Context: Endobronchial tumors are relatively rare. Pathological types are varied, both benign and malignant. Establishing the diagnosis and sleeve resection criteria for such tumors remains a challenge for pulmonologists, bronchoscopists, radiologists, thoracic surgeons, and pathologists. The management of the preoperative assessment of these patients and the establishment of the indication for sleeve resection, represent a big problem. Lung parenchymal sparing surgery remains a challenge, especially in neoplastic patients. Material and methods: We carried out a monocentric retrospective study, during the period 2009-2017, on a number of 57 patients. In our center they benefited from clinical examination, radiography, tomography, respiratory function evaluations, autofluorescence bronchoscopy, cardiological evaluation and detection of blood tumor markers. All the patients benefited from the analysis of the tumorboard of our institute and the establishment of the surgical indication for scleev resection. Results: Sparing of the lung parenchyma was achieved in case of the 57 patients included in the study. The complex evaluations of laboratory parameters, functional tests, CT examination, bronchoscopy, cardiology, were analyzed by the tumor board, so that the indication for surgical intervention was sleeve resection with preservation of the lung parenchyma. Conclusions: We selected patients for sleeve resection, those who presented endobronchial tumors of 2 cm in diameter, with cartilages and bronchial mucosa intact at least 1 cm or 2 cartilages from the formation, on CT and bronchoscopic examination. Cardiological examination and functional tests showed values that do not contradict surgical intervention.

Colorectal cancer is the third most common disease and the second most common cause of death in the world. The drug for second-line treatment depends on the drugs used in first-line treatment and biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers are established for selecting angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be hopeful biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

Manifestation of cystic hygroma in adulthood is very rare. In this study, we reported a rare case of Cervical Cystic Hygroma in Adults. We report 20 years old male with a diagnosis of left-side neck cystic Hygroma and discuss the presentation, diagnosis, and clinical, radiological, and operative aspects of it.

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. In two of them, the optimized geometry was determined in the monomer, cyclic dimer and staking forms using the B3LYP, M06-2X and MP2 methods. The effect of the para-substitution in the aryl ring was evaluated based on the changes in the molecular structure and atomic charge distribution of the triazole ring. Several relationships were obtained that could facilitate the selection of the substituents on the triazole ring for their further synthesis. The observed IR and Raman bands in the solid state of two of these compounds were accurately assigned according to the functional calculations on the monomer and dimer forms, together with the polynomic scaling equation procedure (PSE).

Diminished ovarian reserve can be regarded as a sentinel indicator to foreshadow severe follicular loss and, ultimately, systemic aging. The negative slope of human ovulatory fidelity begins with a robust follicular endowment which gradually declines over time. In contrast, the youthful ovarian phenotype requires the coordinated work of endothelial, granulosa, immune, perivascular, stromal and possibly germline stem cells. Such a diverse tissue matrix can, in general, be influenced by platelet (PLT)-derived factors but this has not yet been specifically confirmed in the ovary after platelet-rich plasma (PRP). How could a comparable response be validated? Here a prospective, experimental study is proposed whereby eligible patients already undergoing scheduled laparoscopy provide ovarian tissue via biopsy submitted for co-culture with autologous Ca⁺² activated PRP. Recognizing the interlocking, central roles of nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α), incubated samples would be assessed for these in vitro before vs. after PRP exposure, in addition to stereomicroscopy. A mathematical model is available to track NF-κB oscillations and estimate gene expression, cell development, growth, apoptosis, and key immune and inflammatory actions. Since NF-κB and TNF-α are discharged in activated PLT releasate (or react to its cargo proteins) this audit permits extraction of response markers observed post-stimulus, thus linking discrete signals to transcriptional output, cellular fitness, and ovarian cytoarchitecture. From this, a hypothesis could emerge where intraovarian PRP is found to make no direct impact on follicles, although modified ovarian field function and curtailed local entropy incidentally favor optimized oocyte competence as a secondary effect.

The right to live with dignity during the final stages of existence, enshrined in national and supranational Charters of Rights, represents a significant step towards humanizing medicine and is integral to the right to health. Palliative Care, rooted in health, dignity, and therapeutic self-determination, has emerged as a fundamental human right and a moral imperative within health systems. It seeks to alleviate suffering, emphasizing the holistic well-being of patients with life-limiting illnesses. This paper provides a comprehensive global perspective on Palliative Care, with special attention to its implementation in Italy. Palliative Care is a crucial dimension of care, designed to enhance the quality of life for patients suffering from progressive and incurable diseases. Despite its growing need due to an aging population and increased prevalence of chronic illnesses, still remains a significant disparity in access to these essential services worldwide. Insufficient resources, legislative constraints, and limited training for healthcare providers pose challenges to the widespread adoption of Palliative Care. In Italy, although laws have been enacted to ensure the provision of Palliative Care, its availability remains inconsistent across different regions. Financial constraints and insufficient support hinder the comprehensive dissemination of these services. Recognizing the significance of Palliative Care, the Catholic Church also endorses its implementation as a response to human suffering and an approach to end-of-life care. Efforts to strengthen Palliative Care are critical to meeting the rising demand and ensuring access to compassionate and dignified care for all individuals in need. Through legislative advancements and adequate resources, Italy can make significant strides in advancing the provision of Palliative Care.

