI‐22136 also showed efficacy in Novel Object Recognition (NOR) behavioral studies and in brain histological analysis studies we observed greater reduction in the AD pathological markers at a dose of 1mg/kg twice daily for 90 days continuous treatment in vivo using the APP/PS AD model double‐transgenic mice. Also, in our brain histological analysis the compound exhibited greater efficacy in reduction of the AD pathology markers such as Aβ signal, and secondary inflammation and activated glia detected by GFAP (astrocytes) and CD11b (microglia) in APP/PS AD model double‐transgenic mice. We further report our progress in testing this compound's effect on biochemical marker evaluation using the cortex and hippocampus regions of the APP/PS AD model double‐transgenic mice. [ABSTRACT FROM AUTHOR]

The 131 days long, high-precision light curves observed in the CoRoT exo-field during LRa01 were investigated for γ Dor and δ Sct-γ Dor hybrid stars. In total 418 γ Dor and 274 δ Sct-γ Dor hybrid candidates were identified. For a fraction of these candidates spectra are available obtained at the Anglo-Australian Observatory. Effective temperatures and surface gravity were derived by fitting synthetic spectra of three Balmer lines, i.e. Hα, Hβ, and Hγ, as well as of the Ca K line at 3933 °A. The bona fide γ Dor and hybrid stars were plotted in an Teff- log g diagram that shows the expected concentration of γ Dor stars at the cool border of the δ Sct strip. In contrast, the hybrids fill the whole δ Sct instability strip without a noticeable concentration. Remarkably, the fraction of constant stars, with no signal above 3 times the noise level, is smallest in the same temperature regime (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Background: Pseudomonas aeruginosa as an opportunistic pathogen produces several virulence factors. This study evaluated the relative frequency of exoenzymes (exo) A, U and S genes and integron classes (I, II, and III) among multi‐drug‐resistant clinical P. aeruginosa isolates from burn patients in Ahvaz, southwest of Iran. Methods: In this cross‐sectional study P. aeruginosa isolates were recovered from 355 wound samples. The antimicrobial susceptibility test was done by disk agar diffusion method on Muller‐Hinton agar according to the Clinical and Laboratory Standards Institute. MDR isolates were defined if they showed simultaneous resistance to 3 antibiotics. Extensively drug‐resistant was defined as nonsusceptibility to at least one agent in all but two or fewer antimicrobial categories. The presence of class I, II, and III integrons and virulence genes was determined using a PCR assay on extracted DNA. Results: Overall, 145 clinical P. aeruginosa isolates were confirmed with biochemical and PCR tests. Overall, 35% (52/145) of the isolates were taken from males and 64% (93/145) from female hospitalized burn patients. The highest resistance rates of P. aeruginosa isolates to antibiotics were related to piperacillin 59% (n = 86/145) and piperacillin‐tazobactam 57% (n = 83/145). A total of 100% of isolates were resistant to at least one antibiotic. MDR and XDR P. aeruginosa had a frequency of 60% and 29%, respectively. The prevalence of integron classes I, II, and III in P. aeruginosa was 60%, 7.58%, and 3.44%, respectively. IntI was more common in MDR and XDR P. aeruginosa isolates. In addition, 70(48%) of P. aeruginosa isolates did not harbor integron genes. Besides, exoA, exoS, and exoU in P. aeruginosa had a frequency of 55%, 55%, and 56%, respectively. Conclusion: It was found that P. aeruginosa as a potent pathogen with strong virulence factors and high antibiotic resistance in the health community can cause refractory diseases in burn patients. [ABSTRACT FROM AUTHOR]

Background: Mantle cell lymphoma (MCL) is a type of B‐cell lymphoma that is currently incurable. Pirtobrutinib shows promising response rates in heavily pretreated MCL patients according to the approval study, but the real‐world data are scarce. Methods: In this study, we retrospectively analyzed the efficacy and safety profile of pirtobrutinib in 10 relapsed/refractory MCL patients from compassionate use program (CUP). Results: On average, the patients underwent three lines of systemic therapy prior to pirtobrutinib and were predominantly BTKi exposed (9/10). The best overall response rate (BORR) was 67%. In a median follow‐up of 8.6 months, the mean duration of response (DOR), progression‐free survival (PFS), and overall survival (OS) were not reached. No new safety signals were documented. Conclusions: In summary, pirtobrutinib represented a safe and effective treatment option in a small real‐world population. [ABSTRACT FROM AUTHOR]

