Pull-down Technique Research Articles

The esophageal pull-down technique improves the outcome of laparoscopic Heller-Dor myotomy in end-stage achalasia

The treatment of patients with end-stage achalasia with a sigmoid-shaped esophagus is particularly challenging. A modified technique (pull-down technique) has been developed to straighten the esophageal axis, but only a limited number of studies on this topic are available in the literature. This study aimed to compare the outcome of patients who underwent the pull-down technique with that of patients who had a classical laparoscopic Heller-Dor (CLHD) myotomy. All patients with a radiologic diagnosis of end-stage achalasia who underwent an LHD myotomy between 1995 and 2022 were considered eligible for the study. All patients underwent symptom score, barium swallow, endoscopy, and manometry tests before and after the procedure was performed. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score (ES) of >3 or the need for retreatment. Of the 94 patients who were diagnosed with end-stage achalasia (male-to-female ratio of 52:42), 60 were treated with CLHD myotomy, and 34 were treated with the pull-down technique. Of note, 2 patients (2.1%), both belonging to the CLHD myotomy group, developed a squamous cell carcinoma during the follow-up. The overall success of LHD myotomy was seen in 76 of 92 patients (82.6%). All patients in both groups achieved a lower ES after surgery. The failure rates were 27.6% (16/58) in the CLHD myotomy group and 5.9% (2/34) in the pull-down technique group (P<.01). Our findings confirm that LHD myotomy is an effective treatment of end-stage achalasia and that the pull-down technique further improves the outcome in patients with end-stage achalasia who are difficult to treat.

Unification and orificing of two functional noncommunicating uterine horns through the created neovagina using peritoneum

ObjectiveTo demonstrate the surgical approach for Müllerian agenesis with bilateral uterine remnants containing functional endometrium. DesignStepwise demonstration of the technique with narrated video footage SettingA Tertiary University Hospital, Reproductive Surgery Unit. PatientAn 18-year-old adolescent was admitted to a tertiary university hospital with complaints of primary amenorrhea and cyclic pelvic pain. Physical examination and MRI scans suggested a complex Müllerian abnormality. The patient had uterine remnants with bilateral functional endometrium and cervico-vaginal agenesis. InterventionAn operation was planned to reconstruct her anatomy by providing a neovagina and anastomosing the uterine remnants. GnRH analogs were prescribed to suppress her menstruation until the procedure. The operation was performed in the third month after the initial diagnosis. A laparoscopy was conducted, revealing approximately 5x6 cm bilateral uterine horns with healthy adnexa.As the first step, a neovagina was created using a modified peritoneal pull-down technique, a standard approach in our clinic. A vaginal incision was made, and a blind vaginal dissection was performed to reach the peritoneum vaginally. Subsequently, an acrylic vaginal mold was inserted. The vaginal orifice was laparoscopically incised using ultrasonic energy with guidance from the inserted vaginal acrylic mold. The orifice was gradually dilated with larger molds. The entire pelvic peritoneum was dissected circularly, and the distal part of the dissected peritoneum was pulled down using four 2.0 Vicryl sutures at 0, 90, 180, and 270 degrees from the opened vaginal orifice. The uterine cavities of both remnants were incised, and two separate Foley catheters were placed in both cavities. A mold with a hole was used to insert the catheters through the vagina. Both catheters were secured in the cavities with Prolene sutures pulled up from the anterior abdominal wall.The next step involved uterine anastomosis. The uterine remnants were unified through continuous suturing, resulting in the formation of a normally shaped uterus. In the final step, the created uterus and neovagina were anastomosed. The patient received instructions on how to perform mold exercises and follow-up care. Main Outcome MeasureDescription of a laparoscopic management of a rare mullerian abnormality. ResultsThe postoperative MRI scan at one month revealed healed unified uterine cavities and vagina. The patient experienced spontaneous menstruation in the second month after surgery and now maintains regular menses with an approximately 9-10 cm functional vagina. Within three months after surgery, the VAS (visual analog scale) scores for chronic pelvic pain and dysmenorrhea decreased from 9 to 2-3. ConclusionsMüllerian abnormalities are exceptionally rare, and their spectrum is broad, making it challenging to identify an exact surgical method to restore functional anatomy. Therefore, a customized surgical approach should be designed for each patient based on their unique condition.

