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Louisiana has high coastal wetland loss rates due to natural processes such as subsidence and anthropogenic activities such as construction of river levees and dams, pervasive alteration of surface hydrology by local industries such as oil and gas, and navigation. With the exception of the Atchafalaya River discharge area, most of Louisiana's marsh coastline is retreating and coastal marshes are degrading. In the inactive degrading delta regions, there exists a previously uncharacterized landform referred to colloquially as coastal ‘land bridge’ marshes. Land bridge marshes are saline or brackish marshes fronting large estuarine bays or lakes with sufficient fetch and wave energy to supply high levels of resuspended sediments to the marsh surface. They are generally linear features that are oriented parallel to the coast and the shoreline front retreats landward due to erosion from wave energy. These marshes persist over time vertically due to input of resuspended sediments but are experiencing rapid edge erosion due to wave attack. Comparison of data from Louisiana's Coastal Reference Monitoring System (CRMS) sites show that land bridge marshes have a greater frequency of higher soil surface elevation and higher soil bulk density than non-land bridge marshes. Because land bridges are vertically stable relative to other coastal wetlands, identification of measures to sustain these landscape features is important. Simulations using MarshMorpho2D, a process-based reduced-complexity morphology model, suggest that protection barriers installed on the seaward side of land bridge marshes will attenuate wave energy and, thus, edge erosion. Shoreline protection that can reduce wave energy but still allow sediment input to marshes include living shorelines, rock barriers, and/or breakwaters. Periodic thin layer nourishment of the marsh surface may be necessary to help sustain vertical growth. Further, marsh creation projects directly landward of land bridge marshes may benefit from their protection from waves and as a source of sediment. Consideration of land bridge marshes as distinct marsh types in the State Master Plan and integrated modeling could help to identify measures to sustain these landscape features.

Background: Metabolic changes induced by the host immune response to pathogens found in patients with community-acquired pneumonia (CAP) may provide insight into its pathogenesis. In this study, we characterized differences in the host metabolic response to common CAP-associated pathogens. Method: Targeted metabolomic profiling was performed on serum samples obtained from hospitalized CAP patients (n = 119) at admission. We quantified 347 unique metabolites across multiple biochemical classes, including amines, acylcarnitines, and signaling lipids. We evaluated if unique associations between metabolite levels and specific CAP-associated pathogens could be identified. Results: Several acylcarnitines were found to be elevated in C. burnetii and herpes simplex virus and lowered in M. pneumoniae as compared to other pathogens. Phenylalanine and kynurenine were found elevated in L. pneumophila as compared to other pathogens. S-methylcysteine was elevated in patients with M. pneumoniae, and these patients also showed lowered cortisol levels in comparison to almost all other pathogens. For the herpes simplex virus, we observed a unique elevation of eicosanoids and several amines. Many lysophosphatidylcholines showed an altered profile in C. burnetii versus S. pneumoniae, L. pneumophila, and respiratory syncytial virus. Finally, phosphatidylcholines were negatively affected by the influenza virus in comparison to S. pneumoniae. Conclusions: In this exploratory analysis, metabolites from different biochemical classes were found to be altered in serum samples from patients with different CAP-associated pathogens, which may be used for hypothesis generation in studies on differences in pathogen host response and pathogenesis of CAP.

