Atypical posterior reversible encephalopathy syndrome: A lentiform fork sign following transplantation.

Key Clinical Message: Posterior Reversible Encephalopathy Syndrome, typically characterized by parieto-occipital vasogenic edema, can present atypically, as a bilateral symmetrical vasogenic edema in the basal ganglia, featuring the called "lentiform fork sign." Prompt recognition of such variations is crucial for accurate diagnosis and tailored management, highlighting the complexity of this syndrome's manifestations. Abstract: Posterior Reversible Encephalopathy Syndrome (PRES) manifests as transient neurological symptoms and cerebral edema, commonly associated with immunosuppressive drugs (ISDs) in transplant recipients. ISDs can lead to endothelial dysfunction and compromise the blood-brain barrier. Typically, PRES exhibits identifiable MRI patterns, often demonstrating vasogenic edema in the bilateral parieto-occipital white matter. Identifying unique presentations, such as the recently observed "lentiform fork sign," commonly seen in uremic encephalopathy, emphasizes this syndrome's broad spectrum manifestations. A 19-year-old male, who underwent bilateral lung and liver transplantation, experienced a bilateral tonic-clonic seizure of unknown onset 47 days post-surgery. MRI findings revealed an unconventional PRES pattern, featuring the "lentiform fork sign" as bilateral symmetrical vasogenic edema in the basal ganglia, surrounded by a hyperintense rim outlining the lentiform nucleus bilaterally. Subsequent management, including ISD modification and magnesium supplementation, resulted in clinical and neuroimaging resolution. An almost complete clinical and radiological resolution was achieved after 14 days. The occurrence of PRES in transplant recipients highlights the intricate interplay among ISDs, physiological factors, and cerebrovascular dynamics, potentially involving direct neurovascular endothelial toxicity and disruption of the blood-brain barrier. Neuroimaging plays a pivotal role in diagnosis. The distinctive "lentiform fork sign" was observed in this patient despite the absence of typical metabolic disturbances. Management strategies usually involve reducing hypertension, discontinuing ISDs, correcting electrolyte imbalances, and initiating antiseizure drugs if necessary. Identifying the presence of the "lentiform fork sign" alongside typical PRES edema in a patient lacking renal failure emphasizes that this manifestation is not solely indicative of uremic encephalopathy. Instead, it might represent the final common pathway resulting from alterations in the blood-brain barrier integrity within the deep white matter. Understanding such atypical imaging manifestations could significantly aid earlier and more precise diagnosis, influencing appropriate management decisions.

Endothelial Protein Disulphide Isomerase-A1 enhances membrane stiffness and platelet-endothelium interaction in hyperglycaemia via SLC3A2 and LAMC1.

BACKGROUND: Diabetes carries an increased risk of cardiovascular disease and thromboembolic events. Upon endothelial dysfunction, platelets bind to endothelial cells to precipitate thrombus formation, however, it is unclear which surface proteins regulate platelet-endothelium interaction. We and others have shown that peri/epicellular (pec) protein disulphide isomerase A1 (pecPDI) influences the adhesion and migration of vascular cells. OBJECTIVES: We investigated whether pecPDI regulates adhesion-related molecules on the surface of endothelial cells and platelets that influence the binding of these cells in hyperglycaemia. METHODS: Immunofluorescence was used to assess platelet-endothelium interaction in vitro, cytoskeleton reorganization and focal adhesions. Hydrogen peroxide production was assessed via Amplex Red assays. Cell biophysics was assessed using atomic force microscopy. Secreted proteins of interest were identified through proteomics (secretomics) and targets were knocked down using siRNA. PDI contribution was assessed using whole-cell PDI or pecPDI inhibitors or siRNA. RESULTS: Platelets of healthy donors adhered more onto hyperglycaemic HUVECs. Endothelial, but not platelet, pecPDI regulated this effect. Hyperglycaemic HUVECs showed marked cytoskeleton reorganization, increased H2O2 production and elongated focal adhesions. Indeed, hyperglycaemic HUVECs were stiffer compared to normoglycaemic cells. PDI and pecPDI inhibition reversed the abovementioned processes in hyperglycaemic cells. A secretomics analysis revealed eight proteins secreted in a PDI-dependent manner by hyperglycaemic cells. Among these, we showed that genetic deletion of LAMC1 and SLC3A2 decreased platelet-endothelium interaction and did not potentiate the effects of PDI inhibitors. CONCLUSIONS: Endothelial pecPDI regulates platelet-endothelium interaction in hyperglycemia through adhesion-related proteins and alterations in endothelial membrane biophysics.

