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AIMS Although routine echocardiographic parameters as ejection fraction are used to risk stratify for death in patients referred for echocardiography, they have limited predictive value. We speculated that non-invasive hemodynamic echocardiographic data, assessing left ventricular (LV) filling pressure and output, stratified based on the clinical Killip score, may have additive prognostic value on top of routine echocardiographic parameters. We created an echocardiographic correlate of this classification, using diastolic grade and stroke volume index (SVI) as indicators of pulmonary congestion and systemic perfusion, respectively, and evaluated the prognostic value of this correlate. METHODS A retrospective study of consecutive patients (hospitalized or not) referred for echocardiography for a range of cardiac diagnoses in a tertiary medical center. We included patients in sinus rhythm who were evaluated by 2 sonographers, and reviewed by a single cardiologist, 565 patients were included. Patients with normal filling pressures and normal SVI (>35ml/m2) were defined as eKillip class-1. Patients with pseudo-normal or restrictive diastolic patterns and normal SVI were ascribed to eKillip class-2 or 3, respectively. Those with pseudo-normal or restrictive diastolic patterns and a sub-normal SVI were defined as eKillip class-4. RESULTS EKillip class-1 was present in 382 (68%) patients, 115 (20%), 26 (5%) and 42 (7%) were in eKillip classes 2-4 respectively. Median follow-up time was 1056 days (IQR 729-1390). A total of 105 deaths occurred, in a univariate Cox regression analysis showed eKillip class was associated with all-cause mortality, hazard ratio (HR) and 95%CI were - 2.73[1.67-4.48], 3.19[1.42-7.17] and 4.79[2.58-8.89] for each eKillip class above 1, respectively (p

Context Given a shortage of specialty palliative care clinicians and geographic variation in availability, telemedicine has been proposed as one way to improve access to palliative care services for patients with cancer. However, the enduring digital divide raises questions about whether unequal access will exacerbate healthcare disparities. Objectives To examine factors associated with utilization of telemedicine as compared to in-person visits by patients with cancer in the ambulatory palliative care setting. Methods We collected data on patients seen in Supportive Oncology clinic by palliative care clinicians with an in-person or telemedicine visit from March 1 to December 30, 2020. A logistic regression with generalized estimating equation was fit to assess the association between visit type and patient characteristics. Results A total of 491 patients and 1783 visits were identified, including 1061 (60%) in-person visits and 722 (40%) telemedicine visits. Female patients were significantly more likely to utilize telemedicine than male patients (OR 1.46; 95% CI 1.11–1.90). Spanish-speaking patients (OR 0.32, 95% CI 0.17–0.61), those without insurance (OR 0.28, 95% CI 0.15–0.52), and those without an activated patient portal (Inactivated: OR 0.46, 95% CI 0.26–0.82; Pending Activation: OR 0.29, 95% CI 0.18–0.48) were less likely to utilize telemedicine. Conclusion Our study reveals disparities in telemedicine utilization in the ambulatory palliative care setting for patients with cancer who are male, Spanish-speaking, uninsured, or do not have an activated patient portal. In the wake of the COVID-19 pandemic, we can better meet the palliative care needs of patients with cancer through telemedicine only if equity is kept at the forefront of our discussions.

Background: Palliative care (PC) services expanded rapidly to meet the needs of coronavirus disease 2019 (COVID-19) patients, yet little is known about which patients were referred for PC consultation during the pandemic. Objective: Examine factors predictive of PC consultation for COVID-19 patients. Design: Retrospective cohort study of COVID-19 patients discharged from four hospitals (March 1–June 30, 2020). Exposures: Patient demographic, socioeconomic, and clinical factors and hospital-level characteristics. Outcome Measurement: Inpatient PC consultation. Results: Of 4319 hospitalized COVID-19 patients, 581 (14%) received PC consultation. Increasing age, serious illness (cancer, chronic obstructive pulmonary disease, and dementia), greater illness severity, and admission to the quaternary hospital were associated with receipt of PC consultation. There was no association between PC consultation and race/ethnicity, household crowding, insurance status, or hospital-factors, including inpatient, emergency department, and intensive care unit census. Conclusions: Although site variation existed, the highest acuity patients were most likely to receive PC consultation without racial/ethnic or socioeconomic disparities.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with diabetic ketoacidosis at the time of colonoscopy. This study aimed to identify factors associated with ketone concentrations in SGLT2i-treated type 2 diabetes compared with non-SGLT2i-treated diabetes, and those with impaired fasting glycaemia (IFG) and normoglycaemia. DESIGN: Cross-sectional, multicentre, observational study June-December 2020 in four Australian tertiary hospitals. PARTICIPANTS: Capillary glucose and ketones were measured in people undergoing colonoscopy: 37 SGLT2i-treated and 105 non-SGLT2i-treated type 2 diabetes, 65 IFG and 151 normoglycaemia. MEASUREMENTS: Body mass index (BMI), age, glucose, fasting duration and where relevant, HbA1c and time since last SGLT2i dose. RESULTS: In SGLT2i-treated diabetes, BMI (ρ = -0.43 [95% confidence interval: -0.67, -0.11]) and duration since last SGLT2i dose (ρ = -0.33 [-0.60, 0.00]) correlated negatively with increasing ketones, but there was no correlation with fasting duration. In non-SGLT2i-treated diabetes, BMI correlated negatively (ρ = -0.24 [-0.42, -0.05]) and fasting duration positively (ρ = 0.26 [0.07, 0.43]) with ketones. In IFG participants, only fasting duration correlated with ketones (ρ = 0.28 [0.03, 0.49]). In normoglycaemic participants, there were negative correlations with BMI (ρ = -0.20 [-0.35, -0.04]) and fasting glucose (ρ = -0.31 [-0.45, -0.15]) and positive correlations with fasting duration (ρ = 0.20 [0.04, 0.35]) and age (ρ = 0.19 [0.03, 0.34]). Multiple regression analysis of the entire cohort showed BMI, age and fasting glucose remained independently associated with ketones, but in SGLT2i-treated participants only BMI remained independently associated. CONCLUSIONS: In SGLT2i-treated diabetes, lower BMI was a novel risk factor for higher ketones precolonoscopy. Pending larger confirmatory studies, extra vigilance for ketoacidosis is warranted in these people.