Functional characterization of Nosema bombycis (microsporidia) trehalase 3.

Nosema bombycis, an obligate intracellular parasite, is a single-celled eukaryote known to infect various tissues of silkworms, leading to the manifestation of pebrine. Trehalase, a glycosidase responsible for catalyzing the hydrolysis of trehalose into two glucose molecules, assumes a crucial role in thermal stress tolerance, dehydration, desiccation stress, and asexual development. Despite its recognized importance in these processes, the specific role of trehalase in N. bombycis remains uncertain. This investigation focused on exploring the functions of trehalase 3 in N. bombycis (NbTre3). Immunofluorescence analysis of mature (dormant) spores indicated that NbTre3 primarily localizes to the spore membrane or spore wall, suggesting a potential involvement in spore germination. Reverse transcription-quantitative polymerase chain reaction results indicated that the transcriptional level of NbTre3 peaked at 6h post N. bombycis infection, potentially contributing to energy storage for proliferation. Throughout the life cycle of N. bombycis within the host cell, NbTre3 was detected in sporoplasm during the proliferative stage rather than the sporulation stage. RNA interference experiments revealed a substantial decrease in the relative transcriptional level of NbTre3, accompanied by a certain reduction in the relative transcriptional level of Nb16S rRNA. These outcomes suggest that NbTre3 may play a role in the proliferation of N. bombycis. The application of the His pull-down technique identified 28 proteins interacting with NbTre3, predominantly originating from the host silkworm. This finding implies that NbTre3 may participate in the metabolism of the host cell, potentially utilizing the host cell's energy resources.

Adipsin inhibits Irak2 mitochondrial translocation and improves fatty acid β-oxidation to alleviate diabetic cardiomyopathy

BackgroundDiabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism.MethodsA high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator.ResultsThe expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC–MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin.ConclusionsAdipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.

Evaluation of dual-ONOFIC method for subthreshold leakage reduction in domino circuit

ABSTRACT A novel dual ON/OFF logic (ONOFIC) pull-down method is presented to reduce subthreshold leakage current in FinFET domino circuit wide OR gates at the 32 nm technology node. An ONOFIC block is inserted in the pull-down network of dynamic and inverted blocks. The HSPICE simulator with the 32 nm BISM4 model is used for the simulation of the proposed work. The outcome of the CLIL (clock is low and inputs are low) state is most effective in reducing the subthreshold leakage current at low and high temperatures. The OR2, OR4, OR8, and OR16 circuits using the proposed method cut down the subthreshold leakage power dissipation up to 48.1% for low power (LP) mode when compared to the LECTOR domino gates in CHIL (clock is high and inputs are low) state, which also reduced subthreshold leakage power dissipation up to 74% for short gate (SG) mode. Due to a lower subthreshold current when all inputs are low at low and high temperatures, the proposed dual-ONOFIC pull-down technique outperforms the ONOFIC pull-up technique in LP mode. When inputs are high at low and high temperatures, the ONOFIC pull-up technique performs better than the dual-ONOFIC pull-down technique.

