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Pyruvate dehydrogenase complex (PDHC) deficiency is an inborn error of metabolism that occurs most commonly due to mutations in the X-linked E1α subunit gene (PDHA1). We report a novel duplication of PDHA1 associated with a mild phenotype in a 15-year-old boy who was diagnosed with PDHC deficiency at 4 years of age following a history of seizures and lactic acidosis. The novel c.1087_1119 mutation in exon 11 resulted in an in-frame duplication of 11 amino acids. Measurements of PDHC activity in cultured skin fibroblasts were low, corresponding to 18.6 and 11.6% of the mean with respect to prior controls, whereas the E1 PDH component was absent. He has borderline intellectual functioning and maintains normal lactate levels on a ketogenic diet in between relapses due to illness. Review of the literature reveals wide variation of clinical phenotype in patients with mutations of the E1α subunit gene (PDHA1). There appears to be a higher incidence of normal or borderline intellectual ability in individuals who have insertions or deletions that are in-frame versus those that are out-of-frame. Furthermore, there is no correlation between mean residual PDH activity and phenotype in these patients.

We report clinical findings in a 12-year-old girl with a mild case of fumarase deficiency who continues to make progress. She has two novel mutations of the fumarase gene [c.521C>G (p.P174R) and c.908T>C (p.L303S)]. A trial of low protein diet did not reduce fumaric aciduria.

Amniotic fluid embolism (AFE) is a potentially fatal maternal condition demanding awareness from obstetricians and anesthesiologists regarding its different manifestations. The typical presentation involves maternal respiratory distress, cardiovascular collapse, neurological changes, and coagulopathy followed by fetal distress. This unusual case study emphasizes that fetal compromise may precede maternal decompensation as the initial sign of AFE. Fetal distress is a known symptom of AFE and is typically seen due to cardiorespiratory issues that lead to reduced uteroplacental perfusion, resulting in fetal hypoxia. In the case presented, fetal bradycardia occurred before any visible maternal symptoms, suggesting that fetal distress could be induced by factors independent of the mother's cardiopulmonary status. A 34-year-old healthy G4P2012 at 41 weeks and 2 days gestation who was initially laboring on the floor was emergently taken to the operating room for a cesarean delivery due to fetal bradycardia. Around the time the fetus was delivered, the patient displayed seizure activity, followed by a complete loss of consciousness and cardiac arrest. The patient was intubated and underwent cardiopulmonary resuscitation and defibrillation, subsequently converting to a wide complex tachycardia. In the operating room, there was evidence of heavy vaginal bleeding, uterine atony, and a fulminant form of disseminated intravascular coagulopathy (DIC), which required aggressive management over the next four hours. After achieving hemodynamic stability, the patient was transferred to the surgical intensive care unit (SICU), extubated on day 3, and discharged home on day 8., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wang et al.)

INTRODUCTION: This paper describes the method for assigning medical diagnostic and treatment capabilities and resources to the database which assists with an updated probabilistic risk analysis (PRA) tool for exploration class medical system planning. The National Aeronautics and Space Administration has used PRA since 2011 to inform mission medical system design, but existing tools are designed only for low Earth orbit. An updated PRA tool was needed to assist with exploration class missions. METHODS: A team of medical experts with a wide range of expertise and experience, including Space Medicine, was assembled to build capability and resource tables for the new PRA tool. This team met over 8 mo and used practice guidelines, literature, and experience to build capability and resource tables (CRTs) for each condition in the new PRA tool database. RESULTS: This process led to CRTs for each condition and a total of 617 distinct capabilities and 839 discrete resources. CONCLUSION: The CRT method is an effective way to translate medical practice guidelines into capabilities and resources usable by PRA tools for exploration class medical system planning. This same method may be used in commercial space ventures and in other applications in which medical predictive analytics are informative. Levin DR, Nelson AM, Zahner C, Stratton ER, Anderson A, Steller J. A method to determine capabilities and resources for spacecraft medical systems . Aerosp Med Hum Perform. 2024; 95(7):403-408.