Objectives Patients with Gaucher disease (GD) are at increased risk of bleeding and have varying degrees of thrombocytopenia, making the analysis of platelet function difficult. This study aimed to provide a clinically relevant quantitative assessment of platelet function and determine its relationship with bleeding and GD-related data. Methods Unstimulated and stimulated platelet function was measured by whole blood flow cytometry of platelet surface-activated αIIbβ3 integrin (detected with monoclonal antibody PAC1), P-selectin (CD62P), and lysosomal-associated membrane protein (LAMP3/CD63) in 149 GD patients. Results GD patients had a higher level of unstimulated CD63 expression than healthy subjects, which was mildly correlated with glucosylsphingosine (lyso-Gb1) levels (r = 0.17, p-value = 0.042). Splenectomized GD patients had a higher level of unstimulated αIIbβ3 integrin and P-selectin expression. Reduced platelet reactivity (−2 standard deviation of reference range) was found in 79 (53%, 95% confidence interval [CI]: 44–61%) patients, of whom 10 (6.7%, 95% CI: 3.3–12%) had more severe platelet dysfunction. In a multivariate model, only lyso-Gb1 levels were associated with the more severe platelet dysfunction. Fifty-four (49%) of 128 adult patients who completed the bleeding tendency questionnaire reported positive bleeding history. In a multivariate logistic model, older age (odds ratio [OR]: 1.05, 95% CI: 1.01–1.1) and low P-selectin reactivity (OR: 2.03, 95% CI: 1.25–3.35) were associated with more than one bleeding manifestation. Conclusion Flow cytometry enables the study of platelet function in thrombocytopenic GD patients. A platelet degranulation defect, but not αIIbβ3 integrin activation defect, is associated with clinical bleeding. In vivo increased CD63 expression may be related to GD-related inflammation.

CONTEXT: High quality communication is essential to older adults’ medical decision-making, quality of life, and adjustment to serious illness. Studies have demonstrated that Geritalk, a two day (16 hours total) in-person communication skills training improves self-assessed preparedness, skill acquisition, and sustained practice of communication skills. Due to the COVID-19 pandemic, Geritalk was adapted to a virtual format (4 days, 10 hours total). OBJECTIVES: Our study evaluated the change in participants’ self-assessed preparedness for serious illness communication before and after the virtual course and satisfaction with the course, and compared these findings to responses from a prior in-person Geritalk course. METHODS: Geriatrics and Palliative Medicine fellows at three urban academic medical centers completed surveys, which employed 5-point Likert scales, before and after the virtual course to assess satisfaction with the course and preparedness for serious illness communication. RESULTS: Of the 20 virtual Geritalk participants, 17 (85%) completed the pre-course assessment, and 14 (70%) completed the post-course assessment. Overall, satisfaction with the course was high (mean 4.9 on a 5‐point scale). Compared to in-person Geritalk participants, virtual course participants reported comparable and significant (p

Introduction: Glial scarring after a spinal cord injury (SCI) can represent both a physical and a molecular barrier for axonal regeneration and thus its removal has been found to be helpful in the recovery process. For this removal to be feasible in humans, an efficient method is needed to clearly identify glial tissue without inflicting more damage. Objective: To evaluate infrared thermography as a tool for identifying glial scar tissue in chronic SCI. Material and methods: An exploratory experimental pilot study was performed on Sprague-Dawley rats divided into sham and SCI (T9). All animals were subjected to a baseline thermography performed after a laminectomy that was either followed by closure of the surgical planes (sham group) or injury infliction (SCI group). Five weeks later, a second thermography was performed. Afterward, the spinal cord (T8-T10) was removed and processed for glial fibrillary acidic protein (GFAP) immunohistochemistry, which was used as a gold standard for identifying reactive astrocytes and glial scar. All animals received the same care throughout the study. Results: The thermography did not reveal a statistical difference for the baseline values (p = 0.24); however, a significant difference in thermography values was found 5 weeks later (p = 0.01). This difference significantly correlated with astrocyte counts at the site of injury (r = –0.57; p = 0.03, Spearman’s correlation). Conclusions: Infrared thermography could be useful to evaluate the extent of glial scar after SCI.

Purpose Spatiotemporal Encoding (SPEN) is an ultrafast imaging technique where the low-bandwidth axis is rasterized in a joint spatial/k-domain. SPEN benefits from increased robustness to field inhomogeneities, folding-free reconstruction of subsampled data, and an ability to combine multiple interleaved or signal averaged scans –yet its relatively high SAR complicates volumetric uses. Here we show how this can be alleviated by merging simultaneous multi-band excitation, with intra-slab multi-echo (ME) phase encoding, for the acquisition of high definition volumetric DWI/DTI data. Methods A protocol involving phase-cycling of simultaneous multi-banded z-slab excitations in independently ky-interleaved scans, together with ME trains that kz-encoded positions within these slabs, was implemented. A reconstruction incorporating a CAIPIRINHA-like encoding of the multiple bands and exploiting SPEN's ability to deliver self-referenced, per-shot phase maps, then led to high-definition diffusivity acquisitions, with reduced SAR and acquisition times vis-a-vis non-optimized 3D counterparts. Results The new protocol was used to collect full brain 3 T DTI experiments at a variety of nominal voxel sizes, ranging from 1.95 to 2.54 mm3. In general, the new protocol yielded superior sensitivity and fewer distortions than what could be observed in comparably timed phase-encoded 3D SPEN, multi-slice 2D SPEN, or optimized EPI counterparts. Conclusions A robust procedure for acquiring volumetric DWI/DTI data was developed and demonstrated.

Introduction For the last three decades, enzyme replacement therapy (ERT) for Gaucher disease (GD) has been available. We aimed to evaluate the effect of ERT on the pregnancy and obstetric outcome in a unique group of multiparous women with type 1 GD (GD1) who had pregnancies with and without ERT. Study design The Gaucher Unit database (1987-2019) was searched for multiparous women who had pregnancies before and after the institution of ERT. Data were collected from the clinic files and study-specific questionnaires. Descriptive, correlation analysis and generalized estimating equations (GEE) were used to study the effect of ERT and confounding variables on study outcomes. Results We identified 19 women with 105 pregnancies, among which 26 (24.7%) terminated in first-trimester miscarriage. The risk for miscarriage was associated with the severity of GD1 genotype and phenotype, but not with ERT usage. Early postpartum hemorrhage (PPH) was reported in 16 (84%) women after 25 deliveries (31.6%, 95% CI 21.6%-43.1%). The risks of early PPH and red blood cell (RBC) transfusions were significantly lower when ERT was used during pregnancy, OR (95% CI) 0.13 (0.03-0.54) and 0.27 (0.08-0.94), respectively, compared to pregnancies without the use of ERT. Conclusion Enzyme replacement therapy during pregnancy is risk reducing for early PPH and RBC transfusions in women with GD1. We suggest considering ERT for the benefit of all pregnant women with GD1, including mild GD1. This article is protected by copyright. All rights reserved.