Summary: Parkinson's disease (PD) is a common degenerative neurological disease leading to a series of familial, medical, and social problems. Although it is known that the major characteristics of PD pathophysiology are the dysfunction of basal ganglia due to injury/loss of dopaminergic neurons in the substantia nigra pars compacta dopaminergic and exhaustion of corpus striatum dopamine, therapeutic modalities for PD are limited in clinical settings up to date. It is of utmost importance to better understand PD pathophysiology and explore new solutions for this serious neurodegenerative disorder. Our recent work and those of others suggest that the delta‐opioid receptor (DOR) is neuroprotective and serves an antiparkinsonism role in the brain. This review summarizes recent progress in this field and explores potential mechanisms for DOR‐mediated antiparkinsonism. [ABSTRACT FROM AUTHOR]

A distinguishing feature of MAX phases and their MXene derivatives is their remarkable chemical diversity. This diversity, coupled with the 2D nature of MXenes, positions them as outstanding candidates for a wide range of electrochemical applications. Chemical disorder introduced by a solid solution can improve electrochemical behavior. Up to now, adding considerable amount of tungsten (W) in MAX phase and MXenes solid solutions, which can enhance electrochemical performance, proved challenging. In this study, the synthesis of M site Ti1‐xWx solid solution MAX phases are reported. The 211‐type (Ti1‐xWx)2AlC exhibits a disordered solid solution, whereas the 312‐type (Ti1‐xWx)3AlC2 displays a near‐ordered structure, resembling o‐MAX, with W atoms preferentially occupying the outer planes. Solid‐solution MXenes, Ti2.4W0.6C2Tz, and Ti1.6W0.4CTz, are synthesized via selective etching of high‐purity MAX powder precursors containing 20% W. These MXenes are evaluated as sodium‐ion battery anodes, with Ti1.6W0.4CTz showing exceptional capacity, outperforming existing multilayer MXene chemistries. This work not only demonstrates the successful integration of W in meaningful quantities into a double transition metal solid solution MAX phase, but also paves the way for the development of cost‐effective MXenes containing W. Such advancements significantly widen their application spectrum by fine‐tuning their physical, electronic, mechanical, electrochemical, and catalytic properties. [ABSTRACT FROM AUTHOR]

The Kalahari Basin in southern Africa, shaped by subsidence and epeirogeny, features the Okavango Rift Zone (ORZ) as a significant structural element characterized by diffused extensional deformation forming a prominent depocenter. This study elucidates the Pleistocene landscape evolution of the ORZ by examining the chronology of sediment formation and filling this incipient rift and its surroundings. Modeling of cosmogenic nuclide concentrations in surficial eolian sand from distinct structural blocks around the ORZ provides insights into sand's residence time on the surface. Sand formation occurred from ∼2.2 to 1.1 Ma, coinciding with regional tectonic events. Notably, provenance analyses of sand within ORZ's lowermost block where large alluvial fans are found indicate different source rocks and depositional environments than those of the eolian sands found at a higher elevation. This suggests that the major phase of rift subsidence and the following incision of alluvial systems into the rift occurred after eolian dune formation. Luminescence dating reveals that deposition in alluvial fan settings in the incised landscape began not later than ∼250 ka, and that a lacustrine environment existed since at least ∼140 ka. The established chronological framework constrains the geomorphological effects of the different tectono‐climatic forces that shaped this nascent rifting area. It highlights two pronounced stages of landscape development, with the most recent major deformation event in the evolving rift probably occurring during the middle Pleistocene transition (1.2–0.75 Ma). This event is reflected as a striking change in the depositional environments due to the configurational changes accompanying rift progression. Plain Language Summary: Early rifting stages mark the beginning of the breakup of continents, making them crucial for understanding plate tectonics and the formation of extensional landscapes. These stages involve seismic activity and create unique environments, helping to assess geological hazards and study past habitats and biodiversity. Early stages of continental rifting in the Okavango Rift Zone, centered in northern Botswana, are described in this work from the perspective of sediment dynamics by constructing a time frame for their evolution. Two major types of sediment and their corresponding time scales are studied. The older sediments are eolian sands that were formed between ∼2.2 and 1.1 million years ago and lie today on elevated structural surfaces above the incised rift. Within the subsiding rift that was significantly geomorphologically modified not earlier than 1 million years ago, sediments were deposited by alluvial fans at least since 250 thousand years ago and were followed by a lacustrine environment with alternating hydrological conditions since at least 140 thousand years ago. Key Points: Nascent continental rifting stages are reflected through sedimentological variationsEolian sand that was formed before alluvial incision into the rift is preserved on elevated surfacesDepositional environments in the incised rift have shifted into alluvial‐lacustrine conditions around the Middle Pleistocene Transition [ABSTRACT FROM AUTHOR]

