Does matrix transducer technology improve quality and repeatability of four-dimensional tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements?

Background: Novel ultrasound technology and software processing allow offline evaluation of tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements. We wished to compare both novel 4D matrix (eM6C) and conventional (RAB6-D) transducers with variable settings (electronic spatiotemporal image correlation, spatiotemporal image correlation and four-dimensional real time) to determine if there was a significant difference in absolute value, quality and repeatability of the resultant reconstructed image and M-mode trace. Methods: A blinded prospective cross-sectional study of normal fetuses from 23 to 38 weeks' gestation were recruited. After routine sonography, four-dimensional volumes were stored and analysed using GE 4DView™ software. Statistical analysis explored variability, correlations and repeatability of the measurements with chi-square analysis, intraclass correlations and the Bland-Altman comparison plots. A scoring system was devised for image quality. Results: Eighteen participants generated 282 data volumes. Absolute values demonstrated some inconsistencies for both tricuspid annular plane systolic excursion and mitral annular plane systolic excursion measurements with variations between transducers: the highest for the RAB6-D/spatiotemporal image correlation setting and the lowest for the four-dimensional real-time settings. The RAB6-D/spatiotemporal image correlation setting was the most repeatable combination (intraclass correlation coefficient = 0.85). Poorest image quality (M-mode trace, four-chamber view, annuli) came from the RAB6-D/four-dimensional real-time combination with the eM6C/electronic spatiotemporal image correlation and RAB6-D/spatiotemporal image correlation settings being nearly identical. Conclusion: We show that transducer and setting combinations influence absolute tricuspid annular plane systolic excursion/mitral annular plane systolic excursion measurements, so need to be articulated in future research. The transducer setting (electronic spatiotemporal image correlation/spatiotemporal image correlation/four-dimensional real time) was a more significant factor than the type of transducer (conventional vs matrix). Subjective image evaluation does not correlate well with repeatability of image acquisition. Further studies are needed to compare measurements using four-dimensional post-processing tools against conventional real-time measurements.

Training Medical Student Counselors for the Rochester Model, a Hospital Tobacco Treatment Program.

Purpose: Providing effective tobacco dependence treatments to hospitalized patients remains a challenge. Prior to 2021, the Rochester Model program used staff nurses for both bedside and post-discharge counseling necessary to maintain abstinence. When nurse shortages and elevated job stress occurred during the COVID Pandemic, we proposed that medical students learn to counsel patients at the bedside and after discharge. Patients and Methods: Due to COVID restrictions, first- and second-year medical students trained using remote Zoom sessions. The total training time was 2.5 hr without role-play or additional evaluations. A survey measured the students' satisfaction, confidence, and counseling barriers. A smoking patient on a participating hospital unit can enroll in the program. Students delivered bedside counseling, then provided follow-up treatment and outcome calls along with New York State Quitline counselors. Results: The survey demonstrated that 89% of the students were satisfied with the training. The bedside counseling confidence was greater than the phone counseling confidence. All students felt the program experience has value to them as future physicians. 124 smoking patients enrolled, and outcomes followed out to 6 months. The 7-day point prevalence quit rates using the as-treated (patients contacted) analysis were 57% at 4 weeks, 48% at 3 months, and 43% at 6 months. The 7-day point prevalence quit rates using the intent-to-treat (all patients) analysis were 31% at 4 weeks, 16% at 3 months and 14% at 6 months. Conclusion: Medical students given minimal training are effective tobacco cessation counselors at no cost to the hospital system. The Rochester Model program using student counseling benefits patients, the students, and the health-care system.

Oral glucose tolerance test and continuous glucose monitoring for gestational diabetes diagnosis: a survey study of women and health care professionals.

