Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer.

Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan-Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC's pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

Elevated tissue expression of RANKL and RANK is associated with poorer survival rates in pancreatic cancer patients.

Pancreatic cancer is a highly lethal malignancy with a growing incidence reported worldwide. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, which is often diagnosed at advanced stages, making its prognosis and medical management difficult. The identification of histopathological biomarkers has allowed a more precise stratification of pancreatic cancer patients, providing additional information about their prognosis and offering possible therapeutic targets to be explored. The prognostic value of the receptor activator of nuclear factor-kappa B (RANK) and its ligand (RANKL) has been evaluated in breast and prostate tumors, however, their usefulness has not been assessed in pancreatic cancer. In the present work, we analyzed the relationship between the protein expression of RANK and RANKL with the survival of 41 patients with pancreatic cancer followed for 60 months, by performing immunohistochemistry and Kaplan-Meier curves. Our results demonstrate a direct association of high expression levels of RANK and RANKL with poorer survival of pancreatic cancer patients in comparison to those with low/medium and null expression levels of both markers. Further studies should be conducted to explore the carcinogenic role of both components in this type of tumor, as well as additional promising translational uses.

Decreased survival in patients with pancreatic cancer may be associated with an increase in histopathological expression of inflammasome marker NLRP3.

Pancreatic cancer is a malignant neoplasm that, despite its low frequency, has a 5-year survival rate of less than 10%. The study of different histopathological markers has allowed a better understanding of the onset and development of this type of tumor as well as facilitating an approach to clinical variables based on their diagnostic, prognostic, and predictive value. In this sense, the NLRP3 protein of the inflammasome has been shown to be a component of great relevance in the initiation and progression of pancreatic cancer, although the value of this biomarker in patients has not yet been clarified. In this study, we selected 41 patients with pancreatic cancer and followed them for 60 months (5 years), evaluating their NLRP3 expression using immunohistochemical techniques. Furthermore, by performing Kaplan-Meier curves, we evaluated the survival of these patients in relation to their NLRP3 expression. Our results show that a significant percentage of our cohort had high expression of this component (90.74%) and that there is an inverse relationship between the expression of NLRP3 and patient survival. High levels of NLRP3 expression are related to lower survival and worse prognosis in these patients, possibly due to an ineffective immune system response and increased tumor-promoted inflammation. Future studies should be aimed at confirming these results in larger groups and evaluating various clinical strategies based on this knowledge.

Effect of Prewarming on Perioperative Hypothermia in Patients Undergoing Loco-Regional or General Anesthesia: A Randomized Clinical Trial.

Background and Objectives: Redistribution hypothermia occurs during anesthesia despite active intraoperative warming. Prewarming increases the heat absorption by peripheral tissue, reducing the central to peripheral heat gradient. Therefore, the addition of prewarming may offer a greater preservation of intraoperative normothermia as compared to intraoperative warming only. Materials and Methods: A single-center clinical trial of adults scheduled for non-cardiac surgery. Patients were randomized to receive or not a prewarming period (at least 10 min) with convective air devices. Intraoperative temperature management was identical in both groups and performed according to a local protocol. The primary endpoint was the incidence, the magnitude and the duration of hypothermia (according to surgical time) between anesthetic induction and arrival at the recovery room. Secondary outcomes were core temperature on arrival in operating room, surgical site infections, blood losses, transfusions, patient discomfort (i.e., shivering), reintervention and hospital stay. Results: In total, 197 patients were analyzed: 104 in the control group and 93 in the prewarming group. Core temperature during the intra-operative period was similar between groups (p = 0.45). Median prewarming lasted 27 (17-38) min. Regarding hypothermia, we found no differences in incidence (controls: 33.7%, prewarming: 39.8%; p = 0.37), duration (controls: 41.6% (17.8-78.1), prewarming: 45.2% (20.6-71.1); p = 0.83) and magnitude (controls: 0.19 °C · h-1 (0.09-0.54), prewarming: 0.20 °C · h-1 (0.05-0.70); p = 0.91). Preoperative thermal discomfort was more frequent in the prewarming group (15.1% vs. 0%; p < 0.01). The interruption of intraoperative warming was more common in the prewarming group (16.1% vs. 6.7%; p = 0.03), but no differences were seen in other secondary endpoints. Conclusions: A preoperative prewarming period does not reduce the incidence, duration and magnitude of intraoperative hypothermia. These results should be interpreted considering a strict protocol for perioperative temperature management and the low incidence of hypothermia in controls.

