In vitro fertilization outcome based on the detailed early luteal phase trajectory of hormones: a prospective cohort study.

BACKGROUND: Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer. METHODS: This prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18-38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile. RESULTS: Ninety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28-3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03-4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth. CONCLUSIONS: These data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF. TRIAL REGISTRATION: NCT04693624 ( www. CLINICALTRIALS: gov ).

Palliative procedures for malignant gastric outlet obstruction: a network meta-analysis.

BACKGROUND: The optimal treatment for malignant gastric outlet obstruction (GOO) remains uncertain. This systematic review aimed to comprehensively investigate the efficacy and safety of four palliative treatments for malignant GOO: gastrojejunostomy, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), stomach-partitioning gastrojejunostomy (PGJ), and endoscopic stenting. METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform for randomized controlled trials (RCTs) and cohort studies comparing the four treatments for malignant GOO. We included studies that reported at least one of the following clinical outcomes: clinical success, 30-day mortality, reintervention rate, or length of hospital stay. Evidence from RCTs and non-RCTs was naïve combined to perform network meta-analysis through the frequentist approach using an inverse variance model. Treatments were ranked by P score. RESULTS: This network meta-analysis included 3617 patients from 4 RCTs, 4 prospective cohort studies, and 32 retrospective cohort studies. PGJ was the optimal approach in terms of clinical success and reintervention (P scores: 0.95 and 0.90, respectively). EUS-GE had the highest probability of being the optimal treatment in terms of 30-day mortality and complications (P scores: 0.82 and 0.99, respectively). Cluster ranking to combine the P scores for 30-day mortality and reintervention indicated the benefits of PGJ and EUS-GE (cophenetic correlation coefficient: 0.94; PGJ and EUS-GE were in the same cluster). CONCLUSION: PGJ and EUS-GE are recommended for malignant GOO. PGJ could be the alternative choice in centers with limited resources or in patients who are unsuitable for EUS-GE.

Enhanced Calvarial Bone Repair Using ASCs Engineered with RNA-Guided Split dCas12a System that Co-Activates Sox 5, Sox6, and Long Non-Coding RNA H19.

Healing of large calvarial bone defects remains challenging. An RNA-guided Split dCas12a system is previously harnessed to activate long non-coding RNA H19 (lncRNA H19, referred to as H19 thereafter) in bone marrow-derived mesenchymal stem cells (BMSCs). H19 activation in BMSCs induces chondrogenic differentiation, switches bone healing pathways, and improves calvarial bone repair. Since adipose-derived stem cells (ASCs) can be harvested more easily in large quantity, here it is aimed to use ASCs as an alternative cell source. However, H19 activation alone using the Split dCas12a system in ASCs failed to elicit evident chondrogenesis. Therefore, split dCas12a activators are designed more to co-activate other chondroinductive transcription factors (Sox5, Sox6, and Sox9) to synergistically potentiate differentiation. It is found that co-activation of H19/Sox5/Sox6 in ASCs elicited more potent chondrogenic differentiation than activation of Sox5/Sox6/Sox9 or H19 alone. Co-activating H19/Sox5/Sox6 in ASCs significantly augmented in vitro cartilage formation and in vivo calvarial bone healing. These data altogether implicated the potentials of the Split dCas12a system to trigger multiplexed gene activation in ASCs for differentiation pathway reprogramming and tissue regeneration.

Drug-Induced Parkinsonism: Too Many Cooks in the Kitchen.

Drug-induced parkinsonism (DIP) is a condition characterized by the development of parkinsonian symptoms as a result of medication use. It is often misdiagnosed and can be challenging to differentiate from Parkinson's disease (PD). In this case presentation, we describe the clinical course of a 64-year-old male who presented with parkinsonian symptoms while using atypical antipsychotics, which was originally misdiagnosed as PD. The case highlights the importance of recognizing the potential iatrogenic effects of medications with antidopaminergic properties, such as antipsychotics and antiepileptic drugs, which are common culprits in causing DIP. We discuss DIP management, long-term impacts, and differentiating DIP from PD through clinical findings and imaging, emphasizing the utility of the (123)I-ioflupane single-photon emission computerized tomography (SPECT) scan in aiding diagnosis. This case serves as a reminder to healthcare providers to remain vigilant in monitoring patients for adverse effects, polypharmacy, and harmful medication interactions.

Mechanical Properties of Ternary Composite from Waste Leather Fibers and Waste Polyamide Fibers with Acrylonitrile-Butadiene Rubber.

