Uterus Transplant in Women With Absolute Uterine-Factor Infertility.

Importance: Uterus transplant in women with absolute uterine-factor infertility offers the possibility of carrying their own pregnancy. Objective: To determine whether uterus transplant is feasible and safe and results in births of healthy infants. Design, Setting, and Participants: A case series including 20 participants with uterine-factor infertility and at least 1 functioning ovary who underwent uterus transplant in a large US tertiary care center between September 14, 2016, and August 23, 2019. Intervention: The uterus transplant (from 18 living donors and 2 deceased donors) was surgically placed in an orthotopic position with vascular anastomoses to the external iliac vessels. Participants received immunosuppression until the transplanted uterus was removed following 1 or 2 live births or after graft failure. Main Outcomes and Measures: Uterus graft survival and subsequent live births. Results: Of 20 participants (median age, 30 years [range, 20-36]; 2 Asian, 1 Black, and 16 White), 14 (70%) had a successful uterus allograft; all 14 recipients gave birth to at least 1 live-born infant. Eleven of 20 recipients had at least 1 complication. Maternal and/or obstetrical complications occurred in 50% of the successful pregnancies, with the most common being gestational hypertension (2 [14%]), cervical insufficiency (2 [14%]), and preterm labor (2 [14%]). Among the 16 live-born infants, there were no congenital malformations. Four of 18 living donors had grade 3 complications. Conclusions and Relevance: Uterus transplant was technically feasible and was associated with a high live birth rate following successful graft survival. Adverse events were common, with medical and surgical risks affecting recipients as well as donors. Congenital abnormalities and developmental delays have not occurred to date in the live-born children. Trial Registration: ClinicalTrials.gov Identifier: NCT02656550.

Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus.

Diabetes mellitus (DM) is a progressive, chronic metabolic disorder characterized by high oxidative stress, which can lead to cardiac damage. Methionine sulfoxylation (MetO) of proteins by excessive reactive oxygen species (ROS) can impair the basic functionality of essential cellular proteins, contributing to heart failure. Methionine sulfoxide reductase B2 (MsrB2) can reverse oxidation induced MetO in mitochondrial proteins, so we investigated its role in diabetic cardiomyopathy. We observed that DM-induced heart damage in diabetic mice model is characterized by increased ROS, increased protein MetO with mitochondria structural pathology, and cardiac fibrosis. In addition, MsrB2 was significantly increased in mouse DM cardiomyocytes, supporting the induction of a protective process. Further, MsrB2 directly induces Parkin and LC3 activation (mitophagy markers) in cardiomyocytes. In MsrB2, knockout mice displayed abnormal electrophysiological function, as determined by ECG analysis. Histological analysis confirmed increased cardiac fibrosis and disrupted cardiac tissue in MsrB2 knockout DM mice. We then corroborated our findings in human DM heart samples. Our study demonstrates that increased MsrB2 expression in the heart protects against diabetic cardiomyopathy.

Total pancreatectomy with islet autotransplantation outcomes in patients with pancreatitis of genetic etiology: A single-center experience with a large cohort of patients.

PURPOSE: Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment for patients with chronic pancreatitis (CP) when other interventions are unsuccessful. CP has many etiologies including heredity. Metabolic and pain relief outcomes after TPIAT are presented among patients with a genetic CP etiology compared with those with a nongenetic etiology in a large cohort of patients who underwent this procedure at our center. METHODS: A retrospective analysis was performed of 237 patients undergoing TPIAT between 2006 and 2023. We analyzed the differences in patients with genetic (n = 56) vs nongenetic CP etiologies (n = 181) in terms of pre-TPIAT factors including patient characteristics and disease state, results from the isolation process, and outcomes such as long-term glycemic and pain control. RESULTS: Patients with genetic CP underwent TPIAT at a significantly younger age (32.3 vs 41.3 years nongenetic; P < .0001) and endured symptoms for a significantly longer period (10 vs 6 years; P < .01). A significantly lower mass of islets was isolated from patients with genetic CP (P < .01), which increased with body mass index in both groups. Despite lower yields, patients with genetic CP maintained metabolic function similar to patients with nongenetic CP, as indicated by insulin independence and C-peptide, blood glucose, and hemoglobin A1C levels after TPIAT. Post-transplant narcotic usage and pain scores significantly decreased compared with those before TPIAT, and more patients with genetic CP were pain free and narcotic free after TPIAT. CONCLUSION: Our data validate TPIAT as a beneficial procedure for patients enduring CP of genetic etiology. Pain that is inevitably recurrent after minor interventions owing to the nature of the disease and favorable TPIAT outcomes should be considered in the decision to perform early TPIAT in cases of genetic CP.