PATELLOFEMORAL INSTABILITY MANAGEMENT IN A PROSPECTIVE PAEDIATRIC COHORT IN EDINBURGH

Patellofemoral instability (PFI) is a common cause of knee pain and disability in the paediatric population. Patella alta, lateralised tibial tubercle, medial patellofemoral ligament (MPFL) deficiency, genu valgum and trochlear dysplasia are well known risk factors.A prospective database was created including patients referred through our physiotherapy pathway following first-time patella dislocation. Patella alta and lateralisation of the tibial tuberosity was treated with a Fulkerson-type tibial tubercle osteotomy(TTO). Medial patellofemoral ligament was reconstructed using quads tendon autograft pull-down technique. A modified Sheffield protocol was used postoperatively allowing weightbearing in a hinged knee brace.Forty patients were identified with 8 patients having bilateral presentations. Male to female ratio was 12:28 with an age range of 4–17 years. Eight patients had congenital PFI, five patients acquired PFI through traumatic patella dislocation and twenty-seven patients developed PFI from recurrent dislocations. Structural abnormalities were found in 38(95%) of patients. Patella alta (Caton-Deschamps index &gt;1.2) was identified in 19(47%) patients, genu valgum in 12(30%) patients, increased tibial tubercle-trochlear groove distance(TT-TG&gt;20mm) was present in 9(22.5%) patients and persistent femoral anteversion(&gt; 20 deg) in 7(17%) patients.Eight patients were treated with TTO and MPFL reconstruction, three patients with MPFL reconstruction alone and five patients had guided growth for genu valgum correction. Ten patients are awaiting surgery. No postoperative patients had recurrence of PFI at their latest follow up.PFI is a common problem in the adolescent paediatric population with identifiable structural abnormalities. Correcting structural pathology with surgery leads to predictable and safe outcomes.

320. ESOPHAGEAL PULL-DOWN TECHNIQUE IMPROVES THE FINAL OUTCOME OF LAPAROSCOPIC HELLER-DOR FOR END-STAGE ACHALASIA

Abstract Background Patients with sigmoid shape have an advanced form of the disease and are considered the most difficult to treat. A modified technique (pull-down) has been proposed to straighten the esophageal axis, but there is a limited amount of data available in literature. In this study, we aimed to compare the final outcome of the pull-down technique (PDLHD) with the results of classical myotomy (CLHD) in patients with end-stage achalasia. Methods From 1995–2022, patients with a radiological diagnosis of end-stage achalasia undergoing laparoscopic myotomy were enrolled in the study. Symptoms were quantified using the Eckardt score. Barium-swallow, endoscopy and manometry were performed before and after the treatment. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score &amp;gt; 3, or the need for retreatment. Results Of the 94 patients with end-stage achalasia (M:F = 52:42), 60 patients were treated with CLHD, and 34 patients with PDLHD. The surgical procedures were completed laparoscopically in all patients. During follow-up, two patients (2.1%) developed squamous cell carcinoma (SCC), both in the CLHD group. All patients in both groups had an improvement in their Eckardt score after surgery, and the failure rates were 27.6% (16/58) after CLHD and 5.9% (2/34) after PDLHD (p &amp;lt; 0.01). Amongst the patients who underwent complete post-operative follow-up, an abnormal acid exposure was detected in 2 patients after PDLH, and in 6 after CLHD (p = n.s.). Conclusions Taken into account the intrinsic limitations of the study (different time window, and different follow-up), the results of this study indicate that performing the pull-down technique during Laparoscopic Heller-Dor improves the final outcome in end-stage achalasia patients.

Circ_PIAS1 Promotes the Apoptosis of ALV-J Infected DF1 Cells by Up-Regulating miR-183.

(1) Background: circRNAs are closed circular molecules with covalent bonds generated by reverse shearing, which have high stability and have different manifestations in different tissues, cells, or physiological conditions and play important roles in various disease processes and physiological processes. In addition, circ_PIAS1 has been screened out and verified, and the bioinformatics analyzed in previous studies. In this study, we investigated the function of circ_PIAS1 and studied its role in ALV-J infection to provide a basis for the role of circRNA in ALV-J infection. (2) Methods: the effect of circ_PIAS1 on apoptosis during ALV-J infection was studied by flow cytometry and detection of apoptotic gene expression, and miR-183 was screened by a biotin-labeled RNA pull-down technique. After overexpression and inhibition of miR-183, the effect of miR-183 on apoptosis in the process of ALV-J infection was studied by flow cytometry and detection of apoptotic gene expression. (3) Results: after overexpression of circ_PIAS1, flow cytometry and apoptotic gene expression showed that circ_PIAS1 promoted apoptosis. The results of RNA pull-down showed that 173 miRNAs could bind to circ_PIAS1, and circ_PIAS1 up-regulated the expression of miR-183. On the other hand, the same results were obtained whether miR-183 was overexpressed or inhibited that miR-183 affected ALV-J infection by promoting cell apoptosis. (4) Conclusions: circ_PIAS1 up-regulated the expression of miR-183 and influenced ALV-J infection by promoting cell apoptosis.