AIMS: The oral glucose tolerance test (OGTT), used for gestational diabetes mellitus (GDM) diagnosis for over 65 years, has poor acceptability and tolerability. Continuous glucose monitoring is being considered as potential alternative. The aim of our study was to formally assess women's and health care professionals' perception of both tests as diagnostic tools for GDM. METHODS: Participants in a pilot study on continuous glucose monitoring for GDM diagnosis were invited to fill two questionnaires, each of 6 Likert-scale and one optional open-ended question. A range of healthcare practitioners were also invited to fill a questionnaire of 13 Likert-scale and 7 optional open-ended questions. RESULTS: Sixty women completed the OGTT and 70 the continuous glucose monitoring questionnaire. OGTT was reported as poorly acceptable. Continuous glucose monitoring was described as significantly more tolerable (81% vs 27% 5/5 general acceptability rate, p < 0.001); ninety-three percent of the participants would recommend it for GDM diagnosis. Thirty health care professionals completed the survey. Most of them (73%) had confidence in OGTT as a diagnostic test for GDM with 66% raising some concerns. Doubts on continuous glucose monitoring were raised in terms of costs, accessibility and accuracy for GDM diagnosis due to "lack of evidence". CONCLUSIONS: Continuous glucose monitoring was substantially better tolerated for women than OGTT. Current lack of evidence for diagnostic accuracy for GDM underlines the need for studies on correlation between continuous glucose monitoring parameters and pregnancy outcomes to strengthen evidence for its use as diagnostic test for GDM.

Ureteral Stents Do Not Increase the Risk for Acute Kidney Injury After Colorectal Surgery.

