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Background: In the surgical management of GERD, the traditional procedure is laparoscopic total (Nissen) fundoplication. However, partial fundoplication has been advocated as providing similar reflux control while potentially minimizing dysphagia. The comparative outcomes of different approaches to fundoplication are a topic of ongoing debate and long-term outcomes remain uncertain. This study aims to compare long-term gastroesophageal reflux disease (GERD) related outcomes following different fundoplication procedures. Methods: MEDLINE, EMBASE, PubMed, and CENTRAL databases were searched up to November 2022 to identify randomized controlled trials (RCTs) comparing different types of fundoplications reporting long-term (> 5 years) outcomes. The primary outcome was incidence of dysphagia. Secondary outcomes included incidence of heartburn/reflux, regurgitation, inability to belch, abdominal bloating, reoperation, and patient satisfaction. DataParty, which uses Python 3.8.10 was used to perform the network meta-analysis. We evaluated the overall certainty of evidence with the GRADE framework. Results: 13 RCTs were included, with 2063 patients across Nissen (360°), Dor (anterior 180°–200°), and Toupet (posterior 270°) fundoplications. Network estimates demonstrated that Toupet had lower incidence of dysphagia compared to Nissen (OR 0.285; 95% CrI 0.06–0.958). There were no differences in dysphagia between Toupet and Dor (OR 0.473, 95% CrI 0.072–2.835) or between Dor and Nissen (OR 1.689, 95% CrI 0.403–7.699). The three fundoplication types were comparable in all other outcomes. Conclusions: All three approaches of fundoplication share similar long-term outcomes, with the Toupet fundoplication likely providing the best long-term durability with lowest odds of developing postoperative dysphagia. [ABSTRACT FROM AUTHOR]

This study aims to assess the impact of endometrioma on embryo quality and cycle outcome in patients who undergo assisted reproductive technology (ART) treatment due to diminished ovarian reserve (DOR). Retrospective case–control study was conducted in women ≤ 40 years of age who underwent ART treatment caused by DOR, defined according to POSEIDON criteria, at a university-based infertility clinic between January 2015 and December 2020. Three groups of patients were selected: group A included patients with an idiopathic DOR, group B included patients with endometrioma(s) who underwent ovarian cystectomy, and group C included patients with endometrioma(s) without surgical treatment. A total of 351 women with DOR were included in the final analysis. Demographic characteristics, including age and AMH, were similar between the groups. Significant differences were observed among groups on mean number of MII oocytes retrieved (1.88 ± 1.59 vs. 2.84 ± 2.89 vs. 2.78 ± 2.41, respectively; p < 0.001) and mean number of embryos (1.04 ± 1.18 vs. 1.87 ± 2.01 vs. 1.66 ± 1.81, respectively; p < 0.001). However, the mean number of top-quality embryos, cycle cancellation, and live birth rates were similar between the groups. Clinical pregnancy (35 (26.5%) vs. 8 (18.2%) vs. 18 (42.9%), respectively; p = 0.038) and miscarriage rates (12 (9.1%) vs. 0 vs. 8 (19.0%), respectively; p = 0.009) were higher in endometrioma group without surgery. Women with DOR appear to have similar ART cycle outcomes regardless of the etiology, in terms of live birth rates. Infertility of endometrioma patients might be related to altered endometrium rather than to decreased oocyte quality. Cystectomy for endometrioma before IVF did not seem to affect the LBR. [ABSTRACT FROM AUTHOR]

Purpose: Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years. However, the etiology of approximately 90% patients remains unknown. Diminished ovarian reserve (DOR) and poor ovarian response (POR) are related to POI in clinic. The main purpose of this review was to evaluate the roles of microRNAs (miRNAs) in the pathogenesis and therapeutic potential for POI, DOR and POR. Methods: A literature search was conducted using six databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and Wangfang Data) to obtain relevant studies. Results: This review enlightens expression profiles and functional studies of miRNAs in ovarian insufficiency in animal models and humans. Functional studies emphasized the role of miRNAs in steroidogenesis, granulosa cell proliferation/apoptosis, autophagy and follicular development by regulating target genes in specific pathways, such as the PI3K/AKT/mTOR, TGFβ, MAPK and Hippo pathways. Differentially expressed circulating miRNAs provided novel biomarkers for diagnosis and prediction, such as miR-22-3p and miR-21. Moreover, exosomes derived from stem cells restored ovarian function through miRNAs in chemotherapy-induced POI models. Conclusion: Differential miRNA expression profiles in patients and animal models uncovered the underlying mechanisms and biomarkers of ovarian insufficiency. Exosomal miRNAs can restore ovarian function against chemotherapy-induced POI, which needs further investigation to develop novel preventive and therapeutic strategies in clinical practice. [ABSTRACT FROM AUTHOR]

Background: The end-stage achalasia is a difficult condition to treat, for the esophageal diameter and conformation of the gullet, that may progress to a sigmoid shape. The aim of this study was to examine the outcome of Laparoscopic Heller-Dor in patients with end-stage achalasia, comparing them with patients who had mega-esophagus without a sigmoid shape. Methods: From 1992 to 2020, patients with a diagnosis of sigmoid esophagus, or radiological stage IV achalasia (the SE group), and patients with a straight esophagus larger than 6 cm in diameter, or radiological stage III achalasia (the NSE group), were all treated with LHD. The two groups were compared in terms of patients' symptoms, based on the Eckardt score, and on barium swallow, endoscopy and manometry performed before and after the treatment. The failure of the treatment was defined as an Eckardt score > 3, or the need for further treatment. Results: The study involved 164 patients: 73 in the SE group and 91 in the NSE group. No intra- or postoperative mortality was recorded. The median follow-up was 51 months (IQR 25–107). The outcome was satisfactory in 71.2% of patients in the SE group, and in 89% of those in the NSE group (p = 0.005). Conclusions: SE is certainly the worst condition of the disease and the final outcome of LHD, in term of symptom control, is inferior compared to NSE. Despite this, almost 3/4 of the SE patients experienced a significant relieve in symptoms after LHD, which may therefore still be the first surgical option to offer to these patients, before considering esophagectomy. [ABSTRACT FROM AUTHOR]

As online social media platforms continue to proliferate, users are faced with an overwhelming amount of information, making it challenging to filter and locate relevant information. While personalized recommendation algorithms have been developed to help, most existing models primarily rely on user behavior observations such as viewing history, often overlooking the intricate connection between the reading content and the user's prior knowledge and interest. This disconnect can consequently lead to a paucity of diverse and personalized recommendations. In this paper, we propose a novel approach to tackle the multifaceted issue of recommendation. We introduce the Dual-Observation-based approach for the Recommendation (DOR) system, a novel model leveraging dual observation mechanisms integrated into a deep neural network. Our approach is designed to identify both the core theme of an article and the user's unique engagement with the article, considering the user's belief network, i.e., a reflection of their personal interests and biases. Extensive experiments have been conducted using real-world datasets, in which the DOR model was compared against a number of state-of-the-art baselines. The experimental results explicitly demonstrate the reliability and effectiveness of the DOR model, highlighting its superior performance in news recommendation tasks. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory response is significant prognostic indicator in patients with various diseases. The relationship between prognostic scoring systems based on the modified Glasgow Prognostic Score (mGPS) and achalasia in patients treated with laparoscopic Heller‑myotomy with Dor‑fundoplication (LHD) remains uninvestigated. This study aimed to examine the role of mGPS in patients with achalasia. Methods: 457 patients with achalasia who underwent LHD as the primary surgery between September 2005 and December 2020 were included. We divided patients into the mGPS 0 and mGPS 1 or 2 groups and compared the patients' background, pathophysiology, symptoms, surgical outcomes, and postoperative course. Results: mGPS was 0 in 379 patients and 1 or 2 in 78 patients. Preoperative vomiting and pneumonia were more common in patients with mGPS of 1 or 2. There were no differences in surgical outcomes. Postoperative upper gastrointestinal endoscopy revealed that severe esophagitis was more frequently observed in patients with mGPS of 1 or 2 (P < 0.01). The clinical success was 91% and 99% in the mGPS 0 and mGPS 1 or 2 groups, respectively (P < 0.01). Conclusions: Although severe reflux esophagitis was more common in patients with achalasia with a high mGPS, good clinical success was obtained regardless of the preoperative mGPS. [ABSTRACT FROM AUTHOR]

