Now showing items 1-20 of 13027

    • From Intention to Action: Operationalizing AGA Diversity Policy to Combat Racism and Health Disparities in Gastroenterology.

      Carr, Rotonya M; Quezada, Sandra M; Gangarosa, Lisa M; Cryer, Byron; Abreu, Maria T; Teixeira, Kathleen; Springer, Jeff; Margolis, Peter; Serena, Thomas J; Weinstein, Michael; et al. (Elsevier Ltd., 2020-11-01)
    • Assessment of brain cholesterol metabolism biomarker 24S-hydroxycholesterol in schizophrenia

      Chiappelli, Joshua; Quinton, Maria S; Volfson, Dmitri; Cwik, Michael; Marshall, Wyatt; Bruce, Heather; Goldwaser, Eric; Kvarta, Mark; Summerfelt, Ann; Kochunov, Peter; et al. (Springer Nature, 2020-11-20)
      Plasma 24S-hydroxycholesterol mostly originates in brain tissue and likely reflects the turnover of cholesterol in the central nervous system. As cholesterol is disproportionally enriched in many key brain structures, 24S-hydroxycholesterol is a promising biomarker for psychiatric and neurologic disorders that impact brain structure. We hypothesized that, as schizophrenia patients have widely reported gray and white matter deficits, they would have abnormal levels of plasma 24S-hydroxycholesterol, and that plasma levels of 24S-hydroxycholesterol would be associated with brain structural and functional biomarkers for schizophrenia. Plasma levels of 24S-hydroxycholesterol were measured in 226 individuals with schizophrenia and 204 healthy controls. The results showed that levels of 24S-hydroxycholesterol were not significantly different between patients and controls. Age was significantly and negatively correlated with 24S-hydroxycholesterol in both groups, and in both groups, females had significantly higher levels of 24S-hydroxycholesterol compared to males. Levels of 24S-hydroxycholesterol were not related to average fractional anisotropy of white matter or cortical thickness, or to cognitive deficits in schizophrenia. Based on these results from a large sample and using multiple brain biomarkers, we conclude there is little to no value of plasma 24S-hydroxycholesterol as a brain metabolite biomarker for schizophrenia.
    • Posterior Femoral Cam Decompression Through an Arthroscopic Anterior Approach With Pre-Bent Hip Burrs

      Ochiai, Derek; Costales, Timothy; Riley, Thomas; Rosado, Michelle; Adib, Farshad (Elsevier Ltd., 2020-11-16)
      Hip arthroscopy has been increasingly used to treat labral tears and cam and pincer lesions found in femoroacetabular impingement. Although the classic impingement with cam deformity at the proximal femoral anterolateral quadrant is most common, there has been evidence of cam impingement extension to the anteromedial and posterior quadrants of the proximal femur. Posterior cam decompression carries a theoretical risk of vascular insult and subsequent osteonecrosis, which have led investigators to approach these posterior lesions through an open surgical correction. Recent improvements have led to the development of pre-bent burs that allow for bonier resection flexibility. Here, we report on an arthroscopic posterior cam decompression using the traditional anterior portals and curved hip burs via a figure-of-four positioning technique.
    • Opinion: For now, it's unethical to use human challenge studies for SARS-CoV-2 vaccine development.

      Kahn, Jeffrey P; Henry, Leslie Meltzer; Mastroianni, Anna C; Chen, Wilbur H; Macklin, Ruth (National Academy of Sciences, 2020-10-29)
    • NQO1 protects obese mice through improvements in glucose and lipid metabolism

      Di Francesco, Andrea; Choi, Youngshim; Bernier, Michel; Zhang, Yingchun; Diaz-Ruiz, Alberto; Aon, Miguel A.; Kalafut, Krystle; Ehrlich, Margaux R.; Murt, Kelsey; Ali, Ahmed; et al. (Springer Nature, 2020-12-01)
      Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of glucose homeostasis, insulin sensitivity, and lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated the association with and inhibition of the translational machinery in skeletal muscle of NQO1 transgenic mice. NQO1-Tg mice on high-fat diet had lower adipose tissue macrophages and enhanced expression of lipogenic enzymes coincident with reduction in circulating and hepatic lipids. Metabolomics data revealed a systemic metabolic signature of improved glucose handling, cellular redox, and NAD+ metabolism while label-free quantitative mass spectrometry in skeletal muscle uncovered a distinct diet- and genotype-dependent acetylation pattern of SIRT3 targets across the core of intermediary metabolism. Thus, under nutritional excess, NQO1 transgenesis preserves healthful benefits.
    • Integrated analysis of microRNA and mRNA expression profiles in Crassostrea gigas to reveal functional miRNA and miRNA-targets regulating shell pigmentation.

