Leukemia is a malignancy initiated by uncontrolled proliferation of hematopoietic stem cell from the B and T lineages, resulting in destruction of hematopoietic system. The conventional leukemia treatments induce severe toxic and a long series of unwanted side-effects which are caused by lack of specificity of anti-leukemic drugs. Recently, nanotechnology have shown tremendous application and clinical impact with respect to diagnosis and treatment of leukemia. According to considerable researches in the context of finding new nanotechnological platform, iron oxide nanoparticles have been gained increasing attention for the leukemia patients use. In this review, a short introduction of leukemia is described followed by the evaluation of the current approaches of iron oxide nanoparticles applied in the leukemia detection and treatment. The enormous advantages of iron oxide nanoparticles for leukemia have been discussed, which consist of the detection of magnetic resonance imaging (MRI) as efficient contrast agents, magnetic biosensors and targeted delivery of anti-leukemia drugs by coating different targeting moieties. In addition, this paper will briefly describe the application of iron oxide nanoparticles in the combined treatment of leukemia. Finally, the shortcomings of the current applications of iron-based nanoparticles in leukemia diagnosis and treatment will be discussed in particular. Leukemia is a tumor of the hematopoietic and lymphoid tissues. Clonal leukemia cells proliferate, accumulate and infiltrate in the bone marrow and other hematopoietic and non-hematopoietic tissues due to abnormal proliferation of differentiated hematopoietic stem cell or progenitor cells, thus affecting the physiological bone marrow of various tissues and organs. Chemotherapy is the most common treatment for leukemia. Radiotherapy is the treatment of malignant tumors with radionuclide alpha, beta, gamma radiation and X-ray, electron and proton beams produced by various X-ray therapy machines or accelerators. Targeted therapy, as one of the treatment modalities for leukemia, has three main therapeutic mechanisms: small molecule inhibitors that target gene mutations, inhibitors that target key signaling pathways, and antibodies or antibody-coupled drugs that target cell surface molecules. Currently, Hematopoietic stem cell transplantation (HSCT) is considered to be an effective treatment for leukemia. The above-mentioned therapies generally have some disadvantages, such as low drug targeting, high adverse reactions, and drug resistance in patients. Therefore, it is very important to develop an efficient and targeted intelligent drug delivery system in the past decades in vivo, has been widely used as magnetic resonance imaging (MRI) contrast agent for tumor diagnosis. Iron oxide nanoparticles (IONPs) in the diagnosis and treatment of cancer has attracted more and more attention. In this paper, the current status of leukemia treatment, the preparation of iron nanoparticles and their application in leukemia detection and treatment are briefly introduced . This arIn recent years, nanotechnology has been widely used in the diagnosis and treatment of various diseases, especially in oncology. As an important endogenous trace element, iron is widely distributed in various tissues of human body to maintain biological health. In recent years, iron-based nanomaterials have been widely used in various fields of biomedicine. 3O4NPs) are closely related to the preparation methods. 3O4NPs include thermal decomposition method, hydrothermal method, co-precipitation method, micro-emulsion method; 3O4NPs preparation is co-precipitation. There are the detailed characteristics of these methods  . DiphospAt present, MRI is mainly used to evaluate the prognosis of leukemia and to screen the complications caused by the treatment of leukemia . IntracrMagnetic hyperthermia was proposed by Gilchrist in 1957. On the basis of the research on the destruction of dog’s lymphoma tissues by magnetic materials, it was proved that magnetic materials could move and gather in the tumor tissues in a targeted manner, and generate heat to destroy the tumor tissue under the action of alternating magnetic field . With thUnlike other diseases, based on the malignant proliferation and metastasis of cancer cells, one of the most effective treatments for cancer is to diagnose leukemia as early as possible. Traditional methods rely on the patient’s clinical symptoms, cytomorphology and cytogenetics to diagnose leukemia. However, traditional methods are less sensitive and leukemia cells can not be detected in the early stages of the disease. Therefore, it is necessary to develop a highly selective and sensitive method for the diagnosis of leukemia. Based on the advantages of good selectivity, high sensitivity, simple equipment and low price, biosensors have been used as diagnostic tools in drug detection, biomedical evaluation, environmental monitoring .3O4/RGO) adapter sensor for detecting the concentration of the leukemia biomarker miRNA-128. The electrical conductivity and the sensitivity of the sensor have been improved by this nanocomposite. Therefore, the quantitative determination of miRNA-128 by the biosensor is realized for the first time, which can be applied to the diagnosis and prognosis of acute lymphocyte leukemia (ALL). Because of the specific expression of miRNA-128 in ALL, the sensor can also be used for differential diagnosis of different types of leukemia, especially with AML, in which miRNA-128 is not expressed.  coated with gold nanoparticles, and then used N-doped graphene nanoplates as the detection electrode, an electrochemical joint sensor was successfully constructed to detect the selectivity and sensitivity of leukemic cells. It is reported that nitrogen-doped graphene had larger functional surface area, more active sites catalytic reactions and higher conductivity compared with graphene nanosheet  can induce apoptosis by activating Caspase-3 and decreasing the expression of BCL-2, which can be used in tyrosine-kinase inhibitor myeloid leukemia . Howeverarticles . The res3O4 nanoparticles can overcome this disadvantage. Chemotherapeutic drugs are encapsulated in nanoparticles to slow or control drug release and thereby improve drug bioavailability. Chloramb is used as an alkylating agent in the chemotherapy of chronic lymph leukemia (CLL) and chronic myeloid leukemia (CML). CS-IONPs with core-shell structure were prepared by Most chemotherapeutic drugs used to treat leukemia have a short half-life and therefore do not reach effective therapeutic concentrations in the bloodstream for long enough to produce a lasting therapeutic effect. For example, the half-life of a chlorambucil is only 1–2 h, and the half-life of a mercaptopurine is 90 min . Fe3O4 nThe clinical use of systemic chemotherapy for leukemia is often hampered by cancer cells and the multiple drug resistance of anticancer drugs. The process of multidrug resistance (MDR) development is very complex, which is related to transporter overexpression, enhanced xenobiotics metabolism, DNA repair ability changes, genetic factors and so on To reverse MDR and minimize serious adverse effects of systemic chemotherapy, Doxorubicin (DOX) is a commonly used drug to treat acute leukemia, but its application is limited because of drug resistance. Studies have shown that over-expression of NPM can lead to multidrug resistance of ALL, and the engineered recombinant NPM binding protein (NPMBP) can knock out NPM by RNA interference, thus reversing multidrug resistance of leukemia cells . Gan D aIONPs can trigger the Fenton reaction, a chemical reaction in which divalent and/or ferric can convert hydrogen peroxide into hydroxyl radicals. The Fenton reaction produces reactive oxygen species (ROS) and mediates lipid peroxidation, which can lead to ferroptosis. 3O4 nanoparticles with cytarabine (Ara-C) inhibited leukemia stem cell (LSC) more than Ara-C alone. They analyzed changes in ROS-related substances such as gp91-phox and SOD1 by measuring ROS levels in LSC and non-LSC under different conditions. It was demonstrated that IONPs and Ara-C might induce LSC apoptosis due to increased ROS levels. Therefore, iron oxide nanoparticles can regulate the oxidative damage and defense balance of cells through the mechanism of iron death, which has a great prospect in the treatment of leukemia.With the development of medical science and technology, the traditional way of drug delivery will be innovated. Due to the convenience and biocompatibility of IONPs, it has a broad application prospects in clinical transformation. The rapid development of nanotechnology has laid a solid foundation for the diagnosis and treatment of leukemia, and more and more application of IONPs in the treatment of leukemia. Furthermore, IONPs are widely used in tumor imaging, magnetic hyperthermia and biomacromolecule magnetic separation because of their magnetic properties. More importantly, IONPs can not only achieve synergistic drug delivery, but also combine with other therapeutic methods to achieve better therapeutic effects, which has become one of the hot research directions.However, the application of iron oxide nanoparticles in the diagnosis and treatment of leukemia still needs to overcome huge obstacles in the clinical transformation process. 1) At present, there is still a lack of high-yield and high-safety methods for the preparation of iron oxide nanoparticles. Although some modified materials have been studied, the synthetic standard of modified materials and whether other new materials can be used for modification are still an urgent problem to be solved. 2) Lack of detailed toxicity test results of iron oxide nanoparticles. Although iron oxide nanoparticles are biocompatible compared to other materials, the long-term side effects of iron oxide nanoparticles on normal cells, tissues and organs need to be further determined, and carefully study the metabolism of this material and degradation of the impact on the body. 3) The detailed mechanism of iron oxide nanoparticles involved in regulating the metabolism of leukemic cells is not completely clear. 4) For the application of IONPs in the treatment of leukemia, most of current studies are devoted to the examination of the drug-carrying function of IONPs, and there are fewer applications regarding the magnetic properties of IONPs, such as magnetic hyperthermia and magnetic separation. 6) The clinical transformation of iron oxide nanoparticles in leukemia has been very slow, and only a small number of studies have been carried out in clinical trials. 7) The design of iron oxide nanoparticles with imaging, diagnosis and therapy, and the realization of multi-treatment of leukemia, may be one of the hot research directions in the future.These questions may inspire future research into the development and improvement of IONPs, providing better opportunities for the treatment of leukemia. In summary, combining multidisciplinary knowledge and research tools to explore effective therapies for leukemia and develop highly biocompatibility, highly targeted iron oxide nanoparticles will be the focus. It is believed that with the joint efforts of researchers, IONPs may be further applied in the clinical treatment of leukemia.