Needs and gaps of faculty development for medical schools.

PURPOSE: Current faculty development (FD) programs are mostly limited to medical education and often lack a comprehensive and systematic structure. Therefore, the present study aimed to explore the current status and needs of FD programs in medical schools to provide a basis for establishing FD strategies. METHODS: We conducted an online survey of medical school FD staff and professors regarding FD. Frequency, regression, and qualitative content analyses were conducted. FD programs were categorized into the classification frameworks. RESULTS: A total of 17 FD staff and 256 professors at 37 medical schools participated. There are gaps between the internal and external FD programs offered by medical schools and their needs, and there are gaps between the programs the professors participated in and their needs. Recent internal and external FD programs in medical schools have focused on educational methods, student assessment, and education in general. Medical schools have a high need for leadership and self-development, and student assessment. Furthermore, professors have a high need for leadership and self-development, and research. The number of participants, topics, and needs of FD programs varied depending on the characteristics of individual professors. CONCLUSION: Medical schools should expand their FD programs to meet the needs of individuals and the changing demands of modern medical education. The focus should be on comprehensive and responsive programs that cover various topics, levels, and methods. Tailored programs that consider professors' professional roles, career stages, and personal interests are essential for effective FD.

Specific contact resistivity reduction in amorphous IGZO thin-film transistors through a TiN/IGTO heterogeneous interlayer.

Oxide semiconductors have gained significant attention in electronic device industry due to their high potential for emerging thin-film transistor (TFT) applications. However, electrical contact properties such as specific contact resistivity (ρC) and width-normalized contact resistance (RCW) are significantly inferior in oxide TFTs compared to conventional silicon metal oxide semiconductor field-effect transistors. In this study, a multi-stack interlayer (IL) consisting of titanium nitride (TiN) and indium-gallium-tin-oxide (IGTO) is inserted between source/drain electrodes and amorphous indium-gallium-zinc-oxide (IGZO). The TiN is introduced to increase conductivity of the underlying layer, while IGTO acts as an n+-layer. Our findings reveal IGTO thickness (tIGTO)-dependent electrical contact properties of IGZO TFT, where ρC and RCW decrease as tIGTO increases to 8 nm. However, at tIGTO > 8 nm, they increase mainly due to IGTO crystallization-induced contact interface aggravation. Consequently, the IGZO TFTs with a TiN/IGTO (3/8 nm) IL reveal the lowest ρC and RCW of 9.0 × 10-6 Ω·cm2 and 0.7 Ω·cm, significantly lower than 8.0 × 10-4 Ω·cm2 and 6.9 Ω·cm in the TFTs without the IL, respectively. This improved electrical contact properties increases field-effect mobility from 39.9 to 45.0 cm2/Vs. This study demonstrates the effectiveness of this multi-stack IL approach in oxide TFTs.

Challenges and potential improvements in the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019) derived through meta-evaluation: a cross-sectional study

PURPOSE: This study aimed to identify challenges and potential improvements in Korea's medical education accreditation process according to the Accreditation Standards of the Korean Institute of Medical Education and Evaluation 2019 (ASK2019). Meta-evaluation was conducted to survey the experiences and perceptions of stakeholders, including self-assessment committee members, site visit committee members, administrative staff, and medical school professors. METHODS: A cross-sectional study was conducted using surveys sent to 40 medical schools. The 332 participants included self-assessment committee members, site visit team members, administrative staff, and medical school professors. The t-test, one-way analysis of variance and the chi-square test were used to analyze and compare opinions on medical education accreditation between the categories of participants. RESULTS: Site visit committee members placed greater importance on the necessity of accreditation than faculty members. A shared positive view on accreditation's role in improving educational quality was seen among self-evaluation committee members and professors. Administrative staff highly regarded the Korean Institute of Medical Education and Evaluation's reliability and objectivity, unlike the self-evaluation committee members. Site visit committee members positively perceived the clarity of accreditation standards, differing from self-assessment committee members. Administrative staff were most optimistic about implementing standards. However, the accreditation process encountered challenges, especially in duplicating content and preparing self-evaluation reports. Finally, perceptions regarding the accuracy of final site visit reports varied significantly between the self-evaluation committee members and the site visit committee members. CONCLUSION: This study revealed diverse views on medical education accreditation, highlighting the need for improved communication, expectation alignment, and stakeholder collaboration to refine the accreditation process and quality.