      Feng, Dandan; Li, Qi; Yu, Hong; Liu, Shikai; Kong, Lingfeng; Du, Shaojun (Springer Nature, 2020-11-19)
      MicroRNAs (miRNAs) regulate post-transcription gene expression by targeting genes and play crucial roles in diverse biological processes involving body color formation. However, miRNAs and miRNA-targets underlying shell color polymorphism remain largely unknown in mollusca. Using four shell colors full-sib families of the Pacific oyster Crassostrea gigas, we systematically identified miRNAs and miRNA-targets in the mantles, which organ could produce white, golden, black or partially pigmented shell. RNA sequencing and analysis identified a total of 53 known miRNA and 91 novel miRNAs, 47 of which were detected to differentially express among six pairwise groups. By integrating miRNA and mRNA expression profiles, a total of 870 genes were predicted as targets of differentially expressed miRNAs, mainly involving in biomineralization and pigmentation through functional enrichment. Furthermore, a total of four miRNAs and their target mRNAs were predicted to involve in synthesis of melanin, carotenoid or tetrapyrrole. Of them, lgi-miR-317 and its targets peroxidase and lncRNA TCONS_00951105 are implicated in acting as the competing endogenous RNA to regulate melanogenesis. Our studies revealed the systematic characterization of miRNAs profiles expressed in oyster mantle, which might facilitate understanding the intricate molecular regulation of shell color polymorphism and provide new insights into breeding research in oyster.
    • Extracellular vesicles from young women's breast cancer patients drive increased invasion of non-malignant cells via the Focal Adhesion Kinase pathway: a proteomic approach.

      Jordan, Kimberly R; Hall, Jessica K; Schedin, Troy; Borakove, Michelle; Xian, Jenny J; Dzieciatkowska, Monika; Lyons, Traci R; Schedin, Pepper; Hansen, Kirk C; Borges, Virginia F (Springer Nature, 2020-11-23)
      Background: Extracellular vesicles (EVs) are small membrane particles that contribute to cancer progression and metastases by transporting biologically significant proteins and nucleic acids. They may also serve as biomarkers of various disease states or important therapeutic targets. Breast cancer EVs have the potential to change the behavior of other cells in their microenvironment. However, the proteomic content of EVs isolated from young women’s breast cancer patients and the mechanisms underlying the influence of EVs on tumor cell behavior have not yet been reported. Methods: In our current translational studies, we compared the proteomic content of EVs isolated from invasive breast cancer cell lines and plasma samples from young women’s breast cancer (YWBC) patients and age-matched healthy donors using mass spectrometry. We analyzed the functionality of EVs in two dimensional tumor cell invasion assays and the gene expression changes in tumor cells after incubation with EVs. Results: We found that treatment with EVs from both invasive breast cancer cell lines and plasma of YWBC patients altered the invasive properties of non-invasive breast cancer cells. Proteomics identified differences between EVs from YWBC patients and healthy donors that correlated with their altered function. Further, we identified gene expression changes in non-invasive breast cancer cells after treatment with EVs that implicate the Focal Adhesion Kinase (FAK) signaling pathway as a potential targetable pathway affected by breast cancer-derived EVs. Conclusions: Our results suggest that the proteome of EVs from breast cancer patients reflects their functionality in tumor motility assays and may help elucidate the role of EVs in breast cancer progression.
    • International Olympic Committee (IOC) Sport Mental Health Assessment Tool 1 (SMHAT-1) and Sport Mental Health Recognition Tool 1 (SMHRT-1): towards better support of athletes' mental health.