Assessment of Tissue Expression of the Oxytocin-Vasopressin Pathway in the Placenta of Women with a First-Episode Psychosis during Pregnancy.

Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations.

Enhancing physicians' radiology diagnostics of COVID-19's effects on lung health by leveraging artificial intelligence.

Introduction: This study aimed to develop an individualized artificial intelligence model to help radiologists assess the severity of COVID-19's effects on patients' lung health. Methods: Data was collected from medical records of 1103 patients diagnosed with COVID-19 using RT- qPCR between March and June 2020, in Hospital Madrid-Group (HM-Group, Spain). By using Convolutional Neural Networks, we determine the effects of COVID-19 in terms of lung area, opacities, and pulmonary air density. We then combine these variables with age and sex in a regression model to assess the severity of these conditions with respect to fatality risk (death or ICU). Results: Our model can predict high effect with an AUC of 0.736. Finally, we compare the performance of the model with respect to six physicians' diagnosis, and test for improvements on physicians' performance when using the prediction algorithm. Discussion: We find that the algorithm outperforms physicians (39.5% less error), and thus, physicians can significantly benefit from the information provided by the algorithm by reducing error by almost 30%.

The Effect of Coronavirus Outbreak on the Utilization of Coronary Revascularization Procedures: An Interrupted Time Series Analysis.

The coronavirus disease 19 (COVID-19) pandemic represented a great challenge for health systems, which had to quickly readapt and dedicate most of their resources to managing this crisis. The postponement of programmed interventions such as coronary revascularization procedures represented a critical issue in the first wave of the COVID-19 pandemic, especially in the hardest-hit countries such as Spain. However, the precise consequences of the delay of coronary revascularizations are not clearly determined. In the present work, interrupted time series (ITS) analysis was used to evaluate the utilization rates and assessment of the risk profiles of patients receiving two main coronary revascularization procedures (percutaneous coronary intervention-PCI and coronary artery bypass graft-CABG) and compared them in the periods before and after March 2020 using the Spanish National Hospital Discharge Database (SNHDD). Our results show that the abrupt reorganization of hospital care that represented the first wave of COVID-19 in March 2020 in Spain led to a reduction in cases, which was accompanied by an increase in the risk profile of CABG patients, but not PCI. On the other hand, the risk profile of both coronary revascularization procedures began before the pandemic, showing a significant temporal trend toward an increase in the risk profile. Future works should be directed to study and validate our results, evaluating other databases, regions, or countries.

The Use of Ultrasound Imaging for Upper Extremity Lymphedema after Breast Cancer: A Systematic Review.

BACKGROUND: The aim of this study was to analyze the different applications of ultrasound (US) in upper extremity lymphedema (UEL) after breast cancer. METHODS: A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to December 2021. Articles describing the application of US in patients with UEL after breast cancer were included. The quality of the study, the level of reproducibility, and the different applications and type of US technique were analyzed. RESULTS: In total, 30 articles with 1,193 patients were included in the final review. Five different applications were found: (1) diagnosis of UEL (14 studies found a direct correlation between lymphedema and morphological and/or functional parameters); (2) staging/severity of UEL (9 studies found a direct correlation between the clinical stage and the soft-tissue stiffness/texture/thickness); (3) therapeutic assessment (3 studies found an improvement in the circulatory status or in the muscle/subcutaneous thickness after conservative treatments); (4) prognosis assessment of UEL (1 study found a correlation between the venous flow and the risk of UEL); and (5) surgical planning (3 studies determined the location of the lymphatic vessel for lymphovenous anastomosis [LVA] surgery). CONCLUSION: Morphological and functional parameters have been correlated with the diagnosis, stage, therapeutic effect, prognosis of UEL, and surgical planning of LVA.

Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients.

SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system-IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII-for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFß, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.

History of Endometriosis Is Independently Associated with an Increased Risk of Ovarian Cancer.

Background: Endometriosis is a complex gynecologic disorder that has been associated with a higher risk of ovarian cancer. The purpose of this work is to determine to what extent a history of endometriosis is a risk factor for ovarian cancer in a Spanish population. Methods: A retrospective case-control study was conducted using de-identified data from the Spanish National Health System's "Primary Care Clinical Database" and "Hospital Minimum Basic Data Set" for the period 2013-2017. Multiple logistics regression analysis was conducted to determine associations between ovarian cancer and endometriosis controlled by sociodemographic characteristics and comorbidities. Results: Data from 608,980 women were analyzed, with 4505 presenting ovarian cancer. Endometriosis patients were shown to have a 2.66-fold increased risk of ovarian cancer when compared to those who did not have endometriosis by controlling age and other relevant comorbidities. Conclusions: This case-control study based on clinical administrative data has found that a history of endometriosis is independently associated with an increased risk of ovarian cancer. More research is needed to determine if a history of endometriosis affects survival results in ovarian cancer patients.

Recapping the Features of SARS-CoV-2 and Its Main Variants: Status and Future Paths.

Over the two years that we have been experiencing the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, our challenges have been the race to develop vaccines and the difficulties in fighting against new variants due to the rapid ability of the virus to evolve. In this sense, different organizations have identified and classified the different variants that have been emerging, distinguishing between variants of concern (VOC), variants of interest (VOI), or variants under monitoring (VUM). The following review aims to describe the latest updates focusing on VOC and already de-escalated variants, as well as to describe the impact these have had on the global situation. Understanding the intrinsic properties of SARS-CoV-2 and its interaction with the immune system and vaccination is essential to make out the underlying mechanisms that have led to the appearance of these variants, helping to determine the next steps for better public management of this pandemic.

Oxidative Stress Markers Are Associated with a Poor Prognosis in Patients with Pancreatic Cancer.

Pancreatic cancer is a malignancy of rising prevalence, especially in developed countries where dietary patterns and sedentariness favor its onset. This malady ranks seventh in cancer-related deaths in the world, although it is expected to rank second in the coming years, behind lung cancer. The low survival rate is due to the asymptomatic course of the early stages, which in many cases leads to metastases when becoming evident in advanced stages. In this context, molecular pathology is on the way towards finding new approaches with biomarkers that allow a better prognosis and monitoring of patients. So the present study aims to evaluate a series of molecular biomarkers, PARP1, NOX1, NOX2, eNOS and iNOS, as promising candidates for prognosis and survival by using immunohistochemistry. The analysis performed in 41 patients with pancreatic cancer showed a correlation between a high expression of all these components with a low survival rate, with high statistical power for all. In addition, a 60-month longitudinal surveillance program was managed, accompanied by several clinical parameters. The derivative Kaplan-Meier curves indicated a low cumulative survival rate as well. Ultimately, our research emphasized the value of these molecules as survival-associated biomarkers in pancreatic cancer, offering new gates for clinical management.

Implication of ERBB2 as a Predictive Tool for Survival in Patients with Pancreatic Cancer in Histological Studies.

Pancreatic cancer will be positioned by the year 2030 as the second cause of oncological death after lung cancer. The pathophysiology of the most common variety, which involves the adenocarcinoma of the pancreas, represents one of the main challenges for current oncology to explain its tumorigenesis and create a targeted treatment. The tumor microenvironment, metastatic capacity, and lack of early diagnosis lead patients to present advanced stages at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcomes and with respect to the improved survival of these patients. For this reason, in recent years, numerous diagnostic tests, treatments, and possible approaches in the fields of radiotherapy, chemotherapy, immunotherapy, and surgery have been developed to find a combination of methods that improves life expectancy in patients diagnosed with this disease. On the other hand, the scientific community has made numerous advances in the molecular bases of pancreatic cancer since several oncogenetic pathways have been described and the markers expressed by the tumor have proven to be useful in the prognosis of pancreatic adenocarcinoma. These molecular alterations allow the study of possible therapeutic targets that improve the prognosis of these patients, but even numerous tumor cell-individual interactions must be explained to understand the underlying pathophysiology causing the high mortality. Therefore, the purpose of our study is to examine the expression of markers such as EGFR, Cyclin D1, andCDK4 in order to find a relationship with the possible long-term prognostic factors of patients affected by pancreatic ductal adenocarcinoma. Our results show that there is a prognostic role for ErbB2, EGFR, beta catenin, cyclin D1, and CDK4. Of these, we highlight the clinical importance of ErbB2 in the survival rates of patients who overexpress this component.

