Lewy body-related α-synucleinopathy (Lewy pathology) has been reported in patients with myotonic dystrophy (DM) type 1 (DM1), but no detailed report has described the prevalence and extent of its occurrence. We studied consecutive full autopsy cases of DM1 at the National Center of Neurology and Psychiatry (NCNP) Brain Bank for intractable psychiatric and neurological disorders. Thirty-two cases, genetically determined to be DM1 (59.0 ± 8.7 years), obtained from the NCNP Brain Bank, were compared with control cases obtained from the Brain Bank for Aging Research (BBAR) in Japan. The investigated anatomical sites followed the Dementia with Lewy Bodies Consensus Guideline, expanding to the peripheral autonomic nervous system, temporal pole, and occipital cortex, in addition to the olfactory epithelium and spinal cord. Of the 32 patients, 11 (34.4%) had Lewy pathology, with a significantly higher prevalence than that in the control cases from the BBAR (20.1%). Lewy pathology detected in DM1 was widespread, but no macroscopic depigmentation of the substantia nigra was observed in any DM1 case; this was commensurate with the microscopic paucity of Lewy pathology in the substantia nigra and amygdala. Lewy pathology in DM1 does not appear to follow either Braak's ascending paradigm or the olfactory-amygdala extension. Lewy neurites and dots in DM1 were very sparse in the cerebral cortex and distinct from those observed in BBAR control cases. This study was the first demonstration of unique Lewy pathology in DM1 and may contribute to the understanding of the protein propagation hypothesis of Lewy pathology.

Keywords: Lewy body; myotonic dystrophy type 1 (DM1); neuropathology; protein propagation; α-synuclein.

Over 1 million isotretinoin prescriptions are authorized in the United States per year. An insight into the frequency, dose dependency, timing, and reversibility of hair loss associated with isotretinoin treatment for acne vulgaris could help guide dosing regimens and patient counseling. The objective of this systematic review was to assess the frequency of hair loss in patients with acne vulgaris on <0.5 mg/kg/d daily doses of isotretinoin versus the frequency of hair loss in patients with acne vulgaris on ≥0.5 mg/kg/d daily doses of isotretinoin. An Embase and MEDLINE search was conducted on July 15, 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review focused on acne vulgaris patients. The treatment of acne vulgaris is the most common use of isotretinoin, and the population is typically younger and with fewer comorbidities. Twenty-two studies reported hair loss with oral isotretinoin treatment. A frequency analysis suggested that patients with acne vulgaris on <0.5 mg/kg/d of isotretinoin experienced hair loss at a frequency of 3.2% (n = 18/565) compared with those on ≥0.5 mg/kg/d, who experienced hair loss at a frequency of 5.7% (n = 192/3375). Inferential statistics were not possible. Physicians should consider counseling patients about the risk of telogen effluvium prior to drug initiation, as is commonly done for other side effects. The potential trend of increased hair loss frequency at a higher daily dosing warrants further investigation using higher-quality research.

Keywords: Accutane; Clarus; Epuris; alopecia; hair loss; hair shedding; hair thinning; high dose; isotretinoin; low dose; telogen effluvium.

Introduction: Early or mid-career physicians have few opportunities to participate in career development programs in health policy and advocacy with experiential and mentored training that can be incorporated into their busy lives.

Aim: The Society of General Internal Medicine (SGIM) created the Leadership in Health Policy (LEAHP) program, a year-long career development program, to prepare participants with a sufficient depth of knowledge, skills, attitudes, and behaviors to continue to build mastery and effectiveness as leaders, advocates, and educators in health policy. We sought to evaluate the program's impact on participants' self-efficacy in the core skills targeted in the curriculum.

Setting/participants: Fifty-five junior faculty and trainees across three scholar cohorts from 2017 to 2021.

Program description: Activities included workshops and exercises at an annual meeting, one-on-one mentorship, monthly webinars and journal clubs, interaction with policy makers, and completion of capstone projects.

Program evaluation: Self-administered, electronic surveys conducted before and following the year-long program showed a significant improvement in mean self-efficacy scores for the total score and for each of the six domains in general knowledge, teaching, research, and advocacy in health policy. Compared to the baseline scores, after the program the total mean score increased from 3.1 to 4.1, an increase of 1.1 points on a 5-point Likert scale (95% CI: 0.9-1.3; Cohen's D: 1.7), with 61.4% of respondents increasing their mean score by at least 1 point. Responses to open-ended questions indicated that the program met scholars' stated needs to improve their knowledge base in health policy and advocacy skills.