The article lists the guest reviewers to whom author wants to acknowledge including Daniel Casasanto, Dor Abrahamson and Darren Abramson.

Conventional and no net flux microdialysis were used to quantify basal and morphine-induced extracellular dopamine (DA) levels and the basal extraction fraction, which provides an estimate of the rate of DA uptake, in the nucleus accumbens (NAc) of wild-type mice and those with a constitutive deletion of mu (MOR)- or delta (DOR)-opioid receptors. Locomotor activity was assessed in these same animals. No difference between genotypes in basal dialysate DA levels was seen. No net flux studies revealed significant decreases in the DA extraction fraction in both MOR- and DOR-knockout mice, indicating decreased basal DA uptake in both genotypes. Extracellular DA, however, was unchanged. Because extracellular neurotransmitter levels are determined by the dynamics of both release and uptake, these findings provide suggestive evidence that basal DA release is decreased in mutant mice. Systemic administration of morphine significantly increased locomotor activity and dialysate DA levels in wild-type mice. MOR-knockout mice failed to exhibit a behavioural response to morphine. The ability of morphine to increase DA levels, however, was reduced but not prevented. No alteration in the effects of morphine was observed in DOR-knockout mice. These data provide genetic evidence for the existence of tonically active MOR and DOR systems that modulate basal DA neurotransmission in the NAc. Furthermore, they demonstrate that in contrast to the locomotor-activating effects of morphine, a small component of morphine-evoked DA release occurs independently of MOR activation. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine if the non‐convulsant delta‐opioid receptor (DOR) agonist, KNT‐127, could inhibit migraine‐associated endpoints. Background: The DOR has been identified as a therapeutic target for migraine. However, the development of delta agonists is limited as some ligands have seizurogenic properties, which may be related to their ability to induce receptor internalization. While both pro‐ and non‐convulsant delta agonists can reduce migraine‐associated allodynia, only the proconvulsant agonist, SNC80, has been shown to decrease cortical spreading depression (CSD). It is unclear if the ability of delta agonists to modulate cortical activity is related to the same signaling mechanisms that produce proconvulsant effects. Methods: The effects of the non‐convulsant delta agonist, KNT‐127, were examined. Repetitive CSD was induced in female C57BL6/J (n = 6/group) mice by continuous application of KCl and the effect of KNT‐127/vehicle (Veh) on both local field potentials and optical intrinsic signals was determined. To assess the effect of KNT‐127 on established chronic migraine‐associated pain, male and female C57BL6/J mice were treated with nitroglycerin (NTG; 10 mg/kg, ip) every other day for 9 days and tested with KNT‐127 (5 mg/kg, sc) or Veh on day 10 (n = 6/group). DOR‐enhanced green fluorescent protein mice (n = 4/group) were used to confirm the internalization properties of KNT‐127 in the trigeminal ganglia, trigeminal nucleus caudalis, and somatosensory cortex. Results: KNT‐127 inhibited CSD events (t(10) = 3.570, p = 0.0051). In addition, this delta agonist also reversed established cephalic allodynia in the NTG model of chronic migraine (F(1, 20) = 12.80, p < 0.01). Furthermore, KNT‐127 caused limited internalization of DOR in key migraine processing regions. Conclusions: This study shows that the antimigraine effects of DOR agonists can be separated from their proconvulsant effects. This data provides valuable information for the continued development of delta agonists for the treatment of migraine. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate whether elevating levels of enkephalin by inhibiting their degradation can attenuate stress‐induced migraine‐like behaviors in mice. Background: Previous studies in animals have suggested the delta opioid receptor (DOR) as a novel migraine target. The primary endogenous ligands for DOR are enkephalins and their levels can be increased by pharmacological inhibition of enkephalinases; however, it is not clear whether enkephalinase inhibition can be efficacious in preclinical migraine models through activation of DOR or whether other opioid receptors might be involved. Further, it is not clear whether opioid receptors in the central nervous system are necessary for these effects. Methods: This study used a model of repetitive restraint stress in mice that induces periorbital hypersensitivity and priming to the nitric oxide donor sodium nitroprusside (SNP; 0.1 mg/kg). Von Frey filaments were used to measure periorbital mechanical thresholds and grimace scores were evaluated by observing mouse facial features. Animals were treated with the dual enkephalinase inhibitor (DENKI) PL37. Results: On day two post‐stress, PL37 given to mice via either intravenous injection (10 mg/kg) or oral gavage (20 mg/kg) significantly attenuated stress‐induced periorbital hypersensitivity and facial grimace responses. Additionally, both intravenous (10 mg/kg) and oral gavage (20 mg/kg) of PL37 prior to SNP (0.1 mg/kg) administration on day 14 post‐stress significantly reduced SNP‐induced facial hypersensitivity. Injection of the DOR antagonist naltrindole (0.1 mg/kg) but not the mu‐opioid receptor antagonist CTAP (1 mg/kg) prior to PL37 treatment blocked the effects. Finally, pretreatment of mice with the peripherally restricted opioid receptor antagonist naloxone methiodide (5 mg/kg) blocked the effects of PL37. Conclusions: These data demonstrate that inhibiting enkephalinases, and thus protecting enkephalins from degradation, attenuates stress‐induced migraine‐like behavior via activation of peripheral DOR. Peripheral targeting of endogenous opioid signaling may be an effective therapeutic strategy for migraine. [ABSTRACT FROM AUTHOR]