Background: Manometry is the gold standard diagnostic test for achalasia. However, there are incidences where manometry cannot be obtained preoperatively, or the results of manometry is inconsistent with the patient's symptomatology. We aim to determine if intraoperative use of EndoFLIP can provide a diagnosis of achalasia and provide objective information during Heller myotomy and Dor fundoplication. Methods: To determine the intraoperative diagnostic EndoFLIP values for patients with achalasia, we determined the optimal cut-off points of the distensibility index (DI) between patients with a diagnosis of achalasia and patients with a diagnosis of hiatal hernia. To evaluate the usefulness of EndoFLIP values during Heller myotomy and Dor fundoplication, we obtained a cohort of patients with EndoFLIP values obtained after Heller myotomy and after Dor fundoplication as well as Eckardt score before and after surgery. Results: Our analysis of 169 patients (133 hiatal hernia and 36 achalasia) showed that patients with DI < 0.8 have a >99% probability of having achalasia, while DI > 2.3 have a >99% probability of having hiatal hernia. Patients with a DI 0.8–1.3 have a 95% probability of having achalasia, and patients with a DI of 1.4–2.2 have a 94% probability of having a hiatal hernia. There were 40 patients in the cohort to determine objective data during Heller myotomy and Dor fundoplication. The DI increased from a median of 0.7 to 3.2 after myotomy and decreased to 2.2 after Dor fundoplication (p < 0.001). The median Eckardt score went down from a median of 4.5 to 0 (p < 0.001). Conclusions: Our study shows that intraoperative use of EndoFLIP can facilitate the diagnosis of achalasia and is used as an adjunct to diagnose achalasia when symptoms are inconsistent. The routine use of EndoFLIP during Heller myotomy and Dor fundoplication provides objective data during the operation in a group of patients with excellent short-term outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To compare the surgical outcomes of redo laparoscopic Heller-Dor procedure and rescue peroral endoscopic myotomy for patients with failed Heller myotomy. Methods: We identified patients who had undergone redo laparoscopic Heller-Dor procedure or rescue peroral endoscopic myotomy from August 1996 to September 2019 and assessed the patients' characteristics, timed barium swallow results, symptom scores before/after surgery, surgical outcomes, and postoperative outcomes. Results: Eleven patients underwent redo laparoscopic Heller-Dor procedure, and 14 underwent rescue peroral endoscopic myotomy. Blood loss (p = 0.001) and intraoperative complications rate (p = 0.003) were lower and the operative time (p > 0.001) and observation period (p = 0.009) shorter in patients who underwent rescue peroral endoscopic myotomy than in patients who underwent redo laparoscopic Heller-Dor procedure. Patients who underwent rescue peroral endoscopic myotomy had a higher rate of postoperative reflux esophagitis (p = 0.033) than those who underwent redo laparoscopic Heller-Dor procedure. After the interventions, the dysphagia symptoms were improved for both groups. Furthermore, both groups expressed satisfaction with their respective procedures. Conclusions: Rescue peroral endoscopic myotomy was associated with better surgical outcomes than redo laparoscopic Heller-Dor for patients with failed Heller myotomy. However, rescue peroral endoscopic myotomy had higher rates of postoperative reflux esophagitis. [ABSTRACT FROM AUTHOR]

The growing number of deep space exploration missions operating simultaneously in the solar system triggers an increasing demand for large ground antennas capable of tracking distant spacecraft. Several space agencies have their own deep space tracking networks, where each antenna belonging to a ground station complex is meant to be shared among different deep space missions in flight, significantly constraining the tracking schedule. A typical ranging and Doppler radio tracking session requires long tracking passes and a single ground antenna, while angular (Delta-DOR) observations require at least two antennas but usually for much shorter tracking sessions. However, during Delta-DOR observations, the baseline between the two receiving antennas should be kept as large as possible, thus reducing the time windows in which Delta-DOR observations are actually feasible. This leaves little room for adaptation of the tracking schedules of these antennas and calls for the need for possible alternatives for the receiving stations. The antennas belonging to the very long baseline interferometry (VLBI) network worldwide meet the requirements to carry out Delta-DOR tracking sessions. Here, we present an experimental activity carried out tracking ESA's GAIA spacecraft using a mixed deep space antenna configuration involving an ESA ESTRACK antenna at New Norcia (Australia) and a VLBI antenna at Medicina (Italy). This baseline was used to form Delta-DOR observables with the aim of demonstrating that VLBI antennas offer the capability to track deep space missions, thus increasing the number of possible baselines and observation time windows. [ABSTRACT FROM AUTHOR]

Background: Achalasia is an esophageal motility disorder that presents as dysphagia and severely affects quality of life. An esophageal myotomy has been the golden standard for treatment. Peroral endoscopic myotomy (POEM) as a first-line therapy has an acceptable outcome. However, after the clinical failure of POEM, appropriate second-line therapy is rather controversial. Here, we present the first published case in English of a patient who was successfully treated using laparoscopic Heller myotomy (LHM) with Dor fundoplication following an unsuccessful POEM. Case presentation: A 64-year-old man with type 1 achalasia who had been previously treated with POEM visited our hospital for further treatment. After undergoing LHM with Dor fundoplication, his Eckardt score improved from 3 to 0 points. On a timed barium esophagogram (TBE), the barium height improved from 119 mm/119 mm (1 min/5 min) to 50 mm/45 mm. No significant complications have occurred postoperatively for 1 year. Conclusion: Treating refractory achalasia is challenging, and treatment options are controversial. LHM with Dor fundoplication after POEM could be a safe and efficient option for the treatment of refractory achalasia. [ABSTRACT FROM AUTHOR]