      Gouttebarge, Vincent; Bindra, Abhinav; Blauwet, Cheri; Campriani, Niccolo; Currie, Alan; Engebretsen, Lars; Hainline, Brian; Kroshus, Emily; McDuff, David; Mountjoy, Margo; et al. (BMJ Publishing Group, 2020-09-18)
      Objectives: To develop an assessment and recognition tool to identify elite athletes at risk for mental health symptoms and disorders. Methods: We conducted narrative and systematic reviews about mental health symptoms and disorders in active and former elite athletes. The views of active and former elite athletes (N=360) on mental health symptoms in elite sports were retrieved through an electronic questionnaire. Our group identified the objective(s), target group(s) and approach of the mental health tools. For the assessment tool, we undertook a modified Delphi consensus process and used existing validated screening instruments. Both tools were compiled during two 2-day meeting. We also explored the appropriateness and preliminary reliability and validity of the assessment tool. Sport Mental Health Assessment Tool 1 and Sport Mental Health Recognition Tool 1: The International Olympic Committee Sport Mental Health Assessment Tool 1 (SMHAT-1) was developed for sports medicine physicians and other licensed/registered health professionals to assess elite athletes (defined as professional, Olympic, Paralympic or collegiate level; aged 16 years and older) potentially at risk for or already experiencing mental health symptoms and disorders. The SMHAT-1 consists of: (i) triage with an athlete-specific screening tool, (ii) six subsequent disorder-specific screening tools and (iii) a clinical assessment (and related management) by a sports medicine physician or licensed/registered mental health professional (eg, psychiatrist and psychologist). The International Olympic Committee Sport Mental Health Recognition Tool 1 (SMHRT-1) was developed for athletes and their entourage (eg, friends, fellow athletes, family and coaches). Conclusion: The SMHAT-1 and SMHRT-1 enable that mental health symptoms and disorders in elite athletes are recognised earlier than they otherwise would. These tools should facilitate the timely referral of those athletes in need for appropriate support and treatment.
    • 60 Years after Kefauver: Household income required to buy prescription drugs in the United States and abroad.

      Mattingly, T Joseph; Seo, Dominique; Ostrovsky, Adam M; Vanness, David J; Conti, Rena M (Elsevier Ltd., 2020-11-16)
      Background: Assessing drug prices relative to income in the US compared to other Organization for Economic Co-Operation and Development (OECD) countries provides context for policymakers seeking to improve access and affordability. Methods: Using current drug p. rice and income data, we recreate a historical analysis presented in 1960 to the Senate Subcommittee on Antitrust and Monopoly led by Sen. Estes Kefauver. We identified frequently prescribed generic and brand name drugs for US and international comparison by drug price category (low-price generics, mid-price brands, and high-price specialty brands) as a function of income. We further extend our analysis to consider US prices relative to the current Federal Poverty Level (FPL). Results: For the low-price drugs, all fell below 1% of all of the US income levels presented. Mid-price drugs were below 10% of income for those at the US median household income level but approached 30% of income for those at the FPL. High-price drugs varied greatly, reaching over 600% FPL for one product. Conclusions: Americans receive bargain prices on par with international comparators for many low-priced generics drugs. For commonly used mid-priced drugs or high-priced specialty products, whether or not drug prices are considered a bargain in the US compared to international markets may depend on individual income. External reference pricing policies may help inform the negotiation for some drug prices, but affordability may still be limited for lower wage earners.
    • Perceptions of Equity and Inclusion in Acute Care Surgery: From the #EAST4ALL Survey.