R3083 --> Buprenorphine is an approved method of treatment for opioid use disorder (OUD), and it is under investigation for cocaine use disorder‐‐ for which there are no FDA‐approved, pharmacological treatments. Buprenorphine is considered a mixed efficacy opioid ligand, and its partial agonist activity at the mu opioid receptor (MOR) is thought to mediate the therapeutic effects for OUD. There is also evidence that it acts as a kappa opioid receptor (KOR) and delta opioid receptor (DOR) antagonist and a nociception/orphanin FQ receptor (NOPR) agonist. However, one recent report found buprenorphine to act as a partial DOR agonist in cells expressing human opioid receptors (Bidlack et al., 2018). The goal of the present study was to investigate the in vivo activity of buprenorphine at DOR in rodents. Male C57BL6/N mice were used to evaluate the effects of buprenorphine on pentylenetetrazol (PTZ)‐induced convulsive activity and in the mouse forced swim test. Buprenorphine did not produce overt convulsions in mice but dose‐dependently increased PTZ‐induced convulsions with 32 mg/kg buprenorphine as the maximally effective dose, and these effects were attenuated by the DOR antagonist naltrindole. Also, buprenorphine (0.01‐0.1 mg/kg) decreased immobility in the mouse forced swim test, which was blocked by pretreatment with naltrindole. Together, these data demonstrate that buprenorphine produces DOR‐mediated antidepressant‐like effects and potentiates PTZ‐induced convulsions, suggesting that buprenorphine acts as a partial DOR agonist in mice. Interestingly, there is a large separation between doses that produce potential antidepressant‐like effects and pro‐convulsive effects. Future studies will investigate whether this large separation between DOR‐mediated effects are due to the complex pharmacology of buprenorphine. Further, these data offer additional insight into the activity of buprenorphine, which could help elucidate the mechanism needed for successful treatment of opioid or cocaine use disorder. These studies were supported in part by R21 DA041565 and DA007315. [ABSTRACT FROM AUTHOR]

We analyze the asynchronous version of the DeGroot dynamics: In a connected graph G$$ G $$ with n$$ n $$ nodes, each node has an initial opinions in [0,1]$$ \left[0,1\right] $$ and an independent Poisson clock. When a clock at a node v$$ v $$ rings, the opinion at v$$ v $$ is replaced by the average opinion of its neighbors. It is well known that the opinions converge to a consensus. We show that the expected time 피(τε) to reach ε$$ \varepsilon $$‐consensus is poly(n)$$ (n) $$ in undirected graphs and in Eulerian digraphs, but for some digraphs of bounded degree it is exponential. Our main result is that in undirected graphs and Eulerian digraphs, if the degrees are uniformly bounded and the initial opinions are i.i.d., then 피(τε)=polylog(n) for every fixed ε>0$$ \varepsilon >0 $$. We give sharp estimates for the variance of the limiting consensus opinion, which measures the ability to aggregate information ("wisdom of the crowd"). We also prove generalizations to non‐reversible Markov chains and infinite graphs. New results of independent interest on fragmentation processes and coupled random walks are crucial to our analysis. [ABSTRACT FROM AUTHOR]