The aberrant sialylation of membrane glycocalyx plays a pivotal role in the regulation of malignant cell behavior and correlates with a worse prognosis and shorter overall survival for patients. The biological and physical properties of sialome determine the negative charge and high hydrophilicity of cell membranes and thereby regulate cell–cell and cell–extracellular matrix interactions. There is increasing evidence that sialic acids influence cellular susceptibility in therapeutic management. Here, we focus on the engagement of sialic acids in chemoresistance and the potential effects of drugs and potential therapeutic agents on sialome-related machinery in malignant cells.A cellular sialome is a physiologically active and dynamically changing component of the cell membrane. Sialylation plays a crucial role in tumor progression, and alterations in cellular sialylation patterns have been described as modulators of chemotherapy effectiveness. However, the precise mechanisms through which altered sialylation contributes to drug resistance in cancer are not yet fully understood. This review focuses on the intricate interplay between sialylation and cancer treatment. It presents the role of sialic acids in modulating cell–cell interactions, the extracellular matrix (ECM), and the immunosuppressive processes within the context of cancer. The issue of drug resistance is also discussed, and the mechanisms that involve transporters, the tumor microenvironment, and metabolism are analyzed. The review explores drugs and therapeutic approaches that may induce modifications in sialylation processes with a primary focus on their impact on sialyltransferases or sialidases. Despite advancements in cellular glycobiology and glycoengineering, an interdisciplinary effort is required to decipher and comprehend the biological characteristics and consequences of altered sialylation. Additionally, understanding the modulatory role of sialoglycans in drug sensitivity is crucial to applying this knowledge in clinical practice for the benefit of cancer patients. According to the concept by Cohen and Varki, cell membrane glycomolecules form a dense network characterized by a high grade of diversity and dynamic variability . It makeStructural studies on cellular glycomes have revealed the glycan epitopes of defined sequences featured in the wide expression of neuraminic acid derivatives routinely called sialic acids. The attachment of sialic acids to the non-reducing end of sugar chains is the last step of glycosylation and results in enhanced microheterogeneity that influences the physical and biochemical properties of glycoconjugates . The speSialome plays a complex and multifaceted role in the structure of cell membranes and the extracellular matrix; therefore, numerous alterations in this field are known to be critical for cancer progression. Similar to normal cells, the decoration of the cellular glycocalyx via sialic acids can impact cellular recognition, signaling, adhesion, molecular trafficking, and migration. However, cancer cells do not express the molecules on their membrane properly, and altered glycosylation and changes in glycoprotein expression are common features of tumorigenesis . Among mChanges in the sialylation controlling machinery were found in several types of cancers and described as markers of sialome-related tumorigenesis. First, the aberrant sialylation processes in malignancies correspond to the altered expression and activity of endogenous sialidases in diverse cellular compartments. Among the four sialidases , the enhanced expression of NEU3 was observed in malignant tissues, whereas the rest of these enzymes tended to be reduced, which led to the accumulation of sialoconjugates . AccordiThe dysregulation of sialyltransferases depends on the mechanisms that involve genetic, epigenetic, transcriptional, and post-transcriptional regulations known to be developed in cancer and closely associated with the glycosylation pattern ,35,36. FGiven the high specificity of the distribution of CD33-related Siglecs and differences in the structure of intracellular signaling domains, the interplay between receptors and their ligands determines the activating or suppressive signaling pathways responsible for the function of the immune cells. It is of particular importance in the context of immune homeostasis maintenance. The sialic acid–Siglec axis modulates the balance between self-recognition and non-recognition and mediates cell signaling and adhesion ,58. HoweDrug resistance is one of the major problems in cancer management. Many drugs are successfully used; however, not fully understanding the molecular profile of cancers does not guarantee a complete cure. Cancer cells develop the ability to resist chemotherapy through many different mechanisms, resulting in no/poor response to therapy. This may be due to the fact that this ability is genetically determined or acquired during the use of chemotherapeutic agents. Multi-drug-resistant (MDR) cancer therapy is a particular challenge, especially in acquired resistance. Tumors of this phenotype are resistant to a wide range of drugs with different structures and mechanisms of action . AlthougScientific reports have suggested that several sialyltransferases, including ST8SIA4, are involved in the activity of the PI3K/AKT pathway ,77. ST8SThere are several groups of drugs that have been shown to affect sialylation either by altering the expression of enzymes involved in sialylation or by directly affecting the sialylated glycoconjugates. Currently, there are no drugs that have been specifically designed to change sialylation, as these processes are complex and not fully understood. Some drugs were developed and approved for well-defined therapeutic indications, and their effects on sialic acid or the expression of sialidases or sialyltransferases may be an unintended consequence of their primary mechanism of action. Several drugs have been developed to inhibit sialidases with the goal of blocking the cleavage of sialic acid residues from glycans. Sialidase, as an enzyme associated with influenza viruses, is responsible for the breakdown of sialic acid on the surface of the cell membrane and facilitates the entry of a virus into the cell . PrimariThe glycosylation pattern is a specific feature of the molecular modification of membrane glycocalyx in various cancers. Among the human gangliosides, unusual sialylation has been described in cancer cells via the attachment of N-glycolylated sialic acid (NeuGc) to ganglioside GM3 . InteresThe new therapeutic approach targets the hypersialylated surface of cancer cells or Siglec-7 and Siglec-9 receptors that bind sialic acid. This action is aimed at enhancing the response of natural killer cells since it is assumed that the sialic acid–Siglec axis may downregulate cytotoxicity . SialidaA study by Qorri et al. demonstrated that aspirin and celecoxib dampen Neu-1 activity in pancreatic cancer cells, inducing apoptosis and necrosis in a dose- and time-dependent manner. This finding may be of significant importance, as it may be the missing link between the anticancer efficacy of NSAIDs and the role of glycosylation in inflammation and sialic acidgenesis . AdditioAs mentioned in previous sections, glycocalyx is an integral part of the cell membrane. Glycan chains associated with proteins and lipids support the malignant cells’ survival via a direct impact on cell growth and survival . The higAccording to Ou et al., the overexpression of ST6Gal-1 attenuates the sensitivity of ovarian cancer cells to several anticancer drugs, including paclitaxel, Adriamycin, and the FGFR1 inhibitor, signed as PD173074 . AlthougMagnolia grandiflora traditionally employed in inflammation treatment. As a bioactive agent, HNK exhibits a diverse range of biological activities and engages with several molecular targets that result in antiviral, anti-inflammatory, antioxidant, and antiangiogenic activities [Sanguisorba officinalis. Its co-administration with 5-fluorouracil (5-FU), a first-line drug used in colorectal cancer (CRC) known for its susceptibility to drug resistance, has been demonstrated to synergistically enhance cytotoxicity against cancer cells [Sanguisorba officinalis also manifests neuraminidase inhibitory activity, further substantiating its potential as an adjunct therapeutic agent with inherent anticancer activity [Ginkgo biloba due to its anti-inflammatory, antibacterial, and cardiovascular effects. Notably, scientific evidence indicates that a bioactive bioflavonoid compound extracted from Ginkgo biloba leaves, known as ginkgetin, possesses anticancer properties [Crocus sativus). These research findings have revealed the extracts’ robust cytotoxic activity against melanoma cells (IGR39), triple-negative breast cancer (MDA-MB-231), and glioblastoma cell lines (U-87) and indicated the potential future utility of saffron in the realm of anticancer therapy [Amomum villosum, Melaphis chinensis, and Flos Caryophylli, exhibit robust neuraminidase inhibitory activity comparable to that of oseltamivir [Lonicerae Japonicae Flos, Yupingfeng San, and Huanglian Jiedu Decoction, have been shown to exert inhibitory effects on human neuraminidases [Since it is well established that the presence of upregulated sialic acid on the surface of cancer cells correlates with metastasis, disease progression, and resistance to chemotherapy, neuraminidase has garnered significant attention as a promising therapeutic target to counter chemotherapy resistance . It was tivities ,145,146.tivities . Additiotivities . Furthertivities ,150. In tivities . Furthertivities . The siger cells . Intriguactivity ,155. Anooperties ,157. Comoperties . These eoperties ,160. Thi therapy . A substltamivir ,162. Addinidases . Consequinidases ,169,170.The discovery of both synthetic and natural substances related to sialome-related therapeutic efficiency is of particular importance in the field of therapy of malignancies of high resistance status. An extremely interesting issue is the role of sialic acids in drug resistance in brain tumors. Of particular interest in this context are gangliosides, which are the dominant sialic acid carriers in the brain. While the concentration of sialic acid can vary, depending on the specific tissue; there is evidence to suggest that the brain contains a relatively high level of sialic acid compared to other organs ,172. FurSialic acids are ubiquitous molecules, and their particular importance is still being discovered in the cancer process and the influence on drug resistance. The study of the molecular mechanisms in which sialic acid is involved is the basis for the development of effective drugs and new therapeutic methods. The complexity of the topic and the lack of a full explanation of how sialic acid works can be a cause for concern, but progress in this field gives hope. Discovering hitherto unknown mechanisms of known drugs opens the door to their new applications, especially to drug-resistant cancers. The most promising therapeutic agents that are still being designed and synthesized include sialyltransferase inhibitors, antibodies and inhibitors targeting Siglecs and selectins, and sialidase antibody conjugates. An interdisciplinary effort is required to decipher the characteristics and biological effects of the altered sialome in order to put this knowledge into practice for the benefit of cancer patients.