Acupuncture Improves Synaptic Plasticity of SAMP8 Mice through the RhoA/ROCK Pathway.

Studies have found synaptic plasticity damage to be an early marker of Alzheimer's disease (AD). RhoA/ROCK pathway is involved in the regulation of synaptic plasticity. Acupuncture can significantly improve the cognitive state of AD. We aimed to use modern biological technology to detect the changes in synaptic plasticity and RhoA/ROCK pathway in SAMP8 mice, as well as the intervention effect of acupuncture. Morris water maze and electrophysiological techniques were used in vivo to detect the changes in spatial memory and LTP of mice. Golgi Cox staining and CASEVIEWER2.1 software were used to quantitatively analyze the changes in the morphology and number of dendritic spines in the hippocampus of mice. The activity of RhoA and ROCK2 in the hippocampus of mice was detected, respectively, by pull-down technique and ELISA. WB technique was used to detect the protein expression of ROCK2 and phosphorylation level of MLC2, LIMK2, and CRMP2 in the hippocampus of mice. The neurobehavior and synaptic plasticity of 8-month-old SAMP8 mice were found to be significantly impaired. Acupuncture could improve the spatial learning and memory ability of SAMP8 mice, and partially prevent the reduction in the number of spines on the secondary branches of the apical dendrites in the hippocampus and the attenuation of LTP. The RhoA/ROCK pathway was significantly activated in the hippocampus of 8-month-old SAMP8 mice, and acupuncture had an inhibitory effect on it. Acupuncture can improve synaptic plasticity by inhibiting the abnormal activation of the RhoA/ROCK pathway, and improve the spatial learning and memory ability of AD, so as to achieve the purpose of treating AD.

A6A-seq: N6-allyladenosine-based cellular messenger RNA metabolic labelling and sequencing

The integration of RNA metabolic labelling by nucleoside analogues with high-throughput RNA sequencing has been harnessed to study RNA dynamics. The immunoprecipitation purification or chemical pulldown technique is generally required to enrich the analogue-labelled RNAs. Here we developed an a6A-seq method, which takes advantage of N6-allyladenosine (a6A) metabolic labelling on cellular mRNAs and profiles them in an immunoprecipitation-free and mutation-based manner. a6A plays a role as a chemical sequencing tag in that the iodination of a6A in mRNAs results in 1,N6-cyclized adenosine (cyc-A), which induces base misincorporation during RNA reverse transcription, thus making a6A-labelled mRNAs detectable by sequencing. A nucleic acid melting assay was utilized to investigate why cyc-A prefers to be paired with guanine. a6A-seq was utilized to study cellular gene expression changes under a methionine-free stress condition. Compared with regular RNA-seq, a6A-seq could more sensitively detect the change of mRNA production over a time scale. The experiment of a6A-containing mRNA immunoprecipitation followed by qPCR successfully validated the high-throughput a6A-seq data. Together, our results show a6A-seq is an effective tool to study RNA dynamics.

Acetylation of the nuclear localization signal in Ku70 diminishes the interaction with importin-α

Proteins are functionally regulated by various types of posttranslational modifications (PTMs). Ku, a heterodimer complex of Ku70 and Ku80 subunits, participates in DNA repair processes. Ku is distributed not only in the nucleus but also in the cytoplasm, suggesting that the function of Ku is regulated by its subcellular localization. Although Ku70 undergoes PTMs including phosphorylation or acetylation, it remains unknown whether the PTMs of Ku70 affect the subcellular localization of Ku. Using a cell-free pull-down assay technique, we show that Nε-acetylation of lysine residues in the synthetic peptide matched to Ku70's nuclear localization signal (NLS) reduces the peptide's interaction with the nuclear transport factor importin-α. The reduced interaction by acetylation was supported by molecular simulation analysis. In addition, when expressed in the endogenous Ku80-defective Chinese hamster ovary xrs-6 cells, some full-size human Ku70 mutants with substitutions of glutamine, a possible structural mimetic of Nε-acetyl–lysine, for lysine at the specific NLS positions exhibited no nuclear distribution. These findings imply that acetylation of particular lysine residues in the Ku70 NLS regulates nuclear localization of Ku.