Nationally reported greenhouse gas inventories are a core component of the Paris Agreement's transparency framework. Comparisons with emission estimates derived from atmospheric observations help identify improvements to reduce uncertainties and increase the confidence in reported values. To facilitate comparisons over the contiguous United States, we present a 0.1° × 0.1° gridded inventory of annual 2012-2018 anthropogenic methane emissions, allocated to 26 individual source categories, with scale-dependent error estimates. Our inventory is consistent with the U.S. Environmental Protection Agency (EPA) Inventory of U.S. Greenhouse Gas Emissions and Sinks (GHGI), submitted to the United Nations in 2020. Total emissions and patterns (spatial/temporal) reflect the activity and emission factor data underlying the GHGI, including many updates relative to a previous gridded version of the GHGI that has been extensively compared with observations. These underlying data are not generally available in global gridded inventories, and comparison to EDGAR version 6 shows large spatial differences, particularly for the oil and gas sectors. We also find strong regional variability across all sources in annual 2012-2018 spatial trends, highlighting the importance of understanding regional- and facility-level activities. Our inventory represents the first time series of gridded GHGI methane emissions and enables robust comparisons of emissions and their trends with atmospheric observations.

Goal: Current Space Medicine operations depend on terrestrial support to manage medical events. As astronauts travel to destinations such as the Moon, Mars, and beyond, distance will substantially limit this support and require increasing medical autonomy from the crew. This paper defines Earth Independent Medical Operations (EIMO) and identifies key elements of a conceptual EIMO system. Methods: The NASA Human Research Program Exploration Medical Capability Element held a 2-day conference at Johnson Space Center in Houston, TX with NASA experts representing all aspects of Space Medicine. Results: EIMO will be a process enabling progressively resilient deep space exploration systems and crews to reduce risk and increase mission success. Terrestrial assets will continue to provide pre-mission screening, planning, health maintenance, and prevention, while onboard medical care will increasingly be the purview of the crew. Conclusions: This paper defines and describes the key components of EIMO., (© 2023 The Authors.)

Given the increased need for palliative care services globally, the education of nurses has become paramount. In response, a group of nurses from Romania and the United States developed diverse nursing educational programs to meet the palliative care educational needs of nurses in Central-Eastern European countries. The purpose of this article is to describe a palliative nursing masterclass that was offered virtually to 59 participants, primarily nurses but also other health care professionals, from 11 Central-Eastern European countries., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 by The Hospice and Palliative Nurses Association. All rights reserved.)

Background and Aims: The increasing number of cancer patients, together with the development of new palliative care services in Romania, warrants the evaluation of nursing strategies meant to improve the level of comfort of patients who are suffering from advanced cancer. The main objective of the study was to evaluate the optimal positioning of the subcutaneous (sc) butterfly, in accordance with its resistance in the insertion tissue, the local complications that may occur, and the evaluation of the time of resistance at the insertion site (puncture) with the daily frequency of injectable opioid administration., Methods: A prospective experimental pilot study was designed and conducted between January and May 2011. Patients admitted to the Hospice Casa Sperantei (Brasov, Romania) with moderate or severe cancer pain, who were receiving subcutaneously opioids, over the age of 18, with normal body index ranging from 18.5 - 22.0, were assigned randomly to one of two groups, after signing the informed consent. In group one, the butterfly was positioned with the needle bevel up - this was considered to be the control group as this modality of inserting the needle is considered standard practice; in group two the butterfly was positioned with the needle bevel down - experimental group. The drugs used for pain relief were sc tramadol for moderate pain and sc morphine for severe pain., Results: Our research supported the hypothesis that the occurrence of local complications coincides with the decrease of sc butterfly resistance in time at the place of insertion, and the sc butterfly has a higher rate of resistance in time at the insertion site if the frequency of injectable opioids administration is lower (twice per day)., Conclusion: The positioning of the butterflies with the bevel down (experimental group) is associated with a longer resistance in time at the site of insertion, and causes fewer local complications compared to the sc butterflies positioned with the bevel up (control group).