This study aimed to improve the mechanical properties of a composite material consisting of waste leather fibers (LF) and nitrile rubber (NBR) by partially replacing LF with waste polyamide fibers (PA). A ternary recycled composite NBR/LF/PA was produced by a simple mixing method and vulcanized by compression molding. The mechanical properties and dynamic mechanical properties of the composite were investigated in detail. The results showed that the mechanical properties of NBR/LF/PA increased with an increase in the PA ratio. The highest tensile strength value of NBR/LF/PA was found to have increased about 1.26 times, that is from 12.9 MPa of LF50 to 16.3 MPa of LF25PA25. Additionally, the ternary composite demonstrated high hysteresis loss, which was confirmed by dynamic mechanical analysis (DMA). The presence of PA formed a non-woven network that significantly enhanced the abrasion resistance of the composite compared to NBR/LF. The failure mechanism was also analyzed through the observation of the failure surface using scanning electron microscopy (SEM). These findings suggest that the utilization of both waste fiber products together is a sustainable approach to reducing fibrous waste while improving the qualities of recycled rubber composites.

Single-cell multi-omics in the medicinal plant Catharanthus roseus.

Advances in omics technologies now permit the generation of highly contiguous genome assemblies, detection of transcripts and metabolites at the level of single cells and high-resolution determination of gene regulatory features. Here, using a complementary, multi-omics approach, we interrogated the monoterpene indole alkaloid (MIA) biosynthetic pathway in Catharanthus roseus, a source of leading anticancer drugs. We identified clusters of genes involved in MIA biosynthesis on the eight C. roseus chromosomes and extensive gene duplication of MIA pathway genes. Clustering was not limited to the linear genome, and through chromatin interaction data, MIA pathway genes were present within the same topologically associated domain, permitting the identification of a secologanin transporter. Single-cell RNA-sequencing revealed sequential cell-type-specific partitioning of the leaf MIA biosynthetic pathway that, when coupled with a single-cell metabolomics approach, permitted the identification of a reductase that yields the bis-indole alkaloid anhydrovinblastine. We also revealed cell-type-specific expression in the root MIA pathway.

A longitudinal assessment of appetite loss and nutritional care among postoperative patients in Vietnam.

Background: Post-operative appetite loss is an important complication affecting surgical outcomes. It has been estimated that nearly 60% of patients having gastrointestinal or major elective surgeries suffer from malnutrition. Appetite refers to the physical desire for food appetite, and losing appetite after surgery may result in a decrease in body weight, impairment of intestinal absorption and eventually, malnutrition among postoperative patients. This study aims to assess appetite status and other relevant factors among abdominal postoperative patients in Vietnam. Methods: A cross-sectional study was conducted on 169 abdominal postoperative patients from June 1st to August 30th, 2016 at Hanoi Medical University Hospital, Hanoi, Vietnam. Appetite score was computed by using the Council on Nutrition Appetite Questionnaire (CNAQ). This study used GEE to account for the potential correlation of outcomes of the longitudinal assessment, assuming an independent correlation structure. Results: The primary and secondary outcome measures: highest average appetite score was recorded in the preoperative day and the score declined throughout seven-day duration. Patients who were female, under general anesthetics and being under open surgery tended to get lower appetite scores. The majority of patients had moderate to good appetite in both the preoperative day and seven days post-operation. Conclusion: Women should receive more care and help in regaining their appetite after surgery. Treatment for appetite loss through non-pharmaceutical measures should be prioritized. Interventions that increase the appetite of patients after abdominal surgery should be targeted on patients being under general anesthetic as well as open surgery and be undertaken with caution.

Split dCas12a activator for lncRNA H19 activation to enhance BMSC differentiation and promote calvarial bone healing.

Healing of large calvarial bone defects in adults is challenging. We previously showed that inducing chondrogenic differentiation of mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ASC) before implantation can switch the repair pathway and improve calvarial bone healing. Split dCas12a activator is a new CRISPR activation system comprising the amino (N) and carboxyl (C) fragments of dCas12a protein, each being fused with synthetic transcription activators at both termini. The split dCas12a activator was shown to induce programmable gene expression in cell lines. Here we exploited the split dCas12a activator to activate the expression of chondroinductive long non-coding RNA H19. We showed that co-expression of the split N- and C-fragments resulted in spontaneous dimerization, which elicited stronger activation of H19 than full-length dCas12a activator in rat BMSC and ASC. We further packaged the entire split dCas12a activator system (13.2 kb) into a hybrid baculovirus vector, which enhanced and prolonged H19 activation for at least 14 days in BMSC and ASC. The extended H19 activation elicited potent chondrogenic differentiation and inhibited adipogenesis. Consequently, the engineered BMSC promoted in vitro cartilage formation and augmented calvarial bone healing in rats. These data implicated the potentials of the split dCas12a activator for stem cell engineering and regenerative medicine.