The characteristics of the breaststroke pullout in elite swimming

Since the rule change permitting the inclusion of one dolphin kick during the underwater breaststroke pullout phase following a swim start or turn, there has been an emergence of several different pullout techniques adopted by elite swimmers. The aim of this study was to characterize the underwater breaststroke pullout technique trends and to assess the effectiveness of each technique as utilized by elite male and female swimmers. The sample included 60 swimmers (n = 26 male, n = 34 female) competing across the 50, 100, and 200 m long-course breaststroke final races from the World Championships 2015, 2017, 2019 and Olympic Games 2016. An above-water camera was used to identify and measure the different phases of the underwater pullout techniques, which was found to be a highly accurate methodological approach (ICC = 0.97). From the 150 trials analyzed, three different pullout techniques were identified: the Fly-Kick First technique, the Combined technique and the Pull-Down First technique. Although the most common underwater pullout technique utilized by elite competitive breaststroke swimmers was the Combined technique (n = 71), followed by the Fly-Kick First technique (n = 65) and the Pull-Down First technique (n = 14), it was observed that technical selection deviates according to gender. This indicates that male and female swimmers should not be coached adhering to the same technical model. This study found no significant difference in terms of performance outcome with respect to each of these techniques, indicating that technique selection should be guided by one's individual preference. It was concluded that the results of this study will serve as an up-to-date resource for coaches and swimmers working with elite breaststroke swimmers and as a useful insight to current underwater pullout trends.

Label-Free Single-Molecule Pulldown for the Detection of Released Cellular Protein Complexes.

Precise and sensitive detection of intracellular proteins and complexes is key to the understanding of signaling pathways and cell functions. Here, we present a label-free single-molecule pulldown (LFSMP) technique for the imaging of released cellular protein and protein complexes with single-molecule sensitivity and low sample consumption down to a few cells per mm2. LFSMP is based on plasmonic scattering imaging and thus can directly image the surface-captured molecules without labels and quantify the binding kinetics. In this paper, we demonstrate the detection principle for LFSMP, study the phosphorylation of protein complexes involved in a signaling pathway, and investigate how kinetic analysis can be used to improve the pulldown specificity. We wish our technique can contribute to uncovering the molecular mechanisms in cells with single-molecule resolution.

CircRNA-0100 positively regulates the differentiation of cashmere goat SHF-SCs into hair follicle lineage via sequestering miR-153-3p to heighten the KLF5 expression.

Circular RNAs (circRNAs) have stable structures, being a covalently closed loop without 5 and 3 free ends. They can function as “miRNA sponges” in regulating the expression of their target genes. It was thought that circRNAs are involved in the development of the secondary hair follicle (SHF) in cashmere goats. In our previous investigation, a new circRNA named circRNA-0100 was identified from the SHF of cashmere goats, but its function is unknown. In this work, we found that circRNA-0100 exhibited significantly higher expression at anagen SHF bulge than its counterpart at telogen in cashmere goats. Based on the use of both overexpression and siRNA interference assays, our data indicated that circRNA-0100 promoted the differentiation of cashmere goat SHF stem cells (SHF-SCs) into hair follicle lineage, which was evaluated by analyzing the transcriptional level changes of six indicator genes in SHF-SCs of cashmere goats. Using the RNA pull-down technique, we showed that circRNA-0100 served as “molecular sponges” of miR-153-3p in SHF-SCs. Through the use of dual-luciferase reporter assays, our data indicated that circRNA-0100 positively regulated the transcriptional expression of the KLF5 gene via the miR-153-3p-mediated pathway. Ultimately, we showed that circRNA-0100 promoted the differentiation of SHF-SCs into hair lineage, which might be achieved via sequestering miR-153-3p to heighten the KLF5 expression in SHF-SCs of cashmere goats. Our results provide novel scientific evidence for revealing the potential molecular regulatory mechanisms on the differentiation of SHF-SCs into hair lineage in cashmere goats.