Stepwise development and expansion of an abdominal normothermic regional perfusion program for donation after circulatory determination of death organ procurement.

INTRODUCTION: Normothermic regional perfusion (NRP) represents an innovative technology that improves the outcomes for liver and kidney recipients of donation after circulatory determination of death (DCD) organs but protocols for abdominal-only NRP (A-NRP) DCD are lacking in the US. METHODS: We describe the implementation and expansion strategies of a transplant-center-based A-NRP DCD program that has grown in volume, geographical reach, and donor acceptance parameters, presented as four eras. RESULTS: In the implementation era, two donors were attempted, and one liver graft was transplanted. In the local expansion era, 33% of attempted donors resulted in transplantation and 42% of liver grafts from donors who died within the functional warm ischemic time (fWIT) limit were transplanted. In the Regional Expansion era, 25% of attempted donors resulted in transplantation and 50% of liver grafts from donors who died within the fWIT limit were transplanted. In the Donor Acceptance Expansion era, 46% of attempted donors resulted in transplantation and 72% of liver grafts from donors who died within the fWIT limit were transplanted. Eight discarded grafts demonstrated a potential opportunity for utilization. CONCLUSION: The stepwise approach to building an A-NRP program described here can serve as a model for other transplant centers.

Factors Associated with Daily Fruit and Vegetable Intakes among Children Aged 1-5 Years in the United States.

To describe child, caregiver, and household characteristics associated with fruit and vegetable intakes among US children aged 1-5 years, we examined fruit and vegetable intakes (less than daily vs. daily) using data from the 2021 National Survey of Children's Health among children aged 1-5 years. Multiple logistic regression provided adjusted odds ratios for factors associated with (1) daily fruit and (2) daily vegetable intakes. Among children aged 1-5 years, 68% (n = 11,124) consumed fruit daily, and 51% (n = 8292) consumed vegetables daily. Both daily fruit and daily vegetable intake were associated with child age, child race and ethnicity, and frequency of family meals. For example, children who ate a family meal 4-6 days/week (aOR 0.69; 95% CI 0.57, 0.83) or 0-3 days/week (aOR 0.57; 95% CI 0.46, 0.72) were less likely to consume fruit daily compared to children who had a family meal every day. Participation in food assistance programs, food insufficiency, and household income were not significantly associated with odds of daily fruit or daily vegetable intake in the adjusted models. Several factors were associated with daily fruit and vegetable intake among children aged 1-5. Strategies aimed at increasing fruit and vegetable consumption in early childhood may consider these child, caregiver, and household characteristics. Pediatric healthcare providers, early childhood education centers, and families of young children may be important partners in this work.

Highly Stretchable Thermoplastic Polyurethane Separators for Li-Ion Batteries Based on Non-Solvent-Induced Phase Separation Method.

The growing interest in wearable and portable devices has stimulated the need for flexible and stretchable lithium-ion batteries (LiBs). A crucial component in these batteries is the separator, which provides a pathway for Li-ion transfer and prevents electrode contact. In a flexible and stretchable LiB, the separator must exhibit stretchability and elasticity akin to its existing counterparts. Here, we developed a non-modified thermoplastic polyurethane (TPU) separator using the non-solvent induced phase separation (NIPS) technique. We compared their performance with commercially available polypropylene (PP) separators. Our results demonstrate that TPU separators exhibit superior elasticity based on repeated stretch/release tests with excellent thermal stability and electrolyte wettability. Furthermore, our findings confirm that TPU separators, even after being repeatedly stretched and released, can function effectively without severe damage in a fabricated coin cell LiB with high oxidative stability, as evidenced by linear sweep voltammetry, like commercially available separators.