Summary: Background: Continuous glucose monitoring (CGM) improves glycaemia for people affected by type 1 diabetes (T1D), but is not funded in Aotearoa/New Zealand. This study explores the impact of non-funded CGM on equity of access and associated glycaemic outcomes. Methods: Cross-sectional population-based study collected socio-demographic (age, gender, prioritised ethnicity, socioeconomic status) and clinical data from all regional diabetes centres in New Zealand with children

Sand and mud reaching the Mississippi River Delta (MRD) via distributary channels created the delta lobes that, in aggregate, make up the current Deltaic Plain (DP). Sediments transported to the west in the coastal boundary current, in turn, have built the “downstream” Chenier Plain (CP). We review options for restoring the CP coast between the beach dune system and the first series of Cheniers that fronts the Gulf of Mexico (GOM) for ∼200 km to the west of the DP, and contributes 30% to total area of the MRD. The CP was built by marine rather than fluvial processes that have resulted in episodic westward and onshore transport of fine-grained sediments delivered to the inner shelf by the Atchafalaya River distributary. Long-term restoration of the MRD is currently proceeding under the Louisiana Coastal Protection and Restoration Authority (CPRA). Projects to stabilize the CP coast are being proposed and built to test whether coastal defense structures like breakwaters and groins designed to retard erosion on sandy coasts can be adapted for use on muddy shores where cohesive sediments predominate. An estimated 30 to 50 Mt y−1 of resuspended mud is moved past the CP coast by the coastal boundary current in a feature described as the “Atchafalaya Mud Stream.” Mid- to late-Holocene MRD lobes on the west side of the DP similarly contributed mud to the same part of the inner shelf. Then, as now, a portion of this near-shore suspended sediment flux was diverted into shore-welded mudflats that were colonized by marsh vegetation that offset local shoreline retreat. The CP is a regressive coastal feature, formed since sea level rise and marine transgression slowed, and it has experienced a 19% wetland loss since the early 1930s. Coastal retreat, up to more than 10 m y−1, prevails along more than half of the CP shore. Most structures built on the CP coast are constructed of lightweight materials to reduce settlement and lower deployment costs. If the generally positive results to date are validated, then designs can be optimized to increase transmissivity of high-density “fluid mud” (>10 g l−1) during low-frequency swell, while reducing energy transmission in the higher frequency band occupied by locally generated seas that seem to be most destructive to newly created mudflats and marshes. We show that restoration in the CP can be enhanced by taking advantage of the land building capabilities of mud stored in the nearshore and delivered to the coast during storms. The goal is to use engineered structures to increase the rate at which mud is deposited and retained at the shore, thereby harnessing natural processes to reinforce the coast. The use of dredged sediments for wetland creation augments coastal shoreline enhancement.

Objective: The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Māori and peoples of Polynesia), with a frequency of up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It remains unclear whether the increased BMI is driven by increased adiposity or by increased lean mass. Methods: We undertook body composition analysis using DXA in 189 young men of Māori and Pacific descent living in Aotearoa New Zealand. Further investigation was carried out in two orthologous Arg458Gln knockin mouse models on FVB/NJ and C57BL/6j backgrounds. Results: The rs373863828 A allele was associated with lower fat mass when adjusted for BMI (p < 0.05) and was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p < 0.05). Supporting the human data, significant reductions in adipose tissue mass were observed in the knockin mice. This was more significant in older mice in both backgrounds and appeared to be the result of reduced age-associated increases in fat mass. The older male knockin mice on C57BL/6j background also had increased grip strength (p < 0.01) and lower levels of myostatin (p < 0.05). Conclusion: Overall, these results prove that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contribute to an age-dependent lowering of fat mass, at least in males.