Diminished ovarian reserve (DOR) is an etiologically heterogeneous disorder that usually leads to poor reproductive outcomes. Does a specific or common pathogenesis exist for DOR subtypes with different etiologies? Two frequently used mouse models, age-related DOR (AR-DOR) and cyclophosphamide (CTX)-induced DOR (CTX-DOR), were successfully established, and RNA sequencing was performed on ovarian tissue samples. Differentially expressed genes (DEGs) in each subtype and common DEGs (co-DEGs) in the two subtypes were identified. Subsequently, we performed comprehensive bioinformatics analyses, including an evaluation of immune cell infiltration. Finally, the genes of interest were further validated by performing RT-qPCR and immunohistochemistry. In AR-DOR mice, functional enrichment analyses showed that upregulated DEGs were mainly involved in the inflammatory/immune response, while downregulated DEGs were involved in DNA damage repair. In CTX-DOR mice, the inflammatory/immune response and cell apoptosis played significant roles. Meanwhile, 406 co-DEGs were identified from the two models. The biological functions of these co-DEGs were associated with inflammatory/immune responses. The analysis of immune cell infiltration showed reduced infiltration of Treg cells, as well as increased infiltration of M0 macrophages, NK resting, and T cells CD4 follicular in both DOR subtypes. The results of the validation experiments were consistent with the RNA sequencing data. In conclusion, the inflammatory/immune response might be the common pathogenesis for the two DOR subtypes, while DNA repair and cell apoptosis may have different roles in the two subtypes. These results may provide potential insights for mechanistic research and therapeutic targets of DOR. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic Heller-myotomy with Dor-fundoplication (LHD) is the standard surgical treatment for achalasia; however, surgical outcomes over a period greater than 10 years have not been well-explored. The objective of this study was to evaluate the long-term outcomes of LHD for achalasia based on a single-center experience. Methods: Patients who underwent LHD between 1994 and 2019 were included. Of these, we excluded patients who had undergone foregut surgery or whose follow-up data were unavailable. Esophagogastroduodenoscopy (EGD) findings and postoperative persistent and/or recurrent symptoms had been assessed annually. Disease-free rates were calculated using Kaplan–Meier analysis. Results: A total of 530 patients (mean age 45.0 years with 267 men) were included. The median follow-up period was 50.5 months. More than 10 years' data were available in 78 patients (14.7%). The cumulative rates of freedom from dysphagia, vomiting, chest pain, and Eckardt score > 3 at 10 years after LHD were 80.1%, 97.5%, 96.3%, and 73.5%, respectively. Probability of esophagitis during 10 years after surgery was 34.4% of patients based on Kaplan–Meier estimation. Approximately 3/4th of patients who had post-LHD esophagitis showed mild esophagitis of Los Angeles classification grade A. Fifteen patients (2.8%) were required a revision of primary LHD. Six patients (1.2%) developed esophageal cancer with an incidence was as high as 219.8/100,000 person-year. All patients with esophageal cancer were found to have early stage tumors that were successfully resected. Conclusions: Symptomatic relief post-LHD lasted for over 10 years. The incidence rate of esophageal cancer was high. Regular EGD surveillance seems to be helpful for early detection of esophageal cancer early. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to explore whether β-EP in serum (sβ-EP) and follicular fluid (ffβ-EP) could predict the in vitro fertilization (IVF) outcomes of patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR). Methods: 90 PCOS women, 50 DOR women, and 100 women with normal ovarian function (control group), who were all undergoing an IVF-embryo transfer trial, were included in the study. Biochemical characteristics, anti-Mullerian hormone (AMH), sβ-EP, ffβ-EP, embryo formation, and pregnancy indicators were assessed in all women. The correlations of AMH and β-EP with oocyte quality were analyzed. Population-based and age-category stratified receiver operating characteristic (ROC) curve analysis of AMH and β-EP for predicting pregnancy and live birth were performed. Results: Compared with the control group, the PCOS group had higher antral follicle count, testosterone, luteinizing hormone, AMH, sβ-EP, and ffβ-EP, which were lower in the DOR group. Meanwhile, the PCOS and DOR groups had higher cycle cancellation and miscarriage rates, and lower high quality embryo numbers. Correlation analysis showed that the oocyte quality were positively correlated with AMH, sβ-EP, and ffβ-EP. The population-based and age-stratified ROC curve analysis showed that sβ-EP and ffβ-EP had high sensitivity and specificity to predict pregnancy and live birth. Meanwhile, age-stratified AMH enhanced the sensitivity for prediction of live birth after IVF. Conclusion: sβ-EP and ffβ-EP are different among women with PCOS, DOR, and normal ovarian function. β-EP can be used as a good predictor of clinical pregnancy and live birth after IVF. [ABSTRACT FROM AUTHOR]

Purpose: To compare the treatment results of needlescopic surgery with those of the conventional method for achalasia, using propensity score-matching. Methods: Propensity score-matching was performed based on five factors: age, gender, body mass index, extended form, and maximum expansion diameter, to extract 28 cases each for a needlescopic group and a conventional group. Results: There were no significant differences between the needlescopic group and the conventional group, in operative time (165 min vs. 170 min, p = 0.682), estimated blood loss (both ≒ 0 ml, p = 0.426), or post-operative hospital stay (4 vs. 4 days, p = 0.248). Although the follow-up period was significantly longer in the conventional group (6 vs. 105 months, respectively; p < 0.001), there was no difference in the post-operative symptom scores for difficulty in swallowing and chest pain or the degree of satisfaction (p = 0.563, p = 0.142, p = 0.342, respectively). Furthermore, there was no difference in the post-operative clearance rate, with both groups found to be favorable (p = 0.758, p = 0.790, p = 1.000, p = 1.000, respectively). Conclusions: The short-term results of needlescopic surgery for achalasia were good and equivalent to those of the conventional method. [ABSTRACT FROM AUTHOR]

Purpose: One diagnostic criterion of esophageal achalasia is that the integrated relaxation pressure (IRP) measured by high-resolution manometry (HRM) is at least 15 mmHg. Moreover, while the standard surgical treatment for esophageal achalasia is laparoscopic Heller-Dor surgery (LHD), there have been insufficient investigations concerning the surgical outcomes from the perspective of the preoperative IRP value. Methods: We split 121 cases in which LHD was performed as an initial treatment on patients with esophageal achalasia, into two categories according to the IRP median value, and performed a comparative investigation of the surgical outcomes with regard to the preoperative pathophysiology and symptoms. Results: The IRP median value was 29.6 mmHg. The high IRP group consisted of younger individuals and low BMI (p = 0.004 and p = 0.0273, respectively), and the percentage of Chicago classification Type II and III was high (p = 0.029) and the regurgitation score in the preoperative symptoms was high (p = 0.0043). However, no differences in the surgical outcomes were confirmed. Conclusion: In patients with esophageal achalasia, the degree of the preoperative IRP value affects the age, BMI, preoperative LESP, and preoperative regurgitation symptoms. However, there were no effects on the surgical outcomes, with the surgical outcomes being satisfactory, regardless of the IRP value. [ABSTRACT FROM AUTHOR]

Diminished ovarian reserve (DOR), generally defined as a decreased number or quality of oocytes, has a significant impact on quality of life and fertility in women. In recent years, the incidence of DOR has been increasing and the ages of patients are younger. The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health. An effective DOR therapy would improve ovarian function, fertility, and quality of life in patients. In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine, and elucidated the characteristics of each treatment. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the copy number variation (CNV) in the X-linked genes BCORL1, POF1B, and USP9X in idiopathic diminished ovarian reserve (DOR). Methods: This case-control study included 47 women, 26 with DOR and 21 in the control group. Age, weight, height, BMI, and FSH level were evaluated, as well as antral follicle count (AFC), oocyte retrieval after controlled ovarian stimulation, and metaphase II (MII) oocytes. The CNVs of BCORL1, USP9X, and POF1B genes were measured by quantitative real time PCR (qPCR) using two reference genes, the HPRT1 (X-linked) and MFN2 (autosomal). Protein–protein interaction network and functional enrichment analysis were performed using the STRING database. Results: The mean age was 36.52 ± 4.75 in DOR women and 35.38 ± 4.14 in control. Anthropometric measures did not differ between the DOR and control groups. DOR women presented higher FSH (p = 0.0025) and lower AFC (p <.0001), oocyte retrieval after COS (p = 0.0004), and MII oocytes (p <.0001) when compared to the control group. BCORL1 and POF1B did not differ in copy number between DOR and control. However, DOR women had more copies of USP9X than the control group (p = 0.028). Conclusion: The increase in the number of copies of the USP9X gene may lead to overexpression in idiopathic DOR and contribute to altered folliculogenesis and oocyte retrieval. [ABSTRACT FROM AUTHOR]

The article presents information about DOR BioPharma's development of an oral, enteric-coated form of the corticosteroid beclometasone diproprionate for treating as well as preventing gastrointestinal graft-versus-host disease. The company's efforts to establish clinical trials for the orBec® product and get approval from the U.S. Food and Drug Administration are discussed. Phase II and phase III randomized trial results indicate mortality is reduced with orBec®.