Introduction: The Ultrasound Screening Exam for Underlying Lesions (USEFUL) was developed in an attempt to establish a role for bedside ultrasound in the primary and preventive care setting. It is the purpose of our pilot study to determine if students were first capable of performing all of the various scans required of our USEFUL while defining such an ultrasound-assisted physical exam that would supplement the standard hands-on physical exam in the same head-to-toe structure. We also aimed to assess the time needed for an adequate exam and analyze if times improved with repetition and previous ultrasound training., Methods: Medical students with ranging levels of ultrasound training received a 25-minute presentation on our USEFUL followed by a 30-minute hands-on session. Following the hands-on session, the students were asked to perform a timed USEFUL on 2-3 standardized subjects. All images were documented as normal or abnormal with the understanding that an official detailed exam would be performed if an abnormality were to be found. All images were read and deemed adequate by board eligible emergency medicine ultrasound fellows., Results: Twenty-six exams were performed by 9 students. The average time spent by all students per USEFUL was 11 minutes and 19 seconds. Students who had received the University of California, Irvine School of Medicine's integrated ultrasound curriculum performed the USEFUL significantly faster (p< 0.0025). The time it took to complete the USEFUL ranged from 6 minutes and 32 seconds to 17 minutes, and improvement was seen with each USEFUL performed. The average time to complete the USEFUL on the first standardized patient was 13 minutes and 20 seconds, while 11 minutes and 2 seconds, and 9 minutes and 20 seconds were spent performing the exam on the second and third patient, respectively., Conclusion: Students were able to effectively complete all scans required by the USEFUL in a timely manner. Students who have been a part of the integrated ultrasound in medicine curriculum performed the USEFUL significantly faster than students who had not. Students were able to significantly improve upon the time it took them to complete the USEFUL with successive attempts. Future endpoints are aimed at assessing the feasibility and outcomes of an ultrasound-assisted physical exam in a primary care setting and the exam's effect on doctor-patient satisfaction. [West J Emerg Med. 2014;15(3):260-266.].

Bisphenols (BPs) are a class of small organic compounds with widespread industrial applications. Previous studies have identified several BPs that interfere with the activity of the ion-translocating enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). In order to define the molecular determinants of BP-mediated SERCA inhibition, we conducted enzyme activity assays with rabbit SERCA to determine the inhibitory potencies of 27 commercially available BPs, which were the basis for structure-activity relationships. The most potent BPs inhibited SERCA at low micromolar concentrations and carried at their two phenyl rings multiple non-polar substituents, such as small alkyl groups or halides. Furthermore, the presence of methyl groups or a cyclohexyl group at the central carbon atom connecting the two phenyl moieties correlated with good potencies. For a characterization and visualization of enzyme/inhibitor interactions, molecular docking was performed, which suggested that hydrogen bonding with Asp254 and hydrophobic interactions were the major driving forces for BP binding to SERCA. Calcium imaging studies with a selection of BPs showed that these inhibitors were able to increase intracellular calcium levels in living human cells, a behavior consistent with that of a SERCA inhibitor., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: Barth syndrome is an X-linked recessive disorder characterized by dilated cardiomyopathy, neutropenia, 3-methylglutaconic aciduria, abnormal mitochondria, variably expressed skeletal myopathy, and growth delay. The disorder is caused by mutations in the tafazzin (TAZ/G4.5) gene located on Xq28. We report a novel exonic splicing mutation in the TAZ gene in a patient with atypical Barth syndrome., Patient & Methods: The 4-month-old proband presented with respiratory distress, neutropenia, and dilated cardiomyopathy with reduced ejection fraction of 10%. No 3-methylglutaconic aciduria was detected on repeated urine organic acid analyses. Family history indicated that his maternal uncle died of endocardial fibroelastosis and dilated cardiomyopathy at 26 months. TAZ DNA sequencing, mRNA analysis, and cardiolipin analysis were performed., Results: A novel nucleotide substitution c.553A>G in exon 7 of the TAZ gene was identified in the proband, predicting an amino acid substitution p.Met185Val. However, this mutation created a new splice donor signal within exon 7 causing mis-splicing of the message, producing two messages that only differ in the presence/absence of exon 5; these retain intron 6 and have only 11 bases of exon 7. Cardiolipin analysis confirmed the loss of tafazzin activity. The proband's mother, maternal aunt, and grandmother carry the same mutation., Conclusions: The identification of a TAZ gene mutation, mRNA analysis, and monolysocardiolipin/cardiolipin ratio determination were important for the diagnosis and genetic counseling in this family with atypical Barth syndrome that was not found to be associated with 3-methylglutaconic aciduria.