Mutations in BRCA1 and CHEK2 genes associated with hereditary breast cancer were tested in 7920 randomly selected individuals of Novosibirsk (Russia). Mutations BRCA1 5382insC and CHEK2 1100delC were the most frequent, they were found in 0.25% and 0.4% of the general population respectively. We suggested to find mutations carriers by the screening of all breast/ovary cancer patients for the most frequent mutations (BRCA1 5382insC and CHEK2 1100delC) with subsequent analysis of the first-line relatives of cancer patients if one of the mutations was found. From June 2013 till January 2015, all patients from Novosibirsk regional oncology hospital with the diagnosis of breast cancer and some patients with the diagnosis of ovary cancer were tested for mutations BRCA1 5382insC and CHEK2 1100delC. A total of 2655 cancer patients were analyzed independently of their family history. We found 122 mutations carriers, among them 99 patients with mutations in BRCA1 gene and 23 patients with mutation CHEK2 1100delC. Among mutation carriers, 105 patients agreed to have a medical genetic counseling and after pedigree analysis 193 first-line relatives aged above 25 years were elucidated. One hundred ten first-line relatives of mutation carriers were analyzed for the mutations presence and 40 mutations carriers were found among relatives. From September 2013 till December 2013, 32 relatives of BRCA mutation carriers underwent breast MRI. In 5 cases, breast cancer was detected by MRI and all cancers except one were confirmed histologically with biopsy analysis. Importantly, all tumors were 5 mm and less in size, stage I cancer was detected in all cases. At a follow-up of 1.5 years, all 105 mutation carrier probands were interviewed by phone regarding possible relapse and/or possible primary cancer in their relatives. Five of 105 probands lost to follow-up may have died. Among responding 100 patients, 2 died as reported by relatives, relapse was reported in 7 probands – mutation carrier probands, primary tumors were reported in 8 relatives of probands. Mutation carrier probands reported one bilateral breast cancer, four ovary cancers, one bladder cancer and one non-specified oncogynecological tumor. There were five cases of primary breast cancer, one ovary cancer, one colon cancer, one lung cancer among relatives of breast cancer patients with mutations. The frequency of tumors found in mutation carriers exceeded the average frequencies of cancer for this population. The economic value of the regional genetic screening can be easily estimated according to the data obtained in this study and data on treatment cost for stage I and stage IV breast cancer. To summarize briefly, the screening of hot-spot mutations provides not only increase of lifespan expectancy and life quality for mutation carriers, but can be also a tool for financial saving of medical system due to the increase of early stage breast cancer detection.

Abstract For hypoplastic left heart syndrome (HLHS), there have been concerns regarding pulmonary artery growth and ventricular dysfunction after first stage surgery consisting of the Norwood procedure modified with a right ventricle-to-pulmonary artery conduit. We report our experience using cardiovascular magnetic resonance (CMR) to determine and follow pulmonary arterial growth and ventricular function in this cohort. Following first stage palliation, serial CMR was performed at 1 and 10 weeks post-operatively, followed by cardiac catheterization at 4 – 6 months. Thirty-four of 47 consecutive patients with HLHS (or its variations) underwent first stage palliation. Serial CMR was performed in 20 patients. Between studies, ejection fraction decreased (58 ± 9% vs. 50 ± 5%, p < 0.05). Pulmonary artery growth occurred on the left (6 ± 1 mm vs. 4 ± 1 mm at baseline, p < 0.05) but not significantly in the right. This trend continued to cardiac catheterization 4–6 months post surgery, with the left pulmonary artery of greater size than the right (8.8 ± 2.2 mm vs. 6.7 +/- 1.9 mm, p < 0.05). By CMR, 5 had pulmonary artery stenoses initially, and at 2 months, 9 had stenoses. Three of the 9 underwent percutaneous intervention prior to the second stage procedure. In this cohort, reasonable growth of pulmonary arteries occurred following first stage palliation with this modification, although that growth was preferential to the left. Serial studies demonstrate worsening of ventricular function for the cohort. CMR was instrumental for detecting pulmonary artery stenosis and right ventricular dysfunction.

Transitional care teams have been shown to improve patient safety. We describe a novel transitional care team with a clinical pharmacist as team leader initiated amid the COVID-19 pandemic. The program focused on Veterans with 2 planned transitions of care: hospital to skilled nursing facility (SNF) and from SNF to home. Ninety older Veterans were enrolled, and 79 medication errors and 80 appointment errors were identified. We conclude that a pharmacist-led program can improve safety in patients with 2 planned transitions of care., Competing Interests: Disclosure The authors declare no conflicts of interest. During the preparation of this work, the authors used Gemini AI to assist with grammar and editing. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication., (Published by Elsevier Inc.)