Immersive virtual reality simulation training for cesarean section: a randomized controlled trial.

BACKGROUND: Caesarean section (CS) is a complex surgical procedure that involves many steps and requires careful precision. Virtual reality (VR) simulation has emerged as a promising tool for medical education and training, providing a realistic and immersive environment for learners to practice clinical skills and decision-making. This study aimed to evaluate the educational effectiveness of a VR simulation program in training the management of patients with premature rupture of membranes (PROM) and CS. MATERIALS AND METHODS: A two-arm parallel randomized controlled trial was conducted with 105 eligible participants randomly assigned to the VR group ( n =53) or the control group ( n =52) in a 1:1 ratio. The VR group received VR simulation training focused on PROM management and CS practice, while the control group watched a video presentation with narrative of clinical scenario and recording of CS. Both groups completed questionnaires assessing their prior experiences with VR, experience in managing patients with PROM and performing CS, as well as their confidence levels. These questionnaires were administered before and after the intervention, along with a mini-test quiz. RESULTS: Baseline characteristics and previous experiences were comparable between the two groups. After the intervention, the VR group had higher confidence scores in all four aspects, including managing patients with PROM, performing CS as an operator, and understanding the indications and complications of CS, compared to the control group. The VR group also achieved significantly higher scores on the mini-test quiz [median (interquartile range), 42 (37-48) in the VR group; 36 (32-40) in the control group, P <0.001]. CONCLUSION: VR simulation program can be an effective educational tool for improving participants' knowledge and confidence in managing patients with PROM and performing CS.

Haze-Suppressed Wideband Light Shutter from Near Ultraviolet to Infrared Rays Utilizing Electrophoretic Carbon Black Particles.

Carbon black (CB) particles that can absorb from near ultraviolet to infrared rays are well dispersed into an isotropic dielectric liquid and their optical properties can be kept even under exposure to sunlight over a long time. The shutter which controls the position of CB particles by electrophoretic force can be applied to switchable light shutters for windows in buildings and automobiles for the purpose of energy savings. Here, a wideband light shutter with three terminal electrodes is proposed, exhibiting excellent dark (transmittance ≈1.4%) and transparent state (transmittance >60%). The device operates at a low field intensity of about 1 V µm-1 to obtain transparent state and its wide temperature range operation from -50 to 120 °C is confirmed while conventional liquid crystal-based shutter cannot perform such levels due to a limited temperature range in the nematic phase. In addition, haze is minimized in a transparent state by adopting an insulation layer over electrodes and a solution is found to keep a transparent state without applying power. It is believed that the proposed broadband shutter with fast response time could open a new chapter in switchable windows owing to its low power consumption and working in a wide temperature range.

Activated somatostatin interneurons orchestrate memory microcircuits.

Despite recent advancements in identifying engram cells, our understanding of their regulatory and functional mechanisms remains in its infancy. To provide mechanistic insight into engram cell functioning, we introduced a novel local microcircuit labeling technique that enables the labeling of intraregional synaptic connections. Utilizing this approach, we discovered a unique population of somatostatin (SOM) interneurons in the mouse basolateral amygdala (BLA). These neurons are activated during fear memory formation and exhibit a preference for forming synapses with excitatory engram neurons. Post-activation, these SOM neurons displayed varying excitability based on fear memory retrieval. Furthermore, when we modulated these SOM neurons chemogenetically, we observed changes in the expression of fear-related behaviors, both in a fear-associated context and in a novel setting. Our findings suggest that these activated SOM interneurons play a pivotal role in modulating engram cell activity. They influence the expression of fear-related behaviors through a mechanism that is dependent on memory cues.

The Process of Sterilizing Tattoo Inks Releases Formaldehyde.