BACKGROUND: Ureteral stents are thought to prevent or help identify ureteral injuries. Studies suggesting that ureteral stents increase the risk of postoperative acute kidney injury show inconsistent conclusions. The large ureteral stenting volume at our institution provided a unique opportunity for granular analysis not previously reported. OBJECTIVE: To determine whether prophylactic ureteral stenting at colorectal surgery increases acute kidney injury. DESIGN: Retrospective analysis of colorectal operations with prophylactic ureteral stents was compared to operations without stents. Adjusted analysis was performed with inverse probability treatment weighting. SETTINGS: Single institution enhanced recovery colorectal surgery service. PATIENTS: Prospective institutional database between July 1, 2018, and December 31, 2021. MAIN OUTCOME MEASURE: The primary outcome was acute kidney injury, defined as increase in creatinine ≥0. 3 mg/dL (definition 1) and 1.5-fold increase in creatinine (definition 2) within 48 hours postoperatively. RESULTS: There were 410 patients in the study population: 310 patients in the stent group and 100 in the no-stent group. There were 8 operative ureteral injuries: 4 (1.29%) in the stent group and 4 (4.0%) in the no-stent group ( p = 0.103). Unadjusted analysis revealed no significant difference in acute kidney injury between groups. After adjustment, there was still no significant difference in acute kidney injury between groups when defined as definition 1 (no-stent 23.76% vs stent 26.19%, p = 0.745) and as definition 2 (no-stent 15.86% vs stent 14.8%, p = 0.867). Subgroup analysis showed that lighted stents were associated with significantly more acute kidney injury than no-stent patients when defined as definition 1 ( p = 0.017) but not when defined as definition 2 ( p = 0.311). LIMITATIONS: Single-institution results may not be generalizable. CONCLUSION: Prophylactic ureteral stenting does not increase the risk of acute kidney injury for patients undergoing enhanced recovery colorectal surgery, although caution and further study may be warranted for lighted stents. Studies further examining contrasting roles of ureter stenting and imaging in open and minimally invasive colorectal surgery are warranted. See Video Abstract. LOS STENTS URETERALES NO AUMENTAN EL RIESGO DE LESIN RENAL AGUDA DESPUS DE LA CIRUGA COLORECTAL: ANTECEDENTES:Se cree que los stents ureterales previenen o ayudan a identificar las lesiones ureterales. Los estudios que sugieren que los stents ureterales aumentan el riesgo de lesión renal aguda post operatoria muestran conclusiones contradictorias. El gran volumen de endoprótesis ureterales en nuestra institución brindó una oportunidad única para el análisis granular que no se informó anteriormente.OBJETIVO:Determinar si la colocación de stent ureteral profiláctico en cirugía colorrectal aumenta el daño renal agudo.DISEÑO:El análisis retrospectivo de operaciones colorrectales con stents ureterales profilácticos se comparó con operaciones sin stents. El análisis ajustado se realizó con ponderación de tratamiento de probabilidad inversa.AJUSTES:Cirugía colorrectal de recuperación mejorada de una sola instituciónPACIENTES:Base de datos institucional prospectiva entre el 01/07/2018 y el 31/12/2021.MEDIDA DE RESULTADO PRINCIPAL:El resultado primario fue la lesión renal aguda definida como un aumento en la creatinina ≥ 0,3 mg/dL (Definición n.° 1) y un aumento de 1,5 veces en la creatinina (Definición n.° 2) dentro de las 48 horas posteriores a la operación.RESULTADOS:Hubo 410 pacientes en la población de estudio: 310 pacientes en el grupo Stent y 100 en el grupo No-Stent. Hubo 8 lesiones ureterales operatorias, 4 (1,29%) en el grupo Stent y 4 (4,0%) en el grupo No-Stent (p = 0,103). El análisis no ajustado no reveló diferencias significativas en la lesión renal aguda entre los grupos. Después del ajuste, todavía no hubo una diferencia significativa en la lesión renal aguda entre los grupos cuando se definió como Definición n.º 1 (sin stent 23,76 % frente a stent 26,19 %, p = 0,745) y por definición n.º 2 (sin stent 15,86 % frente a stent 14,8 %, p = 0,867). El análisis de sub grupos mostró que los stents iluminados se asociaron con una lesión renal aguda significativamente mayor que los pacientes sin stent cuando se definieron como Definición n.º 1 (p = 0,017), pero no cuando se los definió como Definición n.º 2 (p = 0,311).LIMITACIONES:Los resultados de una sola institución pueden no ser generalizables.CONCLUSIÓN:La colocación profiláctica de endoprótesis ureterales no aumenta el riesgo de lesión renal aguda en pacientes que se someten a cirugía colorrectal de recuperación mejorada, aunque es posible que se requiera precaución y estudios adicionales para las endoprótesis iluminadas. Se justifican estudios que examinen más a fondo las funciones contrastantes de la colocación de stents de uréter y las imágenes en la cirugía colorrectal abierta y mínimamente invasiva. (Traducción-Dr. Mauricio Santamaria ).

Integrated Care: A Person-Centered and Population Health Strategy for the COVID-19 Pandemic Recovery and Beyond.

The COVID-19 pandemic has mandated a re-imagination of how healthcare is administered and delivered, with a view towards focusing on person-centred care and advancing population health while increasing capacity, access and equity in the healthcare system. These goals can be achieved through healthcare integration. In 2019, the University Health Network (UHN), a consortium of four quaternary care hospitals in Ontario, Canada, established the first stage of a pilot program to increase healthcare integration at the institutional level and vertically with other primary, secondary and tertiary institutions in the Ontario healthcare system. Implementation of the program was accelerated during the COVID-19 pandemic and demonstrated how healthcare integration improves person-centred care and population health; therefore serving as the foundation for a health system response for the COVID-19 pandemic recovery and beyond.

Optimal Image Gain Intensity of Point-of-care Ultrasound when Screening for Ocular Abnormalities in the Emergency Department.