Background: Clinical trials suggest that long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) may reduce depressive symptoms in adults with major depressive disorder. Therefore, n-3 PUFAs may be a potential treatment for depression in youth., Methods: Participants were 15- to-25 year-old individuals with major depressive disorder who sought care in one of three government-funded mental health services for young people in metropolitan Melbourne, Perth, or Sydney, Australia. Participants were randomly assigned in a double-blind, parallel-arm design to receive either fish oil (840 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid) or placebo capsules as adjunct to cognitive behavioral case management. All participants were offered 50-minute cognitive behavioral case management sessions every 2 weeks delivered by qualified therapists (treatment as usual) at the study sites during the intervention period. The primary outcome was change in the interviewer-rated Quick Inventory of Depressive Symptomatology, Adolescent Version, score at 12 weeks. Erythrocyte n-3 PUFA levels were assessed pre-post intervention., Results: A total of 233 young people were randomized to the treatment arms: 115 participants to the n-3 PUFA group and 118 to the placebo group. Mean change from baseline in the Quick Inventory of Depressive Symptomatology score was -5.8 in the n-3 PUFA group and -5.6 in the placebo group (mean difference, 0.2; 95% CI, -1.1 to 1.5; p = .75). Erythrocyte PUFA levels were not associated with depression severity at any time point. The incidence and severity of adverse events were similar in the two groups., Conclusions: This placebo-controlled trial and biomarker analysis found no evidence to support the use of fish oil for treatment in young people with major depressive disorder., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the vaginoscopic management of longitudinal vaginal septum in the case of obstructive hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome., Design: Surgical video describing step-by-step management., Setting: OHVIRA syndrome also known as Herlyn-Werner-Wunderlich syndrome is a triad of obstructed hemivagina, uterus didelphys, and ipsilateral renal anomaly [1] (Supplimentary Video 1). Patients usually present after menarche with progressive dysmenorrhea, lower abdominal pain, a paravaginal mass, foul mucopurulent discharge, and intermenstrual bleeding due to hemi hematocolpos [2]. Magnetic resonance imaging is the choice of investigation [3]. Surgical resection of the septum is the choice of treatment, which can be done vaginoscopically to reduce postoperative pain and promote enhanced recovery [4]. In this video, we will demonstrate a case of a 28-years old, nulliparous woman diagnosed with uterine didelphys having lower abdominal pain and persistent vaginal discharge., Interventions: The video demonstrates the technique of vaginoscopic excision of the right hemi-vaginal septum that resulted in complete visualization of both cervices. Diagnostic laparoscopy confirmed uterine didelphys. The left cervix was visualized and the hysteroscope was negotiated into the cervical canal (Supplimentary Video 2). The left cavity was normal with left ostia. Intraoperative transrectal-ultrasound was done to localize the cystic collection in the right hemivagina. Needle aspiration of cystic collection was done over the bulging portion of the right hemivagina and mucoid material was aspirated. Longitudinal obstructive vaginal septum was incised using a collins knife and mucoid secretions were drained (Supplimentary Video 3). Hysteroscope inserted into opened right hemivagina, negotiated through the right cervix and right hemiuterus with right ostia was visualized. The residual septum was resected with a loop electrode and hemostasis was ensured. Cystoscopy done, left ureteric orifice with urine reflux visualized. Vaginal examination showed both cervices with near normal reconstructed vagina., Conclusion: The possibility of OHVIRA syndrome should be considered in all cases of uterine didelphys. Vaginoscopic management is a safe and effective method with a minimally invasive approach., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

The Molecular Microscope Diagnostic System (MMDx) analyzes RNA transcripts of transplanted heart tissue to differentiate among T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), injury, and healthy tissue. However, little is known about its performance in relation to other modalities in a real-world heart transplant population. We evaluated whether MMDx performs in agreement with other validated modalities. Two hundred and twenty-eight corresponding endomyocardial biopsies (EMBx) and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed with correlating donor-derived cell-free DNA (dd-cfDNA). Rejection was classified on EMBx in 29 specimens (TCMR ≥ 2R and/or AMR ≥ 1), on MMDx in 56 specimens, and in 74 values with dd-cfDNA ≥0.20%. Despite moderate agreement between EMBx and MMDx (84% agreement, Cohen's kappa, 0.48, p < .001), systematic differences were