Sigma-1 Receptors Control Neuropathic Pain and Peripheral Neuroinflammation After Nerve Injury in Female Mice: A Transcriptomic Study.

The mechanisms for neuropathic pain amelioration by sigma-1 receptor inhibition are not fully understood. We studied genome-wide transcriptomic changes (RNAseq) in the dorsal root ganglia (DRG) from wild-type and sigma-1 receptor knockout mice prior to and following Spared Nerve Injury (SNI). In wildtype mice, most of the transcriptomic changes following SNI are related to the immune function or neurotransmission. Immune function transcripts contain cytokines and markers for immune cells, including macrophages/monocytes and CD4 + T cells. Many of these immune transcripts were attenuated by sigma-1 knockout in response to SNI. Consistent with this we found, using flow cytometry, that sigma-1 knockout mice showed a reduction in macrophage/monocyte recruitment as well as an absence of CD4 + T cell recruitment in the DRG after nerve injury. Sigma-1 knockout mice showed a reduction of neuropathic (mechanical and cold) allodynia and spontaneous pain-like responses (licking of the injured paw) which accompany the decreased peripheral neuroinflammatory response after nerve injury. Treatment with maraviroc (a CCR5 antagonist which preferentially inhibits CD4 + T cells in the periphery) of neuropathic wild-type mice only partially replicated the sigma-1 knockout phenotype, as it did not alter cold allodynia but attenuated spontaneous pain-like responses and mechanical hypersensitivity. Therefore, modulation of peripheral CD4 + T cell activity might contribute to the amelioration of spontaneous pain and neuropathic tactile allodynia seen in the sigma-1 receptor knockout mice, but not to the effect on cold allodynia. We conclude that sigma-1 receptor inhibition decreases DRG neuroinflammation which might partially explain its anti-neuropathic effect.

The Impact of Digital Health Solutions on Bridging the Health Care Gap in Rural Areas: A Scoping Review.

Digital health tools can improve health care access and outcomes for individuals with limited access to health care, particularly those residing in rural areas. This scoping review examines the existing literature on using digital tools in patients with limited access to health care in rural areas. It assesses their effectiveness in improving health outcomes. The review adopts a comprehensive search strategy to identify relevant studies from electronic databases, and the selected studies are analyzed descriptively. The findings highlight the advantages and barriers of digital health interventions in rural populations. The advantages include increased access to health care practitioners through teleconsultations, improved health care outcomes through remote monitoring, better disease management through mobile health applications and wearable devices, and enhanced access to specialized care and preventive programs. However, limited internet connectivity and a lack of familiarity with digital tools are barriers that must be addressed to ensure equitable access to digital health interventions in rural areas. Overall, digital tools improve health outcomes for individuals with limited health care access in rural areas.

Identification of Potential Factors Associated with Cellulitis Following Lymphovenous Bypass Surgery in Breast Cancer Survivors.

BACKGROUND: Breast cancer is one of the most common types of cancer, with around 2.3 million cases diagnosed in 2020. One in five cancer patients develops chronic lymphedema caused by multifactorial triggers and treatment-related factors. This can lead to swelling, skin infections, and limb dysfunction, negatively affecting the patient's quality of life. This retrospective cohort study aimed to determine the associations between demographic and breast cancer characteristics and postoperative cellulitis in breast cancer survivors who underwent lymphovenous bypass surgery (LVB) at Mayo Clinic, Florida. METHODS: We performed a retrospective chart review. Data were collected retrospectively from 2016 to 2022. Sixty adult breast cancer survivors who underwent LVB were included in the final analysis based on specific inclusion and exclusion criteria. Patients were excluded if they did not meet the inclusion criteria or had incomplete follow-up data. Demographic and surgical data were extracted, including body mass index (BMI), type of anastomosis, number of anastomoses, and preoperative cellulitis status. Lymphedema measurements were performed using tape measurements. Fisher's exact test was used to determine statistically significant associations between variables and postoperative cellulitis. RESULTS: Postoperative cellulitis was more common in patients aged 60 to 69 years (43.2%), whites (75.0%), overweight or obese (90.9%), with one to four anastomoses (81.8%), and nonsmokers (79.5%). The mean International Society of Lymphology (ISL) criteria for both postoperative cellulitis and no postoperative cellulitis was 1.93. Statistically significant associations with postoperative cellulitis were found for the number of anastomoses (p = 0.021), smoking status (p = 0.049), preoperative cellulitis (p = 0.04), and the length of years with lymphedema diagnosis variable (p = 0.004). CONCLUSION: Our results suggest that a greater number of anastomoses, smoking, preoperative cellulitis, and years with lymphedema are significantly associated with an increased risk of postoperative cellulitis. Awareness of these risk factors is crucial for monitoring and early treatment of infections following surgery.