The trials were conducted within dedicated dehydration rooms mirroring the environmental conditions typical of two different sites of Northeastern Italy. They dissected the temperature effect from that of the dehydration rate, by excluding the influence of environmental relative humidity. Grape dehydration at higher temperatures (12 °C) promotes the accumulation of oligomeric stilbenes, in parallel with the upregulation of PAL and STS genes. Conversely, withering the grapes in a cooler environment (8 °C) favors the accumulation of organic acids, flavonols and aromatic compounds.Ghiglieno et al. described the effects of strong defoliation on the concentration of some norisoprenoids in Pinot noir and Chardonnay berries, highlighting that high amounts of these compounds are detrimental in sparkling wines, particularly when associated to a drastic reduction of acid concentrations. Asproudi et al. found higher variability among vintages in the accumulation of aroma in berries collected from young Grignolino plants respect to the old ones, whose berries reached a higher concentration of terpenoids. Heat waves with temperatures higher than 30°C, together with water scarcity, vary the berry aromatic profile by increasing the accumulation of benzene derivatives.Variable vineyard microclimatic conditions largely influence berry qualitative traits: Perin et al. tested three times of late pruning , highlighting that late pruning decouples the berry ripening dynamics of sugars and phenols, particularly in Syrah respect to Malbec (both grafted onto 110 Richter), resulting in a general increase of polyphenols at harvest. Late pruning in Syrah induced consistent increases in anthocyanins and flavonols, whereas in Malbec significant variation in hydroxycinnamic acid concentration occurred.Late-pruning is a recent technique proposed to adapt viticulture to climate change: in semi-desert climatic conditions, Rodas et al. applied a crop-forcing technique, consisting in hedging the growing shoots to seven nodes and removing all lateral leaves and clusters to force the bursting of the primary buds in cv Tempranillo, grown in semi-arid climatic conditions. Although a significant season effect was found for almost all the analyzed polyphenols, a general increase in polyphenol concentration was observed in the wines obtained from forced-vines.Ciubotaru et al. The objective was to characterize the poorly explored metabolic signature of cultivars with one gene of resistance and with pyramided resistance in comparison with the susceptible variety Teroldego upon Erysiphe necator infection. Both timing and intensity of metabolite accumulation control the initiation and the establishment of defense responses, discriminating the resistant individuals from the susceptible ones. Ten metabolites, including pallidol and astringin, were exclusively up-accumulated in the resistant genotypes, suggesting their key biological role in the activation of resistance mechanisms.An in-depth analysis of grapevine metabolic compounds acting as resistance trait-associated markers is the subject of the paper by Rugulopteryx okamurae (Ro) is a species of brown macroalgae belonging to the Dictyotaceae family and native to the north-western Pacific, detected at Gibraltar since 2015 and then found on the Andalusian coasts . Its use as a grapevine protection product in viticulture could represent a successful example of circular economy, acquired that some Ro extracts can effectively induce the transcription of defense genes, such as PR10, PAL, STS48 and GST1, and the consequent accumulation of specific secondary metabolites.Ferrandino et al. showcases subjects belonging to both the first and the second main themes addressed by this Research Topic, reaffirming how important is to deepen the knowledge on the biological processes that regulate grapevine stress resilience. The review first considers the impact of environmental cues on the berry secondary metabolism, focusing on the molecular and hormonal signalling cascades that control the accumulation of specific groups of quality- and/or defence-associated molecules. Then, the authors analyse recent findings concerning alterations in secondary metabolic compounds that could underlie tolerance/resistance to diseases.The review article by Bosman et al.) influence product and substrate specificity, impacting on cultivar-specific aroma profiles, a pivotal trait for defining grape quality. However, mono- and sesquiterpenes do play important ecophysiological roles: attraction of pollinators, agents of seed dispersal and herbivores, defense against fungi, promotion of mutualistic rhizobacteria interaction, and their concentration increases upon high light radiation (Bosman and Lashbrooke).A further and transversal sub-group outlines advances on the genetic regulation of specialized classes of secondary metabolites, namely monoterpenes and sesquiterpenes. The functional plasticity of the numerous terpene synthases and the significant duplication of genes encoding structurally diverse terpene synthases (millennia of acclimation. During its evolution, the vine had to live by interacting with biotic and abiotic stresses present in the different areas where it developed and was progressively domesticated. The accumulated secondary metabolites have allowed grapevines to refine strategies of struggle and/or coexistence with the environment and with its microbiome, parasites and/or symbionts, giving to the existing genotypes an optimal level of growth/defense tradeoff. This compromise, the result of at least two millennia of attempts, is what we find in the secondary metabolites of the grapes and their derivatives in the wines, produced in different terroirs, and what allows the attentive taster to recognize the grape origin of the grapes and their history of adaptation to the environment, cultivation and winemaking.In this subgroup, as well as in all the papers, the paradigmatic nature of this Research Topic is evident: the secondary metabolites that the vine accumulates in its various organs characterize the different genotypes, the result of AF: Conceptualization, Data curation, Funding acquisition, Writing – review & editing. CP: Conceptualization, Data curation, Funding acquisition, Writing – review & editing.


Venous stenting has been reported with excellent clinical results; however, inadequate inflow can increase the risk of stent occlusion. When extending the stent into the common femoral vein (CFV), it is essential to ensure adequate inflow from the femoral vein, deep femoral vein (DFV), and great saphenous vein. Accurate identification of the distal landing zone (DLZ) of the stent is crucial to ensure adequate inflow. The DLZ is usually determined by venography or intravascular ultrasound (IVUS) with reference to bony landmarks. However, the uncertainty can lead to misidentification of the DLZ and inadequate stent placement, resulting in stent occlusion.From December 2016 to December 2022, 42 venous stent placements were performed in 40 patients with post-thrombotic iliofemoral vein obstruction and/or stenosis. Three patients had developed early stent occlusion owing to a misidentified DLZ. To improve accuracy in identifying the DLZ during venous stenting, ultrasound-guided placement was performed in the CFV of five patients (four on the left and one on the right) with post-thrombotic changes in the CFV and occlusion of the common iliac vein and external iliac vein. The distal end of the stent was adjusted just above the saphenofemoral junction in two cases and just proximal to the DFV confluence in three cases. Stent placement was verified using both long-axis ultrasound and fluoroscopy.Ultrasound images of the CFV region provided clear visualization of the stent deployment site and accurate landmark locations, such as the saphenofemoral junction and DFV confluence, allowing for precise adjustments during stent deployment. This technique enabled easier and more definitive identification of other branches of the CFV than previously provided by IVUS and venography. No complications were observed in any of the 42 cases, and long-term patency was achieved at the final follow-up after stenting .Ultrasound-guided stenting in the CFV allows for real-time and accurate stent deployment with precise adjustment to the optimal DLZ. Using this technique, combined with venography and IVUS, missed distal lesions and subsequent stent occlusion can be prevented, potentially contributing to better treatment outcomes. Venous stenting is increasingly used to manage femoral-iliocaval venous outflow obstruction or stenosis caused by post-thrombotic syndrome. Many studies have shown good technical results, excellent clinical outcomes, and a high patency rate; however, a higher risk of stent occlusion due to insufficient inflow has also been reported.7,,Inflow into the common femoral vein (CFV) includes the femoral vein (FV), deep FV (DFV), and great saphenous vein (GSV). It is important to ensure sufficient blood flow from these veins as much as possible. In particular, blood flow from the DFV is crucial, and Williams and DillavouTo improve the accuracy of DLZ identification during venous stenting in the CFV, we performed ultrasound-guided stent placement. This technique allowed for easier identification of all branches of the CFV and more precise stent deployment with fine adjustments, potentially contributing to better outcomes in venous stenting.Between December 2016 and December 2022, 42 iliofemoral venous stenting procedures were performed for 40 symptomatic patients with post-thrombotic iliofemoral vein obstruction and/or stenosis. Patient selection and the technical details of stenting have been previously described.From January 2022 to December 2022, ultrasound-guided stenting was performed in the CFV of five patients  for a more precise stent distal landing. All five patients had symptomatic post-thrombotic lesions, such as occlusion and/or stenosis and trabeculae, in the CFV, with CIV and EIV occlusion requiring iliofemoral venous stenting, including the CFV region. Of the lesions, four were in the left lower extremity and one was on the right side. One patient had C4b disease and four had C6 disease. Post-thrombotic changes in the CFV were classified into two types: those extending to the saphenofemoral junction , which showed the location of the SFJ, confluence of the DFV, and other branches. The distal end of the stent was adjusted just above the SFJ in the three patients with post-thrombotic lesions extending to the SFJ , and all the patients provided written informed consent for all procedures and the report of their case details and imaging studies.The use of ultrasound in stent deployment was similar to the technique commonly used for venous access. Ultrasound images of the CFV region provide clear visualization of the stent deployment site and accurate landmark locations, such as the SFJ and DFV confluence, allowing for precise adjustments during stent deployment. Furthermore, this technique enables easier and more definitive identification of other branches of the CFV, reducing the time, effort, contrast material use, and radiation exposure required to identify branch vessels, previously identified using IVUS and venography (data not measured). No complications were observed in any of the five patients, and all patients showed symptom improvement, including ulcer healing. Long-term patency was present at the final follow-up after stenting without any evidence of stent occlusion . Because of the limited number of cases and short follow-up period, it was challenging to perform a statistical comparison of the patency rates before and after ultrasound-guided stenting. However, no acute stent occlusions due to missed inflow have occurred since implementing this approach.,,,In the present study, we have shown the advantages of ultrasound-guided stent placement, including precise deployment of the stent in the CFV and optimal DLZ adjustment. Inflow into the CFV includes the FV, DFV, and GSV, and ensuring adequate blood flow from these vessels is crucial in venous stenting.Ultrasound imaging of the femoral vein region is commonly performed and provides a simple and definite evaluation of CFV lesions, the SFJ, the DFV confluence, and other branches. It is also frequently used for venous access during interventional procedures.Ultrasound-guided stenting in the CFV allows for real-time and accurate stent deployment with precise adjustment to the optimal DLZ, effectively achieving both “ensuring adequate inflow” and “stenting all areas of disease,” which are key elements of successful venous stenting. Using this technique, in combination with venography and IVUS, missed distal lesions and subsequent stent occlusion can be prevented, potentially contributing to better treatment outcomes.,The technique requires a transjugular approach, which necessitates determining the area of stent placement and an appropriate DLZ in advance. A detailed preoperative assessment, including imaging studies such as ultrasound and computed tomography, can help identify the location and extent of venous lesions and the optimal DLZ for stent placement. This information can then be used to plan the procedure and achieve the best possible outcome. Although the final determination of the DLZ should be done using the intraoperative findings, it is essential to note that the vascular configuration can change with balloon predilation and vasospasm during the procedure, potentially resulting in missed lesions if overreliance is placed on the intraoperative imaging findings alone during venous stent placement.,,,Missed lesions at the inflow site have been reported as a major cause of stent occlusion.Ultrasound-guided stenting in the CFV allows for real-time and accurate stent deployment with precise adjustment of the optimal DLZ, potentially contributing to better treatment outcomes. Precise preoperative assessment of the lesion in finer detail can provide a more comprehensive evaluation of the disease, helping to plan the procedure for the best possible outcome. Using these techniques, in combination with venography and IVUS, missed distal lesions and subsequent stent occlusion can be prevented, ultimately improving the success rate of venous stenting.