An important limitation in the clinical use of opiates is progressive loss of analgesic efficacy over time. Development of analgesic tolerance is tightly linked to receptor desensitization. In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the membrane. In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. A first series of experiments demonstrated that agonist binding activates Src and destabilizes a constitutive complex formed by the spontaneous association of DORs with the kinase. Src contribution to DOR desensitization was then established by showing that pre-treatment with Src inhibitor PP2 (20 μM; 1 hr) or transfection of a dominant negative Src mutant preserved DOR signalling following sustained exposure to an agonist. This protection was afforded without interfering with endocytosis, but suboptimal internalization interfered with PP2 ability to preserve DOR signalling, suggesting a post-endocytic site of action for the kinase. This assumption was confirmed by demonstrating that Src inhibition by PP2 or its silencing by siRNA increased membrane recovery of internalized DORs and was further corroborated by showing that inhibition of recycling by monensin or dominant negative Rab11 (Rab11S25N) abolished the ability of Src blockers to prevent desensitization. Finally, Src inhibitors accelerated recovery of DOR-Gαi3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors. [ABSTRACT FROM AUTHOR]

Objective: We have retrospectively analyzed the early and the mid-term results of the operations for modified endoventricular circular patch plasty for left ventricular aneurysm (LVA) repair in our clinic., Patients and Methods: Sixty-seven cases with anterior LVA were included in the study. Mean age of the patients were 64.8 +/- 8.9 (ranged from 51 to 74) years. Fifty-three patients were male and 14 female (M:F = 3.8). Preoperative left ventricular ejection fraction (LVEF) was 30.8% +/- 4.5%, LV end-diastolic diameter (LVEDD) 6.0 +/- 1.9 cm, and end-systolic diameter (LVESD) was 4.6 +/- 0.8 cm in average. Coronary revascularization was performed in 61 patients and mitral ring annuloplasty in five patients., Results: Thirty-day mortality was 5.9%. The surviving 63 patients were followed up for 4.3 +/- 2.3 years on average (ranged from 0.2 to 8.5 years), adding up to 267.8 patient/years. In the immediate postoperative and long-term follow-up, there was a significant improvement in LVEF, LVESD, LVEDD, and mitral valvular function. Four patients died in the follow-up with only a single patient due to cardiac causes. The five years survival was 87.7% +/- 4.1% and the freedom from cardiac death was 98.2% +/- 1.7%., Conclusion: LVA repair with Dor procedure can be performed with low mortality. With appropriate repair of LVA and coronary revascularization, patients may have benefit both for survival and also for clinical status.

Aims To define the relative antitussive effect of dextromethorphan (DEX) and its primary metabolite dextrorphan (DOR) after administration of DEX. Methods Data were analysed from a double-blind, randomized cross-over study in which 22 subjects received the following oral treatments: (i) placebo; (ii) 30 mg DEX hydro-bromide; (iii) 60 mg DEX hydro-bromide; and (iv) 30 mg DEX hydro-bromide preceded at 1 h by quinidine HCl (50 mg). Cough was elicited using citric acid challenge. Pharmacokinetic data from all non-placebo arms of the study were fitted simultaneously. The parameters were then used as covariates in a link PK–PD model of cough suppression using data from all treatment arms. Results The best-fit PK model assumed two- and one-compartment PK models for DEX and DOR, respectively, and competitive inhibition of DEX metabolism by quinidine. The intrinsic clearance of DEX estimated from the model ranged from 59 to 1536 l h-1 , which overlapped with that extrapolated from in vitro data (12–261 l h-1 ) and showed similar variation (26- vs. 21-fold, respectively). The inhibitory effect of quinidine ([I]/Ki) was 19 (95% confidence interval of mean: 18–20) with an estimated average Ki of 0.017 µM. Although DEX and DOR were both active, the potency of the antitussive effect of DOR was 38% that of DEX. A sustained antitussive effect was related to slow removal of DEX/DOR from the effect site (ke0 = 0.07 h-1 ). Conclusions Physiologically based PK modelling with perturbation of metabolism using an inhibitor allowed evaluation of the antitussive potency of DOR without the need for separate administration of DOR. [ABSTRACT FROM AUTHOR]

