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This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth. Utilising data from 1299 women in the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, two models were developed: one for pregnancy and another for postpartum. Key predictors included glucose test results, medical history, and biometric indicators. Of the initial cohort, 124 women developed T2DM within three years. The study identified seven predictors for the antenatal T2DM risk prediction model and four for the postnatal one. The models demonstrated good to excellent predictive ability, with Area under the ROC Curve (AUC) values of 0.76 (95% CI: 0.72 to 0.80) and 0.85 (95% CI: 0.81 to 0.88) for the antenatal and postnatal models, respectively. Both models underwent rigorous validation, showing minimal optimism in predictive capability. Antenatal model, considering the Youden index optimal cut-off point of 0.096, sensitivity, specificity, and accuracy were measured as 70.97%, 70.81%, and 70.82%, respectively. For the postnatal model, considering the cut-off point 0.086, sensitivity, specificity, and accuracy were measured as 81.40%, 75.60%, and 76.10%, respectively. These models are effective for predicting T2DM risk in women with GDM, although external validation is recommended before widespread application. • Developed two models for predicting postpartum T2DM in women with GDM, applicable during and after pregnancy, using a comprehensive South Asian cohort dataset. • Upon internal validation, the models demonstrated high AUC values of 0.76 (antenatal model) and 0.85 (postnatal model). • This marks a significant advancement in clinical practice for identifying post-GDM T2DM risk. [ABSTRACT FROM AUTHOR]

The acceptability of providing women with personalised cardiometabolic risk information using risk prediction tools early in pregnancy is not well understood. To explore women's and healthcare professionals' perspectives of the acceptability of a prognostic, composite risk prediction tool for cardiometabolic risk (gestational diabetes and/or hypertensive disorders of pregnancy) for use in early pregnancy. Semi-structured interviews were conducted to explore the acceptability of cardiometabolic risk prediction tools, preferences for risk communication and considerations for implementation into antenatal care. The Theoretical Framework of Acceptability informed interview questions. Transcripts were thematically analysed. Women ≤24 weeks' gestation (n = 13) and healthcare professionals (n = 8), including midwives (n = 2), general practitioners (n = 2), obstetricians (n = 2), an endocrinologist (n = 1) and cardiologist (n = 1) participated. Participants indicated that providing personalised risk information is only appropriate when preventative measures can be initiated to mitigate risks. Differentiating the risk for each condition (single risk outputs) was often preferred to composite risk outputs to enable targeted monitoring and management. Defining conditions and risks to mother/baby, visually depicting personalised risk scores, and providing clear, patient-centred clinical management plans were recommended. Supportive clinical policy changes, staff engagement/training, and integration into electronic health records were suggested to facilitate uptake into routine antenatal care. Women and healthcare professionals suggested that early pregnancy cardiometabolic risk prediction tools may be acceptable when preventative interventions are available to reduce risks. Risk prediction tools with integrated patient-centred education materials may promote timely access and engagement with preventative interventions to optimise women's current and future health. [ABSTRACT FROM AUTHOR]

Venous thromboembolism is a major cause of perioperative morbidity and mortality. Immobilized medical patients are also at risk. Long-term sequelae represent a significant chronic health burden. Hospitalized patients should be assessed for their risk of thromboembolism and bleeding at regular intervals. Risk stratification using recommended models can be used to guide the choice of thromboprophylaxis. Both mechanical and pharmacological interventions reduce the incidence of venous thromboembolism. Extended prophylaxis is now recommended following high-risk orthopaedic and cancer surgeries and a number of newer oral antithrombotic agents are now available for this. Anaesthesia should be tailored to minimize the risk of venous stasis and maximize early postoperative mobilization. [ABSTRACT FROM AUTHOR]

Employing data for 125 countries and spanning the 1990–2014 period, we empirically examine the impact of human rights on income distribution and poverty. We also investigate how aid and trade can influence poverty and income distribution through human rights. The results suggest that stronger human rights records contribute to greater income equality, as well as to poverty reduction. The interaction of human rights with both ODA and trade show that as aid and trade flows increase, or alternatively as human rights records increase, ODA and trade flows reduce poverty and lead to greater equality in income distribution. [ABSTRACT FROM AUTHOR]