Stroke, a serious systemic inflammatory disease, features neurological deficits and cardiovascular dysfunction. Neuroinflammation is characterized by the activation of microglia after stroke, which disrupts the cardiovascular-related neural network and the blood–brain barrier. Neural networks activate the autonomic nervous system to regulate the cardiac and blood vessels. Increased permeability of the blood–brain barrier and the lymphatic pathways promote the transfer of the central immune components to the peripheral immune organs and the recruitment of specific immune cells or cytokines, produced by the peripheral immune system, and thus modulate microglia in the brain. In addition, the spleen will also be stimulated by central inflammation to further mobilize the peripheral immune system. Both NK cells and Treg cells will be generated to enter the central nervous system to suppress further inflammation, while activated monocytes infiltrate the myocardium and cause cardiovascular dysfunction. In this review, we will focus on microglia-mediated inflammation in neural networks that result in cardiovascular dysfunction. Furthermore, we will discuss neuroimmune regulation in the central–peripheral crosstalk, in which the spleen is a vital part. Hopefully, this will benefit in anchoring another therapeutic target for neuro-cardiovascular dysfunction. Severe neurological dysfunctions, including unilateral weakness, numbness, loss of vision, diplopia, ataxia, and non-upright vertigo, are the common causes of death. Even worse, an injury caused by a secondary stroke is more serious with higher risks Hankey, . ApproxiGrowing evidence suggests that stroke would not only lead to neurological dysfunction, but also cause systemic inflammatory response, immune dysregulations, and further damage to peripheral organs , and a few cardiovascular parasympathetic nerves located in the motor nucleus of the dorsal vagus nerve. Avin Veerakumar's recent dissection of cardiovascular parasympathetic control circuits in mice revealed cardiovascular innervation neurons in the brainstem. Amb is composed of two molecules that are anatomically and functionally distinct subtypes called ambiguus cardiopulmonary (ACP) and ambiguus cardiovascular (ACV). ACV will sense changes in the peripheral blood pressure and selectively activate the cholinergic cardiovascular ganglion neurons, which regulate the cardiovascular function, whereas ACP is recently found and activates the dive reflex which can also induce bronchoconstriction simultaneously  and the advanced glycation end-product receptor (RAGE) are involved in microglia polarization and hypertension , suggesting that these spleen immune cells may contribute to stroke recovery. Some studies believe that spleen-derived monocytes are consistent with the increase in monocytes in the brain after stroke and play an anti-inflammatory role in ischemic stroke (Kim et al., NK cells were used as a bridge in an animal experiment using MCAO mice that can be shown that the activation of catecholamine and HPA axis may be the reason for the spatiotemporal fluctuation of the number of NK cells in the central nervous system and peripheral system. After a stroke, the activation of catecholamine and the HPA axis can reduce the number of peripheral NK cells through the JAK-STAT signal pathway and induce the NK cells of the peripheral system to enter the brain through the blood–brain barrier (Liu et al., The spleen correlated with the inflammation closely, and hemodynamic congestion, and sympathetic stimulation would affect the size of the spleen (Maeda et al., Neuroimmune regulation has long been neglected by cardiologists. A pioneering work in David Harrison's lab (Harrison, ANS activation, brain-derived antigen, and activation of chemokines have been proven to play crucial roles in brain–spleen after stroke (Wang et al., This is a review of the mechanisms of severe neuroinflammation and cardiovascular dysfunction after stroke . DegenerJW and HH initiated this project. JD, CC, and SX performed the literature research and contributed to the original draft. DS and WP participated in the revision of the manuscript. All authors contributed to the article and approved the submitted version.


Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned.An initial stakeholders’ forum was convened to brainstorm on the process for developing the curriculum and some issues deliberated upon include the design approach, development roadmap, curriculum outline and scope, delivery, and evaluation methodologies. A dedicated team of subject matter experts (SMEs), drawn from the project and government ministries, compiled the initial draft of the curriculum and later the training materials. A series of other stakeholders’ meetings were convened to review these materials. The National Antimicrobial Stewardship Interagency Committee (NASIC) of the MOH in Kenya identified a team of experts from academia, research, and government to work with the SMEs in reviewing and providing valuable inputs to the curriculum. Additionally, principles of adult learning and a One Health approach for development were considered as AMR has drivers and impacts across sectors. A validation workshop was held to finalize the documents with a formal launch conducted during the World Antibiotics Awareness Week of 2020.A multisectoral AMR surveillance training curriculum and facilitator and trainee manuals were developed and endorsed by MOH and Ministry of Agriculture, Livestock, Fisheries and Cooperatives within one year. Over 500 healthcare workers in 19 counties were trained, with overwhelming adoption by other stakeholders in Kenya and beyond.This curriculum was developed to standardize training for AMR detection and surveillance. The central role played by the MOH ensured expeditious development and roll-out of this curriculum. The in-service curriculum, now available on an e-learning platform, provides a ready opportunity to build capacity of healthcare professionals. Additional resources are needed to standardize and scale these efforts to reach all healthcare workers. Antimicrobial resistance (AMR) is a growing global public health threat requiring concerted efforts across human, animal, and environmental health sectors . AMR occIn recognition of the growing threat of AMR, in 2015 the World Health Organization developed a Global Action Plan on AMR following a 2014 resolution on AMR at the World Health Assembly (WHA 67.25), which called on the agency to develop a draft global action plan to ensure that all countries have the capacity to combat AMR . In 2017AMR surveillance is one of the strategic objectives of the Kenya National Action Plan. Other objectives include the need to increase knowledge and awareness of AMR, antimicrobial stewardship, infection prevention and control, and research and development. The Joint External Evaluation conducted in 2017 using the International Health Regulations (2005) benchmarks revealed that Kenya had made progress in strengthening its capacity to prevent, detect, report, and respond to public health threats, but significant gaps remained under the AMR core capacity. AMR detection, surveillance and antimicrobial stewardship indicators each had a low score of two (2) out of the possible score of five (5) , 2017. AThe second strategic objective in the Kenya National Action Plan is to strengthen the awareness and the evidence base for AMR . KnowledAMR surveillance in Kenya, like in many other developing countries, is still in its nascent stages, with limited coverage . The devUSAID’s Infectious Disease Detection and Surveillance (IDDS) project is a global health security project strengthening infectious diseases detection and surveillance systems in more than 20 countries, including Kenya. In Kenya, the project works closely with NASIC within the MOH to combat AMR nationally. In this article we discuss the technical assistance provided to the Government of Kenya in the development of an in-service AMR surveillance curriculum and training materials, roll-out, and implementation.The need for an in-service AMR surveillance training curriculum was recognized by stakeholders prior to the start of concerted efforts to combat AMR in the country in 2017 . This waA stakeholders’ forum was convened by NASIC with the support of the USAID IDDS project. An expert from academia made presentations on the curriculum development process. Stakeholders brainstormed several aspects including the curriculum outline and scope, delivery, and evaluation methodologies, and agreed that the new materials would not replace pre-service curricula. Stakeholders emphasized the need to adopt a One Health approach in the development process because AMR drivers are interdisciplinary .NASIC convened all stakeholders’ meetings during the development process for review of materials with technical assistance from IDDS. A team of subject matter experts (SMEs) from IDDS, MOH, Ministry of Agriculture, Livestock, Fisheries and Cooperatives, and key academic institutions worked on curriculum outlines, content outlines, intended learner outcomes, training content, evaluations, and a Monitoring & Evaluation plan for the curriculum. These materials were built on the recommendations from the initial stakeholders’ workshop. The team developed participant and facilitator manuals. The SMEs adopted a peer-to-peer review approach where one peer reviewed materials developed by another. The materials were submitted to an in-country panel of experts identified by NASIC. After their reviews, the materials were submitted to external reviewers and editors. A validation workshop was convened for stakeholders to confirm that the curriculum and its related materials captured the national aspiration to fill knowledge and practice gaps among in-service healthcare professionals. Later in the year, the documents were officially launched by MOH and Ministry of Agriculture, Livestock, Fisheries and Cooperatives. The curriculum was designed to have objectives at two levels: for participants completing pre-analytic modules and participants completing analytical and post-analytic modules. The pre-analytic modules aim to equip participants with knowledge and skills to:i) Develop and deploy customized antimicrobial use and AMR containment and prevention interventions;ii) Apply a One Health approach in addressing AMR agenda; andiii) Coordinate, monitor, and evaluate multisectoral stewardship activities targeted at mitigating AMR.The analytic and post-analytic modules of the course were designed to equip learners with knowledge and skills to:i) Utilize advances in diagnostic techniques  and design methods to incorporate