Discussion: The LEAHP program provides an opportunity for mentored, experiential training in health policy and advocacy, can build the knowledge and amplify the scale of physicians engaged in health policy, and help move physicians from individual patient advocacy in the clinic to that of populations.

Keywords: health policy; training program.

Hypertrophic cardiomyopathy (HCM) is a common but an underdiagnosed condition. Fasciculoventricular bypass tract (FVBT) is rare. Concomitant presence of both conditions is well described in Danon disease. We report a case of familial HCM with FVBT linked to a heterozygous pathogenic variant, c.655G>C (p.Val219Leu), in the cardiac myosin binding protein C3 (MYBPC3) gene. (Level of Difficulty: Advanced.).

Keywords: CMR, cardiac magnetic resonance; Danon disease; ECG, electrocardiogram; FVBT, fasciculoventricular bypass tract; HCM, hypertrophic cardiomyopathy; ICD, implantable cardioverter-defibrillator; LAMP-2, lysosome-associated membrane protein 2; MYBPC3, cardiac myosin binding protein C3; NSVT, nonsustained ventricular tachycardia; WPW, Wolff-Parkinson-White syndrome; accessory pathway; familial; hypertrophic cardiomyopathy.

Correction for 'Encapsulating bacteria in alginate-based electrospun nanofibers' by Emily Diep <i>et al.</i>, <i>Biomater. Sci.</i>, 2021, <b>9</b>, 4364-4373, DOI: 10.1039/D0BM02205E.

The local pharmacies and shops are brimming with various probiotic products that herald a range of health benefits. The poor quality of probiotic products in both dosage and species is symptomatic of this multi-billion-dollar market making it difficult for consumers to single out reliable ones. This study aims to fill the potential gap in the labeling accuracy of probiotic products intended for human consumption. We describe a combinatorial approach using classical culture-dependent technique to quantify and molecular techniques (16 s rRNA gene sequencing, multilocus sequence, and ribotyping) for strain recognition of the microbial contents. The full gamut of probiotic characteristics including acid, bile and lysozyme tolerances, adhesiveness, anti-pathogenicity, and degree of safeness were performed. Their capacity to endure gastro-intestinal (GIT) stresses and select drugs was assessed in vitro. Our results forced us to declare that the local probiotic market is essentially unregulated. Almost none of the probiotic products tested met the label claim. Some (11%) have no viable cells, and a quarter (27%) showing significant inter-batch variation. A lower microbial count was typical with undesirables constituting a quarter of the total (~ 27%). Half of the products contained antibiotic-resistant strains; the unregulated use of these probiotics carries the risk of spreading antibiotic resistance to gut pathobionts. Poor tolerance to gut conditions and mediocre functionalism make the case worse. The current regulatory systems do not take this discrepancy into account. We recommend an evidence-based regular market surveillance of marketed probiotics to ensure the authenticity of the claims and product effectiveness.

Keywords: Antibiotic resistance; Commercial probiotics; Gastrointestinal tract; Regulation; Strain-typing.

Background: Most of the previous studies, investigating determinants of 6-minute walk test (6MWT), were conducted on small sample sizes and/or have not explored different aspects such as freezing of gait, physical activity, gender, dual-task cost, and/or have not been able to explain large portion of variation in 6MWT in people with Parkinson's disease.

Aims: This study aimed to investigate the determinants of 6MWT, including aspects that previous studies have not explored.

Methods: In this descriptive cross-sectional study, 6MWT determinants were investigated upon 42 people with Parkinson's disease. After recording participants' demographic data, walking capacity, disease stage, severity of motor symptoms, freezing of gait, balance, physical activity, fear of falling, functional balance, and dual-task cost values were evaluated and grouped into modifiable and unmodifiable variables to investigate possible therapeutic benefits aiming improvement in walking capacity.

Results: The mean distance for 6MWT was 401.7 ± 92.7 m. Significant differences between women and men were found for height, walking capacity and speed, fear of falling, and functional balance (p<0.05). Hierarchical regression analysis showed that gender, age, and time since diagnosis significantly explained 52.4% of the variance in 6MWT and disease stage, freezing of gait, dual-task cost, and functional balance added an extra 35.6% to the explained variance.

