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Reprogramming energy metabolism is pivotal to tumor development. Ketone bodies (KBs), which are generated during lipid metabolism, are fundamental bioactive molecules that can be modulated to satisfy the escalating metabolic needs of cancer cells. At present, a burgeoning body of research is concentrating on the metabolism of KBs within tumors, investigating their roles as signaling mediators, drivers of post-translational modifications, and regulators of inflammation and oxidative stress. The ketogenic diet (KD) may enhance the sensitivity of various cancers to standard therapies, such as chemotherapy and radiotherapy, by exploiting the reprogrammed metabolism of cancer cells and shifting the metabolic state from glucose reliance to KB utilization, rendering it a promising candidate for adjunct cancer therapy. Nonetheless, numerous questions remain regarding the expression of key metabolic genes across different tumors, the regulation of their activities, and the impact of individual KBs on various tumor types. Further investigation is imperative to resolve the conflicting data concerning KB synthesis and functionality within tumors. This review aims to encapsulate the intricate roles of KBs in cancer metabolism, elucidating a comprehensive grasp of their mechanisms and highlighting emerging clinical applications, thereby setting the stage for future investigations into their therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: Methylmalonic acidemia (MMA), type mut (0) is a rare type of genetic inborn error of metabolism (IEM) that is caused by aberrant malonyl-CoA mutase activity. Diagnosing IEM can be challenging due to its inherited onset and varying degrees of severity. Methods and results: In the present study, a consanguineous Pakistani family suspected of IEM was genetically analyzed using whole exome sequencing. A biallelic variant c.689 C > G (p.Thr230Arg) in MMUT was identified to be the causative factor of the disease, which helped in establishing the accurate diagnosis in the family to be MMA mut(0) type. On the basis of the genetic findings, the patient's condition was appropriately managed through a supportive nutrition plan and administration of oral L-carnitine. Conclusions: Identification of MMUT mutation through whole exome sequencing was helpful in solving the family and devising targeted management strategies. This study highlights the utility of genetic analysis in diagnosing and treating metabolic disorders like MMA in Pakistani inbred population. Highlights: In the present study, a consanguineous Pakistani family suspected of IEM was genetically analyzed using whole exome sequencing. A biallelic variant c.689 C > G (p.Thr230Arg) in MMUT was identified to be the causative factor of the disease, which helped in establishing the accurate diagnosis in the family to be MMA mut(0) type. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common and severe clinical disorder in which endoplasmic reticulum (ER) stress plays an important regulatory role. In this review, we summarize the research progress on the relationship between ER stress and AKI. It emphasizes the importance of maintaining a balance between promoting and protecting ER stress during AKI and highlights the potential of ER stress-targeted drugs as a new therapeutic approach for AKI. The article also discusses the need for developing drugs that target ER stress effectively while avoiding adverse effects on normal cells and tissues. The review concludes that with a more comprehensive understanding of ER stress mechanisms and advancements in research techniques, more effective treatment options for AKI can be developed in the future. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a global health concern and the leading cause of dementia in the elderly. The prevalence of this neurodegenerative condition is projected to increase concomitantly with increased life expectancy, resulting in a significant economic burden. With very few FDA-approved disease-modifying drugs available for AD, there is an urgent need to develop new compounds capable of impeding the progression of the disease. Given the unclear etiopathogenesis of AD, this review emphasizes the underlying mechanisms of this condition. It explores not only well-studied aspects, such as the accumulation of Aβ plaques and neurofibrillary tangles, but also novel areas, including glymphatic and lymphatic pathways, microbiota and the gut–brain axis, serotoninergic and autophagy alterations, vascular dysfunction, the metal hypothesis, the olfactory pathway, and oral health. Furthermore, the potential molecular targets arising from all these mechanisms have been reviewed, along with novel promising approaches such as nanoparticle-based therapy, neural stem cell transplantation, vaccines, and CRISPR-Cas9-mediated genome editing techniques. Taking into account the overlap of these various mechanisms, individual and combination therapies emerge as the future direction in the AD strategy. [ABSTRACT FROM AUTHOR]