      Tseng, Esther S; Zakrison, Tanya L; Williams, Brian; Bernard, Andrew C; Martin, Matthew J; Zebib, Laura; Soklaridis, Sophie; Kaafarani, Haytham M; Zarzaur, Ben L; Crandall, Marie; et al.
      OBJECTIVES AND BACKGROUND: The aim of this study was to characterize equity and inclusion in acute care surgery (ACS) with a survey to examine the demographics of ACS surgeons, the exclusionary or biased behaviors they witnessed and experienced, and where those behaviors happen. A major initiative of the Equity, Quality, and Inclusion in Trauma Surgery Practice Ad Hoc Task Force of the Eastern Association for the Surgery of Trauma was to characterize equity and inclusion in ACS. To do so, a survey was created with the above objectives. METHODS: A cross-sectional, mixed-methods anonymous online survey was sent to all EAST members. Closed-ended questions are reported as percentages with a cutoff of α = 0.05 for significance. Quantitative results were analyzed focusing on mistreatment and bias. RESULTS: Most respondents identified as white, non-Hispanic and male. In the past 12 months, 57.5% of females witnessed or experienced sexual harassment, whereas 48.6% of surgeons of color witnessed or experienced racial/ethnic discrimination. Sexual harassment, racial/ethnic prejudice, or discrimination based on sexual orientation/sex identity was more frequent in the workplace than at academic conferences or in ACS. Females were more likely than males to report unfair treatment due to age, appearance or sex in the workplace and ACS (P ≤ 0.002). Surgeons of color were more likely than white, non-Hispanics to report unfair treatment in the workplace and ACS due to race/ethnicity (P < 0.001). CONCLUSIONS: This is the first survey of ACS surgeons on equity and inclusion. Perceptions of bias are prevalent. Minorities reported more inequity than their white male counterparts. Behavior in the workplace was worse than at academic conferences or ACS. Ensuring equity and inclusion may help ACS attract and retain the best and brightest without fear of unfair treatment.
    • Development of autoimmune diabetes with severe diabetic ketoacidosis and immune-related thyroiditis secondary to durvalumab: a case report.

      Lopes, Ana Rita; Russo, Alessandro; Li, Andrew Y; McCusker, Michael G; Kroopnick, Jeffrey Myles; Scilla, Katherine; Mehra, Ranee; Rolfo, Christian (AME Publishing Company, 2020-10)
      Immune-mediated endocrinopathies are among the most frequent immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICIs) targeting programmed death-ligand 1 (PDL1)/PD-1. However, the development of auto-immune diabetes is an uncommon event during PD(L)-1 blockade, either as monotherapy or in combination therapy. Here we report a case of a 75-year-old male with a mediastinal recurrence from a stage IA squamous cell carcinoma of the lung previously treated with stereotactic body radiotherapy (SBRT) who early developed a severe diabetic ketoacidosis (DKA) caused by new-onset auto-immune diabetes, with positive glutamic acid decarboxylase (GAD65) autoantibodies, during durvalumab consolidation therapy after concurrent chemoradiation. The patient had no personal or family history of diabetes or auto-immune diseases and was admitted after the second cycle of durvalumab to the intensive care unit (ICU) with severe DKA. During his hospitalization, insulin and fluid therapy were started and the patient had a favorable clinical course. Durvalumab treatment was interrupted and thyroiditis was verified during follow-up, without anti-thyroid antibodies, that progressed to subsequent hypothyroidism with need of thyroid hormone replacement therapy. This case highlights the rare irAE of autoimmune type 1 diabetes during anti-PD(L)-1 therapy, which can be life-threatening and requires adequate patient education and prompt medical treatment within a multidisciplinary team, including endocrinology and emergency medicine. Besides its low incidence, this case show how irAE must be taken in account about decision of ICI treatment, especially in curative setting, as they can be potentially fatal and impair overall survival. Furthermore, as reported in the present case, multiple endocrine irAEs can occur in the same patient either simultaneously or sequentially, suggesting that active surveillance is needed in those who develop endocrinopathies as a result of ICI treatment. Immune-mediated endocrinopathies are generally irreversible and cause life-long morbidity, which must be taken into consideration when deciding on further lines of treatment.
    • Orthodontic force induces nerve injury-like transcriptomic changes driven by TRPV1-expressing afferents in mouse trigeminal ganglia.