observed (McNemar's test, p < .001) where MMDx classified 32 of 37 discordant cases as rejection. MMDx and dd-cfDNA demonstrated slight agreement (72% agreement, Cohen's kappa, 0.39, p < .001); however, systematic differences were also apparent where MMDx classified 12 of 50 discordant specimens as rejection when dd-cfDNA was <0.20% (McNemar's test, p < .001). Our findings provide insight on the performance of MMDx relative to other modalities in a heart transplant cohort and have implications on the surveillance and workup of allograft rejection in heart transplantation., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could predict future functional outcome in CHR individuals. The complement and coagulation pathways have previously been identified as being of relevance to the pathophysiology of psychosis and have been found to contribute to the prediction of clinical outcome in CHR participants. Hence, in the second part we extended the analysis to evaluate specifically the relationship of complement and coagulation proteins with psychotic symptoms and functional outcome in CHR., Materials and Methods: We carried out plasma proteomics and measured plasma cytokine levels, and erythrocyte membrane fatty acid levels in a sub-sample (n = 158) from the NEURAPRO clinical trial at baseline and 6 months follow up. Functional outcome was measured using Social and Occupational Functional assessment Score (SOFAS) scale. Firstly, we used support vector machine learning techniques to develop predictive models for functional outcome at 12 months. Secondly, we developed linear regression models to understand the association between 6-month follow-up levels of complement and coagulation proteins with 6-month follow-up measures of positive symptoms summary (PSS) scores and functional outcome., Results and Conclusion: A prediction model based on clinical and biological data including the plasma proteome, erythrocyte fatty acids and cytokines, poorly predicted functional outcome at 12 months follow-up in CHR participants. In linear regression models, four complement and coagulation proteins (coagulation protein X, Complement C1r subcomponent like protein, Complement C4A & Complement C5) indicated a significant association with functional outcome; and two proteins (coagulation factor IX and complement C5) positively associated with the PSS score. Our study does not provide support for the utility of cytokines, proteomic or fatty acid data for prediction of functional outcomes in individuals at high-risk for psychosis. However, the association of complement protein levels with clinical outcome suggests a role for the complement system and the activity of its related pathway in the functional impairment and positive symptom severity of CHR patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Implantable loop recorders (ILRs) are effective in achieving symptom-rhythm correlation. Data on the diagnostic yield of ILRs, on nurse-led syncope clinics, and on nurse-led ILR implants are limited., Objective: We evaluated the safety and efficacy of our nurse-led syncope clinic and nurse-led ILR implants., Methods: A retrospective study of all consecutive patients undergoing nurse-led ILR implantations was performed between April 2016 and April 2018. Patients were referred from both nurse-led and physician-led clinics. Data were collected on baseline demographic characteristics, referral source, symptom-rhythm correlation, ILR findings, and subsequent changes to management. All ILRs were enrolled into remote monitoring with automatic arrhythmia detection, and all immediate (≤24 hours) ILR implant complications were recorded. Comparisons were made between nurse-led and physician-led clinics and subsequent outcomes., Results: A total of 432 patients with an ILR were identified: 164 (38%) from nurse-led and 268 (62%) from physician-led clinics; 200 (46%) were women (mean age 66.5 ± 18.2 years; mean follow-up duration 28.9 ± 9.5 months). Primary ILR indications were syncope (n = 251 [58%]), presyncope (n = 33 [7%]), palpitation (n = 39 [9%]), cryptogenic stroke (n = 78 [18%]), and other reasons (n = 31 [7%]). No immediate ILR implant complications occurred. Overall, 156 patients (36%) had a change in management as a direct result of ILR findings, with no overall differences between nurse-led and physician-led clinics (35% vs 36%; P = .7). More patients had newly diagnosed atrial fibrillation in physician-led clinics (15% vs 7%; P = .01), and more patients had pacemaker implants for bradycardia in nurse-led clinics (23% vs 13%; P < .01)., Conclusion: Nurse-led ILR implantation was safe and effective. Nurse-led syncope clinics achieved good symptom-rhythm correlation with resultant significant changes to management in comparison to physician-led clinics. Larger prospective studies are needed to evaluate their longer-term impact., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Study Objective: To study the reproductive outcomes after laparoscopic myomectomy comparing conventional (nonbarbed) suture with barbed suture used for myometrial defect