Background: Health professionals develop their own approach to patient care based on education, experience and philosophical stance. Literature suggests that this practice approach informs patient care, and clinical outcomes. The Osteopaths' Therapeutic Approaches Questionnaire (Osteo-TAQ) is a novel 36-item instrument developed from qualitative grounded theory research with osteopaths in the United Kingdom. The aim of the study was to develop evidence for the structural and construct validity of the Osteo-TAQ in the Australian osteopathic profession and provide initial descriptive data about the therapeutic approaches of osteopaths in Australia. Methods: A cross-sectional study design was used to collect data from registered osteopaths in Australia using the Osteo-TAQ and analysed with Exploratory Factor Analysis (EFA). The EFA utilised parallel analysis to determine the number of factors to extract and McDonald's omega calculated as the reliability estimation statistic. Results: 691 Australian osteopaths provided data for the study, representing 25% of the Australian osteopathic profession. Empirically the number of factors to extract based on the parallel analysis was seven. Two- and three-factor solutions were evaluated given the underpinning theory identifying two conceptions of practice and three interrelated therapeutic approaches. Both the two- and three-factor solutions were consistent with the underpinning theory with acceptable reliability estimations for each factor. Descriptive data suggested the most common element of the therapeutic approach of Australian osteopaths was establishing rapport, while the least common was 'only talking' with their patients. Conclusions: This study provides evidence for the structural, content and construct validity of the Osteo-TAQ in an Australian osteopathic practitioner population. The results support both a two- and three-factor structure for the Osteo-TAQ in an Australian osteopathic population, with each factor demonstrating acceptable reliability estimations supporting the items comprising each factor as measuring a single construct. From a theoretical and empirical perspective, it can be inferred that the Osteo-TAQ tool encapsulates an osteopaths' conception of practice (professional artistry and technical rational) and three main therapeutic approaches to patient care: Educator, Communicator and Treater. Further research is required to explore each of these therapeutic approaches to better understand how they relate to an individual osteopath's conception of practice, and their associations with other measures of practice including clinical outcomes. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterial and MethodsResultsConclusion\nIMPLICATIONS FOR REHABILITATIONPhantom limb pain (PLP) is a condition that greatly diminishes quality of life. Phantom motor execution (PME), enabled by myoelectric pattern recognition combined with virtual and augmented reality, is a novel treatment for PLP. Here we, aimed to describe patients’ experiences of this treatment.Qualitative, using semi-structured interviews one month after completed PME treatment. Twenty-one Swedish and Dutch patients (mean age 57, 16 males, 16 lower limb amputations) participated. The analysis followed the framework approach.The main themes were 1) treatment effects on the perception of the phantom limb, 2) living with PLP before and after treatment, and 3) facilitators and barriers to treatment. Most participants learned to control their phantom limb, perceived it more positively and as more complete. This control over the phantom limb became a tool for managing PLP. Most participants’ outlook on life and energy levels improved after treatment. Being mentally focused during treatment was important. Therapists were pivotal to the success of the treatment.Controlling the phantom limb improved their perception of it and pain management, self-agency, and quality of life. The therapists’ role was invaluable. We suggest training for patients in phantom limb control before and after amputation.Phantom limb pain is a common and chronic problem after amputation. When informing patients about the phantom limb phenomenon it is important to use positive wording and to acknowledge its existence as normal.Controlling the phantom limb is a key for the success of the phantom motor execution (PME) treatment and should therefore receive clinicians’ attention from the early stages after surgery and onwards.The role of the therapist is invaluable in teaching, supporting and coaching patients receiving PME treatment.In order to facilitate successful outcome of the PME treatment it is important to consider and reduce potential barriers to patient adherence to the treatment.Phantom limb pain is a common and chronic problem after amputation. When informing patients about the phantom limb phenomenon it is important to use positive wording and to acknowledge its existence as normal.Controlling the phantom limb is a key for the success of the phantom motor execution (PME) treatment and should therefore receive clinicians’ attention from the early stages after surgery and onwards.The role of the therapist is invaluable in teaching, supporting and coaching patients receiving PME treatment.In order to facilitate successful outcome of the PME treatment it is important to consider and reduce potential barriers to patient adherence to the treatment. [ABSTRACT FROM AUTHOR]

Purpose: Study the efficacy of olfactory training in smell recovery. Methods: An extensive search was performed through different databases in order to find articles analyzing the efficacy of olfactory training as a treatment for olfactory dysfunction. Methodological quality of primary studies within the final sample was assessed following PRISMA guidelines. Standardized mean differences in pre–post olfactory training groups, and also in experimental-control and pre-follow up if possible, were computed by Hedges' g effect size statistic. Each effect size was weighted by its inverse variance. Results: Final sample was composed of 36 articles (45 pre–post effect sizes). Contrasts were performed separately for odor identification, odor discrimination, odor threshold and general olfactory function. Moderate to large and heterogeneous effect was obtained for olfactory function (g = 0.755, k = 45, SE = 0.093, CI 95% = [0.572, 0.937]), different moderators had a significant effects, such as, training duration, age and anosmia diagnosis. Conclusion: Olfactory training was found to have a positive and significant effect on rehabilitating the olfactory function. [ABSTRACT FROM AUTHOR]

Pancreatic cancer continues to be a deadly disease because of its delayed diagnosis and aggressive tumor biology. Oncogenes and risk factors are being reported to influence the signaling pathways involved in pancreatic embryogenesis leading to pancreatic cancer genesis. Although studies using rodent models have yielded insightful information, the scarcity of human pancreatic tissue has made it difficult to comprehend how the human pancreas develops. Transcription factors like IPF1/PDX1, HLXB9, PBX1, MEIS, Islet-1, and signaling pathways, including Hedgehog, TGF-β, and Notch, are directing pancreatic organogenesis. Any derangements in the above pathways may lead to pancreatic cancer. TP53: and CDKN2A are tumor suppressor genes, and the mutations in TP53 and somatic loss of CDKN2A are the drivers of pancreatic cancer. This review clarifies the complex signaling mechanism involved in pancreatic cancer, the same signaling pathways in pancreas development, the current therapeutic approach targeting signaling molecules, and the mechanism of action of risk factors in promoting pancreatic cancer. [ABSTRACT FROM AUTHOR]

Abstract The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family.

Abstract Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues. Graphical Abstract

Morphine is an important pain reliever employed in pain management, its extended utilize is hindered by the onset of analgesic tolerance and oxidative stress. Long-term morphine administration causes elevated production of reactive oxygen species (ROS), disrupting mitochondrial function and inducing oxidation. Sirtuin 3 (SIRT3), a mitochondrial protein, is essential in modulating ROS levels by regulating mitochondrial antioxidant enzymes as manganese superoxide dismutase (MnSOD). Our investigation focused on the impact of SIRT3 on hyperalgesia and morphine tolerance in mice, as evaluating the antioxidant effect of the polyphenolic fraction of bergamot (BPF). Mice were administered morphine twice daily for four consecutive days (20 mg/kg). On the fifth day, mice received an acute dose of morphine (3 mg/kg), either alone or in conjunction with BPF or Mn (III)tetrakis (4-benzoic acid) porphyrin (MnTBAP). We evaluated levels of malondialdehyde (MDA), nitration, and the activity of SIRT3, MnSOD, glutamine synthetase (GS), and glutamate 1 transporter (GLT1) in the spinal cord. Our findings demonstrate that administering repeated doses of morphine led to the development of antinociceptive tolerance in mice, accompanied by increased superoxide production, nitration, and inactivation of mitochondrial SIRT3, MnSOD, GS, and GLT1. The combined administration of morphine with either BPF or MnTBAP prevented these effects. [ABSTRACT FROM AUTHOR]