This paper presents the observations and characterization of Cloud-to-Ground (CG) lightning activity in Western Antarctica in a region that covers the Amundsen/Bellingshausen Sea (ABS), the Antarctic Peninsula (AP) and the Weddell Sea (WS). Lightning data have been collected by a lightning detector (Boltek LD-350) and an atmospheric electric field mill (EFM-100) sensors deployed at the Carlini Base on the Antarctic Peninsula (CARL: 62.23oS, 58.63oW). The flash rate and flash multiplicity were analysed for three different seasons within a 1,000 km range, starting at the end of summer (February 2017) and ending in winter (July 2017). Three storm days for each month (within the 1,000 km radius from the LD sensor) with three composite active thunderstorms (labelled as Storm region A, B, and C) for each day have been selected from a collection of storm days between February and July 2017. A total of 355,899 flashes have been recorded with 156,190 Positive CG and 199,709 Negative CG flashes from these 54 thunderstorms. In total, Positive CG flash counts made up around 43.9% of the total detected CG flashes. Most of the Positive CG flashes (>80%) had only 1 or 2 strokes with a maximum number of 5. For Negative CG flashes, the average multiplicity and the maximum multiple stroke were 1.2 and 16 respectively. Most CG flashes were detected during the summer and fall months. Positive CG flashes were prevalent in Western Antarctic storms even during the winter. The mean, median and range of the ratio of Positive CG to Negative CG flashes were 0.7, 0.718 and 0.217–1.279, respectively. • Flash rate and stroke multiplicity for CG flashes of 54 thunderstorms are examined. • Positive CG constituted 43.9% of the total detected flashes in the Western Antarctica region. • Most Positive CG flashes had only 1 or 2 strokes with a maximum of 5 strokes. • Most of the CG flashes were detected during the summer and fall between February and April 2017. • Abstract. [ABSTRACT FROM AUTHOR]

Despite the appeal of smartphone-based electrocardiograms (ECGs) for arrhythmia screening, a paucity of data exists on the accuracy of primary care physicians' and cardiologists' interpretation of tracings compared with the device's automated diagnosis. Using 408 ECGs in 51 patients, we demonstrate a variable accuracy in clinician interpretation of smartphone-based ECGs, with only cardiologists demonstrating satisfactory agreement when referenced against a 12-lead ECG. Combining the device automated diagnostic algorithm with cardiologist interpretation of only uninterpretable traces yielded excellent results and provides an efficient, cost-effective workflow for the utilization of a smartphone-based ECG in clinical practice. [ABSTRACT FROM AUTHOR]

Venous thromboembolism is a major cause of perioperative morbidity and mortality. Immobilized medical patients are also at risk. Long-term sequelae represent a significant chronic health burden. Hospitalized patients should be assessed for their risk of thromboembolism and bleeding at regular intervals. Risk stratification using recommended models can be used to guide the choice of thromboprophylaxis. Both mechanical and pharmacological interventions reduce the incidence of venous thromboembolism. Extended prophylaxis is now recommended following high-risk orthopaedic and cancer surgeries and a number of newer oral antithrombotic agents are now available for this. Anaesthesia should be tailored to minimize the risk of venous stasis and maximize early postoperative mobilization. [ABSTRACT FROM AUTHOR]

Brewer’s spent grain (BSG) is a nitrogen and fiber rich waste generated in high volumes in beer manufacturing. Here we have investigated the use of fermentation for value addition to this waste material. In this study we use solid-state fermentation (SSF) using food grade Rhizopus oligosporus to enhance its nutrient content by valorization of BSG. Subsequently, untargeted GC–MS (Gas chromatography mass spectrometry) based metabolomics was used to analyse the constituents. We investigated different solvents to extract extracellular metabolites and best derivatization method, where methanol and silylation provided best results. We observed significant levels of metabolite changes in amino acids, citric acid, vitamins and antioxidants. This data provided insight on metabolites variations during fermentation, proving that fermentation enhanced BSG’s nutrient content. Hence, data from metabolomics studies can be used to find novel applications for food wastes and innovative processing methods for valorization of waste materials. [ABSTRACT FROM AUTHOR]