Conclusions: These results showed that gender, age, disease stage, freezing of gait, dual-task cost, and functional balance values are significant contributors to the variance in 6MWT. Therefore, while planning rehabilitation strategies to improve walking capacity, one should focus on these aspects in people with Parkinson's disease.

Keywords: 6-minute walk test; 6MWT; Determinants; Parkinson’s disease; Walking capacity.

Like all biological and chemical reactions, ion channel kinetics are highly sensitive to changes in temperature. Therefore, it is prudent to investigate channel dynamics at physiological temperatures. However, most ion channel investigations are performed at room temperature due to practical considerations, such as recording stability and technical limitations. This problem is especially severe for the fast voltage-gated sodium channel, whose activation kinetics are faster than the time constant of the standard patch-clamp amplifier at physiological temperatures. Thus, biologically detailed simulations of the action potential generation evenly scale the kinetic models of voltage-gated channels acquired at room temperature. To quantitatively study voltage-gated sodium channels' temperature sensitivity, we recorded sodium currents from nucleated patches extracted from the rat's layer five neocortical pyramidal neurons at several temperatures from 13.5 to 30 °C. We use these recordings to model the kinetics of the voltage-gated sodium channel as a function of temperature. We show that the temperature dependence of activation differs from that of inactivation. Furthermore, the data indicate that the sustained current has a different temperature dependence than the fast current. Our kinetic and thermodynamic analysis of the current provided a numerical model spanning the entire temperature range. This model reproduced vital features of channel activation and inactivation. Furthermore, the model also reproduced action potential dependence on temperature. Thus, we provide an essential building block for the generation of biologically detailed models of cortical neurons.

Keywords: Channel; Inactivation; Kinetics; Model; Sodium; Temperature; Voltage-gated.

Mild heat treatment of fruit juices in combination with natural aroma compounds has been reported as an alternative to conventional pasteurization to better preserve their nutritional value. However, its antimicrobial efficiency varies from one juice to another. This study aims at developing a secondary predictive model of microbial inactivation scale during such combined process. Carvacrol was used as aroma compound and acid-adapted L. monocytogenes as target microorganism. The inactivation kinetics of this bacteria were followed in simulated fruit juices using a Central Composite Design with pH (2-6), °Brix (0-24), temperature (55-65 °C), and carvacrol concentration (0-60 μL/L) as independent variables. Curves were fitted to the Weibull inactivation model, and data collected used to generate two predictive models of the inactivation scale parameter through multiple regression analysis following an empirical and a mechanistic (based on Gamma concept) approach. The best of the two models was then validated using real fruit (orange, pineapple, and watermelon) juices. The empirical model where only the four variables tested were considered showed a lower statistical performance compared to the mechanistic model where octanol-water partition coefficient (Ko/w) and vapour pressure (Vp) of carvacrol at the treatment temperature were integrated (R² 0.6 and 0.9; Accuracy factor 1.5 and 1.3; Sum of Squared Error 3.6 and 1.1, respectively). No significant difference was observed between inactivation scale values obtained with real juices and the predicted values calculated using this mechanistic model. The Ko/w and Vp of the aroma compound used are key parameters that determine the efficiency of the above-described combined treatment.

Keywords: Aroma compounds; Fruit juices; Inactivation; Listeria monocytogenes; Mild heat; Predictive model.

Epidermal basement membrane, a tightly packed network of extracellular matrix (ECM) components, is a source of physical, chemical, and biological factors required for the structural and functional homeostasis of the epidermis. Variations within the ECM create distinct environments, which can affect the property of cells in the basal layer of the epidermis and subsequently affect keratinocyte differentiation and stratification. Very little attention has been paid to mimicking basement membrane in organotypic cultures. In this study, using parameters outlined in a consensus on the quality standard of organotypic models suitable for dermatological research, we have evaluated three basement membrane substitutes. We compared fibronectin with three complex three-dimensional matrices: Matrigel, decellularized dermal fibroblast‒produced and ‒assembled ECM, and a dry human amniotic membrane. Our results suggest that Matrigel is not a suitable substrate for human epidermal equivalent culture, whereas the two other complex three-dimensional substitutes, decellularized dermal fibroblast‒produced and ‒assembled ECM and dry human amniotic membrane, were superior to single layer fibronectin coating. Human epidermal equivalents cultured on either decellularized dermal fibroblast‒produced and ‒assembled ECM or on dry human amniotic membrane generated hemidesmosomes, whereas those on fibronectin did not. In addition, human epidermal equivalent cultured on decellularized dermal fibroblast‒produced and ‒assembled ECM and on dry human amniotic membrane can be maintained in culture 4 days longer than human epidermal equivalent cultured on fibronectin without compromising the barrier function.