The purpose of this study was to examine the effect of traditional acupuncture compared with acupuncture with percutaneous electrical nerve stimulation (PENS) on postoperative surgical pain relief in gynecologic oncology patients. Twenty postoperative gynecologic oncology patients were randomly assigned into the two groups, and the intervention was initiated within 24 hours after surgery. The patients in each group received four treatments in the subsequent 48 hours, with 12 hours between each treatment. Either traditional acupuncture needles or acupuncture needles with a pulsed electric current were applied to stimulate the area of points Sp6 and Sp8 near the saphenous nerve. Pain measurement instruments included a visual analog scale and the McGill Pain Questionnaire. Although the PENS treatment group demonstrated a consistent decrease in pain with each treatment application compared with the traditional acupuncture group, after 48 hours both groups experienced equivalent pain relief., (Copyright © 2012 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Aromatase (CYP19) catalyzes the aromatization reaction of androgen substrates to estrogens, the last and rate-limiting step in estrogen biosynthesis. Inhibition of aromatase is a new and promising approach to treat hormone-dependent breast cancer. We present here the design and development of isoflavanone derivatives as potential aromatase inhibitors. Structural modifications were performed on the A and B rings of isoflavanones via microwave-assisted, gold-catalyzed annulation reactions of hydroxyaldehydes and alkynes. The in vitro aromatase inhibition of these compounds was determined by fluorescence-based assays utilizing recombinant human aromatase (baculovirus/insect cell-expressed). The compounds 3-(4-phenoxyphenyl)chroman-4-one (1h), 6-methoxy-3-phenylchroman-4-one (2a) and 3-(pyridin-3-yl)chroman-4-one (3b) exhibited potent inhibitory effects against aromatase with IC(50) values of 2.4 μM, 0.26 μM and 5.8 μM, respectively. Docking simulations were employed to investigate crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding and heme iron coordination. This report provides useful information on aromatase inhibition and serves as a starting point for the development of new flavonoid aromatase inhibitors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

An international collaboration to support and mentor palliative care nurses was developed between two educational institutions in the New England region of the United States and the Hospice Casa Sperantei in Brasov, Romania. Through teleconferences, onsite visits, research, and shared publications, the collaboration continues to be a dynamic experience for the partners and students. The seven-year relationship has affected the Romanian nursing team by providing professional education and support, as well as validation of clinical practice.

Aims: The purpose of this research was to characterize the nursing actions practiced by Romanian nurses affiliated with Hospices of Hope that promote dignified dying and explore needs to promote a more dignified death., Methods: A survey method used the International Classification for Nursing Practice dignified dying survey. A convenience sample of 43 hospice nurses responded. Descriptive statistics, t-tests and content analysis were used to analyze the data., Results: Characteristics that promoted dignified dying included the use of a formal, iterative process of assessment, interventions that supported pain and symptom management, and spiritual comfort at the end of life. Participants described family-centered hospice care that integrated Christian orthodox tradition that transformed patients as death approached., Conclusion: Dignity for terminally ill Romanian will be enhanced as the nurses implement these interventions. Awareness of cultural and spiritual differences concerning end of life will facilitate dialogue among nurse scientists.