Background: Hospitalized patients with serious illness have significant symptom burden and face complex medical decisions that often require goals of care discussions. Given the shortage of specialty palliative care providers, there is a pressing need to improve the palliative care skills of internal medicine (IM) residents, who have a central role in the care of seriously ill patients hospitalized at academic medical centers. Methods: We conducted an anonymous survey of IM residents at a large, urban, academic medical center to identify which aspects of palliative care trainees find most important and their knowledge gaps in palliative care. The survey measured trainees’ self-assessed degree of importance and knowledge of core palliative care skills and evaluated frequency of completing advance care planning documentation. Results: Overall, 51 (23%) IM residents completed the survey. The majority of trainees considered multiple palliative care skills to be “very important/important”: symptom management, prognostication, introducing the palliative care approach, discussing code status, and breaking serious news. Across these same skills, trainees reported variable levels of knowledge. In our sample, trainees reported completing healthcare proxy forms and Medical Orders for Life-Sustaining Treatment infrequently. Conclusions: IM trainees rated core palliative care skills as important to their practice. Yet, they reported knowledge gaps across multiple core palliative care skills that should be addressed given their role as frontline providers for patients with serious illness.

Communication au congrès KES de 2021 qui s'est déroulé à Szczecin; International audience; Understanding the replication machinery of viruses contributes to suggest and try effective antiviral strategies. Exhaustive knowledge about the proteins structure, their function, or their interaction is one of the preconditions for successfully modeling it. In this context, modeling methods based on a formal representation with a high semantic expressiveness would be relevant to extract proteins and their nucleotide or amino acid sequences as an element from the replication process. Consequently, our approach relies on the use of semantic technologies to design the SARS-CoV-2 replication machinery. This provides the ability to infer new knowledge related to each step of the virus replication. More specifically, we developed an ontology-based approach enriched with reasoning process of a complete replication machinery process for SARS-CoV-2. We present in this paper a partial overview of our ontology OntoRepliCov to describe one step of this process, namely, the continuous translation or protein synthesis, through classes, properties, axioms, and SWRL (Semantic Web Rule Language) rules.

Diffusion-weighted imaging (DWI) can improve breast cancer characterizations, but often suffers from low image quality -particularly at informative b > 1000 s/mm2 values. The aim of this study was to evaluate multishot approaches characterizing Gaussian and non-Gaussian diffusivities in breast cancer. This was a prospective study, in which 15 subjects, including 13 patients with biopsy-confirmed breast cancers, were enrolled. DWI was acquired at 3 T using echo planar imaging (EPI) with and without zoomed excitations, readout-segmented EPI (RESOLVE), and spatiotemporal encoding (SPEN); dynamic contrast-enhanced (DCE) data were collected using three-dimensional gradient-echo T1 weighting; anatomies were evaluated with T2 -weighted two-dimensional turbo spin-echo. Congruence between malignancies delineated by DCE was assessed against high-resolution DWI scans with b-values in the 0-1800 s/mm2 range, as well as against apparent diffusion coefficient (ADC) and kurtosis maps. Data were evaluated by independent magnetic resonance scientists with 3-20 years of experience, and radiologists with 6 and 20 years of experience in breast MRI. Malignancies were assessed from ADC and kurtosis maps, using paired t tests after confirming that these values had a Gaussian distribution. Agreements between DWI and DCE datasets were also evaluated using Sorensen-Dice similarity coefficients. Cancerous and normal tissues were clearly separable by ADCs: by SPEN their average values were (1.03 ± 0.17) × 10-3 and (1.69 ± 0.19) × 10-3 mm2 /s (p

Objective The aims of this study were to follow up the monitoring, health and anxiety from women who became pregnant after an embryo transfer or a intrauterine insemination during the COVID-19 epidemic in France Study Design This is a single centre, retrospective study from December 2019 to March 2020 based on a phone call interview using a specific questionnaire sheet specially developed for this study. Questionnaires from 104 pregnant women were completed and descriptive data are then analyzed. Results Women with ongoing pregnancies (n = 88) did not change their physician visits. The COVID-19 outbreak has created no or few additional stresses for 77 % of pregnant women since the lockdown started. We report a miscarriage rate of 14.4 % (n = 15) and documented 10 patients (11.3 %) who had symptoms related to COVID-19. No severe symptoms and no hospitalization in intensive care unit were identified. Conclusion The epidemic context did not disrupt the medical monitoring of pregnancies and we did not recover an increased rate of miscarriage after ART. None of the patients who had COVID-related symptoms presented with severe clinical manifestations. Surprisingly, pregnant women were psychologically able to experience the lockdown.

Manuka honey (MH) is currently used as a wound treatment and suggested to be effective in Methicillin-resistant Staphylococcus aureus (MRSA) elimination. We sought to optimize the synthesis of MH microneedles (MHMs) while maintaining the MH therapeutic effects. MHMs were synthesized using multiple methods and evaluated with in vitro assays. MHMs demonstrated excellent bactericidal activity against MRSA at concentrations ≥ 10% of honey, with vacuum-prepared honey appearing to be the most bactericidal, killing bacterial concentrations as high as 8 × 107 CFU/mL. The wound-healing assay demonstrated that, at concentrations of 0.1%, while the cooked honey had incomplete wound closure, the vacuum-treated honey trended towards faster wound closure. In this study, we demonstrate that the method of MHM synthesis is crucial to maintaining MH properties. We optimized the synthesis of MHMs and demonstrated their potential utility in the treatment of MRSA infections as well as in wound healing. This is the first report of using MH as a substrate for the formation of dissolvable microneedles. This data supports the need for further exploration of this new approach in a wound-healing model and opens the door for the future use of MH as a component of microneedle scaffolds.

Although gemcitabine is the cornerstone of care for pancreatic ductal adenocarcinoma (PDA), patients lack durable responses and relapse is inevitable. While the underlying mechanisms leading to gemcitabine resistance are likely to be multifactorial, there is a strong association between activating gemcitabine metabolism pathways and clinical outcome. This study evaluated casein kinase 1 delta (CK1δ) as a potential therapeutic target for PDA and bladder cancer, in which CK1δ is frequently overexpressed. We assessed the antitumor effects of genetically silencing or pharmacologically inhibiting CK1δ using our in-house CK1δ small-molecule inhibitor SR-3029, either alone or in combination with gemcitabine, on the proliferation and survival of pancreatic and bladder cancer cell lines and orthotopic mouse models. Genetic studies confirmed that silencing CK1δ or treatment with SR-3029 induced a significant upregulation of deoxycytidine kinase (dCK), a rate-limiting enzyme in gemcitabine metabolite activation. The combination of SR-3029 with gemcitabine induced synergistic antiproliferative activity and enhanced apoptosis in both pancreatic and bladder cancer cells. Furthermore, in an orthotopic pancreatic tumor model, we observed improved efficacy with combination treatment concomitant with increased dCK expression. This study demonstrates that CK1δ plays a role in gemcitabine metabolism, and that the combination of CK1δ inhibition with gemcitabine holds promise as a future therapeutic option for metastatic PDA as well as other cancers with upregulated CK1δ expression.