INTRODUCTION: Point-of-care ultrasound (POCUS) plays a pivotal role in evaluating ocular complaints in the emergency department (ED). The rapid and non-invasive nature of ocular POCUS makes it a safe and informative imaging modality. Previous studies have investigated using ocular POCUS to diagnose posterior vitreous detachment (PVD), vitreous hemorrhage (VH), and retinal detachment (RD); however, there are few studies that assess image optimization techniques and how they impact the overall accuracy of ocular POCUS. METHODS: We performed a retrospective review of ED patients who received ocular POCUS examinations and ophthalmology consultations as part of their evaluation for eye complaints at our urban, Level I trauma center ED from November 2017-January 2021. Of 706 exams, 383 qualified for the study. In this study we primarily investigated how stratified gain levels impact the accuracy of ocular POCUS for detection of any posterior chamber pathology and, secondarily, whether stratified gain levels impact the accuracy of detecting RD, VH, and PVD specifically. RESULTS: The images were found to have an overall sensitivity of 81% (76-86%), specificity of 82% (76-88%), positive predictive value (PPV) of 86% (81-91%), and negative predictive value (NPV) of 77% (70-83%). Images acquired with a gain of (25, 50] had a sensitivity of 71% (61-80%), specificity of 95% (85-99%), PPV of 96% (88-99%), and NPV of 68% (56-78%). Images acquired with a gain of (50, 75] had a sensitivity of 85% (73-93%), specificity of 85% (72-93%), PPV of 86% (75-94%), and NPV of 83% (70-92%). Images acquired with a high gain (75, 100] had a sensitivity of 91% (82-97%), specificity of 67% (53-79%), PPV of 78% (68-86%), and NPV of 86% (72-95%). CONCLUSION: In the ED setting, high (75, 100] gain on ocular POCUS scanning has a higher degree of sensitivity for detecting any posterior chamber abnormality, as compared to low (25, 50] gain levels. Thus, incorporating the use of high gain for ocular POCUS exams produces a more effective tool for ocular pathologies in acute care settings and may be particularly valuable in resource-limited settings.

Experiences and Reported Outcomes of Patients and Caregivers Enrolled in an Integrated Care Program for Thoracic Surgery: A Qualitative Evaluation.

Background: Health care delivery is often poorly coordinated and fragmented. Integrated care (IC) programs represent one solution to improving continuity of care. The aim of this study was to understand experiences and reported outcomes of patients and caregivers in an IC Program that coordinates hospital and home care for thoracic surgery. Methods: A process evaluation was undertaken using qualitative methods. We conducted semi-structured interviews with 10 patients and 8 caregivers who received IC for thoracic surgery and were discharged between June 2019 and April 2020. A phenomenological approach was used to understand and characterize patient and caregiver experiences. Thematic analysis began with a deductive approach complemented by an inductive approach. Results: Four major themes evolved from patient and caregiver interviews, including 1) coordination and timeliness of patient care facilitated by an IC lead; 2) the provision of person-centred care and relational continuity fostered feelings of partnership with patients and caregivers; 3) clear communication and one shared digital record increased informational continuity; and 4) impacts of IC on patient and caregiver outcomes. Conclusions: Patients and caregivers generally reported this IC Program met their health care needs, which may help inform how future IC programs are designed.

Severe Thyrotoxicosis Caused by Molar Pregnancy: A Case Report and Review of the Literature.

Severe thyrotoxicosis is an acute and life-threatening state of hyperthyroidism. While it is a rare presentation of hyperthyroidism, it is clinically significant because of its high mortality and necessitates early identification and treatment to reduce the incidence of poor outcomes. The most common causes of this hypermetabolic state are Graves' disease, toxic thyroid adenoma or multinodular goiter, thyroiditis, iodine-induced hyperthyroidism, and excessive intake of levothyroxine. The less common causes include trauma, medications (i.e., amiodarone), discontinuation of anti-thyroid medications, and interactions with sympathomimetic medications such as ketamine that may be administered during general anesthesia. Regardless of etiology, thyrotoxicosis management should be coordinated using an interdisciplinary team-based approach to optimize outcomes. We discuss a molar pregnancy requiring emergency surgery as an uncommon cause of thyrotoxicosis and highlight appropriate management steps. The patient's symptoms resolved post-operatively, and her post-operative laboratory results (thyroid function and beta-human chorionic gonadotropin {ß-hCG}) were followed until they normalized. The patient's preoperative presentation and preparation with a multidisciplinary team discussion, intraoperative anesthetic considerations and course, and post-operative management and follow-up are described.