INTRODUCTION: Around 12% of Europeans and 20% of Americans have at least one tattoo. Tattoo inks, the substances used to create tattoos on the body, consist of chemicals that contain formaldehyde, which can be harmful to human health. The amount of formaldehyde present in commercially available tattoo inks and its causes are not well understood. METHODS: We investigated the levels of formaldehyde in tattoo ink products sold in different countries and identified the factors contributing to its production. We also explored methods to reduce formaldehyde generation in tattoo inks. Seven tattoo inks from various brands were tested. RESULTS: Formaldehyde release was predominantly associated with gamma radiation sterilization. Formaldehyde levels were observed to be higher in compositions containing organic components compared to those with inorganic components, irrespective of sterilization method and container type. Glycerin released over seven times more formaldehyde than other components during gamma-ray sterilization. CONCLUSION: The results suggest that the presence of hydroxyl groups in carbon organic compounds in tattoo ink leads to photodegradation during gamma-ray radiation sterilization, resulting in increased concentrations of formaldehyde. Further research is needed to examine the chemical reactions occurring during sterilization processes and identify alternative sterilization methods that minimize formaldehyde formation. Additionally, the development of tattoo inks with reduced formaldehyde content and the establishment of strict quality control measures can help ensure the safety of tattooing practices.

Proteomic analysis reveals activation of platelet- and fibrosis-related pathways in hearts of ApoE-/- mice exposed to diesel exhaust particles.

Air pollution is an environmental risk factor linked to multiple human diseases including cardiovascular diseases (CVDs). While particulate matter (PM) emitted by diesel exhaust damages multiple organ systems, heart disease is one of the most severe pathologies affected by PM. However, the in vivo effects of diesel exhaust particles (DEP) on the heart and the molecular mechanisms of DEP-induced heart dysfunction have not been investigated. In the current study, we attempted to identify the proteomic signatures of heart fibrosis caused by diesel exhaust particles (DEP) in CVDs-prone apolipoprotein E knockout (ApoE-/-) mice model using tandem mass tag (TMT)-based quantitative proteomic analysis. DEP exposure induced mild heart fibrosis in ApoE-/- mice compared with severe heart fibrosis in ApoE-/- mice that were treated with CVDs-inducing peptide, angiotensin II. TMT-based quantitative proteomic analysis of heart tissues between PBS- and DEP-treated ApoE-/- mice revealed significant upregulation of proteins associated with platelet activation and TGFß-dependent pathways. Our data suggest that DEP exposure could induce heart fibrosis, potentially via platelet-related pathways and TGFß induction, causing cardiac fibrosis and dysfunction.

Identification of Potential Drug Targets for Antiplatelet Therapy Specifically Targeting Platelets of Old Individuals through Proteomic Analysis.

Aging is a growing problem worldwide, and the prevalence and mortality of arterial and venous thromboembolism (VTE) are higher in the elderly than in the young population. To address this issue, various anticoagulants have been used. However, no evidence can confirm that antithrombotic agents are suitable for the elderly. Therefore, this study aims to investigate the platelet proteome of aged mice and identify antithrombotic drug targets specific to the elderly. Based on the proteome analysis of platelets from aged mice, 308 increased or decreased proteins were identified. Among these proteins, three targets were selected as potential antithrombotic drug targets. These targets are membrane proteins or related to platelet function and include beta-2-glycoprotein 1 (ß2GP1, ApolipoproteinH (ApoH)), alpha-1-acid glycoprotein2 (AGP2, Orosomucoid-2 (Orm2)), and Ras-related protein (Rab11a).

[Analysis of Media Trends and Social Perceptions on Nursing Law Legislation].

PURPOSE: This study aimed to derive considerations for the enactment of nursing law by analyzing the trends and social perceptions of nursing law mentioned in major daily newspapers, cafes, and blogs. METHODS: Main texts and comments that included nursing law as a keyword were collected from major daily news and online postings from January 2021 to August 2022. The data collected through web crawling were analyzed using a TousFlux program used for big data analysis. RESULTS: During the period of study, the awareness level around nursing law enactment increased. In particular, public concern over nursing law enactment intensified due to the two political parties' policy pledges related to nursing law in January 2022 and the failure to introduce the nursing law to the national assembly judiciary committee in May 2022. Except in December 2021, public perception of nursing law enactment was generally favorable, with public opinion tilting more in favor of than against enactment. CONCLUSION: Public opinion should be considered when drafting and implementing the nursing law to make it easier for the people to understand what the law constitutes. In addition, it is necessary to pay attention to and continuously promote the relationship between medical care and nursing in the nursing law system of developed nations. Lastly, nursing law enactment can enhance nurses' retention intention and provide a sense of efficacy to medical services.