Supplementary cementitious materials (SCMs) play an essential role in sustainable construction due to their potential to reduce carbon emissions, promote circular economy principles, and enhance the properties of concrete. However, the inherent diversity of SCMs makes it challenging to predict their degree of reaction (DOR). This study applies machine learning techniques to predict DOR while exploring key parameters affecting it. Five machine learning models are utilized: linear regression, Gaussian process regression (GPR), decision tree regression, support vector machine and extreme gradient boosting, with GPR providing the most accurate and adaptable prediction. The study delves into the impact of various parameters on DOR, revealing their significance. Silica content emerges as the most critical, followed by particle size distribution, specific gravity, and water-to-cement (W/C) ratio. Optimizing DOR requires extending curing time, reducing particle size distribution, and considering optimal silica content and W/C ratio. This research emphasizes the importance of understanding the relationships between parameters and the DOR of SCMs, providing insights to enhance the efficiency of SCMs in cementitious systems through machine learning and data-driven analysis. [ABSTRACT FROM AUTHOR]

Purpose: The optimal management of achalasia in obese patients is unclear. For those who have undergone Heller myotomy and fundoplication, the long-term outcomes and their impressions following surgery are largely unknown. Methods: A retrospective review of patients who underwent laparoscopic Heller myotomy and Dor fundoplication (LHMDF) for achalasia was performed. From this cohort, Class 2 and 3 obese (BMI > 35 kg/m2) patients were identified for short- and long-term outcome analysis. Results: Between 2003 and 2015, 252 patients underwent LHMDF for achalasia, and 17 (7%) patients had BMI > 35 kg/m2. Pre-operative Eckardt scores varied from 2 to 9, and at short-term (2–4 week) follow-up, scores were 0 or 1. Ten (58%) patients had available long-term (2–144 months) follow-up data. Eckardt scores at this time ranged from 0 to 6. Symptom recurrence was worse for patients with BMI > 40 kg/m2 compared to patients with BMI < 40 kg/m2. BMI was largely unchanged at long-term follow-up regardless of pre-intervention BMI. Most patients were satisfied with surgery but would have considered a combined LHMDF and weight-loss procedure had it been offered. Conclusion: LHMDF for achalasia in obese patients is safe and effective in the short term. At long-term follow-up, many patients had symptom recurrence and experienced minimal weight loss. Discussing weight-loss surgery at the time LHMDF may be appropriate to ensure long-term achalasia symptom relief. [ABSTRACT FROM AUTHOR]

The Dor C shipwreck is the remains of a 60-t schooner that plied the Mediterranean during the last decades of the nineteenth century. The various building materials and ceramic ware found inside the shipwreck suggest an established commercial route between southern France and the Holy Land. Three metal objects were found in the bow area of the shipwreck: a lead pipe, an iron rigging hoop, and a brass wick housing. This study aims to understand their manufacturing processes, to propose possible dating and manufacturing locations, and to verify their use. The metallurgical investigation suggests that the objects were designated for marine use and manufactured using processes developed during the second half of the nineteenth century, probably post-1885, which supports the dating of the ship. The tonnage of the ship, the origin of her cargo, the provenance of some of the metal parts, and the location of the shipwreck, all suggest that her last voyage was a delivery of cargo from Marseilles to Dor. [ABSTRACT FROM AUTHOR]

Achalasia is a rare motility disorder of the esophagus. According to the Chicago Classification criteria, there are three clinical types of Achalasia and the treatment is patient-tailored. Laparoscopic Heller-Dor is the gold-standard treatment for the most frequent types of Achalasia. However, robotic surgery is able to combine the clinical advantages of minimally invasive surgery with a powerful dexterity on complex anatomic structures. The aim of this study is to report the institutional experience developed in a referral center of esophageal surgery in the treatment of Achalasia by Robotic Heller-Dor. We retrospectively analyzed data of patients that consecutively underwent Robotic Heller-Dor at our institution between January 2012 and January 2020 using the Da Vinci® Surgical System. Sixty-nine patients underwent Robotic Heller-Dor. Among the patients, 35 (51%) were classified as type I, 29 (42%) as type II, and 5 (7%) as type III. The Da Vinci® SI HD Surgical System and the Da Vinci® XI HD Surgical System were used in 56 (81%) and 13 (19%) patients, respectively. No mucosal perforation was observed and post-operative mortality was absent. The mean follow-up was 23.3 months (6–84). Ten patients (14.5%) reported post-operative complaints. In our opinion, Robotic Heller-Dor is an effective tool in the treatment of Achalasia. Robotic Heller-Dor may be a suitable procedure for learning and teaching robotic surgery in the perspective of pursing more complex esophago-gastric surgical procedures. [ABSTRACT FROM AUTHOR]

Purpose: There is some debate about whether preoperative balloon dilation influences the outcomes of laparoscopic Heller-Dor surgery (LHD), with no consensus opinion as yet. Thus, we investigated if preoperative dilation influences the treatment outcomes of LHD for achalasia.Methods: The subjects of this study were 526 patients with achalasia who underwent LHD as an initial treatment between August 1994 and February 2017. The patients were roughly classified by the status of preoperative balloon dilation and matched with propensity scores for age, sex, BMI, morphologic type, and maximum esophageal transverse diameter. Consequently, 94 subjects each were assigned to the balloon dilation (BD) group and to the non-balloon dilation (non-BD) group. We evaluated patient backgrounds, surgical outcomes, and incidence of postoperative reflux esophagitis.Results: No differences were found in surgical time, intraoperative blood loss, incidence of intraoperative mucosal injury, or postoperative hospital stay between the BD and non-BD groups. The mean patient satisfaction was significantly higher in the non-BD group (4.9) than in the BD group (4.7) and the incidence of postoperative esophagitis was significantly lower in the non-BD group (1.1%) than in the BD group (7.4%).Conclusions: Preoperative balloon dilation had no effect on intraoperative complications but did increase the incidence of postoperative reflux esophagitis in patients undergoing LHD for achalasia. [ABSTRACT FROM AUTHOR]

Diminished ovarian reserve (DOR) is associated with reduced fertility and poor reproductive outcomes. The association between dietary patterns and DOR was not well studied. The purpose of this study was to evaluate the relationship between adhering to the healthy eating index (HEI-2015) and the risk of DOR. In this case–control study, 370 Iranian women (120 with DOR and 250 age- and BMI-matched controls) were examined. A reliable semi-quantitative food frequency questionnaire was used to collect diet-related data. We analyzed the HEI-2015 and their dietary intake data to determine major dietary patterns. The multivariable logistic regression was used in order to analyze the association between HEI-2015 and risk of DOR. We found no significant association between HEI-2015 score and risk of DOR in the unadjusted model (OR 0.78; 95%CI 0.59, 1.03). After controlling for physical activity and energy intake, we observed that women in the highest quartile of the HEI-2015 score had 31% decreased odds of DOR (OR 0.69; 95%CI 0.46, 0.93). This association remained significant even after adjusting for all potential confounders. Overall, increased adherence to HEI may lead to a significant reduction in the odds ratio of DOR. Clinical trials and prospective studies are needed to confirm this association. [ABSTRACT FROM AUTHOR]