their use/application to stewardship initiatives;ii) Perform AMR surveillance monitoring, evaluation, and reporting; andiii) Use antimicrobials judiciously to minimize or eliminate the occurrence of AMR.The recommended course duration for laboratory practitioners is five days, due to the hands-on microbiology techniques module, while three days are recommended for other healthcare cadres. This modular approach can be adapted to respond to specific needs of the target audience. The curriculum mainly targets in-service healthcare workers who play various roles in AMR diagnostics and surveillance across animal and human health sectors. These include clinicians, veterinarians, veterinary paraprofessionals, laboratory personnel, pharmacists, nurses, biomedical engineers, informatics, and records officers. Preliminary modules are designed to raise awareness of AMR, and thus can be offered to leaders for AMR resource mobilization and allocation, especially at the national and county levels.Mixed delivery methods were proposed based on principles of adult learning . DeliverThe curriculum is organized into modules, each focusing on a specific area based on: (a) the need to share information on AMR, or (b) the need to transfer knowledge and skills on AMR diagnosis and surveillance. All modules have multiple choice questions to check participants’ knowledge before and after the training. Both trainer and participant course evaluation forms were developed to capture valuable feedback for improvement of the curriculum and materials. Data collected through these evaluations and other informal feedback mechanisms would be used to assess effectiveness, impact, and inform improvements to the curriculum and course content during the first review cycle (two years after the launch).A validation workshop was convened on January 8, 2020, and attended by 63 AMR stakeholders from multiple sectors; these national and sub-national stakeholders reviewed and approved the curriculum and its associated training materials for publication and implementation.After finalization of the curriculum and training materials, IDDS provided support to NASIC to organize a five-day “training of trainers” session covering the 12 curriculum modules. The training convened participants from human and animal sectors to support roll-out of the curriculum. These included 18 laboratory practitioners, 3 nurses, 3 monitoring and evaluation professionals, 2 pharmacists, 1 public health officer, 1 medical officer, and 2 veterinary officers. Scores increased from a pre-test average of 61% to a post-test average of 87%. This training also served as a pilot through which valuable inputs were provided by both trainers and participants that were helpful with improving the materials. Key feedback guided revision of content scope against time allocated. Some modules content, such as biosafety and biosecurity, were reduced to keep the focus on AMR while more time was allocated to other modules, including the clinical guide.In 2020, IDDS, in collaboration with five counties and NASIC, conducted a two-day AMR surveillance sensitization training based on the new curriculum, to create awareness among different stakeholders of AMR and ensure a robust response to the threat of AMR. The objectives of the training were to improve health workers’ awareness and understanding of AMR surveillance in the counties, build capacity on best practices to adopt and promote appropriate use of antibiotics and avert AMR, and how to conduct AMR surveillance in the counties aligned with Kenya policy guidelines on AMR surveillance.The target audience for the training were clinicians, veterinarians, veterinary paraprofessionals, laboratory personnel, pharmacists, nurses, public health officers, records officers, and health policy– and decision-making authorities.A total of nine of the 12 modules in the AMR surveillance training curriculum were delivered. These included foundational modules that built awareness of AMR, appropriate use of antimicrobial agents; infection prevention and control; drivers of AMR at the human-animal-environment interface; diagnostic stewardship; specimen collection, transport, reception, and storage; specimen referral and reporting; procurement and supply chain management; clinical guide; and prudent use of antimicrobials in veterinary practice. These sessions were facilitated by the individuals trained during the “training of trainer” sessions. Due to the heterogeneity of the participants, pre- and post-training assessments were not administered, however post training feedback was obtained using a structured checklist that evaluated how the participants would use the knowledge acquired, potential barriers to use of the acquired knowledge and overall rating of the training. There was an above-average rating of the training offered across the five counties with recommendations to increase duration of the training or tailor sessions to a particular area each time. A total of 180 healthcare professionals were reached. Distribution is shown in A hands-on training workshop for medical laboratory technologists was organized that included some of the modules in the AMR surveillance curriculum. Modules giving overview of biosafety and biosecurity measures, pre-analytical processes related to specimen collection, transportation to the laboratory, reception, and storage, laboratory diagnostic processes related to organism identification, antimicrobial susceptibility testing, and results reporting, specimen/isolate referral system, supplies quantification, procurement systems, equipment management processes and quality assurance (QA) in a microbiology laboratory were covered. A total of 15 participants were trained. Participants knowledge and attitudes on AMR and AMR detection were evaluated before and after the training. Pre- and post- training scores were 57.6 and 72.8%, respectively.The Kenya AMR surveillance curriculum was developed and finalized in a period of less than a year. This is in contrast to the usual curriculum development timelines that can span years . At the Also, in less than 2 years after finalization of the curriculum and the training materials, over 500 healthcare workers have been trained or sensitized using these materials in human sector from 19 of the 47 Kenyan counties. The curriculum materials were quickly adopted by other stakeholders in the country supporting AMR surveillance and used to build capacity in the counties they support. Key among these are partners in Fleming Fund consortium and global health projects funded by the U.S. Centers for Disease Control and Prevention in Kenya. International collaboration has raised awareness of AMR as a global health challenge and spurred actions within the counties to address the threat. Sensitization of clinicians has promoted utilization of bacteriology services, though the volume of requests still falls below targets. While many healthcare workers in the human health sector have been reached, there is need to scale capacity building of healthcare workers in the animal health sector. One-time sensitization forums may not be adequate to drive the desired behavior change in use of antimicrobials among healthcare professionals. Globally, irrational use of antimicrobials has been escalating over several decades ; thus, tThe Kenya AMR surveillance curriculum and related training materials are set to standardize capacity building initiatives and facilitate building of competencies required in healthcare professionals for the fight against AMR in Kenya. While the curriculum has been well received, additional investments are needed to reach a tangible representation of healthcare workers in both the human and animal health sectors in the country. A dedicated, multisectoral team of SMEs with government ownership and support of curriculum development experts and professional reviewers and editors can accelerate Kenya’s progress toward AMR prevention and mitigation.The original contributions presented in the study are included in the article/JN, JO, SC, DM, and MN primarily created the manuscript with review and input from the AD, AT, ET, EW, RN, RG, SG, and WM. DM handled the project administration. All authors contributed to the article and approved the submitted version.This work was made possible through the support of the United States Agency for International Development (USAID), Global Health under the terms of the Infectious Disease Detection and Surveillance contract GS00Q14OADU119. Views expressed are not necessarily those of USAID or the United States government.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The body of knowledge on the molecular mechanisms that drive lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), is continuously growing. Lung cancer research has revealed a substantial amount of information regarding the oncogenic signaling pathways that promote the pathobiology of NSCLC and SCLC. Yet, the transcriptional circuits that mediate these upstream signaling pathways and downstream functional effects are still largely unknown. Transcription factors are DNA-binding proteins located at the helm of multiple signal transduction cascades and are responsible for orchestrating gene expression programs that ultimately result in changes in cell behavior. Accumulating evidence suggests that mutated (including fused) or deregulated transcription factors are of paramount importance for the development and progression of lung cancer ,2.Transcription factors associated with NSCLC and SCLC have been shown to play a key role in proliferation, invasion, migration, tumor-associated immunity, drug resistance, trans-differentiation and many other malignant features ,6,7,8,9.Given the pivotal role of transcription factors in lung carcinogenesis and malignant progression, these proteins represent promising therapeutic targets . AlthougThe list of transcription factors related to the pathobiology of lung cancers is continuously expanding, and with the help of bioinformatics and the application of machine learning to transcription factor datasets, we can generate lung cancer gene regulatory networks of transcription factors ,15. AutoUnraveling the molecular details of these transcriptional networks will help cancer investigators and clinical oncologists to better understand the malignant behavior of lung cancer. Mapping the interactions of transcription factors with each other and their cofactors  will move the field of lung cancer research forward to decipher the complexity and heterogeneity of NSCLC and SCLC, as well as provide insights that may be translated into effective strategies for the clinical management of lung cancer patients.