The Phosphatidylinositol-3-kinase (PI3K) family is well-known to comprise three classes of intracellular enzymes. Class I PI3Ks primarily function in signaling by responding to cell surface receptor stimulation, while class II and III are more involved in membrane transport. Under normal physiological conditions, the PI3K signaling network orchestrates cell growth, division, migration and survival. Aberrant activation of the PI3K signaling pathway disrupts cellular activity and metabolism, often marking the onset of cancer. Currently, the Food and Drug Administration (FDA) has approved the clinical use of five class I PI3K inhibitors. These small-molecule inhibitors, which exhibit varying selectivity for different class I PI3K family members, are primarily used in the treatment of breast cancer and hematologic malignancies. Therefore, the development of novel class I PI3K inhibitors has been a prominent research focus in the field of oncology, aiming to enhance potential therapeutic selectivity and effectiveness. In this review, we summarize the specific structures of PI3Ks and their functional roles in cancer progression. Additionally, we critically evaluate small molecule inhibitors that target class I PI3K, with a particular focus on their clinical applications in cancer treatment. Moreover, we aim to analyze therapeutic approaches for different types of cancers marked by aberrant PI3K activation and to identify potential molecular targets amenable to intervention with small-molecule inhibitors. Ultimately, we propose future directions for the development of therapeutic strategies that optimize cancer treatment outcomes by modulating the PI3K family. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues. [ABSTRACT FROM AUTHOR]

The therapeutic approach in nursing is a holistic framework that integrates empathy, trust, and effective communication to promote comprehensive care. Nurses play a pivotal role in fostering relationships that address not only the physical but also the emotional and psychological needs of patients. This approach enhances the quality of care, ensuring that patients feel valued and supported throughout their healthcare journey. By emphasizing patient education, individualized care, and collaborative decision-making, nurses contribute to improved patient outcomes and overall wellbeing. Furthermore, the integration of evidence-based practices ensures that nursing interventions are grounded in the latest research, optimizing treatment efficacy and patient safety. This review examines the role of the therapeutic approach in nursing care, focusing on the importance of effective communication, holistic care, and continual professional development (CPD) in achieving better health outcomes and patient satisfaction. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to highlight the feasibility of an olfactory training program entirely monitored through online media in COVID-19 patients. Methods: Classic olfactory training was performed with a sample with olfactory loss due COVID-19 (n = 11). Participants were engaged on a weekly video call in order to improve adherence and collect information regarding the number of correct answers and the individuals' perception of olfactory function. The olfactory status after training was compared to two groups, one composed of participants who contracted COVID-19 but did not report olfactory loss (n = 11) and a sample composed of healthy participants (n = 11). Results: The experimental group showed improvements throughout the training period (TDI score on week 0 was 20.3 (5.6) and 24.6 (4.3) for week 12, and on week 24 was 25.4 (6.2) (F = 5.115, df = 2, 20, p = 0.016), and post hoc tests showed that participants significantly improved their TDI score in W12 compared to W0 (SMD = 0.869, p = 0.041) and in W24 compared to W0 (SMD = 0.859, p = 0.041). The experimental group showed lower scores when compared with both groups, and the no OT COVID-19 group showed lower scores than the healthy control group, even though they did not report olfactory alterations. Conclusions: Findings suggest that the strategies applied to improve adherence were successful since 100% of the sample completed the training adherence, offering a valuable framework for future olfactory training studies. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate the usefulness and relevance of projective techniques such as house‐tree‐person (HTP) and family in individuals with Prader‐Willi syndrome (PWS), who have a limited ability to identify and verbalize emotions and express them often using behaviors. Methods: We included individuals with genetic confirmation of PWS immersed in a regular transdisciplinary treatment in an institution dedicated to rare diseases. All individuals were evaluated using the HTP and family projective techniques. These instruments are commonly administered to the general population and, in this case, to people with mild to moderate intellectual disabilities, including difficulties in their communication abilities. Results: A total of 25 individuals with PWS between 10 and 41 years old (15 men and 10 women) were included. We identified the presence of graphic indicators corresponding to the behavioral phenotype of individuals with PWS, such as anxiety, stubbornness, emotional lability, difficulty in achieving adequate externalization and identification of emotions, impulsivity, aggressive traits, poor social skills, need for support and interaction, low self‐concept, and compulsive behaviors. Conclusions: In the present study, we demonstrated the usefulness of graphic techniques to elucidate aspects of behavior, emotions, and thoughts that individuals with PWS cannot formulate due to expression and communication difficulties. [ABSTRACT FROM AUTHOR]

• Tenascin-C is highly expressed in cancer generating immune suppressive niches. • Tenascin-C is used as tumor biomarker and as zip code for delivery of therapeutic agents. • Tenascin-C is targeted by a huge arsenal of versatile molecular tools. • Numerous clinical trials are supporting tenascin-C targeting as clinical option. • Targeting tenascin-C immune suppression offer novel targeting opportunities. Tenascin-C (TNC) is a matricellular and multimodular glycoprotein highly expressed under pathological conditions, especially in cancer and chronic inflammatory diseases. Since a long time TNC is considered as a promising target for diagnostic and therapeutic approaches in anti-cancer treatments and was already extensively targeted in clinical trials on cancer patients. This review provides an overview of the current most advanced strategies used for TNC detection and anti-TNC theranostic approaches including some advanced clinical strategies. We also discuss novel treatment protocols, where targeting immune modulating functions of TNC could be center stage. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs) normally resulting in organ failure and death. Cardiac fibroblasts (CFs) play an essential role in deleterious cardiac remodeling and dysfunction. In response to injury, quiescent CFs become activated and adopt a collagen-secreting phenotype highly contributing to cardiac fibrosis. In recent years, studies have been focused on the exploration of molecular and cellular mechanisms implicated in the activation process of CFs, which allow the development of novel therapeutic approaches for the treatment of cardiac fibrosis. Transcriptomic analyses using single-cell RNA sequencing (RNA-seq) have helped to elucidate the high cellular diversity and complex intercellular communication networks that CFs establish in the mammalian heart. Furthermore, a significant body of work supports the critical role of epigenetic regulation on the expression of genes involved in the pathogenesis of cardiac fibrosis. The study of epigenetic mechanisms, including DNA methylation, histone modification, and chromatin remodeling, has provided more insights into CF activation and fibrotic processes. Targeting epigenetic regulators, especially DNA methyltransferases (DNMT), histone acetylases (HAT), or histone deacetylases (HDAC), has emerged as a promising approach for the development of novel anti-fibrotic therapies. This review focuses on recent transcriptomic advances regarding CF diversity and molecular and epigenetic mechanisms that modulate the activation process of CFs and their possible clinical applications for the treatment of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