Delaying childbearing age has become a trend in modern times, but it has also led to a common challenge in clinical reproductive medicine—diminished ovarian reserve (DOR). Since the mechanism behind DOR is unknown and its clinical features are complex, physicians find it difficult to provide targeted treatment. Many factors affect ovarian reserve function, and existing studies have shown that genetic variants, upstream regulatory genes, and changes in protein expression levels are present in populations with reduced ovarian reserve function. However, existing therapeutic regimens often do not target the genetic profile for more individualized treatment. In this paper, we review the types of genetic variants, mutations, altered expression levels of microRNAs, and other related factors and their effects on the regulation of follicular development, as well as altered DNA methylation. We hope this review will have significant implications for the future treatment of individuals with reduced ovarian reserve. [ABSTRACT FROM AUTHOR]

Background: Currently available antiretroviral 2-drug regimen (2DR) fixed dose combinations may not be suitable for specific situations including the presence of resistance associated mutations (RAM) or drug − drug interactions (DDI). The data on the use of the non-nucleoside reverse transcriptase inhibitor doravirine (DOR) and the integrase inhibitor dolutegravir (DTG) as an alternative 2DR remain scarce. Methods: People living with HIV with DOR + DTG as a 2DR are being followed in a prospective observational study. Results: This analysis describes 85 participants with a median age of 57 years. Median CD4-nadir was 173/µl and a majority (66%) had a history of HIV-associated or AIDS-defining conditions. Antiretroviral history was mostly extensive, and documentation of RAM was frequent. The main reasons for choosing DOR + DTG were DDI (29%), tolerability (25%), and cardiovascular risk reduction (21%). Plasma viral load at switch was < 50 copies/ml in all but 3 instances, median CD4 count was 600/µl. DOR + DTG was later changed to another regimen in 10 participants after a median of 265 days, the other 75 participants have remained on DOR + DTG for a median of 947 days. Conclusion: DOR + DTG as a 2DR proved to be a durable treatment option even in extensively pretreated individuals. [ABSTRACT FROM AUTHOR]

Our previous study found that activation of adenosine A1 receptor (A1R) induced phosphorylation of delta opioid receptor (DOR) and desensitization of its downstream signaling molecules, cAMP and Akt. To further investigate the effect of A1R agonist on DOR signaling and the underlying mechanism, we examined the effect of A1R activation upon binding of its agonist N6-cyclohexyl-adenosine (CHA) on DOR-mediated Raf-1/MEK/ERK activation, and found that prolonged CHA exposure resulted in downregulation of DOR-mediated Raf-1/MEK/ERK signaling pathway. CHA-treatment time dependently attenuated Raf-1-Ser338 phosphorylation induced by [D-Pen2,5] enkephalin (DPDPE), a specific agonist of DOR, and further caused downregulation of the Raf-1/MEK/ERK signaling pathway activated by DOR agonist. Moreover, CHA exposure time-dependently induced the phosphorylation of Raf-1-Ser289/296/301, the inhibitory phosphorylation sites that were regulated by negative feedback, thereby inhibiting activation of the MEK/ERK pathway, and this effect could be blocked by MEK inhibitor U0126. Finally, we proved that the heterologous desensitization of the Raf-1/MEK/ERK cascade was essential in the regulation of anti-nociceptive effect of DOR agonists by confirming that such effect was inhibited by pretreatment of CHA. Therefore, we conclude that the activation of A1R inhibits DOR-mediated MAPK signaling pathway via heterologous desensitization of the Raf-1/MEK/ERK cascade, which is a result of ERK-mediated Raf-1-Ser289/296/301 phosphorylation mediated by activation of A1R. [ABSTRACT FROM AUTHOR]

Background: There is no consensus regarding the type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller cardiomyotomy (LHCM). The aim of this study was to compare Angle of His accentuation (AOH) with Dor Fundoplication (Dor) as an adjunct to LHCM.Methods: A total of 110 patients with achalasia cardia presenting for LHCM from March 2010 to July 2015 were randomized to Dor and AOH. Symptom severity, achalasia-specific quality of life (ASQOL), new onset heartburn, and patient satisfaction were assessed using standardized scores preoperatively, at 3, 6 months, and then yearly. The primary outcome was relief of esophageal symptoms while secondary outcomes were new onset heartburn and ASQOL.Results: Both groups were comparable with respect to the baseline demographic characteristics. There was no conversion to open and no mortality in either group. Median operative time was 128 min in AOH and 144 min in Dor group (p < 0.01). Mean follow-up was 36 months and was available in 98% patients. There was significant improvement in esophageal symptoms in both groups with no statistically significant difference between the two groups (p > 0.05). There was no difference in cumulative symptom scores between the two groups over the period of follow-up. New onset heartburn was seen in 11% in AOH and 9% in Dor group. Mean ASQOL score improved in both groups with no difference between the two groups (p = 0.83). Patient satisfaction was similar in both groups.Conclusion: AOH is similar to Dor as an adjunct to LHCM in safety and efficacy and can be performed in shorter time.Clinical Registration Number: CTRI: REF/2014/06/007146. [ABSTRACT FROM AUTHOR]

There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether fatty acid changes in granulosa cells (GCs) underly the pathogenic mechanisms of diminished ovarian reserve (DOR). Methods: GCs were obtained from patients with DOR (n = 70) and normal ovarian reserve (NOR, n = 70). Analysis of fatty acids changes in GCs was then analyzed. Results: Patients with DOR had significantly lower levels of antral follicle count and anti-Mullerian hormone and higher levels of follicle-stimulating hormone compared with NOR patients (P < 0.001). The good-quality embryo rate was notably decreased in DOR patients (51.99 vs 39.52%, P < 0.05). A total of 15 significantly decreased fatty acids in GCs from patients with DOR. The ATP levels were markedly lower in DOR patients than in NOR patients (39.07 ± 12.89 vs 23.21 ± 13.69%, P < 0.05). Mitochondrial membrane potential decreased in DOR patients (P < 0.01). In GCs from DOR patients, the β-oxidation genes (HADHA and ACSL) and DNA repair genes (PRKDC and RAD50) were significantly downregulated (P < 0.05). The γH2AX foci/nucleus ratio in DOR patients markedly increased relative to that of NOR patients (0.31 ± 0.03 vs 0.87 ± 0.07, P < 0.001). Meanwhile, the apoptosis rate of GCs was significantly higher in DOR patients (6.43 ± 2.11 vs 48.06 ± 6.72%, P < 0.01). Conclusion: GC apoptosis resulting from the decrease of fatty acids, and associated with reduced ATP production and DNA damage, may contribute to the pathogenic mechanisms responsible for DOR. [ABSTRACT FROM AUTHOR]