Keywords: 3D, three-dimensional; Ca++, calcium ion; ECM, extracellular matrix; HEE, human epidermal equivalent; HSE, human skin equivalent; K, keratin; KC, keratinocyte; TEER, transepithelial electrical resistance; dDF ECM, decellularized dermal fibroblast‒produced and ‒assembled extracellular matrix; dHAM, dry human amniotic membrane.

Congenital diaphragmatic hernia (CDH) can be diagnosed in the prenatal period and its severity can be measured by fetal imaging. There is now level I evidence that, in selected cases, Fetoscopic Endoluminal Tracheal Occlusion (FETO) increases survival to discharge from the neonatal unit as well as the risk for prematurity. Both effects are dependent on the time point of tracheal occlusion. FETO may also lead to iatrogenic death when done in unexperienced centres. The implementation of the findings from our clinical studies, may also vary based on local conditions. These may be different in terms of available skill set, access to fetal therapy, as well as outcome based on local neonatal management. We encourage prior benchmarking of local outcomes with optimal postnatal management, based on large enough numbers and using identical criteria as in the recent trials. We propose to work further on prenatal prediction methods, and the improvement of fetal intervention. In this manuscript, we describe a research agenda from a fetal medicine perspective. This research should be in parallel with innovation in neonatal and pediatric (surgical) management of this condition. This article is protected by copyright. All rights reserved.

Keywords: congenital diaphragmatic hernia; extracellular vesicles; fetoscopic endoluminal tracheal occlusion; pulmonary hypoplasia; treprostinil.

Previous field studies in the Southern Ocean (SO) indicated an increased occurrence and dominance of cryptophytes over diatoms due to climate change. To gain a better mechanistic understanding of how the two ecologically important SO phytoplankton groups cope with ocean acidification (OA) and iron (Fe) availability, we chose two common representatives of Antarctic waters, the cryptophyte Geminigera cryophila and the diatom Pseudo-nitzschia subcurvata. Both species were grown at 2°C under different pCO₂ (400 vs. 900 μatm) and Fe (0.6 vs. 1.2 nM) conditions. For P. subcurvata, an additional high pCO₂ level was applied (1400 μatm). At ambient pCO₂ under low Fe supply, growth of G. cryophila almost stopped while it remained unaffected in P. subcurvata. Under high Fe conditions, OA was not beneficial for P. subcurvata, but stimulated growth and carbon production of G. cryophila. Under low Fe supply, P. subcurvata coped much better with OA than the cryptophyte, but invested more energy into photoacclimation. Our study reveals that Fe limitation was detrimental for the growth of G. cryophila and suppressed the positive OA effect. The diatom was efficient in coping with low Fe, but was stressed by OA while both factors together strongly impacted its growth. The distinct physiological response of both species to OA and Fe limitation explains their occurrence in the field. Based on our results, Fe availability is an important modulator of OA effects on SO phytoplankton, with different implications on the occurrence of cryptophytes and diatoms in the future.

Aim: To develop a drug-disease model describing iron overload and its effect on ferritin response in patients affected by transfusion-dependent haemoglobinopathies and investigate the contribution of interindividual differences in demographic and clinical factors on chelation therapy with deferiprone or deferasirox.

Methods: Individual and mean serum ferritin data were retrieved from 13 published studies in patients affected by hemoglobinopathies receiving deferiprone or deferasirox. A nonlinear mixed effects modelling approach was used to characterise iron homeostasis and serum ferritin production taking into account annual blood consumption, baseline demographic and clinical characteristics. The effect of chelation therapy was parameterised as an increase in the iron elimination rate. Internal and external validation procedures were used to assess model performance across different study populations.