Pathogenesis, Diagnosis and Management of Squamous Cell Carcinoma and Pseudoepithelial Hyperplasia Secondary to Red Ink Tattoo: A Case Series and Review.

The increasing popularity of tattooing has paralleled an increase in associated cutaneous reactions. Red ink is notorious for eliciting cutaneous reactions. A common reaction is pseudoepitheliomatous hyperplasia (PEH), which is a benign condition closely simulating squamous cell carcinoma (SCC). Differentiating PEH from SCC is challenging for pathologists and clinicians alike. The exact pathogenesis of these lesions secondary to red ink is not known, and there are no sources outlining diagnostic and treatment options and their efficacy. We present four study cases with different pathologies associated to red ink tattoos including lichenoid reaction, granulomatous reaction, PEH, and an SCC. Additionally, an extensive review of 63 articles was performed to investigate pathogenesis, diagnostic approaches, and treatment options. Hypotheses surrounding pathogenesis include but are not limited to the carcinogenic components of pigments, their reaction with UV and the traumatic process of tattooing. Pathogenesis seems to be multifactorial. Full-thickness biopsies with follow-up is the recommended diagnostic approach. There is no evidence of a single universally successful treatment for PEH. Low-dose steroids are usually tried following a step up in lack of clinical response. For SCC lesions, full surgical excision is widely used. A focus on clinicians' awareness of adverse reactions is key for prevention. Regulation of the unmonitored tattoo industry remains an ongoing problem.

Preliminary results of laparoscopic cholecystectomy using real-time indocyanine green fluorescence: a cross-sectional study.

Evaluating the results of laparoscopic cholecystectomy (LC) using indocyanine green (ICG) fluorescence. Materials and methods: This is a cross-sectional study of patients with LC using real-time fluorescent ICG to treat gallbladder disease from May 2021 to May 2022 in the 108 Military Central Hospital. Results: There were 68 patients who underwent LC using intraoperative ICG fluorescence for bile duct visualization. The mean age of the patients was 55.4±16.2, and the male/female ratio was 1.52. Chronic cholecystitis caused by stones accounted for the majority (51.47%). The authors detected 7.35% of cases with anatomical changes of the extrahepatic biliary tract using ICG fluorescence and clearly identified the anatomy of the common bile duct and the cystic duct at 100 and 92.65%, respectively. The average surgical time was 42.8±14.6 min. There were no postoperative complications or side effects from ICG; the average hospital stay was 2.8±1.5 days. Conclusions: ICG fluorescence cholangiography allows surgeons to easily identify critical anatomical landmarks in the LC. Thereby helping the surgery to be performed safely, avoiding severe complications due to damage to the biliary tract.

Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib.

BACKGROUND: We have recently shown a frequent upregulation of Src-family kinases (SFK) in head and neck squamous cell carcinoma (HNSCC). Here we tested, if SFK targeting is effective especially in HNSCC cells with upregulated SFK signaling. METHODS: The impact of SFK inhibitors SU6656, PP2 and dasatinib on three HNSCC cell lines with different SFK activity levels was analyzed using proliferation and colony formation assays, Western blot and functional kinomics. RESULTS: Proliferation was blocked by all inhibitors in a micro-molar range. With respect to cell kill, dasatinib was most effective, while SU6656 showed moderate and PP2 minor effects. Cellular signaling was affected differently, with PP2 having no effect on SFK signaling while dasatinib probably has non-SFK specific effects. Only SU6656 showed clear SFK specific effects on signaling. CONCLUSION: The results demonstrate potential benefit of SFK inhibition in HNSCC but they also highlight challenges due to non-specificities of the different drugs.

Encapsulation of Bioactive Compounds from Germinated Mung Bean by Freeze-Drying, Release Kinetics, and Storage Stability.

This research explores the application of germinated mung bean extract, rich in GABA (Gamma-aminobutyric acid) and polyphenols, in enhancing human health. Recognizing the instability of these bioactive compounds in environmental conditions, encapsulation emerges as a pivotal technique to broaden their applications in food and pharmaceuticals. Utilizing response surface methodology and Box-Behnken design, the freeze-drying formulation for encapsulating the aqueous extract was optimized. Second-order polynomial models were developed, exhibiting statistical adequacy in predicting key variables such as encapsulation efficiency for GABA (EE-GABA) and total polyphenol content (EE-TPC), as well as encapsulation yield for GABA (EY-GABA) and total polyphenol content (EY-TPC). The established optimal formulation was validated, resulting in predicted values for EE-GABA, EE-TPC, EY-GABA, and EY-TPC. The release kinetics of encapsulated particles were investigated, highlighting the suitability of the Korsmeyer-Peppas and Higuchi models. Assessing the stability of the encapsulated powder under varying temperatures and humidities revealed degradation rates, half-life, and activation energy, with moisture equilibrium established at 4.70%, indicative of long-term stability. In conclusion, the encapsulated germinated mung bean powder demonstrates high stability, making it a promising candidate for integration into food products and functional ingredients.