closure., Design: Monocentric retrospective cohort study with prospective follow-up survey for reproductive outcomes conducted in April and May 2020., Setting: Tertiary care center (center for advanced gynecologic laparoscopy and infertility)., Patients: Women who underwent laparoscopic myomectomy for uterine leiomyomas from January 2004 to December 2017., Interventions: Laparoscopic myomectomy with closure of the myometrium using either conventional (nonbarbed suture) or barbed suture and follow-up survey regarding reproductive outcomes., Measurements and Main Results: The outcomes measured included the rate of conception, pregnancy complications, mode of delivery, and perioperative complications for both kinds of suture materials used. Of the 399 women who underwent laparoscopic myomectomy, 343 satisfied the inclusion criteria and were followed up; 235 patients responded. A total of 120 patients were included in the nonbarbed group (group A), and 115 patients were included in the barbed group (group B). A total of 182 (group A: 97 vs group B: 85; p = .204) women had actively sought pregnancy postoperatively, of whom 93 (51.09%) in total and 51 (54.8%) in group A vs 42 (45.1%) in group B reported at least 1 pregnancy with no significant difference in the incidence rate ratios between the 2 groups. Of the recorded pregnancies84.9% (group A: 88.2% vs group B: 80.9%) live births, 6.4% (group A: 5.8% vs group B: 7.1%) had first-trimester miscarriages, 2.1% (group A: 1.9% vs group B: 2.3%) had an ectopic pregnancy, and 6 were ongoing pregnancies at the time of the study analysis, which were compared statistically between both study groups. Pregnancy-related complications were noted in 12 of the 93 pregnant women (12.9%), which were comparable in both groups. No case of uterine rupture was reported., Conclusion: Our study supports good reproductive outcomes in women after laparoscopic myomectomy with barbed sutures. Furthermore, the inclusion of nonbarbed sutures as a control group in our study reinforces that barbed sutures in myomectomy are as safe as, and an easier alternative to, conventional sutures without affecting pregnancy outcomes., (Copyright © 2021 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation., (Copyright © 2021. Published by Elsevier Inc.)

Dependent on phosphate availability the yeast Saccharomyces cerevisiae expresses either low or high affinity phosphate transporters. In the presence of phosphate yeast cells still express low levels of the high affinity phosphate transporter Pho84. The regulator Spl2 is expressed in approximately 90% of the cells, and is not expressed in the remaining cells. Here we report that deletion of RRP6, encoding an exonuclease degrading non-coding RNA, or BMH1, encoding the major 14-3-3 isoform, resulted in less cells expressing SPL2 and in increased levels of RNA transcribed from sequences upstream of the SPL2 coding region. SPL2 stimulates its own expression and that of PHO84 ensuing a positive feedback. Upon deletion of the region responsible for upstream SPL2 transcription almost all cells express SPL2. These results indicate that the cell-to-cell variation in PHO84 and SPL2 expression is dependent on a specific part of the SPL2 promoter and is controlled by Bmh1 and Spl2., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Vitamin K antagonists (VKAs), such as warfarin, have remained the cornerstone of oral anticoagulation therapy in the prevention and treatment of thromboembolism for more than half a century. They function by impairing the biosynthesis of vitamin K-dependent (VKD) clotting factors through the inhibition of vitamin K epoxide reductase (VKOR). The challenge of VKAs therapy is their narrow therapeutic index and highly variable dosing requirements, which are partially the result of genetic variations of VKOR., Objectives: The goal of this study was to search for an improved VKA that is tolerant to the genetic variations of its target enzyme., Methods: A series of vitamin K derivatives with benzyl and related side-chain substitutions at the 3-position of 1,4-naphthoquinone were synthesized. The role of these compounds in VKD carboxylation was evaluated by mammalian cell-based assays and conventional in vitro activity assays., Results: Our results showed that replacing the phytyl side-chain with a methylene cyclooctatetraene (COT) moiety at the 3-position of vitamin K 1 converted it from a substrate to an inhibitor for VKD carboxylation. Strikingly, this COT-vitamin K derivative displayed a similar inhibition potency in warfarin-resistant VKOR mutations whose warfarin resistance varied more than 400-fold. Further characterization of COT-vitamin K for the inhibition of VKD carboxylation suggested that this compound targets multiple enzymes in the vitamin K redox cycle. Importantly, the anticoagulation effect of COT-vitamin K can be rescued with high doses of vitamin K 1 ., Conclusion: We discovered a vitamin K analogue that functions as a VKA and is tolerant to genetic variations in the target enzyme., (© 2020 International Society on Thrombosis and Haemostasis.)