A new continuous glucose monitor for the diagnosis of gestational diabetes mellitus: a pilot study.

BACKGROUND: Gestational Diabetes Mellitus (GDM) incidence and adverse outcomes have increased globally. The validity of the oral glucose tolerance test (OGTT) for GDM diagnosis has long been questioned, with no suitable substitute reported yet. Continuous Glucose Monitoring (CGM) is potentially a more acceptable and comprehensive test. The aim of this study was to assess the Freestyle Libre Pro 2 acceptability as a diagnostic test for GDM, then triangulating its results with OGTT results as well as risk factors and sonographic features of GDM. METHODS: Women wore the CGM device for 7 days at 24-28 weeks, undergoing the OGTT before CGM removal. CGM/OGTT acceptability as well as GDM risk factors evaluation occurred via three online surveys. CGM distribution/variability/time in range parameters, combined in a CGM Score of Variability (CGMSV), were triangulated with OGTT results and a risk-factor-based Total Risk Score (TRS). In a subgroup, GDM ultrasound features (as modified Ultrasound Gestational Diabetes Score - m-UGDS) were also incorporated. RESULTS: Of 107 women recruited, 87 (81%) were included: 74 (85%) with negative OGTT (NGT) and 13 (15%) positive (GDM). No significant difference was found between NGT and GDM in terms of demographics (apart from family history of diabetes mellitus), CGM parameters and perinatal outcomes. Women considered CGM significantly more acceptable than OGTT (81% versus 27% rating 5/5, p < 0.001). Of the 55 NGT with triangulation data, 28 were considered 'true negative' (TRS concordant with OGTT and CGMSV): of these 4/5 evaluated at ultrasound had m-UGDS below the cut-off. Five women were considered 'false negative' (negative OGTT with both TRS and CGMSV above the respective cut-offs). Triangulation identified also six 'false positive' women (positive OGTT but TRS and CGM both below the cut-offs). Only one woman for each of the last two categories had m-UGDS evaluated, with discordant results. CONCLUSIONS: CGM represents a more acceptable alternative for GDM diagnosis to the OGTT. CGM triangulation analysis suggests OGTT screening may result in both false positives and negatives. Further research including larger cohorts of patients, and additional triangulation elements (such as GDM biomarkers/outcomes and expanded m-UGDS) is needed to explore CGM potential for GDM diagnosis.

Anterior Chamber Washout During Ahmed Valve Glaucoma Surgery Reduces the Incidence of Hypertensive Phase.

PRCIS: Intraoperative anterior chamber (AC) washout reduces the odds of hypertensive phase (HP) by 95% compared with those not receiving washout during Ahmed glaucoma implant (AGI), suggesting AC washout is an effective prophylaxis for postoperative HP. PURPOSE: To characterize the incidence of postoperative HP in patients receiving AC washout at the time of AGI. PATIENTS AND METHODS: A total of 24 patients with medically refractory glaucoma who underwent AGI surgery at a tertiary academic medical center in Southern California from December 2018 through March 2021 were included in this retrospective comparative case series. Patients who received a pediatric implant and underwent concurrent intraocular surgery or did not complete a minimum of 6 months of follow-up were excluded. Nine patient's eyes received AC washout and 15 controls that were analyzed through 6 months postprocedure. HP was defined as intraocular pressure (IOP) above 21 mm Hg within 6 months postprocedure with maximum tolerated medical therapy. AC washout was performed by irrigating the AC with a 5 mL balanced salt solution before placing the tube of the AGI into the AC. The rate of postoperative HP, defined as peak IOP >21 mm Hg, at 6 months follow-up, was observed as the primary outcome measure. RESULTS: Patients included in the study had a high mean preoperative IOP ( X̅ = 44.11, SD = 13.85). There were no baseline differences between the washout and control groups. The odds of HP were significantly reduced (odds ratio: 0.050; 95% CI: 0.004, 0.706; P = 0.027) for patients who underwent intraoperative AC washout compared with those who did not. Bivariate analysis of subject baseline characteristics revealed that only washout status was significantly different in subjects with HP compared with subjects without HP ( P = 0.015). A multivariate logistic regression model using washout status and autoimmune conditions as covariates was significant in predicting HP ( X2 (2) = 12.337, P = 0.002), with washout as a significant predictor when controlling for autoimmune comorbidities ( P = 0.027). CONCLUSIONS: AC washout significantly decreases the odds of HP after AGI surgery. AC washout with balanced salt solution adds minimal time and risks to surgery and therefore may be an effective adjunct during AGI placement.