Frailty is characterized by an accumulation of deficits that lead to vulnerability to adverse health outcomes. The Frailty Index (FI) quantifies frailty by measuring deficits that increase susceptibility to stressors. This study focused on a population of Mexican Americans living in vulnerable communities in the Rio Grande Valley of south Texas. We used a Frailty Index developed based on common health-related data--the Patient Health Questionnaire (PHQ-9) and a Health-related Quality of Life survey . Quality of life, resilience, and frailty are interrelated and influenced by chronic illness, mental illness, poverty, cognitive impairment, and community support.We used Logistic regression analysis, factor component analysis, receiver operating characteristic curves, and odds ratios to identify potential associations between clinical variables and candidate predictor variables and seven physiological health variables, and two survey instruments. We analyzed data obtained from participants (894) that live in two Colonias located on the Texas-Mexico border. We calculated the FI with seven physiological variables, PHQ-9 score, and the 11 domain-specific Duke Profile scores, for a total of 19 health deficits. We then dichotomized FI (>0.25) and determined ROC curves through model selection to determine best predictors of frailty.n = 622) had a higher starting frailty, and males (n = 272) had a significantly greater change rate with age. Women score higher in anxiety, depression, anxiety/depression, and pain. The frailty index and quality of life markers are strongly inversely related; poorer quality of life leads to greater frailty independent physiological health variables, the PHQ 9, sex, and age.Females (The study highlights the importance of addressing modifiable mental health and social stressors to reduce frailty. Furthermore, it suggests that factors supporting resilience and well-being, such as physical and mental health, social support, and perceived health, play a crucial role in frailty development. The findings have implications for interventions targeting vulnerable populations and emphasize the need for further research on the relationship between health-related quality of life and frailty. Frailty is associated with psychosocial and biological mechanisms, including quality of life, physical decline, and overwhelmed resilience related to stressors –4. FrailHrQoL, resilience, and frailty are intimately interconnected , 16. ChrWe are conducting this study as an extension of our previous research, which highlighted the utility of a FI incorporating standard clinic and HrQoL measures in the healthcare of Mexican Americans in South Texas. Our current investigation aims to assess the influence of HrQoL and resilience on frailty among Mexican Americans facing vulnerable and at-risk living conditions . Our priThe University of Texas Rio Grande Valley Institutional Review Board approved the protocol. All patients signed consent for care. The study adhered to the ethical guidelines of the Declaration of Helsinki. The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: Manusov .Health-related quality-of-life questionnaires and depression surveys are routinely administered as part of the care provided by the mobile medical van clinic (UniMóvil) as part of an effort to address the community’s medical, mental health, and social needs. The clinical team travels to the Colonias bi-weekly and collects information such as body mass index, blood pressure, glycated hemoglobin, lipid levels, glucose level, the PHQ9, and the Duke Health Profile. Other services include diabetes education, nutrition counseling, counseling, health literacy, and preventive care education. The data collection methods are described in detail in our earlier publication . InformaThe community comprises families of Mexican descent who have poor healthcare access, low socioeconomic reserve, and poor transportation resources. The participants represented the general population of the Colonias of Cameron and Hidalgo counties. The Area Deprivation Index (ADI), created to share measures of neighborhood disadvantage for research, program planning, and policy development, ranks the region as the most disadvantaged block groups  and is sThis report further analyzes the convenience sample of 894 patients evaluated on UniMovil between 2016 and 2018 using anonymized linked healthcare data. We calculated a Frailty Index described in an earlier publication . LogistiThe total and sex-specific prevalence for clinical outcomes and the Duke Health Profile by total and sex-specific samples are shown in Similar to the findings of other researchers , we deteAlthough we previously demonstrated that a Frailty Index that uses standard clinical and HrQoL measures is helpful in the South Texas population , what isWhereas function . Dysfunction differentially affects women, possibly due to the increased stress women living in Colonias endure , 39. PerWe know that economic distress in Mexican American neighborhoods is strongly associated with the odds of being frail . ElderlyFurther investigation into how the interaction between resilience and HrQoL affect frailty is needed. Chronic illness affects frailty, but if HrQoL has more predictive power, focusing on reducing mental health and social stressors that increase resilience may reduce frailty in vulnerable populations. The Health Belief Model may explain the importance of HrQoL in developing frailty. The model focuses on individual beliefs about health conditions , which predict individual health-related behaviors. If confidence and self-efficacy can alter behavior, these may protect against frailty through positive behaviors that support resilience, such as diet, reduction of at-risk alcohol/substance use, and sedentary lifestyle. The Resilience Activation Framework may serve as an implementation guide to mitigate adverse responses to biopsychosocial stressors .Our study includes a comprehensive Frailty Index that employs validated measurement tools widely used by clinicians. The sample is a convenience sample; the data are cross-sectional, and the picture of frailty in the Colonias may not be generalizable to other populations. Further research is necessary to determine if other deficits, including cognitive decline, cancer, disease prognosis, and chronic illness complications, change the predictive value of deficits included in a FI.This study is the first to determine the relative importance of HrQoL and subsequent resilience in the development of frailty in Mexican Americans on the U.S.-Mexican border. While FI consistently predicts frailty regardless of the number and type of variables used to calculate frailty, our findings suggest that HrQoL is more critical for predicting frailty in the Mexican American population of South Texas. Our results indicate we can decrease frailty by addressing modifiable mental health and social stressors.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: Manusov .The studies involving humans were approved by University of Texas Rio Grande Institutional Review Board. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.EM was the Principal Investigator on the United Health Foundation grant, collected data, analyzed data, wrote, and was substantially involved in editing the manuscript. VD analyzed the data, completed the statistical analysis, and was substantially involved in editing. SW-B was substantially involved in the development of the concept, manuscript development, and editing. All authors contributed to the article and approved the submitted version.


Further technological advances then led to unique insights into sperm biology at the transcriptomic, proteomic, and epigenetic level. Starting with a historical overview of sperm cell isolation techniques, we provide examples of how these contributed to create our current knowledge of sperm cell biology, and point out remaining challenges.The fusion of male and female gametes is a fundamental process in the perpetuation and diversification of species. During the last 50 years, significant efforts have been made to isolate and characterize sperm cells from flowering plants, and to identify how these cells interact with female gametes to achieve double fertilization. The first techniques and analytical approaches not only provided structural and biochemical characterizations of plant sperm cells but also paved the way for  in vitrofertilization, and omic analysis of isolated male gametes.We provide a historical overview of studies involving sperm cell isolation, their methodologies, and contributions to the structure, biochemistry,  The success of angiosperm reproduction ultimately depends on the fusion of two sperm cells with either the egg or the central cell to generate the future embryo and its nurturing endospermic tissue, respectively. Hence, it is not unexpected that plant male and female gametes have been the subject of systematic studies. Those concentrating on the role of the male gametes are more numerous since their removal from pollen grains is less complex than the separation of the female gametes from the ovule tissues.in vitro observation of isolated sperm cells almost 50 years ago, there have been numerous publications describing different strategies to isolate these cells from several plant species and with different research goals (in vitro fertilization (IVF). In various studies, especially the earliest ones, the main goal was to characterize the structure of isolated sperm cells, providing information about external/internal morphology and cytoplasmic and organellar content. However, in the early 1990s there was a shift towards biochemical aspects such as cell viability and preservation, immunostainings, and the development of antibodies against molecules of the sperm cell surface. The publication of the first IVF study in Zea mays . However, this is the situation for only 30% of flowering plants  in Z. mays, where isolated sperm cells were labelled with radioactive methionine and leucine and showed protein synthesis activity during a time course experiment  to identify gamete-enriched proteins by single-cell type proteomic analysis (The increasing popularity of mass spectrometry (MS) in proteomic analysis enabled the first detailed comparison between generative cells and sperm cells in analysis . These sCurrently, despite all analytical and methodological improvements, proteomic studies on isolated sperm cells are still scarce see . Their iIn the last 10 years, the isolation of pure sperm cells has been essential for exploring their epigenetic status, providing important insight into the patterns and organization of histone modifications, DNA methylation, and small RNA activity. Here we focus on studies involving the analysis of isolated sperm cells and refer the reader to other recent reviews concerning epigenetics studies during sporogenesis and seed development .In most animal species, epigenetic reprogramming of sperm chromatin is achieved by replacing core histones with protamines, which effectively removes all histone marks, leads to chromatin compaction, and blocks transcription . Some chS. lycopersicum  pathway (During the last 20 years of research on the biology of plant sperm cells, early bottlenecks in isolation methods, cell yield, and purity issues were finally overcome. These improvements were essential to avoid contaminations from neighbouring cells and ensure the quality of downstream omic analyses, undeniably expanding our understanding of sperm cell biology across plant species and their central role in plant reproduction.These new approaches will clarify the long-standing debate of heterospermia, its biological function across plant species, and, more importantly, its putative link to preferential fertilization. Such confirmation would have unprecedented biotechnological implications, including but not limited to, a targeted delivery of specific components to each female gamete after sperm cell fusion.Notwithstanding, omic analyses are already aiding in the detection and identification of concealed molecular factors that play important roles in gamete viability and interactions. Here, molecules involved in hybridization barriers or those that protect sperm cells from high temperatures are of special interest for applied research.4 metabolism (A very promising albeit challenging perspective is the holistic analysis at single-cell resolution currently emerging also in plant sciences . The conFurther refinements of isolation methods for plant sperm cells, in particular for crops, in combination with improvements of omics methods down to single-cell level, will eventually lead to a holistic characterization of male gametes across species. In turn, a more detailed understanding of their biology holds the promise of unlocking sperm cell engineering as a new tool for plant biotechnology.