      Wang, Sheng; Chung, Man-Kyo (SAGE Publications Inc., 2020-11-20)
      Orthodontic force produces mechanical irritation and localized inflammation in the periodontium, which causes pain in most patients. Nocifensive behaviors resulting from orthodontic force in mice can be substantially attenuated by intraganglionic injection of resiniferatoxin (RTX), a neurotoxin that specifically ablates a subset of neurons expressing transient receptor potential vanilloid 1 (TRPV1). In the current study, we determined changes in the transcriptomic profiles in the trigeminal ganglia (TG) following the application of orthodontic force, and assessed the roles of TRPV1-expressing afferents in these transcriptomic changes. RTX or vehicle was injected into the TG of mice a week before the placement of an orthodontic spring exerting 10 g of force. After 2 days, the TG were collected for RNA sequencing. The application of orthodontic force resulted in 1279 differentially expressed genes (DEGs) in the TG. Gene ontology analysis showed downregulation of gliogenesis and ion channel activities, especially of voltage-gated potassium channels. DEGs produced by orthodontic force correlated more strongly with DEGs resulting from nerve injury than from inflammation. Orthodontic force resulted in the differential expression of multiple genes involved in pain regulation, including upregulation of Atf3, Adcyap1, Bdnf, and Csf1, and downregulation of Scn10a, Kcna2, Kcnj10, and P2ry1. Orthodontic force-induced DEGs correlated with DEGs specific to multiple neuronal and non-neuronal subtypes following nerve injury. These transcriptomic changes were abolished in the mice that received the RTX injection. These results suggest that orthodontic force produces transcriptomic changes resembling nerve injury in the TG and that nociceptive inputs through TRPV1-expressing afferents leads to subsequent changes in gene expression not only in TRPV1-positive neurons, but also in TRPV1-negative neurons and non-neuronal cells throughout the ganglia. Orthodontic force-induced transcriptomic changes might be an active regenerative program of trigeminal ganglia in response to axonal injury following orthodontic force.
    • Atopic dermatitis as a multifactorial skin disorder. Can the analysis of pathophysiological targets represent the winning therapeutic strategy?

      Magnifico, Irene; Petronio, Giulio Petronio; Venditti, Noemi; Cutuli, Marco Alfio; Pietrangelo, Laura; Vergalito, Franca; Mangano, Katia; Zella, Davide; Di Marco, Roberto (MDPI AG, 2020-11-01)
      Atopic dermatitis (AD) is a pathological skin condition with complex aetiological mechanisms that are difficult to fully understand. Scientific evidence suggests that of all the causes, the impairment of the skin barrier and cutaneous dysbiosis together with immunological dysfunction can be considered as the two main factors involved in this pathological skin condition. The loss of the skin barrier function is often linked to dysbiosis and immunological dysfunction, with an imbalance in the ratio between the pathogen Staphylococcus aureus and/or other microorganisms residing in the skin. The bibliographic research was conducted on PubMed, using the following keywords: ‘atopic dermatitis’, ‘bacterial therapy’, ‘drug delivery system’ and ‘alternative therapy’. The main studies concerning microbial therapy, such as the use of bacteria and/or part thereof with microbiota transplantation, and drug delivery systems to recover skin barrier function have been summarized. The studies examined show great potential in the development of effective therapeutic strategies for AD and AD-like symptoms. Despite this promise, however, future investigative efforts should focus both on the replication of some of these studies on a larger scale, with clinical and demographic characteristics that reflect the general AD population, and on the process of standardisation, in order to produce reliable data.
    • Severe Housing Insecurity during Pregnancy: Association with Adverse Birth and Infant Outcomes.

      Leifheit, Kathryn M; Schwartz, Gabriel L; Pollack, Craig E; Edin, Kathryn J; Black, Maureen M; Jennings, Jacky M; Althoff, Keri N (2020-11-21)
      Introduction: Housing insecurity is increasingly commonplace among disadvantaged women and children. We measured the individual- and population-level impact of severe housing insecurity during pregnancy on adverse birth and infant outcomes. Methods: We analyzed data from 3428 mother-infant dyads enrolled in the Fragile Families and Child Wellbeing Study, a prospective cohort study representing births in 20 large U.S. cities from 1998 to 2000. Severe housing insecurity was defined as threatened eviction or homelessness during pregnancy. Outcomes included low birth weight and/or preterm birth, admission to a neonatal intensive care unit (NICU) or stepdown facility, extended hospitalization after delivery, and infant health and temperament. We estimated exposure-outcome associations with risk ratios adjusted for pre-pregnancy maternal sociodemographic and heath factors and calculated a population attributable fraction (PAF) of outcomes attributable to severe housing insecurity. Results: We found statistically significant associations between severe housing insecurity during pregnancy and low birth weight and/or preterm birth (risk ratio (RR] 1.73, 95% confidence interval (CI) 1.28, 2.32), NICU or stepdown stay (RR 1.64, CI 1.17, 2.31), and extended hospitalization (RR 1.66, CI 1.28, 2.16). Associations between housing insecurity and infant fair or poor health (RR 2.62, CI 0.91, 7.48) and poor temperament (RR 1.52, CI 0.98, 2.34) were not statistically significant. PAF estimates ranged from 0.9-2.7%, suggesting that up to three percent of adverse birth and infant outcomes could be avoided by eliminating severe housing insecurity among low-income, pregnant women in US cities. Conclusions: Results suggest that housing insecurity during pregnancy shapes neonatal and infant health in disadvantaged urban families.
    • Choline Plus Working Memory Training Improves Prenatal Alcohol-Induced Deficits in Cognitive Flexibility and Functional Connectivity in Adulthood in Rats.