Application of Immunohistochemistry in Cytology.

Immunohistochemistry (IHC), also referred to as immunocytochemistry in cytology literature, has revolutionized the practice of cytopathology. Because of the complexity of cytology preparation and limited diagnostic material, performing IHC remains a challenge. Formalin-fixed paraffin-embedded (FFPE) cell block (CB) is the optimal choice for IHC. In this review, the approaches for improving CB preparation will be discussed. When CB material is not available, various cytology specimens can also be used for IHC. With the utilization of Antigen Retrieval (AR) technique, these nonformalin-fixed cytology specimens can achieve successful IHC staining, comparable with the results from FFPE tissue sections. In the last part of this review, we will discuss the use of positive controls and the important role of AR in standardization of IHC in cytology.

Outcomes of higher-order multiple pregnancies in an Australian setting.

BACKGROUND: Higher-order multiple (HOM) pregnancies are associated with significant maternal and neonatal morbidity, especially consequent to preterm birth. Multi-fetal pregnancy reduction (MFPR) may be provided, though its benefits in prolonging gestation and improving neonatal outcomes must be weighed against its risks. AIMS: The aim was to compare outcomes of HOM pregnancies where expectant management was chosen (EM) with those where MFPR was provided. METHODS: The method involved a retrospective study of HOM pregnancies referred to a single quaternary hospital between 2007 and 2016. The primary outcome was gestational age. Secondary outcomes included miscarriage, nursery admission, hospital stay, Apgar scores, early fetal loss, stillbirth, neonatal death and composite fetal loss. RESULTS: Fifty-seven pregnancies were eligible for inclusion. Median gestation at birth (weeks) was significantly higher for MFPR (35.3 vs 33.1, P < 0.01). Pregnancies after MFPR were less likely to lead to preterm birth (63.2 vs 100.0%, P < 0.001), half as likely to birth before 34 weeks (31.6 vs 60.0%, P = 0.09) but similarly likely to extremely preterm birth (<28 weeks, 8.6 vs 10.5%, P = 0.58). Miscarriage was more likely after MFPR (13.6 vs 0%, P = 0.05). EM neonates were more likely to be admitted to the nursery (P < 0.01) and have longer hospital stay (29.6 vs 20.2 days, P = 0.05); however, they had similar Apgar scores. CONCLUSION: Our study demonstrates that MFPR is associated with an increase in gestational age, with a reduction by almost half of births before 34 weeks, but no difference in extremely preterm births; the latter represents the highest risk group. This should be used to guide management counselling for HOM pregnancies.

Medical student exam performance and perceptions of a COVID-19 pandemic-appropriate pre-clerkship medical physiology and pathophysiology curriculum.