Purpose: To develop schemes that deliver faithful 2D slices near field heterogeneities of the kind arising from non-ferromagnetic metal implants, with reduced artifacts and shorter scan times. Methods: An excitation scheme relying on cross-term spatio-temporal encoding (xSPEN) was used as basis for developing the new inhomogeneity-insensitive, slice-selective pulse scheme. The resulting Fully refOCUSED cross-term SPatiotemporal ENcoding (FOCUSED-xSPEN) approach involved four adiabatic sweeps. The method was evaluated in silico, in vitro and in vivo using mice models, and compared against a number of existing and of novel alternatives based on both conventional and swept RF pulses, including an analogous method based on LASER's selectivity spatial selectivity. Results: Calculations and experiments confirmed that multi-sweep derivatives of xSPEN and LASER can deliver localized excitation profiles, centered at the intended positions and endowed with enhanced immunity to B0 and B1 distortions. This, however, is achieved at the expense of higher SAR than non-swept counterparts. Furthermore, single-shot FOCUSED-xSPEN and LASER profiles covered limited off-resonance ranges. This could be extended to bands covering arbitrary off-resonance values with uniform slice widths, by looping the experiments over a number of scans possessing suitable transmission and reception offsets. Conclusions: A series of novel approaches were introduced to select slices near metals, delivering robustness against Bo and B1+ field inhomogeneities., Comment: 7 figures, 9 figures in the supporting information

Purpose Diffusion weighted imaging (DWI) is increasingly used in evaluating breast cancer, as complement to DCE measurements of superior spatial resolution. Extracting fine morphological features in DWI is complicated by limitations that sequences such as EPI face, when applied to heterogeneous organs. This study investigates the ability of spatiotemporal encoding (SPEN) MRI to screen breast cancers and define diffusivity features at mm and sub-mm resolutions on a 3T scanner METHODS: Twenty-one patients with biopsy-confirmed breast cancer lesions were examined by T2-weighted and DCE protocols, by EPI-based DWI, and by SPEN-based protocols optimized for SNR, robustness and spatial resolution, respectively. Results Excellent agreement was found between the diffusivity parameters measured by all SPEN protocols and by EPI, with the lower ADCs characteristic of tumors being readily detected. SPEN provided systematically better SNR and improved qualitative results, particularly when dealing with small lesions surrounded by fatty tissue, or lesions close to tissue/air interfaces. SPEN-derived ADC maps collected at sub-mm in-plane resolutions recapitulated the high-resolution morphology shown by lesions using more sensitive DCE protocols. Conclusion Measurements on a patient cohort validated SPEN's ability to quantify the diffusivity changes associated with the presence of breast cancers, while imaging the lesions with reduced distortions at sub-mm resolutions.

Context Myotonic dystrophy (DM) is an autosomal dominant disorder characterized mainly by myotonia but also by primary hypogonadism. No study has reported on fertility management of patients affected by DM type 1 (DM1). Objective This study investigates the impact of CTG repeats in the DMPK gene on semen quality and preimplantation genetic diagnosis (PGD) outcome. Design This is a monocentric retrospective observational study conducted from January 2003 to January 2019. Setting Antoine Béclère University Hospital, Clamart, France. Patients Three groups were compared in this study: male DM1 patients (Group A, n = 18), unaffected partners of DM1 female patients (Group B, n = 30), and proven fertile men (Group C, n = 33). Reproductive outcomes after PGD were compared between groups A and B. Results Sperm volume was reduced in group A (2.0 mL) when compared with groups B (3.0 mL; P < 0.01) and C (3.5 mL; P < 0.01). Progressive motility in raw sperm was also decreased in group A (30%) as compared to group C (40%; P < 0.01). The median number of progressive spermatozoa retrieved after sperm preparation was 2.7 million (M) in group A, which was significantly less than those of groups B (10.0 M; P < 0.01) and C (62.2 M; P < 0.01). Sperm motility was inversely correlated to the number of CTG repeats (Spearman r2 = 0.48, Pearson r2 = 0.35). Cumulative live birth rate per transfer was similar between groups, with 32.2% in group A versus 26.8% in group B. Conclusions As a precautionary measure, we advise physicians to perform regular monitoring of semen quality in affected males, which would allow sperm cryopreservation should semen parameters fall. PGD allows good reproductive outcomes without disease transmission.

Purpose To develop a pulse sequence for acquiring robust, quantitative T2 relaxation maps in real time. Methods The pulse scheme relies on fully refocused spatiotemporally encoded multi-spin-echo trains, which provide images that are significantly less distorted than spin-echo echo planar imaging-based counterparts. This enables single-shot T2 mapping in inhomogeneity-prone regions. Another advantage of these schemes stems from their ability to interleave multiple scans in a reference-free manner, providing an option to increase sensitivity and spatial resolution with minimal motional artifacts. Results The method was implemented in preclinical and clinical scanners, where single-shot acquisitions delivered reliable T2 maps in ≤200 ms with ≈250 µm and ≈3 mm resolutions, respectively. Ca. 4 times higher spatial resolutions were achieved for the motion-compensated interleaved versions of these acquisitions, delivering T2 maps in ca. 10 s per slice. These maps were nearly indistinguishable from multi-scan relaxometric maps requiring orders-of-magnitude longer acquisitions; this was confirmed by mice head and real-time mice abdomen 7T scans performed following contrast-agent injections, as well as by 3T human brain and breast scans. Conclusion This study introduced and demonstrated a new approach for acquiring rapid and quantitative T2 data, which is particularly reliable when operating at high fields and/or targeting heterogeneous organs or regions.

A recent case series of diabetic ketoacidosis (DKA) associated with colonoscopy in sodium–glucose cotransporter 2 inhibitor (SGLT2i)-treated diabetes (1) prompted a clinical alert update to include colonoscopy (2). That update advised colonoscopy cancellation when capillary ketone concentrations are >1.0 mmol/L (if blood gas analysis is unavailable) when SGLT2i have not been withheld for 72 h. However, those guidelines were formulated in the absence of data regarding the normal range for capillary ketone concentrations at the time of colonoscopy. Unnecessary colonoscopy cancellation carries risks, including delays in possible cancer detection, and psychological consequences, whereas a ketone cutoff that is too high increases the risk of DKA. To define a ketone concentration that may serve as an empirical determinant of the need for further investigation, we now report a nondiabetic reference interval for capillary ketone concentrations at the time of colonoscopy from a multicenter observational study conducted between June and December 2020 at four tertiary health services (Alfred, Austin, Eastern, and Western Health) in Melbourne, Australia. Multisite approval was granted by the Alfred Human Research Ethics Committee. Inclusion criteria for the reference population were community-dwelling, normoglycemic adults undergoing colonoscopy. Exclusion criteria were a history of diabetes, pancreatitis, pancreatic cancer, pancreatic surgery, hemochromatosis, cystic fibrosis, starvation ketosis (defined as fasting >72 h), pregnancy, or the discovery during recruitment of a fasting capillary glucose >5.5 mmol/L (100 mg/dL). Participants with type 2 diabetes were also recruited to compare capillary ketone concentrations with the reference interval population. Except for physician-adjudicated …