      Waddell, Jaylyn; Hill, Elizabeth; Tang, Shiyu; Jiang, Li; Xu, Su; Mooney, Sandra M (MDPI AG, 2020-11-14)
      Fetal alcohol spectrum disorder (FASD) is the leading known cause of intellectual disability, and may manifest as deficits in cognitive function, including working memory. Working memory capacity and accuracy increases during adolescence when neurons in the prefrontal cortex undergo refinement. Rats exposed to low doses of ethanol prenatally show deficits in working memory during adolescence, and in cognitive flexibility in young adulthood. The cholinergic system plays a crucial role in learning and memory processes. Here we report that the combination of choline and training on a working memory task during adolescence significantly improved cognitive flexibility (performance on an attentional set shifting task) in young adulthood: 92% of all females and 81% of control males formed an attentional set, but only 36% of ethanol-exposed males did. Resting state functional magnetic resonance imaging showed that functional connectivity among brain regions was different between the sexes, and was altered by prenatal ethanol exposure and by choline + training. Connectivity, particularly between prefrontal cortex and striatum, was also different in males that formed a set compared with those that did not. Together, these findings indicate that prenatal exposure to low doses of ethanol has persistent effects on brain functional connectivity and behavior, that these effects are sex-dependent, and that an adolescent intervention could mitigate some of the effects of prenatal ethanol exposure.
    • Preclinical Metrics Correlate With Drug Activity in Phase II Trials of Targeted Therapies for Non-Small Cell Lung Cancer

      Rybinski, Brad; Hosgood, H. Dean; Wiener, Sara L.; Weiser, Daniel A. (Frontiers Media S.A., 2020-11-05)
      Novel oncology drugs often fail to progress from preclinical experiments to FDA approval. Therefore, determining which preclinical or clinical factors associate with drug activity could accelerate development of effective therapies. We investigated whether preclinical metrics and patient characteristics are associated with objective response rate (ORR) in phase II clinical trials of targeted therapies for non-small cell lung cancer (NSCLC). We developed a reproducible process to select a single phase II trial and supporting preclinical publication for a given drug-indication pair, which we defined as the pairing of a small molecule inhibitor (e.g., crizotinib) with the specific patient population for which it was designed to work (e.g., patients with an ALK aberration). We demonstrated that robust drug activity in mice, as measured by change in tumor size, is independently associated with improved ORR in phase II clinical trials. The number of mice utilized in experiments, the number of publications referencing the drug for NSCLC before the phase II clinical trial, and whether the drug was approved for a cancer other than NSCLC also significantly correlated with ORR. Among clinical characteristics, sex, race, histology, and smoking history were significantly associated with ORR. Further research into metrics that correlate with drug activity has the potential to optimize selection of novel therapies for clinical trials and enrich the drug development pipeline, particularly for patients with targetable genetic aberrations and rare cancers.
    • Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease.