Photoluminescence and magnetic properties of isostructural europium(III), gadolinium(III) and terbium(III) oxamate-based coordination polymers.

Developing and investigating advanced multifunctional materials with magnetic properties as candidates for assembling spin qubits for quantum computing is imperative. A new polytopic ligand based on oxamate and aniline was used to promote the synthesis of three neutral homometallic lanthanide-coordinated polymers. New complexes with the formula {Ln(phox)3(DMSO)2(H2O)}n, where Ln = Eu3+ (1), Gd3+ (2), and Tb3+ (3) [phox = N-(phenyl)oxamate and DMSO = dimethylsulfoxide], were synthesized and well characterized by spectroscopic methods as well as X-ray crystallographic analysis. All crystalline structures comprise neutral zigzag chains. The lanthanide ions are linked by three phox ligands, in which two oxygen atoms from two different ligands are responsible for connecting the trivalent lanthanide ions, and one phox ligand completes the coordination sphere in a bis-bidentate mode, together with two DMSO molecules and one water coordination molecule. The coordination sphere of lanthanide ions consisted of spherical capped square antiprism (CSAPR-9) symmetry. The magnetic properties of 1-3 were investigated in the 2-300 K temperature range. The dynamic (ac) magnetic properties of 2 reveal a frequency dependence involving the phonon bottleneck mechanism below 33 K under nonzero applied dc magnetic fields, resulting in an example of a field-induced single-molecule magnet. Solid-state photophysical measurements for Eu3+ (1) and Tb3+ (3) complexes indicate that the N-(phenyl)oxamate ligands are very efficient in sensitizing the lanthanide(III) ions in the visible region of the electromagnetic spectrum. Compounds 1 and 3 exhibited an emission in the red and green regions, respectively. Experimental results and theoretical calculations using the Sparkle/RM1 method support a quantum efficiency of ∼72% for 1, suggesting its potential as a candidate for light conversion molecular devices (LCMDs).

Fucoidan as a Promising Drug for Pain Treatment: Systematic Review and Meta-Analysis.

Fucoidan is a polymer of L-fucose and L-fucose-4-sulphate naturally found in marine sources that inhibits p-selectin, preventing neutrophil recruitment to the site of injury. Fucoidan is employed in many studies as a tool to investigate the contribution of neutrophils to pain, showing analgesic effects. We performed a systematic review and meta-analysis to quantify the analgesic effects of pretreatment with fucoidan reported in the available preclinical studies. In addition, we summarized the articles which have studied the therapeutic effects of fucoidan in pathological pain at preclinical and clinical levels. The results of this systematic review reveal that pretreatment with fucoidan is a powerful tool which reduces neutrophil infiltration by 70-90% at early time points. This meta-analysis showed that preventative treatment with fucoidan produced a significant pain reduction. In addition, several preclinical studies have observed that fucoidan treatment reduces the pain that is associated with various pathologies. Finally, fucoidan has also been tested in several clinical trials, with some degree of analgesic efficacy, but they were mostly small pilot studies. Considering all the above information, it can be concluded that fucoidan is not only a preclinical tool for studying the role of neutrophils in pain but also a promising therapeutic strategy for pain treatment.

Modelling and mapping carbon capture potential of farmed blue mussels in the Baltic Sea region.

This study applies a regional Dynamic Energy Budget (DEB) model, enhanced to include biocalcification processes, to evaluate the carbon capture potential of farmed blue mussels (Mytilus edulis/trossulus) in the Baltic Sea. The research emphasises the long-term capture of carbon associated with shell formation, crucial for mitigating global warming effects. The model was built using a comprehensive pan-Baltic dataset that includes information on mussel growth, filtration and biodeposition rates, and nutrient content. The study also examined salinity, temperature, and chlorophyll a as key environmental factors influencing carbon capture in farmed mussels. Our findings revealed significant spatial and temporal variability in carbon dynamics under current and future environmental conditions. The tested future predictions are grounded in current scientific understanding and projections of climate change effects on the Baltic Sea. Notably, the outer Baltic Sea subbasins exhibited the highest carbon capture capacity with an average of 55 t (in the present scenario) and 65 t (under future environmental conditions) of carbon sequestrated per farm (0.25 ha) over a cultivation cycle - 17 months. Salinity was the main driver of predicted regional changes in carbon capture, while temperature and chlorophyll a had more pronounced local effects. This research advances our understanding of the role low trophic aquaculture plays in mitigating climate change. It highlights the importance of developing location-specific strategies for mussel farming that consider both local and regional environmental conditions. The results contribute to the wider discourse on sustainable aquaculture development and environmental conservation.