Sand transport and its deposition in deep marine basins are controlled by diverse climatic, tectonic, physiographic and oceanographic processes. Disentangling the impact of each of these drivers on the sedimentary record is a fundamental challenge in the study of source to sink systems. In this study, we investigate seismic and borehole data by combining statistical and spectral analyses to identify the factors controlling sand deposition in the deep Levant Basin (Eastern Mediterranean) during the Pliocene–Quaternary (PQ). We interpret the sand content in boreholes from gamma ray (GR) logs and identify two major trends in sand/shale ratios. On a million‐year scale, we demonstrate that since the Early Pliocene (5.3 Ma), sand content gradually increased until it formed a ca. 100 m thick and widespread sheet of sand at the top of the section. On a shorter time scale, we identify oscillations in sand content depicting significant power of periodic components at the 350–450 ky, 90–150 ky and 10s ky bands. The long‐term increase in sand content reaching the deep Levant Basin is interpreted as a result of the Nile Delta propagation, which had continuously shortened the distance between the edge of the Nile delta that is the source of sand, and the deep Levant Basin. The superimposed short‐term oscillations are interpreted as Milanković cycles, reflecting hydroclimatic oscillations of water and sediment discharge into the Eastern Mediterranean Sea by the Nile River. This demonstrates the hydroclimatic control on sand deposition in the deep Levant Basin. Our observations are consistent with the development of a submarine channel system along with the accretion of the Nile delta, which may have served as a pathway for sand delivery via high‐energy turbidity currents that reached the Levant Basin. [ABSTRACT FROM AUTHOR]

Background: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri‐operative and post‐operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice‐cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS). Methods: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single‐blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three‐time intervals post‐HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function. Results: The incidence of IRI at weeks 1, 4, and 8 post‐HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow‐up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor‐specific antibodies and overall survival between the groups. Conclusion: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool. [ABSTRACT FROM AUTHOR]

Photon‐number‐splitting (PNS) is a well‐known theoretical attack on quantum key distribution (QKD) protocols that employ weak coherent states produced by attenuated laser pulses. However, beyond the fact that it has not yet been demonstrated experimentally, its plausibility and effect on quantum bit error rate are questioned. In this work, an experimental scheme is presented for PNS attack employing demonstrated technological capabilities, specifically a single‐photon Raman interaction (SPRINT) in a cavity‐enhanced three‐level atomic system. Several aspects of the proposed implementation are addressed, analytically and simulatively, and the eavesdropper's information gain by the attack is calculated. Furthermore, it is analytically shown that the scheme results in a small (yet non‐zero) quantum bit error rate, and a comparison to purely theoretical analyses in the literature is presented. It is believed that the inherent nonlinearity of the PNS attack unavoidably affects the optical modes sent to the receiver, and accordingly will always result in some error rate. [ABSTRACT FROM AUTHOR]