Purpose: We compared the outcomes of Toupet fundoplication with those of Dor fundoplication in patients with achalasia who underwent laparoscopic Heller myotomy. Methods: Seventy-two patients with achalasia and dysphagia underwent laparoscopic Heller myotomy with fundoplication performed by a single surgeon. Heller-Toupet fundoplication (HT) was performed in 30 patients, and Heller-Dor fundoplication (HD) was done in 42. The symptoms and esophageal function were retrospectively assessed in both groups. Results: The dysphagia scores significantly decreased after both the HT and HD procedures, and did not differ significantly between them. The incidence of reflux symptoms was significantly higher after HT (26.7 %) than after HD (7.1 %). The lower esophageal sphincter (LES) resting pressure significantly decreased after both HT and HD. Upon endoscopic examination, the incidence of reflux esophagitis was significantly higher after HT (38.5 %) than after HD (8.8 %). During esophageal pH monitoring, the fraction time at pH <4 was similar in the patients who underwent HT and HD. Conclusions: Laparoscopic Heller myotomy provided significant improvements in the dysphagia symptoms of achalasia patients, regardless of the type of fundoplication. The incidences of reflux symptoms and reflux esophagitis were higher after HT than after HD. However, the results of pH monitoring did not differ between the procedures. [ABSTRACT FROM AUTHOR]

Purpose: Decreased ovarian reserve function is mainly characterized by female endocrine disorders and fertility decline. Follicular fluid (FF) exosomal microRNAs (miRNAs) have been shown to regulate the function of granulosa cells (GCs). The present study explored differentially expressed miRNAs (DEmiRNAs) in patients with diminished ovarian reserve (DOR). Methods: FF was collected from 12 DOR patients and 12 healthy controls. DEmiRNAs between the two groups were identified and analyzed using high-throughput sequencing technology and validated by real-time quantitative PCR (RT-qPCR). Results: A total of 592 DEmiRNAs were identified using high-throughput miRNA sequencing, of which 213 were significantly upregulated and 379 were significantly downregulated. The sequencing results were further validated by RT-qPCR. These DEmiRNA target genes were mainly involved in the cancer pathway, phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, regulation of actin cytoskeleton signaling pathway, and biological processes related to protein binding, nucleoplasm, cytoplasm, and cell membrane. Conclusion: FF exosomal miRNAs are significantly differentially expressed in DOR patients versus non-DOR patients, underscoring their crucial role in regulating the pathogenesis of DOR. [ABSTRACT FROM AUTHOR]

Background: Our prior randomized controlled trial of Heller myotomy alone versus Heller plus Dor fundoplication for achalasia from 2000 to 2004 demonstrated comparable postoperative resolution of dysphagia but less gastroesophageal reflux after Heller plus Dor. Patient-reported outcomes are needed to determine whether the findings are sustained long-term.Methods: We actively engaged participants from the prior randomized cohort, making up to six contact attempts per person using telephone, mail, and electronic messaging. We collected patient-reported measures of dysphagia and gastroesophageal reflux using the Dysphagia Score and the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) instrument. Patient-reported re-interventions for dysphagia were verified by obtaining longitudinal medical records.Results: Among living participants, 27/41 (66%) were contacted and all completed the follow-up study at a mean of 11.8 years postoperatively. Median Dysphagia Scores and GERD-HRQL scores were slightly worse for Heller than Heller plus Dor but were not statistically different (6 vs 3, p = 0.08 for dysphagia, 15 vs 13, p = 0.25 for reflux). Five patients in the Heller group and 6 in Heller plus Dor underwent re-intervention for dysphagia with most occurring more than five years postoperatively. One patient in each group underwent redo Heller myotomy and subsequent esophagectomy. Nearly all patients (96%) would undergo operation again.Conclusions: Long-term patient-reported outcomes after Heller alone and Heller plus Dor for achalasia are comparable, providing support for either procedure. [ABSTRACT FROM AUTHOR]

Tel Dor overlooks the eastern Mediterranean on the southern Levantine coastline of Israel. Underwater surveys and a coastal excavation in the North Bay of Dor have produced evidence of an anchorage at the 4th–7th century CE Byzantine city of Dora. The existence of such an anchorage at the northwestern extremity of the city had been contemplated in the past. Also identified are traces of maritime activity from the time period between the 1st century BCE and 3rd century CE and from earlier periods. The concurrent use of the North Bay and the nearby South Bay and Tantura Lagoon during late antiquity mostly took advantage of the natural coastal morphology, augmented only modestly by man-made infrastructure. These three sites served local and interregional maritime traffic at Dor, a clear attestation to a decentralized resource management that resists strict categorization. The resulting image of the maritime interface(s) at Dor does not fit perceptions of a harbor as a spatially rigid, centralized managed phenomenon. Such a seemingly disheveled use of the scarce resource of natural anchorages has shown remarkable tenacity over the longue durée in the southern Levant, as typified by Dor in late antiquity. [ABSTRACT FROM AUTHOR]

A 31-year-old man, referred to our hospital for investigation of dysphagia, was found to have a spindle-shaped lower esophagus on a contrasted esophagram. The dysphagia was initially treated conservatively, but after 4 years of unsatisfactory control, he requested surgery. Our surgical team has been performing laparoscopic Heller-Dor fundoplication for achalasia since August, 1994, and 265 patients have undergone this procedure so far. Based on our experience, we decided to perform Heller-Dor fundoplication through a single incision for this patient. The operative time was 236 min with minimal blood loss and there were no perioperative complications. His postoperative course was uneventful and he was discharged on postoperative day 4, completing the clinical pathway used for conventional laparoscopic Heller-Dor fundoplication. [ABSTRACT FROM AUTHOR]

Random integers, sampled uniformly from [1, x], share similarities with random permutations, sampled uniformly from Sn. These similarities include the Erdős–Kac theorem on the distribution of the number of prime factors of a random integer, and Billingsley's theorem on the largest prime factors of a random integer. In this paper we extend this analogy to non-uniform distributions. Given a multiplicative function α: ℕ → ℝ≥0, one may associate with it a measure on the integers in [1, x], where n is sampled with probability proportional to the value α(n). Analogously, given a sequence {θi}i≥1 of non-negative reals, one may associate with it a measure on Sn that assigns to a permutation a probability proportional to a product of weights over the cycles of the permutation. This measure is known as the generalized Ewens measure. We study the case where the mean value of α over primes tends to some positive θ, as well as the weights α(p) ≈ (log p)γ. In both cases, we obtain results in the integer setting which are in agreement with those in the permutation setting. [ABSTRACT FROM AUTHOR]

Background: The type of fundoplication that should be performed in conjunction with Heller myotomy for esophageal achalasia is controversial. We prospectively compared anterior fundoplication (Dor) with partial posterior fundoplication (Toupet) in patients undergoing laparoscopic Heller myotomy. Methods: A multicenter, prospective, randomized-controlled trial was initiated to compare Dor versus Toupet fundoplication after laparoscopic Heller myotomy. Outcome measures were symptomatic GERD scores (0-4, five-point Likert scale questionnaire) and 24-h pH testing at 6-12 months after surgery. Data are mean ± SD. Statistical analysis was by Mann-Whitney U test, Wilcoxon signed rank test, and Freidman's test. Results: Sixty of 85 originally enrolled and randomized patients who underwent 36 Dor and 24 Toupet fundoplications had follow-up data per protocol for analysis. Dor and Toupet groups were similar in age (46.8 vs. 51.7 years) and gender (52.8 vs. 62.5% male). pH studies at 6-12 months in 43 patients (72%: Dor n = 24 and Toupet n = 19) showed total DeMeester scores and % time pH < 4 were not significant between the two groups. Abnormal acid reflux was present in 10 of 24 Dor group patients (41.7%) and in 4 of 19 Toupet patients (21.0%) ( p = 0.152). Dysphagia and regurgitation symptom scores improved significantly in both groups compared to preoperative scores. No significant differences in any esophageal symptoms were noted between the two groups preoperatively or at follow-up. SF-36 quality-of-life measures changed significantly from pre- to postoperative for five of ten domains in the Dor group and seven of ten in the Toupet patients (not significant between groups). Conclusion: Laparoscopic Heller myotomy provides significant improvement in dysphagia and regurgitation symptoms in achalasia patients regardless of the type of partial fundoplication. Although a higher percentage of patients in the Dor group had abnormal 24-h pH test results compared to those of patients who underwent Toupet, the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