The two alternative NADH:quinone oxidoreductases from Staphylococcus aureus: two players with different molecular and cellular roles.

Staphylococcus aureus is an opportunistic pathogen that has emerged as a major public health threat due to the increased incidence of its drug resistance. S. aureus presents a remarkable capacity to adapt to different niches due to the plasticity of its energy metabolism. In this work, we investigated the energy metabolism of S. aureus, focusing on the alternative NADH:quinone oxidoreductases, NDH-2s. S. aureus presents two genes encoding NDH-2s (NDH-2A and NDH-2B) and lacks genes coding for Complex I, the canonical respiratory NADH:quinone oxidoreductase. This observation makes the action of NDH-2s crucial for the regeneration of NAD+ and, consequently, for the progression of metabolism. Our study involved the comprehensive biochemical characterization of NDH-2B and the exploration of the cellular roles of NDH-2A and NDH-2B, utilizing knockout mutants (Δndh-2a and Δndh-2b). We show that NDH-2B uses NADPH instead of NADH, does not establish a charge-transfer complex in the presence of NADPH, and its reduction by this substrate is the catalytic rate-limiting step. In the case of NDH-2B, the reduction of the flavin is inherently slow, and we suggest the establishment of a charge transfer complex between NADP+ and FADH2, as previously observed for NDH-2A, to slow down quinone reduction and, consequently, prevent the overproduction of reactive oxygen species, which is potentially unnecessary. Furthermore, we observed that the lack of NDH-2A or NDH-2B impacts cell growth, volume, and division differently. The absence of these enzymes results in distinct metabolic phenotypes, emphasizing the unique cellular roles of each NDH-2 in energy metabolism.IMPORTANCEStaphylococcus aureus is an opportunistic pathogen, posing a global challenge in clinical medicine due to the increased incidence of its drug resistance. For this reason, it is essential to explore and understand the mechanisms behind its resistance, as well as the fundamental biological features such as energy metabolism and the respective players that allow S. aureus to live and survive. Despite its prominence as a pathogen, the energy metabolism of S. aureus remains underexplored, with its respiratory enzymes often escaping thorough investigation. S. aureus bioenergetic plasticity is illustrated by its ability to use different respiratory enzymes, two of which are investigated in the present study. Understanding the metabolic adaptation strategies of S. aureus to bioenergetic challenges may pave the way for the design of therapeutic approaches that interfere with the ability of the pathogen to successfully adapt when it invades different niches within its host.

A synchronized, large-scale field experiment using Arabidopsis thaliana reveals the significance of the UV-B photoreceptor UVR8 under natural conditions.

This study determines the functional role of the plant ultraviolet-B radiation (UV-B) photoreceptor, UV RESISTANCE LOCUS 8 (UVR8) under natural conditions using a large-scale 'synchronized-genetic-perturbation-field-experiment'. Laboratory experiments have demonstrated a role for UVR8 in UV-B responses but do not reflect the complexity of outdoor conditions where 'genotype × environment' interactions can mask laboratory-observed responses. Arabidopsis thaliana knockout mutant, uvr8-7, and the corresponding Wassilewskija wild type, were sown outdoors on the same date at 21 locations across Europe, ranging from 39°N to 67°N latitude. Growth and climatic data were monitored until bolting. At the onset of bolting, rosette size, dry weight, and phenolics and glucosinolates were quantified. The uvr8-7 mutant developed a larger rosette and contained less kaempferol glycosides, quercetin glycosides and hydroxycinnamic acid derivatives than the wild type across all locations, demonstrating a role for UVR8 under field conditions. UV effects on rosette size and kaempferol glycoside content were UVR8 dependent, but independent of latitude. In contrast, differences between wild type and uvr8-7 in total quercetin glycosides, and the quercetin-to-kaempferol ratio decreased with increasing latitude, that is, a more variable UV response. Thus, the large-scale synchronized approach applied demonstrates a location-dependent functional role of UVR8 under natural conditions.