Results: An indirect response model was identified, including baseline ferritin concentrations and annual blood consumption as covariates. The effect of chelation on iron elimination rate was characterised by a linear function, with different slopes for each drug [0.0109 (90% CI: 0.0079-0.0131) vs. 0.0013 (90% CI: 0.0008-0.0018) L/mg.month]. In addition to drug-specific differences in the magnitude of the ferritin response, simulation scenarios indicate that ferritin elimination rates depend on ferritin concentrations at baseline.

Conclusions: Modelling of serum ferritin following chronic blood transfusion enabled the characterisation of drug-induced changes in iron elimination rate and ferritin production. The use of a semi-mechanistic parameterisation allowed us to disentangle disease-specific factors from drug-specific properties. Despite comparable chelation mechanisms, deferiprone appears to have a significantly larger effect on the iron elimination rate than deferasirox.

Keywords: chelating agents; deferasirox; deferiprone; disease modelling; ferritin; pharmacokinetic-pharmacodynamic relationships; thalassaemia.

During the coronavirus disease 2019 pandemic, nurse leaders and managers have been compelled to prioritise immediate issues in their clinical areas and put aside the professional development of staff. However, leadership development for individuals and teams is essential to ensure nurses feel valued and develop the skills required for team cohesion, problem-solving, decision-making and innovation. Simple and effective approaches to staff leadership development are needed. Two such approaches are coaching and action learning. This article provides an introduction to coaching and action learning as approaches nurse leaders and managers can use to promote leadership development among individual team members and within the team. It describes how coaching and action learning work and their potential benefits and challenges. It explains how the two approaches can be used to underpin effective problem-solving and goal setting, and support nurses in their professional development, the ultimate aim being to deliver safe and effective patient care.

Keywords: career development; leadership; leadership development; leadership models; morale; professional; professional development; professional issues; staff welfare; workforce; workforce development.

Experienced drug-handling problems and inadequately considered expectations for drug therapy have an unfavorable influence on therapy. We performed a questionnaire survey in (i) parents of 0-5-year-old children and (ii) 6-17-year olds and their parents. We assessed (A) experienced drug-handling problems and (B) expectations for drug therapy. (i) Forty-six parents and (ii) 103 children and their parents participated in the study. Experienced drug-handling problems were described by (i) 100% of parents and (ii) 62% of children and 70% of parents. Problems concerned with the preparation of the drug, dosing, compliance with the time interval, and acceptance. (i) Sixty-five percent of parents preferred a peroral route of drug administration, while (ii) 74% of children and 86% of parents did so. Preferred characteristics of peroral drug formulations, e.g., liquid versus solid drug formulations or flavor, were highly heterogeneous. Preferences of 6-17-year-old children and their parents matched in 43 to 66%. Conclusion: Most children and their parents had already experienced drug-handling problems. Preferences concerning the ideal pediatric drug were highly heterogeneous and in about half of cases, preferences of children and their parents differed. Thus, the children should be approached directly. If information is solely gained from parents, the children's needs might remain unmet. What is Known: • Pediatric drug administration is complex and therefore error-prone. • Experiences and expectations of children and their parents should be considered. What is New: •Most pediatric patients and their parents have already experienced drug-handling problems. • Expectations concerning the ideal pediatric drug are highly heterogeneous. Parents are often insufficiently aware of those expectations in their children.

Keywords: Children; Drug administration; Drug administration routes; Drug formulations; Drug-handling problems; Parents.

Aortic surgeries in congenital conditions, such as hypoplastic left heart syndrome (HLHS), aim to restore and maintain the conduit and reservoir functions of the aorta. We proposed a method to assess these two functions based on 4D flow MRI, and we applied it to study the aorta in pre-Fontan HLHS. Ten pre-Fontan HLHS patients and six age-matched controls were studied to derive the advective pressure difference and viscous dissipation for conduit function, and pulse wave velocity and elastic modulus for reservoir function. The reconstructed neo-aorta in HLHS subjects achieved a good conduit function at a cost of an impaired reservoir function (69.7% increase of elastic modulus). The native descending HLHS aorta displayed enhanced reservoir (elastic modulus being 18.4% smaller) but impaired conduit function (three-fold increase in peak advection). A non-invasive and comprehensive assessment of aortic conduit and reservoir functions is feasible and has potentially clinical relevance in congenital vascular conditions.

Keywords: 4D flow; Aorta; Conduit function; Hypoplastic left heart syndrome; Reservoir function.