• Computer simulations and the Lipinski rule evaluate the pharmacokinetic and toxicological aspects of methyl eugenol as a drug candidate. • Treatment with methyl eugenol (ME) during and after the initiation of acute respiratory distress syndrome (ARDS) can prevent the progression of acute inflammation. • In vivo and in silico tests indicate that ME oil is an orally bioavailable drug that exerts multifunctional cytoprotective activities. • ME oil can treat and prevent intestinal I/R-induced ARDS in rats. Acute respiratory distress syndrome (ARDS) is an inflammatory disease that affects the lungs with rupture of the alveolar-capillary barrier and loss of lung compliance, orchestrated by an intense inflammatory process mediated by neutrophils that culminates in diffuse alveolar data and tissue hypoxia. In this context, no specific drug has yet been applied to treat the syndrome. Therefore, finding new therapeutic targets that can treat the syndrome has become a research study. In view of this, methyl-eugenol (ME) has become the target of this study. The aim of this work was to carry out an in silico pharmacological and toxicological analysis with ADMET, as well as to determine, by means of molecular docking, the interaction affinity of the 5-LOX and COX-2 enzymes with ME and then the in vivo tests; in which male rats were distributed into five groups with five rats each, in which some groups were subjected to the process of ischemia and reperfusion (I/R). Groups G4 and G5 were treated by inhalation with ME (10 %). After completing these procedures, statistical analysis and lung histology were carried out. In the ADMET prediction, ME showed high intestinal absorption and a medium-permeability blood-brain barrier. ME had no violations of Lipinski's rule, demonstrating high potential as a drug candidate. Molecular docking showed that ME had the highest binding affinity with the 5-LOX enzyme. Finally, the statistical and histological analyses of the in vivo test showed acute and accentuated lung damage in the G1 group, while in the G4 and G5 groups, ME showed pharmacological efficacy, reducing the number of inflammatory cells, free macrophages and free radicals. The results indicate that ME oil is a favorable therapeutic approach in the treatment of ARDS. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive decline in cognitive ability and behavior which eventually disrupts daily activities. AD has no cure and the progression rate varies unlikely. Among various causative factors, heavy metals are reported to be a significant hazard in AD pathogenesis. Metal‐induced neurodegeneration has been focused globally with thorough research to unravel the mechanistic insights in AD. Recently, heavy metals suggested to play an important role in epigenetic alterations which might provide evidential results on AD pathology. Epigenetic modifications are known to play towards novel therapeutic approaches in treating AD. Though many studies focus on epigenetics and heavy metal implications in AD, there is a lack of research on heavy metal influence on epigenetic toxicity in neurological disorders. The current review aims to elucidate the plausible role of cadmium (Cd), iron (Fe), arsenic (As), copper (Cu), and lithium (Li) metals on epigenetic factors and the increase in amyloid beta and tau phosphorylation in AD. Also, the review discusses the common methods of heavy metal detection to implicate in AD pathogenesis. Hence, from this review, we can extend the need for future research on identifying the mechanistic behavior of heavy metals on epigenetic toxicity and to develop diagnostic and therapeutic markers in AD. [ABSTRACT FROM AUTHOR]

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.

Reprogramming energy metabolism is pivotal to tumor development. Ketone bodies (KBs), which are generated during lipid metabolism, are fundamental bioactive molecules that can be modulated to satisfy the escalating metabolic needs of cancer cells. At present, a burgeoning body of research is concentrating on the metabolism of KBs within tumors, investigating their roles as signaling mediators, drivers of post-translational modifications, and regulators of inflammation and oxidative stress. The ketogenic diet (KD) may enhance the sensitivity of various cancers to standard therapies, such as chemotherapy and radiotherapy, by exploiting the reprogrammed metabolism of cancer cells and shifting the metabolic state from glucose reliance to KB utilization, rendering it a promising candidate for adjunct cancer therapy. Nonetheless, numerous questions remain regarding the expression of key metabolic genes across different tumors, the regulation of their activities, and the impact of individual KBs on various tumor types. Further investigation is imperative to resolve the conflicting data concerning KB synthesis and functionality within tumors. This review aims to encapsulate the intricate roles of KBs in cancer metabolism, elucidating a comprehensive grasp of their mechanisms and highlighting emerging clinical applications, thereby setting the stage for future investigations into their therapeutic potential.