Cell-Based Therapies Induce Tolerance of Vascularized Composite Allotransplants: A Systematic Review.

INTRODUCTION: Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance. METHODS: Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization. RESULTS: Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αß-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance. CONCLUSIONS: Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.

Quantitative effects of overlay clutter and information access effort: Examining the scan-clutter trade-off in displays with geospatial maps.

Overlaying images from multiple geospatial databases increases clutter and imposes attentional costs by disrupting focusing attention on each database and dividing attention when comparing databases. Costs of overlay clutter may offset the benefits of reduced scanning between two images displayed separately. In two experiments, we examine these attention issues using computational metrics to quantify clutter. We also examine how the scan-clutter trade-off is modified by different levels of clutter, display separation, and task attentional requirements. Participants viewed information from a geographical terrain database and a schematic map database and made judgments that required focusing attention on either database or integrating information across both. In Experiment 1, databases were presented as either overlaid or adjacent displays, and in Experiment 2, as either overlay, adjacent, or more separated displays. Results showed that response time was modulated by the magnitude of clutter, spatial separation, and task type. Results also revealed that clutter costs dominated those of spatial separation, particularly in tasks requiring focused attention. A computational feature congestion metric of clutter effectively predicted performance but could be improved by incorporating an overlay component, which amplified the costs of clutter. The results provide design guidelines for overlay displays (e.g., head-mounted displays) that will minimize the scan-clutter trade-off. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A narrative review of telemedicine and its adoption across specialties.

Background and Objective: Telemedicine and video consultation are crucial advancements in healthcare, allowing remote delivery of care. Telemedicine, encompassing various technologies like wearable devices, mobile health, and telemedicine, plays a significant role in managing illnesses and promoting wellness. The corona virus disease 2019 (COVID-19) pandemic accelerated the adoption of telemedicine, ensuring convenient access to medical services while maintaining physical distance. Legislation has supported its integration into clinical practice and addressed compensation issues. However, ensuring clinical appropriateness and sustainability of telemedicine post-expansion has gained attention. We south to identify the most friendly and resistant specialties to telemedicine and to understand areas of interest within those specialties to grasp potential barriers to its use. Methods: We aimed to identify articles that incorporated telemedicine in any medical or surgical specialty and determine the adoption rate and intent of this new form of care. Additionally, a secondary search within these databases was conducted to analyze the advantages, disadvantages, and implementation of telemedicine in the healthcare system. Non-English articles and those without full text were excluded. The study selection and data collection process involved using search terms such as "medicine", "surgery", "specialties", "telemedicine", and "telemedicine". Key Content and Findings: Telemedicine adoption varies among specialties. The pandemic led to increased usage, with telemedicine consultations comprising 30.1% of all visits, but specialties like mental health, gastroenterology, and endocrinology showed higher rates of adoption compared to optometry, physical therapy, and orthopedic surgery. Conclusions: The data shows that telemedicine uptake varies by specialty and condition due to the need for physical exams. In-person visits still dominate new patient visits despite increased telemedicine use. Telemedicine cannot fully replace in-person care but has increased visit volume and is secure. The adoption of telemedicine is higher in medical practices than in surgical practices, with neurosurgery and urology leading. Further research is needed to assess telemedicine's suitability and effectiveness in different specialties and conditions.

Bilateral abducens and facial nerve palsies following fourth ventriculoperitoneal shunt with laparoscopic-assisted abdominal catheter placement.

Introduction: Hydrocephalus, altering cerebrospinal fluid (CSF) dynamics, affects 175 per 100,000 adults worldwide. Ventriculoperitoneal shunts (VPS) manage symptomatic hydrocephalus, with 125,000 cases annually. Despite efficacy, VPS face complications, necessitating interventions. Research question: "What are the mechanisms and risk factors for bilateral VIth and VIIth lower motor neuron palsies in hydrocephalus patients with a fourth ventriculoperitoneal shunt?" Material and methods: This study details a 36-year-old female with a neonatal meningitis history, multiple shunt replacements, admitted for abdominal pain secondary to pelvic inflammatory disease. An abdominal shunt catheter removal and external ventricular drain placement occurred after consultation with a general surgeon. A cardiac atrial approach and subsequent laparoscopic abdominal approach were performed without complications. Results: After one month, the patient showed neurological complications, including decreased facial expression, gait instability, and bilateral VIth and VIIth lower motor neuron palsies, specifically upgazed and convergence restriction. Discussion: The complication's pathophysiology is discussed, attributing it to potential brainstem herniation from over-drainage of CSF. Literature suggests flexible endoscopic treatments like aqueductoplasty/transaqueductal approaches into the fourth ventricle. Conclusions: This study underscores the need for increased awareness in monitoring neurological outcomes after the fourth ventriculoperitoneal shunt, particularly in cases with laparoscopic-assisted abdominal catheter placement. The rarity of bilateral abducens and facial nerve palsies emphasizes the importance of ongoing research to understand pathophysiology and develop preventive and therapeutic strategies for this unique complication.