Assessing the in vitro Binding Affinity of Protein-RNA Interactions Using an RNA Pull-down Technique.

RNA is a vital component of the cell and is involved in a diverse range of cellular processes through a variety of functions. However, many of these functions cannot be performed without interactions with proteins. There are currently several techniques used to study protein-RNA interactions, such as electrophoretic mobility shift assay, fluorescence anisotropy, and filter binding. RNA-pulldown is a technique that uses biotinylated RNA probes to capture protein-RNA complexes of interest. First, the RNA probe and a recombinant protein are incubated to allow the in vitro interaction to occur. The fraction of bound protein is then captured by a biotin pull-down using streptavidin-agarose beads, followed by elution and immunoblotting for the recombinant protein with a His-tag-reactive probe. Overall, this method does not require specialized equipment outside what is typically found in a modern molecular laboratory and easily facilitates the maintenance of an RNase-free environment. This protocol was validated in: Nucleic Acids Res (2020), DOI: 10.1093/nar/gkaa029 Graphical abstract.

Laparoscopic Vaginoplasty Procedure Using a Modified Peritoneal Pull-Down Technique with Uterine Strand Incision in Patients with Mayer–Rokitansky–Küster–Hauser Syndrome: Kisu Modification

Various vaginoplasty procedures have been developed for patients with Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome. Here, we describe a novel laparoscopic vaginoplasty procedure, known as the Kisu modification, using a pull-down technique of the peritoneal flaps with additional structural support to the neovaginal apex using the incised uterine strand in patients with MRKH syndrome. Ten patients with MRKH syndrome (mean age at surgery: 23.9 ± 6.5 years, mean postoperative follow-up period: 17.3 ± 3.7 months) underwent construction of a neovagina via laparoscopic vaginoplasty. All surgeries were performed successfully without complications. The mean neovaginal length at discharge was 10.3 ± 0.5 cm. Anatomical success was achieved in all patients, as two fingers were easily introduced, the neovagina was epithelialized, and the mean neovaginal length was 10.1 ± 1.0 cm 1 year postoperatively. No obliteration, granulation tissue formation at the neovaginal apex, or neovaginal prolapse was recorded. Five of the 10 patients attempted sexual intercourse and all five patients were satisfied with the sexual activity, indicating functional success. Although the number of cases in this case series is few, our favorable experience suggests that the Kisu modification of laparoscopic vaginoplasty procedure is an effective, feasible, and safe approach for neovaginal creation in patients with MRKH syndrome.

625 EFFICACY OF MYOTOMY IN PATIENTS WITH SIGMOID MEGAESOPHAGUS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Megaesophagus progress to sigmoid megaesophagus (SM) in 10–15% of patients, presenting tortuosity and sigmoid colon aspect. Esophagectomy is the choice treatment but is associated with high complications and mortality rates. To avoid the esophagectomy inherent morbidity, several authors recommend Heller myotomy (HM) with pull-down technique for SM, mainly for patients with comorbidities and the elderly. This systematic review and meta-analysis is the first to analyze the effectiveness of HM for treating SM. Methods A systematic review was conducted in PubMed, Embase, Cochrane Library Central, Lilacs (BVS), and manual search of references. Inclusion criteria were: a) clinical trials, cohort studies, case series; b) patients with SM and esophageal diameter ≥ 6 cm; and c) patients undergoing primary myotomy. The exclusion criteria were: a) reviews, case reports, cross-sectional studies, editorials, letters, congress abstracts, full-text unavailability; b) animal studies, c) previous surgical treatment for achalasia; and d) pediatric studies. There were no restrictions on language or date of publication, and no filters were applied for the selection process. Random model and a 95% confidence interval (CI) were used. Results Sixteen articles were selected, encompassing 231 patients. The mean age ranged from 36 to 61 years old, and the mean follow-up ranged from 16 to 109 months. The analyzed outcomes include mortality, complications (pneumonia, pneumothorax, gastroesophageal reflux), need for reintervention (remyotomy, dilation and esophagectomy), and results classified as ‘good’ and ‘excellent’. Mortality rate was 0.035 (CI: 0.017–0.07; p &amp;lt; 0.01). Complications rate was 0.08 (CI: 0.04–0.153; p = 0.01). Need for retreatment rate was 0.161 (CI: 0.053–0.399; p &amp;lt; 0.01). Probability of good or excellent outcomes after myotomy was 0.762 (CI: 0.693–0.819; p &amp;lt; 0,01). Conclusion Heller myotomy is an option for avoiding esophagectomy in achalasia, with a low morbimortality rate and good results. It is effective for most patients but will fail in a minority of patients and demand retreatment, be it a remyotomy, endoscopic treatment or esophagectomy.