BACKGROUND: Medical schools were compelled to abruptly transition pre-clerkship curricula to remote learning formats due to the emergence of the Coronavirus Disease 2019 (COVID-19) pandemic. We evaluated student perceptions of remote learning, exam performance, and utilization of third-party learning resources to assess the implementation of a newly developed pandemic-appropriate physiology curriculum. METHODS: This was an observational study based on a survey conducted in the Spring of 2021 at the University of California, Irvine, School of Medicine (UCISOM). This study aimed to assess first (MS1) and second year (MS2) medical students' perceptions of satisfaction, support, academic performance, and connectedness before and during the COVID-19 pandemic. The MS1 class began medical school during the first year of the COVID-19 pandemic, whereas the MS2 class did so prior to the start of the pandemic. A survey instrument was developed and validated to identify the impact remote learning had on student self-perceptions of the Medical Physiology and Pathophysiology course. Surveys were distributed to all students and responses were collected on a voluntary basis. Exam scores on a customized National Board of Medical Examiners (NBME) physiology shelf exam were also compared to objectively identify how the remote curriculum during the pandemic impacted academic performance. RESULTS: Of 204 students enrolled, 74 responses were analyzed, with 42 MS1 (40% of MS1s) and 32 MS2 (31% of MS2s) responses. Overall, MS1s and MS2s were satisfied with the curriculum they received (95 and 97% respectively) and the school's support of their concerns (86 and 100% respectively). Notably, only 50% of MS1s felt connected to their peers, compared to 94% of MS2s. Lecture attendance and self-perception of their academic performance were similar between both classes. Interestingly, the intra-pandemic class's NBME exam average in 2020 (60.2% ± 8.9, n = 104) was significantly higher than the pre-pandemic class average in 2019 (56.8% ± 11.3, n = 100). Both classes primarily used course materials over third-party learning resources. An additional set of survey questions distributed only to the MS1 class found that the majority of MS1s reported minimal barriers with regards to accessibility, including internet connectivity, study-conducive environments, and balancing family commitments. Overall, pre-clerkship medical students had positive perceptions of the newly developed pandemic-appropriate physiology curriculum. CONCLUSIONS: Changes to the pre-clerkship physiology curriculum during the COVID-19 pandemic were met with overall satisfaction from the students and an increase in NBME scores. More attention to student connectedness is needed to improve how remote learning can be best optimized into future curricula development.

Continuous Glucose Monitoring for the Diagnosis of Gestational Diabetes Mellitus: A Pilot Study.

Background: Gestational diabetes mellitus (GDM) is diabetes first diagnosed in pregnancy. GDM, together with its short- and long-term negative outcomes, is increasing in incidence all over the world. The current diagnostic method for GDM, the oral glucose tolerance test (OGTT), is dated and has been reported as inconvenient for women as well as poorly reproducible and reliable. Aims: We aimed at assessing the acceptability, feasibility, and accuracy of continuous glucose monitoring (CGM) as a diagnostic test for GDM and explore its correlation with the OGTT and risk factors for GDM. Methods: In this prospective cohort study, pregnant women due for or having completed OGTT underwent CGM for seven days, performing daily finger-prick blood glucose levels before completing an acceptability questionnaire. Data on GDM risk factors and CGM variability were analyzed and compared with OGTT results. Results: Seventy-three women completed CGM (40 GDM, 33 normal glucose tolerances); 34 concurrently underwent OGTT. CGM was acceptable and generally well-tolerated, with skin irritation/itchiness the only adverse event (11 mild, one severe). CGM and OGTT strongly correlated for fasting glucose values (r = 0.86, p < 0.05) only. Triangulating GDM risk factors, OGTT results and CGM variability parameters with the application of machine learning highlighted the possibility of unmasking false positive (11 showed low CGM variability and demographic risks but positive OGTT) and false-negative OGTT diagnoses (1 showed high CGM variability and demographic risks but negative OGTT). Conclusions: CGM was well-tolerated, showing poorer glycaemic control in GDM, and revealing potential misdiagnosis of the OGTT when combined with GDM risk factors. Future research is needed to determine cut-off values for CGM-defined and OGTT-independent screening criteria for GDM.

AAA + ATPase Thorase inhibits mTOR signaling through the disassembly of the mTOR complex 1.