Background New therapies that do not reach patients in need, have not achieved their goal. Drug and Therapeutics Committees in hospitals ensure access to patients by compiling a formulary on rational grounds. An evolving landscape of innovative molecules challenges timely formulary adaptation after national reimbursement. Aim To integrate national reimbursement reports in the hospital's appraisal, thereby promoting access for patients without delay. Method For 2019, the rationale for new molecules at Ghent University Hospital, Belgium, was compared with the public assessment report of the National Institute for Health and Disability Insurance, assessing a medicine in a specific indication following a reimbursement request by the manufacturer. Decision criteria (therapeutic value and cost) between matching medicines in both databases (national & hospital) were retrospectively compared [no (%), mean (SD)]. Results Two-hundred public reports and 30 formulary decisions were analysed (with antineoplastic & immunomodulating as most prevalent class: 41.0% resp. 36.7%). National decision often concerned hospital-only medicines (89; 44.5%) without patient co-payment (101; 50.5%). Of 13 matched medicines (same indication), time delay between national decision and formulary admission was on average 3.1 (SD 2.3) months. Comparative analysis showed that assessment in both committees was mostly based on the efficacy endpoints of Randomised Controlled Trials. Literature used in hospital appraisals was of more recent publication date: + 0.78 (SD 2.2) years. Using public reports as a horizon scan could enable quick identification of new indications. Conclusion To speed up patient access, the scientific evidence of national reimbursement reports can be used for the purpose of hospital formulary decisions.

Keywords: Access to treatment; Availability; Drug and Therapeutics Committee; Drug reimbursement; Formulary; Health technology assessment; Hospital; Innovative; National; Orphan; Patient access; Unmet need.

Background: Uterine leiomyomas, also known as uterine fibroids or myomas, are the most common benign gynecological tumors and are found in women of reproductive and postmenopausal age. There is an exceptionally high prevalence of this tumor in women by the age of 50 years. Black women are particularly affected, with an increased incidence, earlier age of onset, larger and faster growing fibroids and greater severity of symptoms as compared to White women. Although advances in identifying genetic and environmental factors to delineate these fibroids have already been made, only recently has the role of epigenomics in the pathogenesis of this disease been considered.

Objective and rationale: Over recent years, studies have identified multiple epigenomic aberrations that may contribute to leiomyoma development and growth. This review will focus on the most recent discoveries in three categories of epigenomic changes found in uterine fibroids, namely aberrant DNA methylation, histone tail modifications and histone variant exchange, and their translation into altered target gene architecture and transcriptional outcome. The findings demonstrating how the altered 3D shape of the enhancer can regulate gene expression from millions of base pairs away will be discussed. Additionally, translational implications of these discoveries and potential roadblocks in leiomyoma treatment will be addressed.

Search methods: A comprehensive PubMed search was performed to identify published articles containing keywords relevant to the focus of the review, such as: uterine leiomyoma, uterine fibroids, epigenetic alterations, epigenomics, stem cells, chromatin modifications, extracellular matrix [ECM] organization, DNA methylation, enhancer, histone post-translational modifications and dysregulated gene expression. Articles until September 2021 were explored and evaluated to identify relevant updates in the field. Most of the articles focused on in the discussion were published between 2015 and 2021, although some key discoveries made before 2015 were included for background information and foundational purposes. We apologize to the authors whose work was not included because of space restrictions or inadvertent omission.

Outcomes: Chemical alterations to the DNA structure and of nucleosomal histones, without changing the underlying DNA sequence, have now been implicated in the phenotypic manifestation of uterine leiomyomas. Genome-wide DNA methylation analysis has revealed subsets of either suppressed or overexpressed genes accompanied by aberrant promoter methylation. Furthermore, differential promoter access resulting from altered 3D chromatin structure and histone modifications plays a role in regulating transcription of key genes thought to be involved in leiomyoma etiology. The dysregulated genes function in tumor suppression, apoptosis, angiogenesis, ECM formation, a variety of cancer-related signaling pathways and stem cell differentiation. Aberrant DNA methylation or histone modification is also observed in altering enhancer architecture, which leads to changes in enhancer-promoter contact strength, producing novel explanations for the overexpression of high mobility group AT-hook 2 and gene dysregulation found in mediator complex subunit 12 mutant fibroids. While many molecular mechanisms and epigenomic features have been investigated, the basis for the racial disparity observed among those in the Black population remains unclear.