Towards an Accurate Estimation of COVID-19 Cases in Kazakhstan: Back-Casting and Capture-Recapture Approaches.

Background and Objectives: Coronavirus disease 19 (COVID-19) has emerged as the most devastating syndemic of the 21st century, with worrisome and sustained consequences for the entire society. Despite the relative success of vaccination programs, the global threat of the novel coronavirus SARS-CoV-2 is still present and further efforts are needed for its containment and control. Essential for its control and containment is getting closer to understanding the actual extent of SARS-CoV-2 infections. Material and Methods: We present a model based on the mortality data of Kazakhstan for the estimation of the underlying epidemic dynamic-with both the lag time from infection to death and the infection fatality rate. For the estimation of the actual number of infected individuals in Kazakhstan, we used both back-casting and capture-recapture methods. Results: Our results suggest that despite the increased testing capabilities in Kazakhstan, official case reporting undercounts the number of infections by at least 60%. Even though our count of deaths may be either over or underestimated, our methodology could be a more accurate approach for the following: the estimation of the actual magnitude of the pandemic; aiding the identification of different epidemiological values; and reducing data bias. Conclusions: For optimal epidemiological surveillance and control efforts, our study may lead to an increased awareness of the effect of COVID-19 in this region and globally, and aid in the implementation of more effective screening and diagnostic measures.

Prognostic role of IRS-4 in the survival of patients with pancreatic cancer.

Pancreatic cancer is a malignancy of rising incidence, especially in developed countries due to causes such as sedentary lifestyles, tobacco smoking and ultraprocessed high fat and high sugar diets, amongst others. It is in fact the 7th cause of cancer-related deaths worldwide, and, in the following years, it is expected to climb upwards to 2nd position, after lung cancer. This is because it may have an asymptomatic course, and when it becomes evident it is in advanced stages, accompanied by metastasis generally. For this reason, survival rates are so low and, even in the few successful cases there is a high possibility of recurrence. Identifying new molecular biomarkers is arising as a highly useful tool for pancreatic cancer clinical management, although much research and work remain to be done in this field. Thus, the present study aims to analyze a series of molecules (IRS-4, Rb1, Ki-67 y COX-2) as candidates for prognosis and survival by immunohistochemistry techniques. Additionally, a 60-month longitudinal surveillance program was conducted, associated with diverse clinical parameters. Kaplan-Meier curves estimating the time of survival according to tumoral expression of those molecules denoted a low cumulative survival rate. Importantly, we observed that high levels of IRS-4 were significantly associated with a bad prognosis of the disease, increasing 160 times the mortality risk. In this way, our research showed a relevant value of these biomarkers in pancreatic cancer patients' survival, opening a pathway for future research areas designed to inhibit these components.

Overexpression of glycolysis markers in placental tissue of pregnant women with chronic venous disease: a histological study.

Chronic Venous Disease (CVD) refers to a wide variety of venous disorders being the varicose veins its most common manifestation. It is well-established the link between pregnancy and the risk of suffering CVD, due to hormonal or haematological factors, especially during the third trimester. In the same manner, previous studies have demonstrated the detrimental effect of this condition in the placental tissue of pregnant women, including in the normal physiology and the metabolomic profile of this organ. In this context, the aim of this study was to evaluate the glucose homeostasis in the placental tissue of women presenting CVD. Through immunohistochemistry, we studied the protein expression of the glucose transporter 1 (GLUT-1), Phosphoglycerate kinase 1 (PGK1), aldolase (ALD), Glyceraldehyde-3-phosphate dehydrogenase (GA3PDH) and lactate dehydrogenase (LDH). Our results have reported a significative increase in the expression of GLUT-1, PGK1, ALD, GA3PDH and the isoenzyme LDHA in placentas of women with CVD. This work has proven for the first-time an altered glucose metabolism in the placental tissue of women affected by CVD, what may aid to understand the pathophysiological mechanisms of this condition in more distant organs such as placenta. Furthermore, our research also supports the basis for further studies in the metabolic phenotyping of the human placenta due to CVD, which may be considered during the late pregnancy in these women.