Metastatic organotropism: a brief overview.

Organotropism has been known since 1889, yet this vital component of metastasis has predominantly stayed elusive. This mini-review gives an overview of the current understanding of the underlying mechanisms of organotropism and metastases development by focusing on the formation of the pre-metastatic niche, immune defenses against metastases, and genomic alterations associated with organotropism. The particular case of brain metastases is also addressed, as well as the impact of organotropism in cancer therapy. The limited comprehension of the factors behind organotropism underscores the necessity for efficient strategies and treatments to manage metastases.

Giant uterine tumor and miscarriage: how to proceed?

Expanding uterine masses can be the cause of pregnancy loss and add technical difficulties to uterus evacuation due to the intense anatomical distortion of the endocervical canal and uterine cavity. The literature is scarce in the peculiarities of the management of missed abortions in uterus with important distorted anatomies. We report a case of a primigravida patient who presented a rapid and expressive increase of abdominal volume due to a giant uterine mass, evolving to miscarriage. Ultrasound can be a useful tool, allowing visualization of the endocervical path and uterine cavity, helping to perform uterine evacuation in the presence of anatomical distortion without compromising the reproductive future. To the best of our knowledge, no such case has been previously reported.

Late Diagnosis of Langerhans Cell Histiocytosis by Skin Biopsy in a Lung Transplant Candidate Patient.

We present the case of a lung transplant candidate under veno-venous membrane oxygenation assistance (VV ECMO) whose diagnosis of emphysema of undetermined etiology was redefined as Langerhans cell histiocytosis (LCH) due to a scalp skin biopsy performed years after the beginning of his respiratory symptoms. A 20-year-old patient started three years before his admission with progressive dyspnea leading to a diagnosis of bullous emphysema of undetermined cause, which evolved into respiratory failure and evaluation for bilateral lung transplant. Three years later, he developed bilateral pneumonia requiring mechanical ventilation. When refractory hypoxemia ensued, he had to be placed on VV ECMO. Under these conditions, he was transferred to our center and listed for a bilateral pulmonary transplantation. Forty-eight hours after admission, and due to intense polyuria, central diabetes insipidus was diagnosed. In this clinical context, the presence of cutaneous lesions on the scalp was reconsidered and biopsied under the presumption of possible LCH, with pathology analysis confirming the diagnosis. He continued to be assisted with VV ECMO for 66 more days as a bridge to transplantation, developing multi-organ failure and passing away before a donor organ was available. The diagnosis of LCH should be considered in any adult patient with bullous emphysema of undetermined cause. Given the possibility of early therapeutic interventions, the search for its clinical associations (e.g., diabetes insipidus and/or skin lesions) should be a systematic part of the etiologic workup. The availability of skin specimens to reach a diagnosis makes its thorough search an important part of the diagnostic approach.

Disturbed flow regulates protein disulfide isomerase A1 expression via microRNA-204.

Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation. Here, we showed that PDIA1 mRNA and protein levels were upregulated (average 5-fold) in the intima and media/adventitia following partial carotid ligation (PCL). Our search identified that miR-204-5p and miR-211-5p (miR-204/211), two broadly conserved miRNAs, share PDIA1 as a potential target. MiR-204/211 was downregulated in vascular layers following PCL. In isolated endothelial cells, gain-of-function experiments of miR-204 with miR mimic decreased PDIA1 mRNA while having negligible effects on markers of endothelial activation/stress response. Similar effects were observed in vascular smooth muscle cells (VSMCs). Furthermore, PDIA1 downregulation by miR-204 decreased levels of the VSMC contractile differentiation markers. In addition, PDIA1 overexpression prevented VSMC dedifferentiation by miR-204. Collectively, we report a new mechanism for PDIA1 regulation through miR-204 and identify its relevance in a model of vascular disease playing a role in VSMC differentiation. This mechanism may be regulated in distinct stages of atherosclerosis and provide a potential therapeutic target.