Wider implications: A comprehensive understanding of the exact pathogenesis of uterine leiomyoma is lacking and requires attention as it can provide clues for prevention and viable non-surgical treatment. These findings will widen our knowledge of the role epigenomics plays in the mechanisms related to uterine leiomyoma development and highlight novel approaches for the prevention and identification of epigenome targets for long-term non-invasive treatment options of this significantly common disease.

Keywords: 3D-chromatin structure; DNA methylation; enhancer architecture; epigenomics; histone modification; stem cells; uterine leiomyoma.

Aim: To evaluate whether the first Covid-19 lockdown for Italian citizens (March to July 2021) might have altered the incidence of gestational diabetes mellitus (GDM).

Methods: A retrospective single-center study in a tertiary referral center. Primary outcome was the incidence of GDM among pregnant women. GDM incidence, from June 11, 2019 to December 4, 2020, was compared by dividing the study time as follows: from the beginning of the study to before Covid-19 lockdown (from June 11, 2019, to March 9, 2020) and lockdown period (from March 10, 2020, to December 4, 2020). GDM was diagnosed with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 gestational weeks.

Results: Concerning 1295 women, GDM incidence increased during the lockdown period (9.3% vs. 3.4%, p < 0.001). Higher pregnancy weight gain with an increased body mass index (BMI) at the delivery was reported during the lockdown (31.3 vs. 28.4 kg/m² , p = 0.02 and mean weight gain of 9.3 vs. 6.6 kg, p = 0.007). There was no difference in other comorbidity incidence and OGTT values between the two groups.

Conclusions: Pregnant women during the Covid-19 lockdown might have experienced higher BMI and pregnancy weight gain with increased GDM diagnoses. This may be related to physical limitations and emotional distress experienced during the lockdown. However, evidence is limited due to restricted study duration and random variations of outcomes across time. More studies are needed to understand the dietary patterns and the physical activity changes during the Covid-19 lockdown and its impact on fetal outcomes.

Keywords: Covid-19; SARS-CoV-2; diabetes gestational mellitus; gestational diabetes; lockdown; pregnancy; pregnancy outcomes.

Purpose: Study reported that C-reactive protein (CRP) would peak at 48 h after the initiation of an acute inflammatory response. We proposed that the ratio of CRP level on postoperative day 3 to day 2 (POD3/2 CRP) can be used to early predict major postoperative complications (PCs) for patients who underwent laparoscopic radical gastrectomy.

Methods: Patients were randomized into training cohort and validation cohort at a ratio of 7:3. PCs greater than grade II or more, according to Clavien-Dindo classification, were defined as major PCs. Three predictive models for major PCs based on CRP level were constructed, including POD3/2 CRP, the CRP level on POD3 (POD3 CRP), and the ratio of CRP level on POD3 to POD1 (POD3/1 CRP). The performances of three prediction models were assessed by AUC. Univariate and multivariate logistic regression analyses were performed to identify risk factors of major PCs.

Results: 344 patients were included. Major PCs were observed in 57 patients (16.6%). In the training cohort, POD3/2 CRP provided the best diagnostic accuracy with an AUC of 0.929 at an optimal cut-off value of 1.08, and the sensitivity and specificity were 0.902 and 0.880, respectively. In the validation cohort, the corresponding AUC was 0.917. BMI ≥ 25 kg/m² and POD3/2 CRP > 1 were identified as risk factors for major PCs.

Conclusion: POD3/2 CRP is a reliable marker to predict major PCs after laparoscopic radical gastrectomy. If CRP is higher on POD3 than on POD2, major PCs are highly likely.

Keywords: C-reactive protein; Gastric cancer; Laparoscopic radical gastrectomy; Postoperative complications.

An 82-year-old woman with nonischemic cardiomyopathy underwent cardiac resynchronization therapy by the use of His bundle pacing. After the procedure, the patient had repolarization abnormality with severely prolonged QTc and anterior inferior T-wave inversions, likely resulting from memory T waves associated with the correction of long-standing left bundle branch block. These changes could be potentially arrhythmogenic. (Level of Difficulty: Intermediate.).

Keywords: ECG, electrocardiography; HBP, His bundle pacing; LBBB, left bundle branch block; RV, right ventricle; acute heart failure; cardiac pacemaker; cardiomyopathy.