The firUsing machine learning by identifying key risk factors of NCDs over the early lifespan, a predictive disease model and a digital twin system (DTs) will be created.The current literature for DTs applications in healthcare is relatively new compared to other fields. DTs has been reported in various area of precision medicine including management of asthma , diabeteThe use of DTs in the setting of maternal and fetal medicine may represent a perspective approach to protect maternal and fetal health and to reduce the burden of diseases. Sharing the opinions has the power to make an opportunity to debate on the topic and to explore the potential of DTs.2.To address the challenges of the NCDs, monitoring the health and growth of babies from conception to age two has been recognized as a “golden window of opportunity” for reducing neonatal morbidity and mortality and promoting individual health –4.Currently, gynecological obstetrical ultrasounds are routinely used in prenatal care to monitor the fetal growth and development, and identify potential health concerns . HoweverIn the era of DTs advanced technologies including ultrasound imaging, data analytics, and artificial intelligence (AI) are revolutionizing the monitoring and care of pregnant women and fetus. DTs have gained attention in the medical field in recent years . A DT coStudies have shown that using DTs leads to more accurate monitoring of fetal growth and development, especially in managing high-risk pregnancies . DTs alsBy combining state-of-the-art ultrasound machines, cutting-edge image processing algorithms, and sophisticated modeling techniques, highly detailed and precise virtual representations of the fetus can be generated. The DT system can incorporate data on maternal and paternal risk factors, as well as environmental factors, to assess the overall risk to the newborn. Real-time data collection and analysis through the DT system enable early detection of maternal and fetal health risks, empowering healthcare providers to intervene proactively and make informed decisions. This approach supports personalized care plans, facilitates shared decision-making with expectant parents, and enhances patient engagement. In The DT provides healthcare professionals with an immersive and dynamic platform for monitoring the well-being of both mother and baby throughout pregnancy, childbirth, and the postnatal period. DT can dynamically reflect the changes in the maternal-fetal binomial. As reported AI uses and algorithm has been reported to predict fetal lung maturity , perinatAdditionally, DTs can be utilized to gain insights through simulations , 15. By This approach enables the creation of predictive models that can anticipate the likelihood of developing diseases . The int3.Accurate predictions of both normal and pathological states in patients rely on a comprehensive understanding of how genes and the environment interact, both at an individual and population level. The emerging field of systems medicine embraces a holistic and integrative approach to patient care. By introducing digital and technological advancements during the first 1,000 days of life, we can offer an innovative perspective that improves various aspects of the diagnostic process. This approach includes constructing predictive models, obtaining indicators of biological processes and pharmacological responses to therapeutic interventions, and ultimately reducing the burden of morbidity and early mortality.


Cubital tunnel syndrome is a common disorder that affects the upper limb and involves compression of the ulnar nerve. However, this syndrome is rarely caused by multiple intraneural ganglion cysts. Of all intraneural ganglion cysts, only 9% affect the elbow. This study presents a case report of a 73-year-old female patient who manifested pain, numbness, tingling, and paralysis of the medial aspect of her left forearm, fourth, and fifth fingers of the left hand for six months. Intraoperative findings showed multiple intraneural cysts at the left elbow, which were confirmed via histopathology. The cysts were surgically excised, whereas the ulnar nerve was released into the cubital tunnel and anteriorly transposed. Complete sensory and motor recovery were achieved. Although similar cases of intraneural cysts were reported in the literature, this case has the uniqueness of the unusual number and site of intraneural cysts in the ulnar nerve on the background of osteoarthritic changes. Therefore, the aim of reporting this case is to increase awareness of the presence of these cysts when the symptoms are severe. Following carpal tunnel syndrome, cubital tunnel syndrome is the most prevalent nerve compression neuropathy in the upper limb . A knownPatients usually present with compression symptoms such as pain, numbness, and loss of normal hand movements. Advanced stages of this syndrome lead to irreversible muscle atrophy and contracture of the hand (clawing). Symptoms can be relieved by ulnar nerve decompression, which prevents progression into advanced stages of dysfunction. Furthermore, it can be treated surgically using a variety of techniques . the intA 73-year-old female patient presented to the outpatient department complaining about pain, numbness, tingling, and paralysis in the medial aspect of her left forearm, fourth and fifth digits of the left hand. She had osteoarthritis of the elbow due to an old intercondylar distal humerus fracture 16 years ago, which was managed by nonoperative treatment. The pain started six months back, and was continuous, gradually increasing, and throbbing in nature. There were neither aggravating nor relieving factors. It affected her daily life activity greatly, and the condition was refractory to conservative treatments, which were in the form of nonsteroidal anti-inflammatory drugs (NSAIDS), rest with braces, and physiotherapy.On examination, tenderness was observed in the left elbow at the medical aspect, the range of motion was 10-degree fixed flexion to 140-degree flexion, Tinel’s and Froment’s signs were positive. There were decreased sensations of the fourth and fifth fingers and a weak distal interphalangeal joint flexion of the fourth and fifth digits, however, no muscle atrophy of the first dorsal interosseous muscle. The compression of the ulnar nerve was later confirmed by a nerve conduction study. Computed tomography (CT) studies showed marginal, medial, and anterior osteophytes involving the humeroulnar joint with moderate to severe osteoarthritic changes. However, there was no obvious direct compression by the osteophyte at the cubital tunnel.After explaining the procedure to the patient and obtaining consent, open surgery for release of the ulnar nerve was carried out. After incising 12 cm along the cubital tunnel, multiple intraneural cysts were observed in the ulnar nerve. Furthermore, no osteophyte compressing the nerve could be found at the tunnel  or ultrasonography (US). Cubital tunnel syndrome is a common pathology, therefore, using such methods of diagnosis is neither routinely done nor cost-effective when the etiology is clear. However, the necessity for such methods could be justified when the etiology is vague. Thus, a diagnosis of multiple intraneural cysts was made by US along the ulnar nerve near the elbow in the case presented by Suparno et al. . In thisThe excision of the articular branch and decompression of the swollen nerves is usually the treatment method of these intraneural ganglionic cysts ,11. The In a review of the literature, Desy et al. discovered a higher risk of recurrence following initial surgery . Hence, Table In this case, multiple intraneural cysts were found upon exploration of the ulnar nerve, and there exist different treatment options. Decompression of the ulnar nerve is most commonly treated with medial epicondylectomy, simple decompression, or anterior transposition  . HoweverThe etiology of cubital tunnel syndrome as multiple intraneural cysts compressing the ulnar nerve is rare. However, patients presenting with severe symptoms of ulnar compression and a history of osteoarthritis should raise the clinical suspicion of the presence of such an etiology. Finally, complete recovery could be achieved by anterior transposition and release of the ulnar nerve.


CFTR RNA, directly and indirectly CFTR-targeting drugs, non-viral and viral gene transfer, and other treatments. Our results support the nPD representing a reliable method for testing treatment effects in both animal models and human patients, as well as for diagnosing CF. However, we also observed the need for improved reporting to ensure reproducibility of the experiments and quantitative comparability of the results within and between species . Currently, data gaps warrant further primary studies.To address unmet treatment needs in cystic fibrosis (CF), preclinical and clinical studies are warranted. Because it directly reflects the function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), the nasal potential difference test (nPD) can not only be used as a reliable diagnostic test for CF but also to assess efficacy of experimental treatments. We performed a full comprehensive systematic review of the effect of CF treatments on the nPD compared to control conditions tested in separate groups of animal and human subjects. Our review followed a preregistered protocol. We included 34 references: 20 describing mouse studies, 12 describing human studies, and 2 describing both. We provide a comprehensive list of these studies, which assessed the effects of antibiotics, bone marrow transplant, CFTR protein,  CFTR gene resulting in functional defects in the CFTR channel) )As described in the introduction, we defined an SR as a “review comprising a full search resulting in a complete literature overview, inclusion of papers following strict criteria, tabulation of extracted data, risk of bias assessment of included studies, and meaningful  synthesis of the data.” This definition is more stringent than some others , but weWhereas the nPD remains a reliable test for diagnosing CF and for testing treatment effects in animal models and human patients, there is a huge need to improve the reporting of the results to ensure reproducibility of the experiments within and between species. Particularly because the technique of measuring the nPD is complicated, and because different laboratories use different protocols, it is crucial for primary studies to report the actual outcome data together with the associated variance, numbers of subjects, and all study design parameters. This SR shows that missing data from several of the included studies made the planned analyses impossible, limiting the value of our efforts.