Breast cancer, the most prevalentmalignant tumor among women globally, is significantly influenced by the Wnt/β-catenin signaling pathway, which plays a crucial role in its initiation and progression. While conventional chemotherapy, the standard clinical treatment, suffers from significant drawbacks like severe side effects, high toxicity, and limited prognostic efficacy, Traditional Chinese Medicine (TCM) provides a promising alternative. TCM employs a multi-targeted therapeutic approach, which results in fewer side effects and offers a high potential for effective treatment. This paper presents a detailed analysis of the therapeutic impacts of TCM on various subtypes of breast cancer, focusing on its interaction with the Wnt/β-catenin signaling pathway. Additionally, it explores the effectiveness of both monomeric and compound forms of TCM in the management of breast cancer. We also discuss the potential of establishing biomarkers for breast cancer treatment based on key proteins within the Wnt/β-catenin signaling pathway. Our aim is to offer new insights into the prevention and treatment of breast cancer and to contribute to the standardization of TCM. [ABSTRACT FROM AUTHOR]

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice. [ABSTRACT FROM AUTHOR]

Pancreatic cancer continues to be a deadly disease because of its delayed diagnosis and aggressive tumor biology. Oncogenes and risk factors are being reported to influence the signaling pathways involved in pancreatic embryogenesis leading to pancreatic cancer genesis. Although studies using rodent models have yielded insightful information, the scarcity of human pancreatic tissue has made it difficult to comprehend how the human pancreas develops. Transcription factors like IPF1/PDX1, HLXB9, PBX1, MEIS, Islet-1, and signaling pathways, including Hedgehog, TGF-β, and Notch, are directing pancreatic organogenesis. Any derangements in the above pathways may lead to pancreatic cancer. TP53: and CDKN2A are tumor suppressor genes, and the mutations in TP53 and somatic loss of CDKN2A are the drivers of pancreatic cancer. This review clarifies the complex signaling mechanism involved in pancreatic cancer, the same signaling pathways in pancreas development, the current therapeutic approach targeting signaling molecules, and the mechanism of action of risk factors in promoting pancreatic cancer.

Neurological disorders have become severe and dreadful issues around the globe that are rarely directly mediated because of the blood-brain barrier (BBB). Despite the various therapeutic strategies, including the utilization of cholinesterase inhibitors, metal chelators, molecular chaperones, and anti-body treatment that have been put forth, drug delivery to the brain has remained a problem in the treatment of neurodegenerative disorders (NDD). Chitosan, one of nature's multifunctional polymers, is acknowledged as a useful chemical in the medical and pharmaceutical industries due to its distinctive and flexible biological characteristics. By using Chitosan and its derivatives as drug delivery methods, it is possible to give medications in a sustained and regulated way, increase their stability, and lessen the likelihood of adverse drug reactions. In the current review, we have concentrated on the significance of Chitosan and its derivatives to become a hotspot in drug delivery, particularly for NDDs. This review also explains their properties as drug delivery vectors and their ability to cross the BBB, which is a significant obstacle to medication administration in NDDs. In conclusion, this review suggests that expanding the scope of such research would make it possible to develop NDD drug delivery systems that are more efficient.

Obesity or excessive weight gain is identified as the most important and significant risk factor in the development and progression of type 2 diabetes mellitus (DM) in all age groups. It has reached pandemic dimensions, making the treatment of obesity crucial in the prevention and management of type 2 DM worldwide. Multiple clinical studies have demonstrated that moderate and sustained weight loss can improve blood glucose levels, insulin action and reduce the need for diabetic medications. A combined approach of diet, exercise and lifestyle modifications can successfully reduce obesity and subsequently ameliorate the ill effects and deadly complications of DM. This approach also helps largely in the prevention, control and remission of DM. Obesity and DM are chronic diseases that are increasing globally, requiring new approaches to manage and prevent diabetes in obese individuals. Therefore, it is essential to understand the mechanistic link between the two and design a comprehensive approach to increase life expectancy and improve the quality of life in patients with type 2 DM and obesity. This literature review provides explicit information on the clinical definitions of obesity and type 2 DM, the incidence and prevalence of type 2 DM in obese individuals, the indispensable role of obesity in the pathophysiology of type 2 DM and their mechanistic link. It also discusses clinical studies and outlines the recent management approaches for the treatment of these associated conditions. Additionally, in vivo studies on obesity and type 2 DM are discussed here as they pave the way for more rigorous development of therapeutic approaches. [ABSTRACT FROM AUTHOR]

Immature sacrococcygeal teratoma represents a histological form with rapid tumor growth, a risk of premature birth, an enhanced rate of complications, an increased risk of recurrence, and a higher mortality rate than the mature type. Thus, prenatal diagnosis of immature forms would significantly improve the prognosis of these cases. To this end, we performed an extensive literature review on the diagnosis, therapeutic management, and follow-up of immature teratomas. Regarding this medical conduct, we also presented our case. In conclusion, the early identification of immature sacrococcygeal teratomas with or without other associated structural abnormalities and their correct therapeutic approach are basic principles for a favorable evolution of these cases. [ABSTRACT FROM AUTHOR]

Every day, we come across frantic headlines in the media about alcohol consumption, but this subject is not given a qualitative and rational debate, scientifically based and attached to the reality we live in. I have been wondering for some time what makes people use this drug and why the way they react after consumption differs so much from one individual to another who consumes the same beverage, and how they should be treated so as to reduce addictive consumption. [ABSTRACT FROM AUTHOR]