This study introduces a novel index based on expectations concordance for explaining stock-price volatility when novel events that are each somewhat unique cause unforeseeable change and Knightian uncertainty in the process driving outcomes. Expectations concordance measures the degree to which KU events are associated with directionally similar expectations of future returns. Narrative analytics of daily news reports allow for the assessment of bullish versus bearish views in the stock market. Increases in expectations concordance across all KU events results in reinforcing effects and an increase in stock market volatility. Lower expectations concordance produces a stabilizing effect wherein the offsetting views reduce market volatility. The empirical findings hold for ex post and ex ante measures of volatility and for OLS and GARCH estimates.

Postoperative patients of intestinal reconnection in Morelia, Mexico, are usually in for 3–5 days of oral fast, which increases protein catabolism in the patient, thus lengthening their hospital stay and increasing the risk of developing metabolic comorbidities. Hypocaloric peripheral parenteral nutrition (HPPN) reduces proteolysis and improves inflammatory markers in these patients. The aim of this case report is to determine whether or not peripheral parenteral nutrition (PPN) improves inflammation, lessening the postoperative risk. A 62-year-old female patient and her cancer diagnosis and intestinal reconnection surgery are discussed. PPN is not commonly used in this type of patients due to the short duration of the fast, although its use is common before surgery. However, postoperative use can be beneficial as well, and given the delicate postoperative state these patients are in, it is worth it (at least in these cases) to give them all the strength and tools available for a better recovery. PPN in the case discussed herein improved the patient’s inflammatory marker levels in a shorter period.

Facial infra-red imaging (IRI) is a contact-free technique complimenting the traditional psychophysiological measures to characterize physiological profile. However, its full potential in affective research is arguably unmet due to the analytical challenges it poses. Here we acquired facial IRI data, facial expressions and traditional physiological recordings (heart rate and skin conductance) from healthy human subjects whilst they viewed a 20-min-long unedited emotional movie. We present a novel application of motion correction and the results of spatial independent component analysis of the thermal data. Three distinct spatial components are recovered associated with the nose, the cheeks and respiration. We first benchmark this methodology against a traditional nose-tip region-of-interest based technique showing an expected similarity of signals extracted by these methods. We then show significant correlation of all the physiological responses across subjects, including the thermal signals, suggesting common dynamic shifts in emotional state induced by the movie. In sum, this study introduces an innovative approach to analyse facial IRI data and highlights the potential of thermal imaging to robustly capture emotion-related changes induced by ecological stimuli.

PURPOSE Pathogenic variants in GJB2 are the most common cause of autosomal recessive sensorineural hearing loss. The classification of c.101T>C/p.Met34Thr and c.109G>A/p.Val37Ile in GJB2 are controversial. Therefore, an expert consensus is required for the interpretation of these two variants. METHODS The ClinGen Hearing Loss Expert Panel collected published data and shared unpublished information from contributing laboratories and clinics regarding the two variants. Functional, computational, allelic, and segregation data were also obtained. Case-control statistical analyses were performed. RESULTS The panel reviewed the synthesized information, and classified the p.Met34Thr and p.Val37Ile variants utilizing professional variant interpretation guidelines and professional judgment. We found that p.Met34Thr and p.Val37Ile are significantly overrepresented in hearing loss patients, compared to population controls. Individuals homozygous or compound heterozygous for p.Met34Thr or p.Val37Ile typically manifest mild to moderate hearing loss. Several other types of evidence also support pathogenic roles for these two variants. CONCLUSION Resolving controversies in variant classification requires coordinated effort among a panel of international multi-institutional experts to share data, standardize classification guidelines, review evidence, and reach a consensus. We concluded that p.Met34Thr and p.Val37Ile variants in GJB2 are pathogenic for autosomal recessive nonsyndromic hearing loss with variable expressivity and incomplete penetrance.

This essay decodes how Marlon James’s A Brief History of Seven Killings uses the history of Jamaican music, culminating in the conflict between roots reggae and dancehall, to chart the Cold War’s temporality, futurity, and ideological conflicts over time, temporality, and futurity. A Brief History of Seven Killings points readers to a jaded, subaltern temporality encoded in a dancehall music that rejects the revolutionary utopianism woven into postindependence Jamaican music. The novel stages this temporal conflict at the center of Jamaican popular music through the status of revolutionary Cuba and the riddim-based technique of dancehall song composition, both of which converge in the itinerary of the “Death in the Arena” riddim. The novel thus invites readers to process the Cold War’s conflict over time and space through the lens of Jamaican music, attuned both to how geopolitics inflected that music and to how that music inflected geopolitics. Reading the evolution of Jamaican music since independence, this essay reveals how the form of James’s novel replicates the spectral and shattered assemblages of dancehall music in order to borrow some of its fugitive, subaltern autonomy.

We provide new evidence that a disruption in credit supply played a quantitatively significant role in the unprecedented contraction of employment during the Great Depression using a novel, hand-collected dataset of large industrial firms. Our identification strategy exploits preexisting variation in the need to raise external funds at a time when public bond markets essentially froze. Local bank failures inhibited firms’ ability to substitute public debt for private debt, which exacerbated financial constraints. We estimate a large and negative causal effect of financing frictions on firm employment. We find that the lack of access to credit likely accounted for a substantial fraction of the aggregate decline in employment of large firms between 1928 and 1933.

We investigate thin film resistive thermometry based on metal-to-insulator-transition (niobium nitride) materials down to very low temperature. The variation of the NbN thermometer resistance have been calibrated versus temperature and magnetic field. High sensitivity in tempertaure variation detection is demonstrated through efficient temperature coefficient of resistance. The nitrogen content of the niobium nitride thin films can be tuned to adjust the optimal working temperature range. In the present experiment, we show the versatility of the NbN thin film technology through applications in very different low temperature use-cases. We demonstrate that thin film resistive thermometry can be extended to temperatures below 30 mK with low electrical impedance., Comment: Article accepted for publication in JLTP

This essay reexamines the figure of Franz Kafka (1883–1924) in light of his largely ignored, recursive links to circum-Caribbean and Black Atlantic processes of racialized exploitation and corporal punishment. When we centre Kafka’s extensive biographical and literary engagements with these processes, the persistent debate over Kafka’s status as a Holocaust prophet emerges in a new light. Kafka’s archival trail connects his lifelong attention to African enslavement and New World plantation economies to his nightmarish vision of murderous bureaucracies – a connection that crystallizes concretely in his 1919 short story “In the Penal Colony.” The archival and aesthetic connections direct us to a historiographical one, namely the increasingly excavated genealogical linkages between the Holocaust and anterior genocidal depredations in Africa and the New World under the auspices of European colonialism. This historiographical reorientation allows us to recast, in a global frame, the debate over Kafka’s status as a prophet of world history, a debate that has heretofore operated through the exclusion of the transatlantic slave trade. Kafka’s extensively documented attunement to colonial political economies provides formal, figural mechanisms that not only link the juridical–economic worlds of Caribbean slavery and Hitler’s Third Reich, but also anticipate, and disable, the dehistoricized, Eurocentric appropriation of his textual archive as a premonition of Auschwitz.