In recent years, numerous approaches have been developed to comprehend the molecular altera-tions underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumour cells from apoptosis, triggering invasion and metastasis through enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumour angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as met-astatic lesions, exhibit overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, para-crine, intracrine, and neuroendocrine processes, including the regulation of tumour burden. Con-sequently, the secretion of SP from TC results in increased SP levels in plasma, which are signifi-cantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumour action. They impair cancer cell proliferation on one side and induce apoptosis of tumour cells on the other side. Furthermore, it has been demonstrat-ed that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Tourette syndrome is a complex neuropsychiatric condition that manifests in childhood and is often associated with other psychiatric comorbidities. This case describes a young male with Tourette syndrome with major depressive disorder and attention deficit hyperactivity disorder (ADHD), who experienced troublesome side-effects due to his existing medications (escitalopram, risperidone and methylphenidate). In order to control his tics, ameliorate depressive symptoms, and eliminate side-effects of stiffness and sedation, risperidone was switched to cariprazine, a third-generation antipsychotic medication with D3-D2 partial agonism. In addition, the antidepressant dose was also increased. With the new combination, the patient reported good control of his tics, together with significant improvement in depressive symptoms and no side-effects. Based on this case and the reviewed literature, cariprazine might be a viable option for patients with Tourette syndrome with other comorbid illnesses, whom are prone to side effects of medication.

(1) Background: In orthognathic surgery, segmental Le Fort I osteotomies are a valuable method to correct maxillary deformities or transversal discrepancies. However, these procedures are technically challenging, and osteosynthesis can be prone to error. (2) Methods: In this retrospective, monocentric cohort study, patients were enrolled who underwent a virtually planned segmental maxillary osteotomy during their combined treatment. Positioning and osteosynthesis were achieved by either a 3D-printed splint and conventional mini plates or Patient-Specific Implants (PSI). The preoperative CT data, virtual planning data, and postoperative CBCT data were segmented. The deviation of all segments from the desired virtually planned position was measured using the analysis function of the IPS Case Designer. (3) Results: 28 Patients in the PSI Group and 22 in the conventional groups could be included. The PSI group showed significantly lower deviation from the planned position anteroposteriorly (-0.63±1.62mm vs. -1.3±2.54mm) and craniocaudally (-1.39±1.59mm vs. -2.7±3.1mm). For rotational deviations, the Pitch (0.64±2.59° vs. 2.91±4.08°) as well as the inward rotation of the lateral segments was positively influenced by PSI. (4). Conclusions: The presented data show that patient-specific osteosynthesis significantly reduces deviations from the preoperative plan in virtually planned cases. Especially transversal expansions and vertical positioning can be addressed better.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. The treatment target is slowing down the disease course and mitigating the symptoms. Approximately 30 to 50% of patients do not respond optimally to Disease Modifying Therapies (DMTs), in which therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of HLA DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3), was used to classify therapeutic response. Patients were classified as follows: a) control: patients who achieved NEDA-3 b) case: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were: GG 50.5%, GA 34.3% and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p=0.6). We concluded that in Mexican patients with MS, HLA DRB1*0403 was not associated with therapeutic response to DMTs.

Abstract The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up of the patient’s clinical course is essential to identify and treat each complication. This study focused on treatment-related complications during induction and consolidations in patients with APL who received ATRA plus ATO. We retrospectively analyzed 26 adult patients diagnosed with APL between 2019 and 2022 at our center to identify the incidence rate, severity and time of onset of short-term non-hematologic adverse events relative to the initiation of the ATRA and ATO regimen. Additionally, we review the existing literature regarding the toxic side effects of ATO in APL and discuss how its most frequent toxicities should be managed. The median follow-up of our patients was 21.5 months (range, 1-48 months) and the most common adverse events were hepatic toxicity (69.2%), infections (46.1%), differentiation syndrome(23%) and QT prolongation (11.5%). All patients experienced at least one adverse event and grade 3 and 4 toxicities occurred in 57.6 % patients; these generally consisted of liver enzyme elevations, QTc prolongation, but also some rare manifestations such as musculoskeletal pain syndrome (1 patient) and ATO-related pancreatitis (1 patient). Most patients developed side-effects during induction. This is the first study about Romanian patients diagnosed with APL. Our results suggest that all treatment-related adverse events, except for differentiation syndrome are manageable, self-limiting and reversible. All patients, except for two (one died during induction and one died during consolidation), were able to complete the treatment consolidation with ATO and ATRA.