Background: Nurses are faced with the sexual behavior of the patients. These behaviors do not mean that the patient cannot meet their sexual needs. It is not known how often nurses encounter such behaviors, how nurses' approach sexual patient behaviors, and whether nurses have a therapeutic approach. Purpose: This study was carried out in order to reveal how often nurses encounter sexual behaviors of patients and to determine whether nurses show a therapeutic approach to sexual patient behaviors. Methods: The cross-sectional study was conducted with 276 nurses. The data were collected by using a Questionnaire Form. Data were analyzed using descriptive and chi-square test. Results: The mean age of the nurses participating in the study was 31.12 ± 7.26. 93.8% of them were women, 61.6% were married, 57.2% were undergraduate graduates and the average duration of working life was 9.24±7.11. Compared with the nurses in the other groups, the older nurses, the married ones, those with distant education undergraduate degree, those with 13 years or more working experience and those working in intensive care units were more likely to expose to inappropriate sexual behaviors of the patients (p < .05). Nurses stated that 42.4% of them were exposed to the patients with inappropriate sexual behaviors. The types of inappropriate sexual behaviors that the nurses were exposed to were as follows; "verbal or written" (51.1%), "nonverbal" (37.6%), "physical" (11.3%). The approaches of the nurses towards these patients were "non-therapeutic" (68.1%). Conclusion: It was determined that almost half of the nurses encountered sexual patient behaviors and had difficulty in approaching patients who behaved sexually, and most of the nurses had non-therapeutic approaches to patients who behaved sexually. [ABSTRACT FROM AUTHOR]

Deubiquitylating enzymes (DUBs) maintain relative homeostasis of the cellular ubiquitome by removing the post‐translational modification ubiquitin moiety from substrates. Numerous DUBs have been demonstrated specificity for cleaving a certain type of ubiquitin linkage or positions within ubiquitin chains. Moreover, several DUBs perform functions through specific protein–protein interactions in a catalytically independent manner, which further expands the versatility and complexity of DUBs' functions. Dysregulation of DUBs disrupts the dynamic equilibrium of ubiquitome and causes various diseases, especially cancer and immune disorders. This review summarizes the Janus‐faced roles of DUBs in cancer including proteasomal degradation, DNA repair, apoptosis, and tumor metastasis, as well as in immunity involving innate immune receptor signaling and inflammatory and autoimmune disorders. The prospects and challenges for the clinical development of DUB inhibitors are further discussed. The review provides a comprehensive understanding of the multi‐faced roles of DUBs in cancer and immunity. [ABSTRACT FROM AUTHOR]

Non-small Cell Lung Cancer (NCLC) is the predominant form of lung cancer, representing the primary cause of cancer-related mortality on a global scale. In recent decades, significant research has been conducted on tumor angiogenesis in treating NCLC, owing to its pivotal role in advancing cancer. Numerous anti-angiogenic pharmaceuticals, including Recombinant Endostatin (RE), have undergone extensive assessment in preclinical and clinical settings, yielding varied outcomes that frequently fall short of expectations. Nevertheless, there is a growing fascination with RE owing to its capacity to induce a circulatory normalizing window, thereby potentially enhancing the therapeutic effectiveness of the conventional treatment for NCLC. This work aimed to assess the potential benefits of RE in enhancing the effectiveness and safety of Platinumbased Radiotherapy (PRT) when administered through intravenous and pulmonary infusions for patients with stage IIIA/B-NCLC. This paper presents a comprehensive review of both experimental and clinical investigations that have examined the combined administration of REPRT as a therapeutic approach for NCLC treatment. Out of the total sample size of 14 individuals who were assessed, the treatment's combined effectiveness is 77.6%. This percentage indicates a substantial proportion of positive results about the therapeutic intervention. The disease control rate, encompassing patients who display complete or partial responses, exhibits a noteworthy rise of 89.6%. The results underscores the effectiveness of RE-PRT in successfully arresting or reversing the advancement of the NCLC [ABSTRACT FROM AUTHOR]

Dengue is an arbovirus infection which is transmitted by Aedes mosquitoes. Its prompt detection and effective treatment is a global health challenge. Various nanoparticle-based vaccines have been formulated to present immunogen (antigens) to instigate an immune response or prevent virus spread, but no specific treatment has been devised. This review explores the role of nanomedicine-based therapeutic agents against dengue virus, taking into consideration the applicable dengue virus assays that are sensitive, specific, have a short turnaround time and are inexpensive. Various kinds of metallic, polymeric and lipid nanoparticles with safe and effective profiles present an alternative strategy that could provide a better remedy for eradicating the dengue virus. [ABSTRACT FROM AUTHOR]

Background: Viral warts, induced by infection by different HPV genotypes, are highly frequent in the general population, particularly during infancy and among adolescents. The effectiveness of the 595 nm Pulse dye‐laser in treating viral warts on the hands and feet in both adults and children was investigated in this study. Materials and Methods: A selection of 203 patients with multiple viral warts was made. All patients underwent 4–5 treatment sessions with a 595 nm pulse Dye Laser (PDL). Treatment outcome was assessed by a quartile scale: 1 indicates no or low results (0%–25% of the lesion area cleared), 2 indicates slight clearance (25%–50% of the lesion area cleared), 3 indicates moderate‐good clearance (50%–75%), and 4 indicates excellent clearance (75%–100%). Patients were asked for a subjective evaluation of the perceived overall results by means of the following score: unsatisfied (1), not very satisfied (2), satisfied (3), and very satisfied (4). Possible side effects were monitored. Results obtained were judged with a photographic evaluation, immediately and at the control visit (6 months after the last laser session). Results: All patients observed global improvements. Most of the lesions were completely removed after laser therapy. A total of 95% of patients achieved excellent clearance and they were very satisfied following the laser treatment. Relevant side effects were absent in all patients. Conclusion: PDL treatment with the study device using a wavelength of 595 nm has proven to be a tolerable and safe therapy for viral warts management. [ABSTRACT FROM AUTHOR]