Impact of the Innate Inflammatory Response on ICU Admission and Death in Hospitalized Patients with COVID-19.

OBJECTIVE: To describe the capacity of a broad spectrum of cytokines and growth factors to predict ICU admission and/or death in patients with severe COVID-19. DESIGN: An observational, analytical, retrospective cohort study with longitudinal follow-up. SETTING: Hospital Universitario Príncipe de Asturias (HUPA). PARTICIPANTS: 287 patients diagnosed with COVID-19 admitted to our hospital from 24 March to 8 May 2020, followed until 31 August 2020. MAIN OUTCOME MEASURES: Profiles of immune response (IR) mediators were determined using the Luminex Multiplex technique in hospitalized patients within six days of admission by examining serum levels of 62 soluble molecules classified into the three groups: adaptive IR-related cytokines (n = 19), innate inflammatory IR-related cytokines (n = 27), and growth factors (n = 16). RESULTS: A statistically robust link with ICU admission and/or death was detected for increased serum levels of interleukin (IL)-6, IL-15, soluble (s) RAGE, IP10, MCP3, sIL1RII, IL-8, GCSF and MCSF and IL-10. The greatest prognostic value was observed for the marker combination IL-10, IL-6 and GCSF. CONCLUSIONS: When severe COVID-19 progresses to ICU admission and/or death there is a marked increase in serum levels of several cytokines and chemokines, mainly related to the patient's inflammatory IR. Serum levels of IL-10, IL-6 and GCSF were most prognostic of the outcome measure.

Applications of Polymeric Composites in Bone Tissue Engineering and Jawbone Regeneration.

Polymer-based composites are a group of biomaterials that exert synergic and combined activity. There are multiple reported uses of these composites in multiple biomedical areas, such as drug carriers, in wound dressings, and, more prominently, in tissue engineering and regenerative medicine. Bone grafting is a promising field in the use of polymeric composites, as this is the second most frequently transplanted organ in the United States. Advances in novel biomaterials, such as polymeric composites, will undoubtedly be of great aid in bone tissue engineering and regeneration. In this paper, a general view of bone structure and polymeric composites will be given, discussing the potential role of these components in bone tissue. Moreover, the most relevant jawbone and maxillofacial applications of polymeric composites will be revised in this article, collecting the main knowledge about this topic and emphasizing the need of further clinical studies in humans.

Mouse Models for Human Skin Transplantation: A Systematic Review.

Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation.

Chronic venous disease patients show increased IRS-4 expression in the great saphenous vein wall.

OBJECTIVES: Chronic venous disease (CVeD) is a multifactorial and debilitating condition that has a high prevalence in Western countries and an important associated socioeconomic burden. Varicose veins (VVs) are the most common manifestations of CVeD. Pathologically, many morphological and functional changes have been described in VVs, which most notably affect venous wall integrity. Previous studies have found several molecular alterations that negatively affect normal cell signaling pathways. Insulin receptor substrate (IRS)-4 is a central adaptor protein that is closely related to insulin/insulin-like growth factor-1 signaling upstream, phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinases downstream, and other proteins. These molecular pathways have been implicated in CVeD pathogenesis. Thus, the aim of our study was to identify the role of IRS-4 in VV tissue. METHODS: We conducted a histopathological study to analyze IRS-4 protein expression in CVeD patients compared with healthy controls. RESULTS: Our results demonstrate a significant increase in IRS-4 expression in VV tissue. CONCLUSIONS: IRS-4 may be implicated in CVeD development and progression. Therefore, IRS-4 could be a potential diagnostic or therapeutic target for patients with this condition.