This article explores the synthesis of β-N-oxalyl-l-α,β-diaminopropionic acid (β-ODAP) in grass pea, a legume commonly grown in Asia and Africa. The authors present conflicting findings regarding the enzymes responsible for β-ODAP synthesis. They challenge a previous study's claim that the enzyme LsAAE3 is involved, instead proposing that LsBOS is responsible. The authors provide evidence supporting their own two-step mechanism for β-ODAP synthesis and refute the claim that LsAAE3 has evolved to repurpose its activity. Understanding the production of β-ODAP is crucial for developing grass pea cultivars without the neurotoxic compound. [Extracted from the article]

orBec® is an oral enteric-coated tablet formulation of the corticosteroid beclometasone, which has been developed by Enteron Pharmaceuticals, a subsidiary of Corporate Technology Development (now DOR BioPharma). orBec® is being developed for the treatment of gastrointestinal graft-versus-host disease (GVHD) and an NDA has been filed in the US. DOR BioPharma has also filed an MAA in Europe for the same indication. orBec® is designed to reduce the need for systemic immunosuppressive drugs, thereby improving the outcome of bone marrow and stem cell transplantation. DOR BioPharma may seek a marketing partner in the US and elsewhere for orBec® in GVHD and will seek a partner for other potential indications of the drug. In December 2001, Corporate Technology Development was acquired by Endorex Corporation (now DOR BioPharma). In October 1998, Enteron Pharmaceuticals (DOR BioPharma) entered into an exclusive, worldwide, royalty bearing license agreement with George B. McDonald, MD, including the right to grant sublicenses, for the rights to the intellectual property and know-how relating to orBec®. In January 2007, DOR BioPharma received $U53 million under a non-binding letter of intent from Sigma-Tau Pharmaceuticals. The agreement grants Sigma-Tau an exclusive right to negotiate terms and conditions for a possible business transaction or strategic alliance regarding orBec® and potentially other DOR pipeline compounds until 1 March 2007. Under the terms of the agreement, Sigma-Tau purchased $US 1 million of DOR's common stock, with an additional $US2 million paid in cash. If no agreement is reached by 1 March 2007, DOR will return the $US2 million to Sigma-Tau within 60 days. DOR BioPharma received an unsolicited proposal from Cell Therapeutics, Inc. to acquire DOR BioPharma in January 2007. Because of the non-binding agreement already signed with Sigma-Tau, DOR BioPharma's board of directors cannot consider Cell Therapeutics' merger proposal at this time. orBec® has been filed for approval in the US for the treatment of gastrointestinal GVHD. The US FDA accepted the NDA filing and has established a target date of 21 July 2007 for completion of review of the NDA. In November 2006, the EMEA determined that the MAA for orBec® for the treatment of gastrointestinal GVHD is complete and that the review process has begun. The data provided in the MAA and NDA submissions demonstrate that orBec® safely provides a lower risk of mortality compared with the current standard of care. Both filings are supported by data from two rndomised, double-blinded, placebo-controlled clinical trials. The first was a 129-patient pivotal phase lU clinical trial for orBec® conducted at 16 bone marrow/stem cell transplant centres in the US and France. The second trial was a 60-patient phase II clinical trial conducted at the Fred Hutchinson Cancer Research Centre. In the primary endpoint of its pivotal trial, time to treatment failure through day 50, orBec® failed to achieve statistical significance (p-value 0.1177). However, orBec® did achieve statistical significance in the secondary endpoints of time to treatment failure through day 80, and a reduction in mortality compared with placebo. In this trial, patient survival at the prespecified endpoint of 200 days post-transplant showed a statistically significant 66% reduction in mortality among patients randomised to orBec®. DOR BioPharma believes the primary endpoint was not achieved due to a higher than expected rate of treatment failures during the initial 10 days in both treatment groups. The mortality benefit in favour of orBec® was confirmed in a retrospective analysis of the phase II study, in which there was a 55% reduction in mortality at 200 days post-transplant.… [ABSTRACT FROM AUTHOR]

AA Dor is an eclipsing, close, post common-envelope binary (PCEB) consisting of a sdOB primary star and an unseen secondary with an extraordinary small mass (M2 ≈ 0.066 M⊙)—formally a brown dwarf. The brown dwarf may have been a former planet which survived a common envelope (CE) phase and has even gained mass. A recent determination of the components' masses from results of NLTE spectral analysis and subsequent comparison to evolutionary tracks shows a discrepancy compared to masses derived from radial-velocity and the eclipse curves. Phase-resolved high-resolution and high-SN spectroscopy was carried out in order to investigate this problem. We present results of a NLTE spectral analysis of the primary, an analysis of its orbital parameters, and discuss possible evolutionary scenarios. [ABSTRACT FROM AUTHOR]

Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia-induced myocardial infarction and lethal ventricular arrhythmias. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown. This study examined the contributions of DOR and ROS in mediating intermittent hypoxia-induced cardioprotection. Mongrel dogs completed a 20 day program consisting of 5–8 daily, 5–10 min cycles of moderate, normobaric hypoxia (FIO2 0.095–0.10), with intervening 4 min room air exposures. Subsets of dogs received the DOR antagonist naltrindole (200 μg/kg, sc) or antioxidant N-acetylcysteine (250 mg/kg, po) before each hypoxia session. Twenty-four hours after the last session, the left anterior descending coronary artery was occluded for 60 min and then reperfused for 5 h. Arrhythmias detected by electrocardiography were scored according to the Lambeth II conventions. Left ventricles were sectioned and stained with 2,3,5-triphenyl-tetrazolium-chloride, and infarct sizes were expressed as percentages of the area at risk (IS/AAR). Intermittent hypoxia sharply decreased IS/AAR from 41 ± 5 % (n = 12) to 1.8 ± 0.9 % (n = 9; P < 0.001) and arrhythmia score from 4.1 ± 0.3 to 0.7 ± 0.2 (P < 0.001) vs. non-hypoxic controls. Naltrindole (n = 6) abrogated the cardioprotection with IS/AAR 35 ± 5 % and arrhythmia score 3.7 ± 0.7 (P < 0.001 vs. untreated intermittent hypoxia). N-acetylcysteine (n = 6) interfered to a similar degree, with IS/AAR 42 ± 3 % and arrhythmia score 4.7 ± 0.3 (P < 0.001 vs. untreated intermittent hypoxia). Without the intervening reoxygenations, hypoxia (n = 4) was not cardioprotective (IS/AAR 50 ± 8 %; arrhythmia score 4.5 ± 0.5; P < 0.001 vs. intermittent hypoxia). Thus DOR, ROS and cyclic reoxygenation were obligatory participants in the gradually evolving cardioprotection produced by intermittent hypoxia. [ABSTRACT FROM AUTHOR]