The Illustration of Altered Glucose Dependency in Drug-Resistant Cancer Cells.

A chemotherapeutic approach is crucial in malignancy management, which is often challenging due to the development of chemoresistance. Over time, chemo-resistant cancer cells rapidly repopulate and metastasize, increasing the recurrence rate in cancer patients. Targeting these destined cancer cells is more troublesome for clinicians, as they share biology and molecular cross-talks with normal cells. However, the recent insights into the metabolic profiles of chemo-resistant cancer cells surprisingly illustrated the activation of distinct pathways compared with chemo-sensitive or primary cancer cells. These distinct metabolic dynamics are vital and contribute to the shift from chemo-sensitivity to chemo-resistance in cancer. This review will discuss the important metabolic alterations in cancer cells that lead to drug resistance.

Stress induces behavioral abnormalities by increasing expression of phagocytic receptor MERTK in astrocytes to promote synapse phagocytosis.

Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated synapse phagocytosis. Using in vitro, in vivo, and human brain organoid experiments, we showed that stress hormones increased the expression of the Mertk phagocytic receptor in astrocytes through glucocorticoid receptor (GR). In post-natal mice, exposure to early social deprivation (ESD) specifically activated the GR-MERTK pathway in astrocytes, but not in microglia. The excitatory post-synaptic density in cortical regions was reduced in ESD mice, and there was an increase in the astrocytic engulfment of these synapses. The loss of excitatory synapses, abnormal neuronal network activities, and behavioral abnormalities in ESD mice were largely prevented by ablating GR or MERTK in astrocytes. Our work reveals the critical roles of astrocytic GR-MERTK activation in evoking stress-induced abnormal behaviors in mice, suggesting GR-MERTK signaling as a therapeutic target for stress-induced mental health conditions.

Multisensory integration in the mammalian brain: diversity and flexibility in health and disease.

Multisensory integration (MSI) occurs in a variety of brain areas, spanning cortical and subcortical regions. In traditional studies on sensory processing, the sensory cortices have been considered for processing sensory information in a modality-specific manner. The sensory cortices, however, send the information to other cortical and subcortical areas, including the higher association cortices and the other sensory cortices, where the multiple modality inputs converge and integrate to generate a meaningful percept. This integration process is neither simple nor fixed because these brain areas interact with each other via complicated circuits, which can be modulated by numerous internal and external conditions. As a result, dynamic MSI makes multisensory decisions flexible and adaptive in behaving animals. Impairments in MSI occur in many psychiatric disorders, which may result in an altered perception of the multisensory stimuli and an abnormal reaction to them. This review discusses the diversity and flexibility of MSI in mammals, including humans, primates and rodents, as well as the brain areas involved. It further explains how such flexibility influences perceptual experiences in behaving animals in both health and disease. This article is part of the theme issue 'Decision and control processes in multisensory perception'.

Diffuse calcification of pancreas impairs endocrine function and predicts poor outcome in total pancreatectomy with islet autotransplantation.

In patients with chronic pancreatitis, pancreatic calcification is a risk factor for diabetes development, poor islet yield, and metabolic outcomes after total pancreatectomy with islet autotransplantation (TPIAT). We investigated whether calcification pattern based on computed tomography is associated with outcomes using our database of 200 consecutive TPIAT procedures. Three groups were compared: noncalcification (NC); focal calcification, limited to the pancreas head, body, or tail; and diffuse calcification (DC), with calcification in >2 sections. Maximum changes in outcomes were seen in the DC vs focal calcification group. In the DC group, preoperative hemoglobin A1c levels were higher (P < .01), and stimulated C-peptide levels were lower (P < .01) than in the NC group. Islet isolation from the DC pancreas resulted in the lowest islet equivalent (IEQ) yield and IEQ/kg among the 3 groups (P < .0001), with no insulin independence 12 months posttransplant (P < .05 vs NC group). Notably, at 12 months, the DC group was 91.7% narcotic-free, significantly higher than the NC group (P < .05). Although DC is a sign of diabetes risk after TPIAT, the DC group showed exceptional pain relief. These findings suggest that TPIAT can be beneficial for patients with chronic pancreatitis with severe calcification.