How to do it: Splenic flexure mobilisation via medial trans-mesocolic approach.

Complete splenic flexure mobilization is a critical step in left-sided colorectal resections. Surgeons use three approaches-anterior, medial, and lateral-to divide peritoneal ligaments connecting the left colon. The decision to perform mobilization varies, with minimal impact on post-operative outcomes but longer surgery times and rare complications. Pancreatic injury risk is low, though other structures, like arteries and the duodenum, may be at risk. Our video outlines the medial trans-mesocolic approach, with the patient positioned in lithotomy. We expose the duodenal-jejunal flexure, ligate the inferior mesenteric vein, and perform medial to lateral dissection, completing splenic flexure mobilization. This video vignette outlines how to perform this technique for left sided colorectal resections.

Differential Cytotoxicity of Curcumin-Loaded Micelles on Human Tumor and Stromal Cells.

Although curcumin in the form of nanoparticles has been demonstrated as a potential anti-tumor compound, the impact of curcumin and nanocurcumin in vitro on normal cells and in vivo in animal models is largely unknown. This study evaluated the toxicity of curcumin-loaded micelles in vitro and in vivo on several tumor cell lines, primary stromal cells, and zebrafish embryos. Breast tumor cell line (MCF7) and stromal cells (human umbilical cord vein endothelial cells, human fibroblasts, and human umbilical cord-derived mesenchymal stem cells) were used in this study. A zebrafish embryotoxicity (FET) assay was conducted following the Organisation for Economic Co-operation and Development (OECD) Test 236. Compared to free curcumin, curcumin PM showed higher cytotoxicity to MCF7 cells in both monolayer culture and multicellular tumor spheroids. The curcumin-loaded micelles efficiently penetrated the MCF7 spheroids and induced apoptosis. The nanocurcumin reduced the viability and disturbed the function of stromal cells by suppressing cell migration and tube formation. The micelles demonstrated toxicity to the development of zebrafish embryos. Curcumin-loaded micelles demonstrated toxicity to both tumor and normal primary stromal cells and zebrafish embryos, indicating that the use of nanocurcumin in cancer treatment should be carefully investigated and controlled.

Aberrant artery embolization prior to pulmonary sequestration surgery: A case series report.

OBJECTIVES: Pulmonary sequestration is a rare congenital malformation, and part of its treatment requires the removal of the aberrant artery by surgical means. MATERIALS AND METHODS: Five patients treated at Military Hospital 103 - Department of Thoracic Disease were diagnosed with PS via CT scan, MS-CT, and DSA, and histopathological data were evaluated retrospectively between January and December 2019. RESULTS: In all patients, surgery is the preferred option, with two cases of video-assisted thoracoscopic surgery (one lobectomy and one wedge resection), and three cases of hybrid video-assisted thoracoscopic surgery (adhesive inflammation was observed, the bronchus is challenging to reveal, to resect, and tend to bleed when resecting). The average length of stay following surgery is 11.6 ± 8.1 days. The mean duration of postoperative follow-up is 13.8 ± 3.3 months, all patients had a good quality of life, and no respiratory problems such as hemoptysis or pneumonia were detected. CONCLUSION: The excellent outcomes obtained in all patients in our study during the follow-up period (13.8 ± 3.3 months) established the appropriate indication and treatment. However, these are preliminary findings; a longer study period with a larger sample size is required to draw more valid conclusions.

Pilot randomized sham-controlled trial of self-acupressure to manage the symptom cluster of insomnia, depression, and anxiety in cancer patients undergoing chemotherapy.