Background: A key clinical challenge in the management of individuals at clinical high risk for psychosis (CHR) is that it is difficult to predict their future clinical outcomes. Here, we investigated if the levels of circulating molecular lipids are related to adverse clinical outcomes in this group., Methods: Serum lipidomic analysis was performed in 263 CHR individuals and 51 healthy control subjects, who were then clinically monitored for up to 5 years. Machine learning was used to identify lipid profiles that discriminated between CHR and control subjects, and between subgroups of CHR subjects with distinct clinical outcomes., Results: At baseline, compared with control subjects, CHR subjects (independent of outcome) had higher levels of triacylglycerols with a low acyl carbon number and a double bond count, as well as higher levels of lipids in general. CHR subjects who subsequently developed psychosis (n = 50) were distinguished from those that did not (n = 213) on the basis of lipid profile at baseline using a model with an area under the receiver operating curve of 0.81 (95% confidence interval = 0.69-0.93). CHR subjects who became psychotic had lower levels of ether phospholipids than CHR individuals who did not (p < .01)., Conclusions: Collectively, these data suggest that lipidomic abnormalities predate the onset of psychosis and that blood lipidomic measures may be useful in predicting which CHR individuals are most likely to develop psychosis., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Study Objective: Cervical insufficiency occurs in 0.1% to 1 % of all pregnancies and is associated with a high risk of second-trimester abortion and/or preterm delivery [1]. Laparoscopic encerclage is highly recommended for a previous failed vaginal encerclage and is superior to the laparotomy approach in terms of low morbidity and faster recovery [2]. Laparoscopic encerclage in pregnancy is more challenging than that in the nonpregnant state. This is because of the enlarged uterine size, engorged uterine vessels, and infeasibility of using a uterine manipulator. The standardization and description of the technique are the main objectives of this video (Video 1). We have described the surgery in 6 steps that could make this procedure easier and safer., Design: A step-by-step video demonstration of the technique., Setting: Paul's Hospital, Centre for Advanced Endoscopy & Infertility Treatment, Kochi, India. A 29-year-old pregnant woman, gravida 3 abortions 2, at 13 weeks period of gestation, with a history of 2 second-trimester abortions owing to cervical insufficiency. The patient had a failed vaginal cervical encerclage at 18 weeks in the second pregnancy., Interventions: This is a step-wise laparoscopic approach for successful cervical encerclage in pregnancy. In this video, we demonstrate our technique for laparoscopic cervical encerclage in a pregnant woman's uterus in 6 steps using a Mersilene tape (Ethicon US, LLC, Somerville, NJ) as follows: (1) Opening the uterovesical fold and dissecting the bladder, (2) opening the left broad ligament and creating a window, (3) opening the right broad ligament and creating a window, (4) placing the Mersilene tape on the left side medial to the uterine vessels at the cervicoisthmic junction, (5) placing the Mersilene tape on the right side medial to the uterine vessels at the cervicoisthmic junction, (6) tying the Mersilene tape anteriorly., Conclusion: The standardization of laparoscopic cervical encerclage in pregnancy using the above 6 steps could make this procedure easier and safer to perform. Moreover, the standardization of the surgical technique could shorten the learning curve., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer patients with triple-negative or human epidermal growth factor receptor 2 (HER2)-overexpressing phenotypes are recommended to receive chemotherapy for primary tumors greater than 1 cm regardless of nodal status. Neoadjuvant chemotherapy may eradicate subclinical nodal metastases and reduce the extent of axillary surgery performed., Patients and Methods: A query of the National Cancer Database Participant User File was performed for new cases of female breast cancer from 2012 to 2015. Inclusion criteria were clinical N0 status, receipt of chemotherapy, and receipt of