Theuse of a combination of clinical and electroneuromyography data often makes it possibleto identify a specific neurological disorder. In the upper extremities, some of the mostcommon neurological disorders are carpal tunnel syndrome, cubital tunnel syndrome, andcervical radiculopathy. Although in many cases magnetic resonance imaging (MRI)continues to be the gold standard for nerve imaging, especially for the identificationof deep nerves, ultrasound has become an essential imaging technique because of itsability to offer dynamic information, its more widespread availability, and its lowercost (in comparison with MRI),as published in the previous issue of Radiologia Brasileira, that high-resolutionultrasound provides information complementary to that obtained by electroneuromyography,especially on the morphology of nerve fascicles and the vascularization of peripheralnerves. Those authors also stated that, as well as being noninvasive and rapidlyexecuted, high-resolution ultrasound can be used in order to assess neural dimensions,locate compression zones within fibrous tunnels, identify tumors, and diagnose traumaticpathologies. Given the lackof data on this topic in the literature, it is important that the authors demonstratedthat the peripheral nerve cross-sectional areas were lower in a sample of the Brazilianpopulation than in most of the other samples described in the literature. On the basisof their findings, Voltan et al.proposed cross-sectional area reference values for the Brazilian population: for themedian nerve ; for the ulnar nerve ; and for the common fibular nerve (near the fibular head). Those reference valueswill certainly help radiologists in daily practice.I totally agree with Voltan et al.. In addition, high-resolution isotropic volumetric 3D MRN enablesmultiplanar depiction of peripheral nerves, as well as allowing anatomical andfunctional characterization of various neural diseases. In summary, imaging techniques ranging from ultrasoundto high-resolution isotropic 3D volumetric MRN are essential to evaluate conditions anddiseases affecting the peripheral nerves, including entrapments, trauma, inflammatory orinfectious neuropathies, and neoplasms.Although ultrasound and MRI are currently the gold standards for peripheral nerveanalyses, I would like to highlight the importance that magnetic resonance neurography(MRN) has taken on in recent years. It is a technique that improves selectivemultiplanar visualization of the peripheral nerves and of nerve pathologies by combiningtwo-dimensional, three-dimensional (3D), and diffusion imaging pulse sequences. Imagesacquired with MRN provide a highly accurate depiction of the relationships betweenlesions and the nerve architecture, and the technique makes it possible to visualizeneuromuscular alterations directly, thus facilitating an objective evaluation of theconsequences of neuromuscular pathology


Accumulating evidence indicates that a variety of distal and proximal factors might impact a risk of suicide. However, the association between both groups of factors remains unknown. Therefore, in the present study, we aimed to investigate the interplay between distal and proximal correlates of the current suicidal ideation.A total of 3,000 individuals , who had reported a negative history of psychiatric treatment, were enrolled through an online computer-assisted web interview. Self-reports were administered to measure: (a) distal factors: a history of childhood trauma (CT), reading disabilities (RDs), symptoms of attention-deficit/hyperactivity disorder (ADHD), lifetime history of non-suicidal self-injury (NSSI), lifetime problematic substance use as well as family history of schizophrenia and mood disorders; (b) proximal factors: depressive symptoms, psychotic-like experiences (PLEs), and insomnia; and (c) sociodemographic characteristics.Suicidal ideation was directly associated with unemployment, being single, higher level of RD, lifetime history of NSSI as well as higher severity of PLEs, depression, and insomnia. The association of distal factors with suicidal ideation was fully (a history of CT and symptoms of ADHD) or partially (a history of NSSI and RD) mediated by proximal factors .Main findings from this study posit the role of distal factors related to neurodevelopmental disorders, CT and NSSI in shaping suicide risk. Their effects might be partially or fully mediated by depression, PLEs, and insomnia. Suicide is increasingly being perceived as a complex phenomenon that appears to be the consequence of interactions between multiple psychological, biological, and social factors. It has been shown that people tend to underreport suicidal ideation , and mosTo date, a number of theoretical models of suicide have been proposed . These There are certain suicide risk models, for example, the narrative crisis model  and the There are studies showing that assessment of distal and proximal risk factors might serve as a valid empirical model of progression from chronic to near-term suicidal risk. These studies clearly indicate that pre-existing neurodevelopmental vulnerabilities, including, for example, CT history, trait impulsivity, and perfectionism might interact with proximal factors, for example, suicidal narratives, fear of humiliation, recent life stressors in shaping near-term suicidal risk , 37. HowThe snowball sampling method was used to recruit participants. All questionnaires were administered through the computer-assisted web interview. The survey was posted in social media and survey websites between April and October, 2022. Participants were informed about confidentiality and anonymous character of the survey. All of them represented inhabitants of three large Polish cities, including Szczecin, Warsaw, and Wroclaw. They were included in case of meeting two inclusion criteria, that is, age between 18 and 35 years and a negative lifetime history of psychiatric treatment. The results of the present study are part of a bigger project addressing epigenetic mechanisms of psychosis proneness. The protocol of the study was approved by the Ethics Committees at the Institute of Psychology , Wroclaw Medical University , and Pomeranian Medical University .Supplementary Material.A history of four categories of CT (under the age of 17 years), including emotional abuse and neglect, physical abuse as well as sexual abuse was recorded. To obtain information about emotional neglect and abuse, as well as bullying we used three items of the Traumatic Experience Checklist (TEC) . AdditioThe Adult Reading Questionnaire (ARQ) was used to assess the severity of RD . The ARQThe Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptoms. It is a self-report questionnaire with nine items measuring inattention and nine items measuring impulsivity/hyperactivity over the period of the preceding 6 months . Each itSupplementary Material): (a) the Revised Hallucination Scale [For the purpose of this study, we developed a 16-item questionnaire that records the presence of PLEs during the preceding month. Participants were asked to assess the presence of specific PLEs that cannot be attributed to substance use on a four-point scale . Specific items were obtained from the following questionnaires  was administered to measure the level of depressive symptoms . It inclThe level of insomnia was assessed using four items from the Insomnia Severity Index (ISI) . The ISIThere were no missing data in the present analysis. Before performing data analysis, variables potentially associated with a risk of suicidal ideation were divided into the following groups: (a) sociodemographic characteristics ; (b) distal factors ; and (c) proximal factors . Symptoms of ADHD and RD were included as distal factors as they represent disorders with the onset in the early neurodevelopmental period.2  or the Mann–Whitney U test (continuous variables). Next, binary logistic regression analyses were performed in a step-by-step procedure. The current suicidal ideation was included as a dependent variable. First, we tested the effects of proximal factors, distal factors, and sociodemographic characteristics as independent variables separately. Then, we combined these sets of variables in two blocks, that is, distal and proximal factors with and without sociodemographic characteristics. The Hosmer–Lemeshow test was implemented to assess the goodness of fit for logistic regression models. In this part, the results of data analysis were considered statistically significant in case of a p-value lower than 0.05. Finally, we analyzed the mediating effect of proximal factors in the association between distal factors and suicidal ideation using the PROCESS Macro (model 4) [A series of bivariate comparisons of individuals with and without the current suicidal ideation were performed using the χmodel 4) . MediatiA total of 3,000 young adults were enrolled . General characteristics of the sample are shown in The results of the binary logistic regression analyses are presented in The results of mediation analyses are shown in In the present study, we found that both sociodemographic factors , as well as clinical characteristics , play a role in the development of suicidal ideation. However, further analysis showed that the effects of CT history and ADHD symptoms on the risk of suicidal ideation are fully mediated by the effects of proximal factors, including PLEs, depression, and insomnia. In turn, other distal factors, including RD and NSSI may directly and indirectly  increase the risk of suicidal ideation. To the best of our knowledge, this is, the first investigating potential mechanisms by which symptoms of ADHD and RD together with other distal factors interact with proximal factors represented by depressive symptoms, PLEs, and insomnia to shape the current suicidal ideation. Previous studies have investigated only some of variables that we have combined in our model providing grounds for more comprehensive analysis of the interplay and significance of proximal and distal factors.Childhood traumatic events, especially a history of sexual or physical abuse, have been shown to cause at least a threefold increase in lifetime suicide attempts and lifetime suicidal ideation –56. SomeIn our study, we found that CT history is associated with the risk of suicidal thoughts through the mediating effect of the severity of PLEs, depression, and insomnia. This is in agreement with previous studies, showing that PLEs increase the risk of suicide –70. MoreOur results on the significance of the association between ADHD symptoms and the risk of suicidal ideation are in line with a recent systematic review and meta-analysis . MoreoveIn our study, we found that RD are directly and indirectly associated with the risk of suicidal ideation. Dyslexia is a developmental disability characterized by difficulties in reading comprehension and writing without overall sensory or intelligence deficits . AccumulAnother observation from our study is that the lifetime history of NSSI is directly and indirectly associated with the risk of suicidal ideation. Importantly, logistic regression analysis revealed that lifetime history of NSSI was associated with about twofold higher risk of suicidal ideation, and this magnitude of the effect was the highest among all potential correlates analyzed in the present study. By definition, NSSI describes deliberate behaviors that inflict pain and/or cause damage to the body without suicidal intent . It has The results of our study should be interpreted bearing in mind several limitations. First, internet-based surveys can be characterized by a variety of limitations related to insufficient accuracy of self-reports, difficulties in tracking non-response rates and a selection bias , 111. SeIn sum, the findings of this study demonstrate that the risk of suicide ideation is associated with the interplay of distal  and proximal factors . Longitudinal studies in clinical samples are needed to confirm our findings before their translation into clinical practice. Nevertheless, implications from the present study suggest that patients with neurodevelopmental disorders should be carefully assessed for their suicidal risk, and the current psychiatric symptoms should be treated accordingly in order to decrease the risk of suicidal behaviors.