• Hydrophobic interaction in the pole helix in TRPC3 is important for TRPC channel function. • Mutation interrupting pole helix hydrophobic interaction attenuates calcium dependent inactivation. • TRPC3 has calcium dependent feedback regulation either by direct biding of calcium to CBSs and calcium/calmodulin dependent regulation to CIRB. Recent structural studies have shown that the carboxyl-terminus of many TRP channels, including TRPC3, are folded into a horizontal rib helix that is connected to the vertical pole helix, which play roles in inter-structural interactions and multimerization. In a previous work we identified I807 located in the pole helix with a role in regulation of TRPC3 by STIM1 (Lee et al., 2014, Liu et al., 2022). To further determine the role of the pole helix in TRPC3 function, here we identified key hydrophobic residues in the pole helix that form tight tunnel-like structure and used mutations to probe their role in TRPC3 regulation by Ca2+ and Calmodulin. Our findings suggest that the hydrophobic starch formed by the I807-L818 residues has several roles, it modulates gating of TRPC3 by Ca2+, affects channel selectivity and the channel Ca2+ permeability. Mutations of I807, I811, L814 and L818 all attenuated the Ca2+-dependent inactivation (CDI) of TRPC3, with I807 having the most prominent effect. The extent of modulation of the CDI depended on the degree of hydrophobicity of I807. Moreover, the TRPC3(I807S) mutant showed altered channel monovalent ion selectivity and increased Ca2+ permeability, without affecting the channel permeability to Mg2+ and Ba2+ and without changing the pore diameter. The CDI of TRPC3 was reduced by an inactive calmodulin mutant and by a pharmacological inhibitor of calmodulin, which was eliminated by the I807S mutation. Notably, deletion of STIM1 caused similar alteration of TRPC3 properties. Taken together, these findings reveal a role of the pole helix in CDI, in addition to its potential role in channel multimerization that required gating of TRPC3 by STIM1. Since all TRPC and most TRP channels have pole helix structures, our findings raise the possibility that the pole helix may have similar roles in all the TRP family. [Display omitted] [ABSTRACT FROM AUTHOR]

Venous thromboembolism is a major cause of perioperative morbidity and mortality. Immobilized medical patients are also at risk. Long-term sequelae represent a chronic health burden. Hospitalized patients should be assessed for their risk of thromboembolism and bleeding at regular intervals. Risk stratification, using recommended models can be used to guide the choice of thromboprophylaxis. Both mechanical and pharmacological interventions reduce the incidence of venous thromboembolism. Extended prophylaxis is now recommended following high-risk orthopaedic and cancer surgeries and a number of newer oral antithrombotic agents are now available for this. Anaesthesia should be tailored to minimize the risk of venous stasis and maximize early postoperative mobilization. [ABSTRACT FROM AUTHOR]

Abstract: Herpes simplex encephalitis (HSE) in children is a potentially devastating condition which is occasionally complicated by a clinical relapse. An autoimmune component has long been suspected in these relapses and recent findings suggest that antibodies against N-methyl-d-aspartate receptors (NMDARs) may be part of this mechanism. We here report an 11 months old girl with acute HSE and with negative NMDAR antibody serology at presentation who after an initial response to antiviral treatment deteriorated with seizures, abnormal movements, focal neurologic deficits and psychiatric symptoms. We show that this relapse occurred as production of NMDAR antibodies developed and that clinical improvement followed immunotherapy with a concomitant decrease in NMDAR antibody titers in CSF. She also developed a characteristic 15–20 Hz activity over both hemispheres which has been previously described as an electroencephalographic presentation of anti-NMDAR encephalitis. We conclude that relapse or persisting symptoms in HSE in children may represent an immune-mediated mechanism rather than a viral reactivation and that NMDAR antibodies should be analyzed as this may be of importance for the choice of therapy. [Copyright &y& Elsevier]

Background In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making. Materials and methods Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival (OS). Patient management was per standard of care, blinded to ctDNA data. Results Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N  =   42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre-operative setting was associated with inferior recurrence-free survival (RFS) [hazard ratio (HR) 4.1; P  =   0.002)] and OS (HR 4.1; P  =   0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P  <   0.0001) and OS (HR 4.0; P  =   0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy. Conclusion ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment intensification strategies for patients with detectable ctDNA post-operatively who appear at very high risk of recurrence despite gemcitabine-based adjuvant therapy. [ABSTRACT FROM AUTHOR]