• The ethanolic extract was prepared from the leaves of P. insignis. • GC-MS analysis performed on the ethanolic extract of P. insignis leaves revealed the presence of 60 phytocompounds. • HPLC analysis identified the flavonoid catechin which justifies the anti-inflammatory effect of P. insignis in the treatment of acute respiratory distress syndrome. Platonia insignis Mart., popularly known as bacuri, is a plant in which all its parts are indicated for use in folk medicine. The decoction of the seeds, for example, is used to treat diarrhea, while the oil from the seeds is used to treat skin diseases, otitis, rheumatism, arthritis, and cicatrization. The objective of this work was to perform a phytochemical analysis of the ethanolic extract of P. insignis leaves and to evaluate the pharmacological action of the extract on acute respiratory distress syndrome (ARDS) by intestinal ischemia and reperfusion in rats. For the induction of ARDS, male rats were distributed into seven groups. The negative control group was submitted to ischemia and reperfusion but was not treated. The test groups were treated by inhalation with ethanolic extract of freeze-dried P. insignis leaves (500 mg/kg) and associations. Lung structural and inflammatory changes were evaluated by histological examination. The preliminary phytochemical screening found that the leaf extract contained alkaloids, saponins, and triterpenes. The GCMS– analysis verified that the extract presented 60 compounds, in which phytol (10.54%), gamma-sitosterol (9.88%), and hexadecanoic acid (9.84%) were the major compounds identified. Analysis by CLAE revealed the secondary metabolite catechin in the extract. Finally, the extract was able to stagnate the marked dilation of terminal and respiratory bronchioles and alveoli. The results suggest that the ethanolic extract of P. insignis leaves is a promising therapeutic option to treat ARDS. [ABSTRACT FROM AUTHOR]

Monkeypox infection outbreaks have been observed sporadically in Africa, usually as a result of interaction with wildlife reservoirs. The genomes of the new strain range in size from 184.7 to 198.0 kb and are identified with 143–214 open reading frames. Viral cores are rapidly carried on microtubules away from the cell's perimeter and deeper into the cytoplasm once the virus and cell membranes fuse. Depending on the kind of exposure, patients with monkeypox may experience a febrile prodrome 5–13 days after exposure, which frequently includes lymphadenopathy, malaise, headaches, and muscle aches. A different diagnostic approach is available for monkeypox, including histopathological analysis, electron microscopy, immunoassays, polymerase chain reaction, genome sequencing, microarrays, loop‐mediated isothermal amplification technology and CRISPR (i.e., "clustered regularly interspaced short palindromic repeats"). There are currently no particular, clinically effective treatments available for the monkeypox virus. An initial treatment is cidofovir. As a monophosphate nucleotide analog, cidofovir is transformed into an inhibitor of viral DNA polymerase by cellular kinases, which is analogous to cidofovir's function in inhibiting viral DNA synthesis. The European Medicine Agency and the Food and Drug Administration have both granted permission for IMVAMUNE, a replication‐deficient, attenuated third‐generation modified vaccinia Ankara vaccine, to be used for the prevention of smallpox and monkeypox in adults. [ABSTRACT FROM AUTHOR]

Background: Impaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes. Purpose of review: Although many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review. Recent findings: Although complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value. Summary: The adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals’ patients. The target-specific proinflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy. [ABSTRACT FROM AUTHOR]

Cardiac repair after myocardial infarction (MI) is orchestrated by multiple intrinsic mechanisms in the heart. Identifying cardiac cell heterogeneity and its effect on processes that mediate the ischemic myocardium repair may be key to developing novel therapeutics for preventing heart failure. With the rapid advancement of single-cell transcriptomics, recent studies have uncovered novel cardiac cell populations, dynamics of cell type composition, and molecular signatures of MI-associated cells at the single-cell level. In this review, we summarized the main findings during cardiac repair by applying single-cell transcriptomics, including endogenous myocardial regeneration, myocardial fibrosis, angiogenesis, and the immune microenvironment. Finally, we also discussed the integrative analysis of spatial multi-omics transcriptomics and single-cell transcriptomics. This review provided a basis for future studies to further advance the mechanism and development of therapeutic approaches for cardiac repair.

Objective: This research was carried out to reduce the fear, anxiety and pain of 4–6 age circumcised children with therapeutic play and video animation interventions. Methods: This research was conducted as a randomized controlled study between November 2019 and April 2021. Using block randomization, 30 (n = 30) children were assigned to the control group, 30 (n = 30) to the therapeutic puppet group and 30 (n = 30) to the video animation group. Before the circumcision surgery, therapeutic puppet and video animation interventions were applied to children with scenario prepared with psychodrama technique. Fear, anxiety, and pain findings of children before and after surgery were determined. Results: The fear and anxiety scores of the children were similar before the nursing intervention in all groups, and that the fear and anxiety scores of therapeutic puppet play and video animation intervention groups had statistically lower than the control group after nursing intervention. The pain scores of the children from the therapeutic puppet play and video animation groups had lower pain scores than the control group after surgery (F = 5.24, p = 0.007). Conclusions: Therapeutic play and video animation intervention can be effective in reducing fear and anxiety of children aged 4–6 before and after circumcision surgery. [ABSTRACT FROM AUTHOR]

1) Background: Temporomandibular joint (TMJ) is responsible for vital functions like mastication, swallowing, and suction reflex and other relational functions, like talking and phonation. The etiology of temporomandibular joint disorders is multifactorial and involves subjective and objective clinical symptomatology. (2) Methods: The therapy is complex and encompasses a series of methods that interconnects various medical specialties. Bad habits and parafunction are risk factors that may initiate and exacerbate a temporomandibular joint pathology. This prospective study aimed to show the positive impact of correct multidisciplinary therapy on the complex of TMJ disorders - pain and bad oral behaviors. The therapy methods used in this study were: medical, prosthetic, orthodontic, surgical, and physiotherapy (PKT). (3) Results: The data obtained showed good results if the oral habits and TMJ disorders are treated correctly and simultaneously. (4) Conclusions: All therapeutical approaches addressed in this study had beneficial effects on the recovery of the temporomandibular joint. [ABSTRACT FROM AUTHOR]

Vesicants are compounds that cause severe toxic effects on various tissues. Such chemical action causes tissue necrosis, with clinical expression of skin lesions with a burning character and characteristic blisters. Clinical toxic effects of cutaneous vesicles are correlated with the absorbed dose and exposure time. The goals of the study are to evaluate in vitro the skin toxicity produced by the vesicant chemical compound 2-chloroethyl-ethyl sulfide (CEES), to develop a complex antidote formula, and to optimize the therapeutic efficacy by inclusion in controlled release systems. The experimental protocol aims at the in vitro evaluation of the cytotoxicity of the vesicant compound CEES and of the optimized complex antidote, using the MTT cell viability test. Optimization of the complex antidote formula was achieved by developing and in vitro and in vivo testing of a fixed combination of active substances with anti-inflammatory and antioxidant effects, formulated as a solution with cutaneous administration. In vitro cytotoxicity tests on fibroblast cultures revealed the protective effect of the newly developed antidote solution, specifically a dose-related effect in the case of vesicant exposure.

BackgroundImpaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes.Purpose of reviewAlthough many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review.Recent findingsAlthough complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value.SummaryThe adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals’ patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.

Background and Objectives: Fetal ovarian cysts (FOCs) are a very rare pathology that can be associated with maternal–fetal and neonatal complications. The aim of this study was to assess the influence of ultrasound characteristics on FOC evolution and therapeutic management. Materials and Methods: We included cases admitted to our perinatal tertiary center between August 2016 and December 2022 with a prenatal or postnatal ultrasound evaluation indicative of FOC. We retrospectively analyzed the pre- and postnatal medical records, sonographic findings, operation protocols, and pathology reports. Results: This study investigated 20 cases of FOCs, of which 17 (85%) were diagnosed prenatally and 3 (15%) postnatally. The mean size of prenatally diagnosed ovarian cysts was 34.64 ± 12.53 mm for simple ovarian cysts and 55.16 ± 21.01 mm for complex ovarian cysts (p = 0.01). The simple FOCs ≤ 4 cm underwent resorption (n = 7, 70%) or size reduction (n = 3, 30%) without complications. Only 1 simple FOC greater than 4 cm reduced its size during follow-up, while 2 cases (66.6%) were complicated with ovarian torsion. Complex ovarian cysts diagnosed prenatally underwent resorption in only 1 case (25%), reduced in size in 1 case (25%), and were complicated with ovarian torsion in 2 cases (50%). Moreover, 2 simple (66.6%) and 1 complex (33.3%) fetal ovarian cysts were postnatally diagnosed. All of these simple ovarian cysts had a maximum diameter of ≤4 cm, and all of them underwent size reduction. The complex ovarian cyst of 4 cm underwent resorption during follow-up. Conclusions: Symptomatic neonatal ovarian cysts, as well as those that grow in size during sonographic follow-up, are in danger of ovarian torsion and should be operated on. Complex cysts and large cysts (with >4 cm diameter) could be followed up unless they become symptomatic or increase in dimensions during serial ultrasounds. [ABSTRACT FROM AUTHOR]

Solution-focused approaches are one approach to treatment used in a wide variety of settings in modern mental healthcare services. As yet, there has been no overall synthesis of how this approach is understood in the adult mental health literature. This conceptual review aimed to synthesize the ways that solutionfocused approaches have been conceptualized and understood, within the adult mental health literature, in the five decades since their conception. A systematic search followed by multiple techniques from the narrative synthesis approach were used to develop a conceptual framework of the extracted data. Fifty-six papers published between 1993 and 2019 were included in the review. These papers spanned a variety of clinical contexts and countries, but despite this the underlying key principles and concepts of solution-focused approaches were remarkably similar over time and setting. Thematic analysis of extracted data outlined five key themes relevant to the conceptualization of this approach. This conceptual framework will help support clinicians using solution-focused techniques or therapies by giving them a coherent understanding of such approaches, by what mechanisms they work, and how key principles of this approach can be utilized in adult mental health settings. [ABSTRACT FROM AUTHOR]

To describe MDD patients starting antidepressant (AD) treatment by pharmacological approach and identify factors associated with a longer sick leave (SL) duration. Retrospective study on IQVIA German Disease Analyser (specialists) and Spanish Longitudinal Patient Database (general practitioners and specialists). MDD patients initiating AD treatment between July 2016–June 2018 were grouped by therapeutic approach (AD monotherapy vs. combination/switch/add-on) and their characteristics were analysed descriptively. Multiple logistic regression models were run to evaluate factors affecting SL duration (i.e., >30 days). One thousand six hundred and eighty-five patients (monotherapy: 58%; combination/switch/add-on: 42%) met inclusion criteria for Germany, and 1817 for Spain (monotherapy: 83%; combination/switch/add-on: 17%). AD treatment influenced SL duration: combination/switch/add-on patients had a 2-fold and a 4-fold risk of having >30 days of SL than monotherapy patients, respectively in Germany and Spain. Patients with a gap of time between MDD diagnosis and AD treatment initiation had a higher likelihood of experiencing a longer SL both in Germany and Spain (38% higher likelihood and 6-fold risk of having >30 days of SL, respectively). A careful and timely selection of AD treatment approach at the time of MDD diagnosis may improve functional recovery and help to reduce SL, minimising the socio-economic burden of the disease. The major depressive disorder has a substantial impact on work absenteeism. The present study aimed to describe MDD patients starting antidepressant (AD) treatment depending on the pharmacological approach and to identify factors associated with longer sick leave (SL) duration. Patients receiving AD monotherapy had a lower likelihood of having more than 30 days of sick leave than those receiving AD combination/switch/add-on. Patients for whom a gap of time between MDD diagnosis and initiation of AD treatment was observed, showed a higher likelihood of having more than 30 days of sick leave. Because findings from this analysis relied on secondary data, the authors would like to claim the urgency of conducting prospective observational studies that further investigate the effect that different AD therapeutic approaches and timely initiation of treatment might exert on patients' recovery. [ABSTRACT FROM AUTHOR]