The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and the mTOR complex 2 to maintain cellular and organismal homeostasis. Failure to finely tune mTOR activity results in metabolic dysregulation and disease. While there is substantial understanding of the molecular events leading mTORC1 activation at the lysosome, remarkably little is known about what terminates mTORC1 signaling. Here, we show that the AAA + ATPase Thorase directly binds mTOR, thereby orchestrating the disassembly and inactivation of mTORC1. Thorase disrupts the association of mTOR to Raptor at the mitochondria-lysosome interface and this action is sensitive to amino acids. Lack of Thorase causes accumulation of mTOR-Raptor complexes and altered mTORC1 disassembly/re-assembly dynamics upon changes in amino acid availability. The resulting excessive mTORC1 can be counteracted with rapamycin in vitro and in vivo. Collectively, we reveal Thorase as a key component of the mTOR pathway that disassembles and thus inhibits mTORC1.

Morally excused but socially excluded: Denying agency through the defense of mental impairment.

Defendants can deny they have agency, and thus responsibility, for a crime by using a defense of mental impairment. We argue that although this strategy may help defendants evade blame, it may carry longer-term social costs, as lay people's perceptions of a person's agency might determine some of the moral rights they grant them. Three randomized between-group experiments (N = 1601) used online vignettes to examine lay perceptions of a hypothetical defendant using a defense of mental impairment (versus a guilty plea). We find that using a defense of mental impairment significantly reduces responsibility, blame, and punitiveness relative to a guilty plea, and these judgments are mediated by perceptions of reduced moral agency. However, after serving their respective sentences, those using the defense are sometimes conferred fewer rights, as reduced agency corresponds to an increase in perceived dangerousness. Our findings were found to be robust across different types of mental impairment, offences/sentences, and using both manipulated and measured agency. The findings have implications for defendants claiming reduced agency through legal defenses, as well as for the broader study of moral rights and mind perception.

Development and evaluation of an online questionnaire to identify women at high and low risk of developing gestational diabetes mellitus.

BACKGROUND: Established risk factors for Gestational Diabetes Mellitus (GDM) include age, ethnicity, family history of diabetes and previous GDM. Additional significant influences have recently been demonstrated in the literature. The oral glucose tolerance test (OGTT) used for GDM diagnosis has sub-optimal sensitivity and specificity, thus often results in GDM misdiagnoses. Comprehensive screening of risk factors may allow more targeted monitoring and more accurate diagnoses, preventing the devastating consequences of untreated or misdiagnosed GDM. We aimed to develop a comprehensive online questionnaire of GDM risk factors and triangulate it with the OGTT and continuous glucose monitoring (CGM) parameters to better evaluate GDM risk and diagnosis. METHODS: Pregnant women participating in two studies on the use of CGM for GDM were invited to complete the online questionnaire. A risk score, based on published literature, was calculated for each participant response and compared with the OGTT result. A total risk score (TRS) was then calculated as a normalised sum of all risk factors. Triangulation of OGTT, TRS and CGM score of variability (CGMSV) was analysed to expand evaluation of OGTT results. RESULTS: Fifty one women completed the questionnaire; 29 were identified as 'high-risk' for GDM. High-risk ethnic background (p < 0.01), advanced age, a family diabetic history (p < 0.05) were associated with a positive OGTT result. The triangulation analysis (n = 45) revealed six (13%) probable misdiagnoses (both TRS and CGMSV discordant with OGTT), consisting of one probable false positive and five probable false negative by OGTT results. CONCLUSIONS: This study identified pregnant women at high risk of developing GDM based on an extended evaluation of risk factors. Triangulation of TRS, OGTT and CGMSV suggested potential misdiagnoses of the OGTT. Future studies to explore the correlation between TRS, CGMSV and pregnancy outcomes as well as additional GDM pregnancy biomarkers and outcomes to efficiently evaluate OGTT results are needed.