Our objective was to establish the efficiency of single-incision laparoscopic Heller myotomy and Dor fundoplication (SILHD) as treatment for esophageal achalasia. A 58-year-old man underwent SILHD for achalasia. The left triangular ligament was retracted using a suture thread and fixed to the body surface, providing a good operative field at the cardia. We performed a 7-cm long myotomy, extending 2 cm into the gastric wall, using a tissue-sealing device or L-shaped electrocautery. Oral intake resumed on postoperative day 1, and hospital stay was 4 days. No morbidity was observed. Based on our experience, we believe that the SILHD can be performed safely and seems to offer at least short-term benefits for selected patients with esophageal achalasia, when performed by surgeons experienced in laparoscopic and esophageal surgery. [ABSTRACT FROM AUTHOR]

We present an on-going study of CoRoT 102931335. Our preliminary results indicate that the target is an eclipsing binary system with an orbital period of $3{.\!\!\vphantom{0}^{\mathrm{d}}}979$ and a primary component pulsating in the frequency range 0.6–0.8 c/d. The results of a ground-based follow-up program provided four-colour Strömgren photometry and allowed us to infer the spectral class and the primary effective temperature. We devised and applied an iterative procedure to disentangle the effects of binarity from those of pulsations and could test that a detailed binary modelling is essential for the purpose. Our results suggest that the pulsating component of CoRoT 102931335 could be a γ Dor variable, a rare occurrence in an eclipsing system. [ABSTRACT FROM AUTHOR]

Purpose: Esophageal dysmotility and disorders of the lower esophageal sphincter are well documented in morbidly obese patients. Esophageal achalasia has been reported in up to 1% of obese patients but the development of such esophageal motility disorder after laparoscopic sleeve gastrectomy (LSG) is extremely rare. The purpose of this video was to demonstrate the management of a type II esophageal achalasia diagnosed in a 46-year-old female patient 4-year after LSG. Materials and Methods: An intraoperative video has been anonymized and edited to demonstrate the feasibility of laparoscopic Heller myotomy and anterior Dor fundoplication on the mentioned patient. Results: The operation started with the section of the perigastric adhesions. Proceeding in a clockwise direction, the esophagogastric junction, the anterior esophageal wall, and the His angle were freed. A residual slightly dilated fundus was found and isolated. After mobilization of the distal esophagus and identification of the anterior vagus nerve, a "hockey stick" myotomy was carried out for 6 cm on the esophagus and for 2 cm on the gastric side. An anterior Dor fundoplication was fashioned using the residual gastric fundus. Conclusion: Esophageal achalasia in patients that previously underwent LSG is exceptional but should always be suspected in case of pathognomonic symptoms onset. In tertiary referral centers, laparoscopic Heller myotomy and, if technically feasible, an anterior Dor fundoplication seem safe and effective to relieve gastroesophageal outflow obstruction and prevent gastroesophageal reflux. [ABSTRACT FROM AUTHOR]

Laparoscopic Heller myotomy and Dor fundoplication is considered a safe and effective treatment for achalasia. Robotic-assisted Heller–Dor procedure (RAHD) has emerged as an alternative approach due to improved visualization and fine motor control. The aim of this prospective study was to evaluate clinical, and functional results of RAHD. We evaluated a group of 66 patients with achalasia that underwent robotic-assisted Heller–Dor operation. Before treatment all patients underwent a diagnostic work-up such as upper endoscopy, esophageal barium swallow and high resolution manometry. The presence of postoperative gastroesophageal reflux disease was diagnosed by impedance and pH monitoring (MII-pH). Dysphagia improved in 92.4% of patients after treatment. Barium swallow series showed esophageal emptying in 100% of patients and a significant reduction of the esophageal diameter (p = 0.00235). Forty-five of 66 patients (68.2%) underwent upper endoscopy and 35 of 66 (53%) underwent MII-pH. Esophageal erosions were found in 4/45 (8,8%) and MII-pH showed abnormal results in 3/35 patients (8.6%). RAHD ensures a meticulous esophageal and gastric myotomy, allowing to visualize and divide each muscle fibers with a low rate of intraoperative and postoperative complications. resulting in turn in good clinical outcomes, radiological findings and functional results even if robotic tecnique definitely increases the surgical cost in the treatment of these functional esophageal disorders. [ABSTRACT FROM AUTHOR]

This research aims to study the safety and efficacy of doravirine in the treatment of HIV-1 (human immunodeficiency virus) patients. We conducted an electronic search in eight databases for the inclusion of eligible studies. We have only included randomized controlled trials (RCTs) that study the safety and efficacy of doravirine in the treatment of HIV-1 adult patients. Six papers were included in this meta-analysis. For network (direct and indirect) estimates, the doravirine 100 mg treatment strategy found to have the highest efficacy (P score = 0.786) followed by doravirine 25 mg (P score = 0.684), efavirenz 600 mg (P score = 0.574), doravirine 200 mg (P score = 0.532), 100 mg ritonavir and plus 800 mg darunavir (P score = 0.416), and placebo (P score = 0.009), respectively. Regarding drug-related AE, the placebo group found to have the highest safety profile with the least AE rates (P score = 0.927) followed by doravirine 100 mg (P score = 0.720), 100 mg ritonavir and plus 800 mg darunavir (P score = 0.717), doravirine 25 mg (P score = 0.336), doravirine 200 mg (P score = 0.258), and efavirenz 600 mg (P score = 0.043), respectively. Nevertheless, there was no significant difference between DOR 100 mg in comparison with 100 mg ritonavir and plus 800 mg darunavir (OR = 1.14; 95% CI = 0.23–5.74), DOR 25 mg (OR = 0.37; 95% CI = 0.06–2.34), DOR 200 mg (OR = 0.89; 95% CI = 0.17–4.59), or efavirenz 600 mg (OR = 0.58; 95% CI = 0.17–1.98). Moreover, the pairwise (direct only) comparisons did not show a significant difference between doravirine (all doses) and other treatment groups. Doravirine could be counted as an efficacious, safe, and well-tolerated treatment option that is preferable to other regimens for the initial therapy of individuals with HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background: The type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller's cardiomyotomy (LHCM) in Achalasia cardia is controversial. We compared Angle of His accentuation and Dor fundoplication in a randomized controlled trial. Methods: From May 2010 to October 2013, 62 patients undergoing LHCM were randomized to receive either Dor fundoplication (Dor group) or Angle of His accentuation (AOH group) as an anti-reflux procedure. Symptomatic outcome was evaluated using modified Mellow and Pinkas scale for dysphagia and modified DeMeester's score for regurgitation and heartburn. Achalasia-specific quality-of-life (QOL) questionnaire was used to assess quality of life. The primary outcome was symptomatic relief and the secondary outcome was postoperative heartburn. Statistical analysis was done using SPSS software. Results: All the procedures were completed laparoscopically with no mortality. Morbidity was similar in the two groups (6.4 %). Median operative time was higher in Dor group (170 vs 130 min). At a median follow-up of 21 months relief of dysphagia, regurgitation, and heartburn was seen in 87, 90.3, and 90.3 % patients in Dor group versus 93.5, 96.7, and 77.4 % in AOH group patients with significant improvement in symptom scores. Improvement was similar in both groups with no statistically significant difference in the symptom scores ( p = 0.48 for dysphagia, p = 0.37 for regurgitation, and p = 0.19 for heartburn). The QOL improved in both groups [62.3 to 12.3 ( p = 0.02) in Dor group and 63.9-13 ( p = 0.02) in AOH group] with no statistically significant difference between the two groups ( p = 0.96). There was no statistically significant difference in the postoperative heartburn between the two groups ( p = 0.19). Conclusion: Laparoscopic Heller's cardiomyotomy with either Angle of His accentuation or Dor fundoplication leads to similar improvement in symptoms and quality of life. [ABSTRACT FROM AUTHOR]