PURPOSE: The aim of this study was to evaluate the outcomes of frozen oocytes or embryos cryopreserved after controlled ovarian stimulation (COS) or in vitro maturation (IVM) for female cancer patients who underwent a fertility preservation (FP) prior to gonadotoxic therapy. METHODS: A retrospective cohort study from 2009 to December 2017 was conducted. Among the 667 female cancer patients who underwent oocytes or embryos cryopreservation for FP, 40 (6%) have returned to the fertility clinic between 2011 and 2019 to use their frozen material after being cured. We compared these thaw cycles outcomes according to the techniques used at the time of cryopreservation. RESULTS: Among the 40 women cancer survivors who used their cryopreserved material, thirty patients have benefited from at least one embryo transfer. Ten patients did not have an embryo transfer since the oocytes did not survive after the thawing process or because no embryo was obtained after fertilization. We related three live births following FP using IVM (two from frozen oocytes and one after embryo cryopreservation). Five live births were obtained when COS was performed at the time of FP (one from frozen oocytes and four after embryo cryopreservation). CONCLUSIONS: Our preliminary results, although they are obtained in a small sample, are encouraging and show that different FP techniques can be used in female cancer patients and lead to live births. IVM is one of the options available that does not delay the start of chemotherapy or if ovarian stimulation using gonadotropins is contraindicated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02168-3.

Penile prothesis (PP) is the gold-standard treatment of drug-refractory erectile dysfunction (ED). While postoperative outcomes have been widely described in the literature, there are few data about patient satisfaction and intraoperative events. We aimed to assess long-term patient satisfaction and perioperative outcomes after PP implantation in a single-centre cohort of unselected patients using validated scales.A total of 130 patients received a PP (median age: 62.5 years [IQR: 58-69]; median International Index of Erectile Function (IEEF-5) score: 6 [IQR: 5-7]). Median follow-up was 6.3 years [IQR: 4-9.4]. Thirty-two (24.6%) patients underwent surgical revision, of which 20 were PP removals (15.4%). Global PP survival rate was 84.6% and previous PP placement was a risk factor for PP removal (p = 0.02). There were six (4.6%) non-life-threatening intraoperative events including two which resulted in non-placement of a PP (1.5%). EAUiaic grade was 0 for 124 procedures (95.4%), 1 for four procedures (3.1%) and 2 for two procedures (1.5%). Of patients who still had their PP at the end of the study, 91 (80.5%) expressed satisfaction.PP implantation is a last-resort treatment for ED with a satisfactory outcome. PPs are well accepted by patients.RéSUMé: CONTEXTE: La prothèse pénienne (PP) est. le traitement de référence de la dysfonction érectile (DE) réfractaire aux médicaments. Le but de ce travail est. d’évaluer les résultats à long terme chez les patients traités par prothèses péniennes (PP) dans notre hôpital. RéSULTATS: Un total de 130 patients a eu une pose de PP (âge médian: 62,5 ans [IQR: 58–69]; score médian de l’indice international de la fonction érectile (IEEF-5): 6 [IQR: 5–7]). Le suivi médian était de 6.3 ans [IQR: 4–9.4]. Trente-deux (24,6%) patients ont eu une reprise chirurgicale, dont 20 étaient des retraits de PP (15,4%). La durée de vie global des PP était de 84,6% et la pose antérieure de PP était un facteur de risque pour l’ablation (p = 0,02). Il y a eu six (4,6%) événements peropératoires ne mettant pas la vie en danger, dont deux qui ont empêché la pose de PP (1,5%). Le score EAUiaic était de 0 pour 124 procédures (95,4%), 1 pour quatre procédures (3,1%) et 2 pour deux procédures (1,5%). Parmi les patients qui avaient encore leur PP à la fin de l’étude, 91 (80,5%) ont exprimé leur satisfaction. CONCLUSIONS: L’implantation de PP est. un traitement de dernier recours pour la dysfonction érectile avec un résultat satisfaisant. Les PP sont bien acceptés par les patients.

Background Routine, short-term use of inotropic agents is still applied in advanced heart failure (HF) patients either as a bridge to definitive treatment or as a mean to improve quality of life, despite the paucity of scientific evidence. Intermittent levosimendan was shown to be efficacious compared to placebo in advanced HF patients, however no prospective data comparing it to other inotropes and in particular, to milrinone are available. We aimed to assess the clinical effects of intermittent levosimendan in a small group of milrinone-treated advanced HF patients. Methods This was a prospective, un-blinded study. Consecutive ambulatory advanced HF patients intermittently treated with ≥ 4 cycles of once-weekly 6-hours 0.25–0.5 mg/kg/min milrinone at our HF outpatient clinic, were switched to levosimendan. All patients were evaluated using B-natriuretic peptide (BNP) levels, echocardiography, cardio-pulmonary exercise test and HF questionnaire before and after 4 weeks of intermittent once-weekly 6-hours therapy with levosimendan 0.1–0.2 mcg/kg/min. Results The cohort included 11 patients, 10 men, mean age 76±12 years. After 4 weeks of levosimendan therapy, Vo2 max improved by a mean of 2.28 ml/kg [95% CI -0.22-3.38, p = 0.05], BNP levels decreased from a median of 1015 ng/l [261–1035] to 719 ng/l [294–739], (p

The growth of the internet and networked systems has exposed software to an increased amount of security threats. One of the responses from software developers to these threats is the introduction of security activities in the software development lifecycle. This paper describes an approach to reduce the need for costly human expertise to perform risk analysis in software, which is common in secure development methodologies, by automating threat modeling. Reducing the dependency on security experts aims at reducing the cost of secure development by allowing non-security-aware developers to apply secure development with little to no additional cost, making secure development more accessible. To automate threat modeling two data structures are introduced, identification trees and mitigation trees, to identify threats in software designs and advise mitigation techniques, while taking into account specification requirements and cost concerns. These are the components of our model for automated threat modeling, AutSEC. We validated AutSEC by implementing it in a tool based on data flow diagrams, from the Microsoft security development methodology, and applying it to VOMS, a grid middleware component, to evaluate our model's performance.