The current study explored longitudinally whether oxytocin receptor gene methylation (OXTRm) changes moderated the association between parental sensitivity changes and children's attachment changes over three waves. Six hundred six Flemish children (10–12 years, 42.8%–44.8% boys) completed attachment measures and provided salivary OXTRm data on seven CpG sites. Their parents reported their sensitive parenting. Results suggest that OXTRm changes hardly link to attachment (in)security changes after the age of 10. Some support was found for interaction effects between parental sensitivity changes and OXTRm changes on attachment changes over time. Effects suggest that for children with increased OXTRm in the promotor region and decreased methylation in the inhibitor region over time, increased parental sensitivity was associated with increased secure attachment and decreased insecure attachment over time. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is aggressive type of hematological malignancy. Its poses challenges in early diagnosis, necessitating the identification of an effective biomarker. This study aims to assess the diagnostic accuracy of long noncoding RNAs (lncRNA) in the diagnosis of AML through a meta‐analysis. The study is registered on the PROSPERO website with the number 493518. Method: A literature search was conducted in the PubMed, Embase, Hinari, and the Scopus databases to identify relevant studies. We pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristics (ROC) using Stata 14.1 software. Heterogeneity between studies was determined through the I2 statistic and Cochran‐Q test. A random effect model was chosen due to significant heterogeneity among included studies. Meta‐regression and subgroup analysis were performed to assess the potential source of heterogeneity. Furthermore, potential publication bias was estimated using Deek's funnel plot asymmetry test. Results: A total of 14 articles covering 19 studies were included in this meta‐analysis comprising 1588 AML patients and 529 healthy participants. The overall pooled sensitivity, specificity, PLR, NLR, DOR, and the area under the summary ROC curve were 0.85 (95% CI = 0.78–0.91), 0.82 (95% CI = 0.72–0.89), 4.7 (95% CI = 2.9–7.4), 0.18 (95% CI = 0.12–0.28), 26 (95% CI = 12–53), and 0.90 (95% CI = 0.87–0.93), respectively. Moreover, lncRNAs from non‐bone marrow mononuclear cells (BMMC) had superior diagnostic value with pooled sensitivity, specificity, and AUC were 0.93, 0.82, and 0.95, respectively. Conclusion: This meta‐analysis demonstrated that circulating lncRNAs can serve as potential diagnostic markers for AML. High accuracy of diagnosis was observed in non‐BMMC lncRNAs, given cutoff value, and the GADPH internal reference gene used. However, further studies with large sample size are required to confirm our results. [ABSTRACT FROM AUTHOR]

Background and Aims: Multidrug and extensive drug‐resistant Pseudomonas aeruginosa was extracted from burn patients referring to burn centers in southwest Iran so that biofilm generation and antibiotic resistance could be investigated. Methods: A specific primer was used to confirm all our considered 110 P. aeruginosa culture‐positive reports on 345 burn patients. The resistance of P. aeruginosa to seven antibiotics and Colistin with minimum inhibitory concentration (MIC) was assessed. Biofilm formation was assessed by the phenotypic study of specimens under Congo red agar and microtiter plate assays. Results: One hundred and 10 clinical P. aeruginosa isolates taken from burn wound infections were validated. Among P. aeruginosa isolates, Piperacillin, Ceftazidime, Maeropenem, Gentamycin, and Gatifloacin had the highest resistance to antibiotics, while Ticarcillin‐Clavulanic acid and Ceftolozane‐Tazobactam showed the least resistance. MICs were then evaluated via the E test. Seven isolates were resistant to colistin. Colistin reference MICs for multidrug‐resistant P. aeruginosa prevalence was 38%, while it was 22% for extensively drug‐resistant (XDR) P. aeruginosa. One P. aeruginosa was pandrug‐resistant (PDR). Under Congo red agar test, 66 isolates (67%) formed biofilms and black colonies, whereas 44 isolates (50%) had red colonies. In MTP, 76% formed biofilm. 40%, 32%, 21% of the isolates were strong, moderate, and weak biofilm formers, respectively, while 43% did not form biofilms. Conclusion: The P. aeruginosa resistance to antimicrobial agents has largely challenged the control of the infection. Accordingly, a higher resistance occurred when the isolates were transferred to the patients. Less than 50% P. aeruginosa samples generated strong biofilms. Consequently, hygienic measurements are essential to inhibit P. aeruginosa transmission to hospitalized patients. [ABSTRACT FROM AUTHOR]

We consider the hyperbolic relaxation of the viscous Cahn-Hilliard equation with a symport term. This equation is characterized by the presence of the additional inertial term τDΦtt that accounts for the relaxation of the diffusion flux. We suppose that τD is dominated by the viscosity coefficient δ. Endowing the equation with Dirichlet boundary conditions, we show that it generates a dissipative dynamical system acting on a certain phase-space, depending on τD. This system is shown to possess a global attractor that is upper semicontinuous at τD = δ = 0. Then, we construct a family of exponential attractors ℑτD,δ which is a robust perturbation of an exponential attractor of the Cahn-Hilliard equation; namely, the symmetric Hausdorff distance between ℑτD,δ and ℑ0,0 tends to 0 as (τD,δ) tends to (0,0) in an explicitly controlled way. Finally, we present numerical simulations of the time evolution of weak solutions as a function of parameters. [ABSTRACT FROM AUTHOR]