      Ravel, Jacques; Moreno, Inmaculada; Simón, Carlos (Elsevier Ltd., 2020-10-19)
      Bacterial vaginosis, pelvic inflammatory disease, and endometritis are infections of the genital tract that can lead to many adverse health outcomes, including infertility. Bacterial vaginosis is characterized by a lower prevalence of lactobacilli and a higher prevalence of anaerobic bacteria, including Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae. Endometritis and pelvic inflammatory disease are caused by the ascension of pathogenic bacteria to the uterus, although the mechanisms by which they do so are unclear. Bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease have been linked to infertility in retrospective and prospective trials. Similarly, the causes of bacterial vaginosis and endometritis-related infertility are likely multifactorial and stem from inflammation, immune targeting of sperm antigens, the presence of bacterial toxins, and increased risk of sexually transmitted infections. Diagnosis and treatment of bacterial vaginosis, chronic endometritis, and pelvic inflammatory disease before attempting conception may be important components of preconceptional care for symptomatic women to improve outcomes of natural and assisted reproduction.
    • Rapid, Ultrasensitive, and Quantitative Detection of SARS-CoV-2 Using Antisense Oligonucleotides Directed Electrochemical Biosensor Chip.

      Alafeef, Maha; Dighe, Ketan; Moitra, Parikshit; Pan, Dipanjan (American Chemical Society, 2020-10-20)
      A large-scale diagnosis of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is essential to downregulate its spread within as well as across communities and mitigate the current outbreak of the pandemic novel coronavirus disease 2019 (COVID-19). Herein, we report the development of a rapid (less than 5 min), low-cost, easy-to-implement, and quantitative paper-based electrochemical sensor chip to enable the digital detection of SARS-CoV-2 genetic material. The biosensor uses gold nanoparticles (AuNPs), capped with highly specific antisense oligonucleotides (ssDNA) targeting viral nucleocapsid phosphoprotein (N-gene). The sensing probes are immobilized on a paper-based electrochemical platform to yield a nucleic-acid-testing device with a readout that can be recorded with a simple hand-held reader. The biosensor chip has been tested using samples collected from Vero cells infected with SARS-CoV-2 virus and clinical samples. The sensor provides a significant improvement in output signal only in the presence of its target-SARS-CoV-2 RNA-within less than 5 min of incubation time, with a sensitivity of 231 (copies μL-1)-1 and limit of detection of 6.9 copies/μL without the need for any further amplification. The sensor chip performance has been tested using clinical samples from 22 COVID-19 positive patients and 26 healthy asymptomatic subjects confirmed using the FDA-approved RT-PCR COVID-19 diagnostic kit. The sensor successfully distinguishes the positive COVID-19 samples from the negative ones with almost 100% accuracy, sensitivity, and specificity and exhibits an insignificant change in output signal for the samples lacking a SARS-CoV-2 viral target segment (e.g., SARS-CoV, MERS-CoV, or negative COVID-19 samples collected from healthy subjects). The feasibility of the sensor even during the genomic mutation of the virus is also ensured from the design of the ssDNA-conjugated AuNPs that simultaneously target two separate regions of the same SARS-CoV-2 N-gene.
    • Abdominal Wall Transplantation: Indications and Outcomes

      Honeyman, Calum; Dolan, Roisin; Stark, Helen; Fries, Charles Anton; Reddy, Srikanth; Allan, Philip; Vrakas, Giorgios; Vaidya, Anil; Dijkstra, Gerard; Hofker, Sijbrand; et al. (Springer Nature, 2020-11-07)
      Purpose of Review: This article aims to review published outcomes associated with full-thickness vascularized abdominal wall transplantation, with particular emphasis on advances in the field in the last 3 years. Recent Findings: Forty-six full-thickness vascularized abdominal wall transplants have been performed in 44 patients worldwide. Approximately 35% of abdominal wall transplant recipients will experience at least one episode of acute rejection in the first year after transplant, compared with rejection rates of 87.8% and 72.7% for hand and face transplant respectively. Recent evidence suggests that combining a skin containing abdominal wall transplant with an intestinal transplant does not appear to increase sensitization or de novo donor-specific antibody formation. Summary: Published data suggests that abdominal wall transplantation is an effective safe solution to achieve primary closure of the abdomen after intestinal or multivisceral transplant. However, better data is needed to confirm observations made and to determine long-term outcomes, requiring standardized data collection and reporting and collaboration between the small number of active transplant centres around the world.