This study explored the usefulness of multiple quantitative MRI approaches to detect pancreatic ductal adenocarcinomas in two murine models, PAN-02 and KPC. Methods assayed included 1 H T1 and T2 measurements, quantitative diffusivity mapping, magnetization transfer (MT) 1 H MRI throughout the abdomen and hyperpolarized 13 C spectroscopic imaging. The progress of the disease was followed as a function of its development; studies were also conducted for wildtype control mice and for mice with induced mild acute pancreatitis. Customized methods developed for scanning the motion- and artifact-prone mice abdomens allowed us to obtain quality 1 H images for these targeted regions. Contrasts between tumors and surrounding tissues, however, were significantly different. Anatomical images, T2 maps and MT did not yield significant contrast unless tumors were large. By contrast, tumors showed statistically lower diffusivities than their surroundings (≈8.3 ± 0.4 x 10-4 for PAN-02 and ≈10.2 ± 0.6 x 10-4 for KPC vs 13 ± 1 x 10-3 mm2 s-1 for surroundings), longer T1 relaxation times (≈1.44 ± 0.05 for PAN-02 and ≈1.45 ± 0.05 for KPC vs 0.95 ± 0.10 seconds for surroundings) and significantly higher lactate/pyruvate ratios by hyperpolarized 13 C MR (0.53 ± 0.2 for PAN-02 and 0.78 ± 0.2 for KPC vs 0.11 ± 0.04 for control and 0.31 ± 0.04 for pancreatitis-bearing mice). Although the latter could also distinguish early-stage tumors from healthy animal controls, their response was similar to that in our pancreatitis model. Still, this ambiguity could be lifted using the 1 H-based reporters. If confirmed for other kinds of pancreatic tumors this means that these approaches, combined, can provide a route to an early detection of pancreatic cancer.

Background It is now acknowledged that the input of patients in health outcome assessment is vital to understanding the impact of diseases and interventions for those diseases. This study is the first report of patient-reported outcome measures (PROM) in a large cohort of patients with type 1 Gaucher disease (GD1) enabling us to study predictors of the reported outcomes. Method The PROM was sent via a mobile phone survey to 405 adult patients with GD1. Demographics, clinical data, and treatment status were extracted from clinic charts. Age, sex, severity score index (SSI) at presentation and treatment status were used as variables to assess outcomes. Results A total of 192 patients with GD1 (111 females) responded (47.4% response rate), of whom 124 (64.5%) had received GD1-specific therapy. Around 40% of patients reported that GD had restricted their education/job and fun activities and were concerned about being emotional and financial burdens on others. Concerns regarding the risk of bone disease and Parkinson disease were also high (60%). The severity of GD1 (reflected by the need for GD1-specific therapy and a high SSI) was associated with GD1-related restrictions and concerns, fatigue, physical weakness, bone pain, and worry regarding the future. Conclusions The use of GD1 specific PROM highlights personal problems that are not captured by traditional outcome parameters and that need to be addressed to improve health-related quality of life. Validated PROM should be included among the outcome measures in clinical practice and future prospective studies for patients with chronic and rare diseases.

SARS-CoV-2 infection (COVID-19) results in local and systemic activation of inflammation and coagulation. In this review article, we will discuss the potential role of coagulation factor Xa (FXa) in the pathophysiology of COVID-19. FXa, a serine protease, has been shown to play a role in the cleavage of SARS-CoV-1 spike protein (SP), with the inhibition of FXa resulting in the inhibition of viral infectivity. FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages. Considering that patients with preexisting conditions, including cardiopulmonary disease, are at an increased risk of severe COVID-19, we discuss the potential role of increased levels of FX in these patients, resulting in a potential increased propensity to have a higher infectious rate and viral load, increased activation of coagulation and inflammation, and development of fibrosis. With these observations in mind, we postulate as to the potential therapeutic role of FXa inhibitors as a prophylactic and therapeutic treatment for high-risk patients with COVID-19.

International audience; Objective: To study the efficacy of combined administration of subcutaneous and vaginal progesterone for priming frozen blastocysts transfers, looking at progesterone levels and ART outcome.Design: Retrospective study.Setting patients: Three hundred and twenty frozen blastocyst transfer cycles conducted in 213 women aged up to 42 years, BMI between 18 and 30 kg/m2, with anatomically normal uterus who underwent frozen embryo transfers (FETs) from February 2019 to December 2019 with a combined luteal-phase support (LPS) associating subcutaneous and vaginal progesterone. Patients with recurrent pregnancy loss (RPL) were excluded.Results: When using combined vaginal and subcutaneous LPS, SPL >10.50 ng/mL in 95% of cases, with a minimum value of 7.02 ng/mL. CPR, OPR, and global miscarriage rates were 38.4%, 30.9%, and 19.5%, respectively. Analyzing results per quartiles, revealed that miscarriage rates were significantly inferior, and IR were higher in the upper two quartiles of serum progesterone (>21.95 ng/mL) on the day before FET, while there was no difference in CPR and OPR.Conclusions: We report ART outcome of frozen blastocyst transfers performed using a combination of vaginal and subcutaneous progesterone for LPS. ART results were honorable and SPL favorable 1-2 days before FET in 99% of cases.

Highlights • Globally, there was a significant correlation between healthy life expectancy (HALE), non-communicable disease DALYs and mortality, with COVID-19 caseload and deaths. • There was a positive independent association between HALE and COVID-19 cases. • The number of tourists was also associated with COVID-19 mortality. • Our integrated model of global data is valuable for health policymakers, allowing for the implementation of optimal preventative measures at national and global scales., Background The interaction between coronavirus disease 2019 (COVID-19) and non-communicable diseases may increase the global burden of disease. We assessed the association of COVID-19 with ageing and non-communicable diseases. Methods We extracted data regarding non-communicable disease, particularly cardiovascular disease, deaths, disability-adjusted life years (DALYs), and healthy life expectancy (HALE) from the Global Burden of Disease Study (GBD) 2017. We obtained data of confirmed COVID-19 cases, deaths, and tests from the Our World in Data database as of May 28, 2020. Potential confounders of pandemic outcomes analyzed include institutional lockdown delay, hemispheric geographical location, and number of tourists. We compared all countries according to GBD classification and World Bank income level. We assessed the correlation between independent variables associated with COVID-19 caseload and mortality using Spearman's rank correlation and adjusted mixed model analysis. Findings High-income had the highest, and the Southeast Asia, East Asia, and Oceania region had the least cases per million population (3050.60 vs. 63.86). Sub-saharan region has reported the lowest number of COVID-19 mortality (1.9). Median delay to lockdown initiation varied from one day following the first case in Latin America and Caribbean region, to 34 days in Southeast Asia, East Asia, and Oceania. Globally, non-communicable disease DALYs were correlated with COVID-19 cases (r = 0.32, p