Pull-down Fitness Technique Analysis using Motion Capture

Exercise is an essential contributor to physical and psychological well-being. Regular exercise reduces many chronic diseases, such as heart diseases, diabetes, hypertension, obesity, etc. Pull-down is one of the Weight Training exercises. Engaging in physical activities such as Weight training, stretching exercises and aerobic exercises requires proper execution and awareness of the exercises to avoid bodily injuries and get maximal results. In this study, software that can analyse technique exercise of Pull-down. As research material, because of a degree, each human elbow is different, distribution data of Trainer elbow degree is calculated using measure standard deviation and displayed as a normal distribution graph. The method used in this study to analyse proper Pull-down exercise technique is compared to elbow angle Trainee with elbow angle Trainer. The output of this software is elbow angle, the correctness of the methods performed by the Trainee. The average percentage of accuracy from the results of testing the analysis software using the value of the angle of 56.87 ° ± 7 ° Trainer is 88%.

Curvas de fragilidad basadas en análisis numérico de muros de mampostería frente a subsidencia, utilizando el software Abaqus/CAE e implementando la técnica del pulldown

Curvas de fragilidad basadas en análisis numérico de muros de mampostería frente a subsidencia, utilizando el software Abaqus/CAE e implementando la técnica del pulldown

Abstract NT-119: TARGET DISCOVERY OF NATURAL PRODUCT INSPIRED PHYLLANTHUSMINS FOR TREATMENT OF HIGH GRADE SEROUS OVARIAN CANCER

Abstract BACKGROUND: High grade serous ovarian cancer (HGSOC) is a lethal gynecological malignancy with a need for new therapeutic agents. Many of the most widely used chemotherapeutic drugs are either derived from or are semi-synthetic derivatives of natural products. We developed potent synthetic analogs (PHYs) of the phyllanthusmin class inspired by prior natural product isolated from Phyllanthus poilanei Beille. MATERIALS &amp; METHODS: HGSOC cell lines, OVCAR3 and OVCAR8, and non-tumorigenic controls, IOSE80 and FT33, were used in this study. Cytotoxicity assays included sulforhodamine B assay, and annexin X/PI staining and Western blotting for confirmation of apoptosis induction. A photo affinity labeling method was used to attach PHY analogs to solid phase support. Targets were isolated using a pulldown technique and mass spectrometry. CRISPR-Cas9 genome editing was used to knockout and confirm putative targets. RESULTS: The most potent analog, PHY34, has nanomolar potency in HGSOC cell lines in vitro and displayed cytotoxic activity through late-stage autophagy inhibition and activation of apoptosis. PHY34 was readily bioavailable through intraperitoneal administration in vivo where it significantly reduced HGSOC tumor burden. Targets were identified using photo affinity labeling-aided protein pulldown and mass spectrometry, and confirmed by generating knockout cell lines of targets. CONCLUSIONS: This class of compounds holds promise as a potential, novel chemotherapeutic approach and demonstrates the effectiveness of pleiotropically targeting autophagy and apoptosis as a viable strategy for combating high grade serous ovarian cancer. Citation Format: Alexandria N. Young, Steven Kurina, Andrew Huntsman, Rathnayake A. Rathnayake, Melissa Korkmaz, A. Douglas Kinghorn, Leslie Aldrich, Stephanie Cologna, James R. Fuchs, Joanna E. Burdette. TARGET DISCOVERY OF NATURAL PRODUCT INSPIRED PHYLLANTHUSMINS FOR TREATMENT OF HIGH GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-119.