axillary surgery. Exclusions included hormone-positive/HER2-negative tumors and/or distant metastatic disease. Subjects were divided into groups by receipt of neoadjuvant or adjuvant chemotherapy. The primary end point was the extent of axillary surgery, defined as sentinel lymph node biopsy alone or axillary lymph node dissection (ALND). Subgroup analyses were performed on the basis of tumor phenotype and surgery of the primary site., Results: A total of 66,771 female patients were included, 15,967 of whom underwent neoadjuvant chemotherapy. ALND rates were higher in patients who received adjuvant chemotherapy (30.6% vs. 28.8%, P < .001). Among tumor phenotypes, the extent of axillary surgery was reduced most significantly for hormone-negative, HER2-positive disease (30.0% vs. 25.8%, P < .001). ALND rates were more substantially reduced for patients who underwent mastectomy (41.3% vs. 36.1%, P < .001) compared to partial mastectomy (21.8% vs. 20.1%, P = .002). Adjuvant chemotherapy was an independent predictor of ALND (odds ratio, 1.26; 95% confidence interval, 1.19-1.33)., Conclusion: Neoadjuvant chemotherapy reduces the extent of axillary surgery in clinically node-negative, nonluminal breast cancers., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Study Objective: To demonstrate a technique of laparoscopy-assisted neocervicovaginal reconstruction in a case of cervicovaginal aplasia., Design: Step-by-step demonstration of the surgery in an instructional video., Setting: Cervicovaginal aplasia is a rare congenital anomaly that occurs in 1 in 80 000 to 100 000 live births [1]. Occasionally, there can be other associated anomalies. Epigenetic modifications of homeobox and Wnt genes (wingless-type mouse mammary tumor virus integration site family) are hypothesized to cause defects in the development of the müllerian reproductive tract by interfering with cell migration during organogenesis [2]. Our patient was a 15-year-old girl who had a unicornuate uterus along with cervicovaginal aplasia (American Society for Reproductive Medicine class Ia, Ib, and IIc and European Society of Human Reproduction and Embryology class U4a, C4, and V4). The most common approach to treat this particular anomaly is hysterectomy, but there are many reports of neocervicovaginal reconstruction with good results [3]., Interventions: Laparoscopic assessment showed a right unicornuate uterus with hematometra, right hematosalpinx, and a left noncavitary rudimentary horn with endometriosis. A vertical incision was made over the most prominent bulging part of the uterine fundus, and the hematometra was drained. Laparoscopic inspection of the uterine cavity showed an irregular cavity with thickened endometrium. The cervical canal could not be identified. The inspection of the external genitalia revealed complete vaginal aplasia. An inverted T incision was made over the vestibule and neovagina created by blunt digital dissection. The bladder was laparoscopically mobilized down. A Maryland dissector was inserted into the uterine cavity through the incision in the fundus and directed toward the neovagina. The myometrium was then punctured while simultaneously visualizing the neovagina to create a neocervix. A 16-F Foley's catheter was then pulled into the uterine cavity with the Maryland dissector from the vaginal end. The neocervix was enlarged around the catheter and then sutured to the vestibular epithelium with 6 interrupted 1-0 polyglactin sutures. The Foley's catheter was anchored to the myometrium laparoscopically, and the uterine incision was closed with interrupted 1-0 polyglactin sutures. The right hematosalpinx was then excised. The intravaginal plastic mold was removed after 4 days. The patient was advised to use the bulb of a plastic pipette to help maintain vaginal patency. She resumed her menses 3 weeks after the surgery. Follow-up at 8 months revealed a normal-sized uterus on transabdominal ultrasound and a vaginal length of 5.5 cm on speculum examination. She currently reports regular cyclic menstruation with mild dysmenorrhea and has not yet begun sexual activity., Conclusion: Cervicovaginal aplasia can be successfully treated by laparoscopy-assisted neocervicovaginal reconstruction as demonstrated in the video., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)