International audience; Modeling, verifying, and validating are essential steps in order to build systems and software that do what designers expect. If formal verification, and especially model-checking, is a popular method for proving the correctness of properties, its efficiency depends on the accuracy of the used models and the quality of abstractions. As a consequence, applying verification techniques on large-scale complex software like video games is hard without strong assumptions and simplifications. Simulation models are generally more accurate than verification models, but it is often harder to verify them. Combined formalisms that take the benefits of both model-checking and discrete-event simulation represent a good deal between both of these families, although strong engineering expertise remains necessary to define the relevant tests and scenarios. This paper proposes an approach to build this kind of formalism through the example of DEv-PROMELA, which is built by combining Discrete-event System Specification formalism and PROMELA language. Then, it shows how combined formalisms can be used for modeling, verifying, and validating complex software like video games by using both formal-based and simulation-based verification and validation.

Lifestyle choices are of the utmost importance when discussing disease prevention and treatment. Time and again, doctors...

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients. We investigated the possible implication of TR among STEMI patients. Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patients records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded. Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR was 3% (n = 32). Patients with significant TR demonstrated worse echocardiographic parameters, more likely to have in-hospital complications and had higher long-term mortality (28% vs. 6%; p

Objective To investigate the etiology and longitudinal clinical, neuropsychological, psychosocial, and surgical outcome profile of patients with medication refractory epilepsy and temporal encephaloceles with a view to highlight diagnostic clues and management strategies. Methods The comprehensive epilepsy program databases at two surgical epilepsy centers from January 2000 to October 2018 were reviewed for this observational study, to identify patients with encephaloceles causing temporal lobe epilepsy (TLE) and treated with surgical resection. Their clinical, radiological, neuropsychological, psychiatric, and surgical data were obtained. Body mass index (BMI) data were also reviewed due to possible correlation between idiopathic intracranial hypertension and encephaloceles. Results Thirteen patients (eight female) were identified; only three were recognized on initial magnetic resonance imaging (MRI) report. Temporal encephaloceles were identified on the left in eight patients, on the right in three patients, and bilaterally in two patients. One patient had a strong family history of encephaloceles. The median BMI for patients with seizure onset ≤20 years of age was 22.4, whereas for patients with onset >20 years median BMI was 32.6 (P = .06). Five patients underwent a focal lesionectomy, three patients had limited temporal lobectomy, and five patients had standard anterior temporal lobectomy. Median postoperative follow-up was 5.5 years. All but one patient were free of disabling seizures. Nine of ten neuropsychologically tested patients had no discernable cognitive decline postoperatively. Postoperative psychosocial adjustment features were present in four patients. Significance Genetic factors and a possible association with idiopathic intracranial hypertension (given female predominance and elevated BMI) may contribute to the causation of temporal lobe encephaloceles. It is notable that a targeted surgical approach in the management of patients with TLE associated with encephaloceles has an excellent long-term clinical and neuropsychological outcome. Subtle encephaloceles should be actively searched for in patients with drug-resistant TLE because they significantly change surgical strategy and prognostication.

Predictive formulas to estimate body composition in children have been explored for some time, to this date, the most accurate obesity diagnostic tool is to determine fat mass. The aim of this study is to establish cutoff points that allow for a precise interpretation of nutritional status using the Fat Mass Index (FMI) in a Mexican pediatric population. A literature review using PubMed and Cochrane databases was made, searching for research articles on childhood obesity that compared BMI, FM percentage, and FMI, as well as those proposing diagnostic cutoff points. Mathematic formulas and linear regressions were then used to make a proposal on accurate cutoff points for this population. Our findings show that FM percentage is less precise than BMI and FMI in diagnosing obesity, and FMI seems to be a more complete tool for assessment as it differentiates fat and muscle mass of the total body weight. Both BMI and FMI should be considered when clinical evaluations regarding weight, with BMI complementing FMI by establishing fat-free mass. Our proposed cutoff points need to be validated in this population.

Vaginal delivery is typically avoided in the extremely preterm breech population due to the concern of entrapment by the cervix of the aftercoming head. A mechanical device concept is presented to enable vaginal delivery by preventing retraction of the cervix against the fetus during delivery. The two-part device was designed to dilate the cervix, prevent prolapse of small fetal parts and maintain sufficient dilation during delivery. The two-part device was designed and manufactured with the following modules: an inflatable saline-filled cervical balloon for dilation and a cervical retractor composed of semirigid beams to stabilize the cervix and maintain adequate dilation. The device was tested using a cervical phantom designed to simulate the compressive force the cervix exerts. The cervical balloon reached a maximum dilation of 8.5 cm, after which there was leakage of saline from the balloon. While this dilation was less than the target goal of 10 cm, the leaking was attributed to prototype manufacturing defects, which could be resolved with further development. The cervical retractor was able to withstand between 1–3 kPa. Although estimates of cervical pressure values can be upward of 30 kPa, there are no in vivo measurements to formally identify the pressure values for patients in preterm labor. This device serves as a viable proof-of-concept for utilizing an inflatable balloon device to prevent cervical retraction in the setting of extremely preterm vaginal breech delivery. Further manufacturing improvements and design changes could improve the device for continued development and testing.

Enterohepatic circulation (EHC) is a process that many drugs go through, in which, after extravascular administration, they are absorbed in the intestine, secreted in the bile and then reabsorbed during one or more circulation cycles that alter plasmatic concentrations of said drugs. The aim of this study was to compare a new pharmacokinetic model of EHC with the classic model of extravascular administration after administering Simvastatin. A single-center, randomized, controlled, prospective, longitudinal, single-dose, cross-over study was performed with a 7-day washout period, in healthy Mexican subjects. The plasma samples obtained were quantified with HPLC-MS / MS using a validated analytical method. Cmax, tmax, AUC0-24h and AUC0-∞ were determined, and both models were compared with the Akaike Information Criterion (AIC) and r^2. Results show that the pharmacokinetic parameters calculated with the EHC model are fairly similar to those obtained with the trapezoidal model, even more so than those obtained with the classic model. The AIC and r^2 criteria were lower for the EHC model (AIC=11.256 and 12.555, r^2=0.568 and 0.440) vs the classic model (AIC=9.382 and 9.195, r^2= 0.884 and 0.922). In conclusion, a new pharmacokinetic model for EHC was developed, and results confirmed that it adjusts well to experimental data, offering an alternative way to calculate Cmax, tmax and AUC0-t, and can also be adapted to other drugs that exhibit EHC as well.