PURPOSE: Current evidence for using self-acupressure to manage the cancer-related symptom cluster of insomnia, depression, and anxiety, while promising, is unknown. This study evaluated the feasibility of self-acupressure to manage this symptom cluster and to explore its potential effectiveness. METHODS: Participants were assigned randomly to three study groups, namely the true acupressure (TAP), the sham acupressure (SAP), and the enhanced standard care group (ESC). Participants in the TAP and SAP groups received a training session on acupressure and were required to practice self-acupressure at home once per day for 28 days. The duration of participant involvement was 8 weeks. Patients completed a Numerical Rating Scale (NRS) for each symptom, the Insomnia Severity Index, the Hospital Anxiety and Depression Scale, and the Functional Assessment of Cancer Therapy-General at baseline (T1), post-intervention (T2, week 4), and post follow-up (T3, week 8). RESULTS: The results indicated that the intervention had clinical significance in improving the targeted symptoms and quality of life. In the TAP group, the symptom cluster severity was significantly lower than in the other groups at T2 (p < 0.05). The insomnia severity and anxiety scores in the TAP and SAP groups were significantly lower than those in ESC at T2 and T3 (p < 0.05). CONCLUSION: The trial was feasible. The promising results of the study suggest that further testing of self-acupressure is warranted to inform its effectiveness on the targeted symptom cluster in patients with cancer. A placebo effect was evident alongside therapeutic effects. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT03823456) on January 30th, 2019.

RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells.

RARA and RXRA contribute to myeloid maturation in both mice and humans, and deletion of Rxra and Rxrb augments leukemic growth in mice. While defining the domains of RXRA that are required for anti-leukemic effects in murine KMT2A-MLLT3 leukemia cells, we unexpectedly identified RXRA DT448/9PP as a constitutively active variant capable of inducing maturation and loss of their proliferative phenotype. RXRA DT448/9PP was associated with ligand-independent activity in reporter assays, with enhanced co-activator interactions, reduced engraftment in vivo, and activation of myeloid maturation transcriptional signatures that overlapped with those of cells treated with the potent RXRA agonist bexarotene, suggestive of constitutive activity that leads to leukemic maturation. Phenotypes of RXRA DT448/9PP appear to differ from those of two other RXRA mutations with forms of constitutive activity (F318A and S427F), in that DT448/9PP activity was resistant to mutations at critical ligand-interacting amino acids (R316A/L326A) and was resistant to pharmacological antagonists, suggesting it may be ligand-independent. These data provide further evidence that activated retinoid X receptors can regulate myeloid maturation and provide a novel constitutively active variant that may be germane for broader studies of retinoid X receptors in other settings.

Impact of single-stage laparoscopic trans-cystic exploration on hospital procedures, admissions and length-of-stay in common bile duct stone clearance.

BACKGROUND: Single-stage approach with bile duct exploration is considered the most efficient and cost-effective method of bile duct clearance. In Australia, apart from centres with subspecialty interests, notably in Brisbane, Queensland, a multi-stage approach with endoscopic retrograde cholangiopancreatography (ERCP) is used more frequently. We aim to evaluate the impact of single stage laparoscopic trans-cystic exploration (LTCE) versus multi-stage approach for choledocholithiasis. METHODS: This was a retrospective cohort study. Medicare Benefits Schedule codings were used to identify patients who had the following procedures between December 2011 and December 2019: laparoscopic cholecystectomy (LC) and ERCP, LC and LTCE, LC and LTCE and ERCP. Primary outcomes were number of hospital procedures, admissions and additive length of stay (aLOS), the cumulative hospital stay from admission to discharge. RESULTS: Of 607 patients, 204 (34%) patients received a single-stage LTCE, while 403 (66%) patients had a multi-stage approach. In the LTCE group, 82% (168) patients and 93% (190) patients had one procedure and one admission respectively for stone clearance (P = 0.001). The median aLOS was 4 days for LTCE versus 7 days for multi-stage approach (P = 0.001; 95% CI for difference - 3 to -2). In the multi-stage group, 16% (65) patients had three or more procedures and 49% (199) patients required two or more hospital admissions to achieve stone clearance. CONCLUSION: LTCE for stone clearance can be successfully accomplished with reductions in hospital admissions, number of procedures and length of stay. This has further economic and health resource implications.

A novel stop codon mutation in exon 5 (c.639G>A) of the cadherin-1 gene in a Vietnamese man with hereditary diffuse gastric cancer: a case report.

BACKGROUND: Germline pathogenic variants in the cadherin-1 (CDH1) gene cause a predisposition to hereditary diffuse gastric cancer (HDGC). We report an HDGC case in Vietnam and identify a novel mutation in the CDH1 gene. CASE PRESENTATION: A 28-year-old Vietnamese man was diagnosed with HDGC and a novel mutation at c.639G>A. All exons of CDH1 were sequenced in his pedigree, which revealed the c.639G>A mutation in the proband, his father, and uncle. The patient refused treatment and died 4 months after diagnosis. Endoscopic surveillance of the father and the uncle showed structural abnormalities in the father. CONCLUSION: In cases of HDGC, identification of the CDH1 gene mutation is very important for better counseling and more effective strategies to prevent the development of diseases, such as prophylactic gastrectomy for family members with genetic mutations.