The incidence of liver diseases is on the leading rise worldwide, but there is a lack of exact research models mimic liver diseases. Using the normothermic machine perfusion (NMP) platform to study diseased livers recovered from the liver transplantation (LT) recipients seems promising. Therefore, the aim of this study was to establish the first machine perfusion system called Life-XDL to cultivate diseased liver. Four diseased livers recovered from LT recipients within different diagnoses were collected. The diseased livers were connected to the Life-XDL machine perfusion system that circulated Life-XDL perfusate providing oxygen and nutrients. The pressure and flow of the device was recorded and blood gas analysis and laboratory test of perfusate and bile was examined to analyze the function of the diseased livers. Liver tissues after perfusion were collected for histological analysis. Experiments showed that Life-XDL kept the diseased livers at the physiological state with providing stable hemodynamics and suitable partial pressure of oxygen and carbon dioxide. The results of blood gas analysis and laboratory test results demonstrated restoration and maintenance of metabolism and less damage. Moreover, the bile production of case 1, 3 and 4 diseased livers represented its vivid functionality. The pathological characteristics were kept stable before and after NMP. Overall, we successfully establish the Life-XDL machine perfusion system which specially for diseased human whole liver and develop a new diseased human whole organ model in vitro through normothermic machine perfusion that recapitulate the main features of the human liver disease, which showing great promise as disease modeling platforms.

Tamanu oil has traditionally been used to treat various skin problems. The oil has wound-healing and skin-regenerating capabilities, and encourages the growth of new skin cells, all of which are helpful for fading scars and hyperpigmentation, as well as promoting an all-around glow. The strong nutty odor and high viscosity are the major disadvantages associated with their application. The aim of this study was to create bigels using tamanu oil for its anti-scarring properties. Bigels were prepared with Tamanu oil ranging from 5 to 20% along with micronized xanthan gum and evaluated for their pH, viscosity, and spreadability. In silico studies were performed to analyze the binding affinity of the protein with the drug, and the anti-scarring activity was established using a full-thickness excision wound model. In silico studies have reported that the components Calanolide A, Inophyllum C, and 4-Norlanosta-17(20),24-diene-11,16-diol-21-oic acid, and 3-oxo-16,21-lactone had docking scores of -9.8, -11.3, and -11.1, respectively with the cytokine TGF- β1 receptor. An acute dermal irritation study in rabbits showed no irritation, erythema, eschar, or edema. In vivo excisional wound healing studies performed on wistar rats and subsequent histopathological studies showed that bigels had better healing properties when compared to the commercial formulation (Murivenna oil). This study substantiates the wound healing and scar reduction potential of Tamanu oil bigels.

In recent years, the field of radiotherapy has witnessed remarkable advancements with the integration of artificial intelligence (AI) technologies into clinical practice. Traditionally, radiotherapy treatment planning has been a labor-intensive process, requiring meticulous manual segmentation and optimization. With the advent of AI, particularly deep learning algorithms, the accuracy and efficiency of target delineation and organ-at-risk segmentation have significantly improved. AI-driven algorithms analyze voluminous medical imaging data, enabling rapid and precise contouring, thus expediting the planning phase and reducing inter-observer variability. Furthermore, AI's role extends to treatment plan optimization, where it intelligently explores vast parameter spaces to generate optimal plans tailored to individual patients. This not only saves dosimetrists' time but also enhances plan quality by accounting for complex anatomical variations and personalized clinical goals. In the realm of treatment delivery, AI-powered real-time image guidance enhances the accuracy of patient positioning, ensuring precise radiation targeting. Adaptive radiotherapy, enabled by AI, allows on-the-fly plan modifications in response to anatomical changes, significantly improving treatment accuracy in scenarios like tumor shrinkage or weight loss. Beyond planning and delivery, AI algorithms contribute to outcome prediction by analyzing historical patient data and treatment responses. This predictive capability aids clinicians in making informed decisions and refining treatment strategies for better prognoses. Despite the revolutionary potential, challenges remain in seamlessly integrating AI into clinical workflows. Ethical considerations, data privacy, and algorithm interpretability necessitate cautious implementation. Additionally, fostering interdisciplinary collaboration between AI experts and radiation oncologists is imperative to harness the technology's full potential. This paper explores the impact of AI in four key areas of radiotherapy: automated segmentation, dosimetric and machine quality assurance, adaptive radiation therapy, and clinical outcome prediction.

Objective: To explore the application effect of Atropine injection combined with nursing intervention on the interventional treatment of PATENTS with ST-segment elevation myocardial infarction. Methods: A total of 60 patients with ST-segment elevation myocardial infarction treated in our hospital from January 2022 to January 2023 were selected as the research objects. According to different nursing methods, they were divided into conventional group (n = 30) and systematic group (n = 30), both groups were treated with percutaneous coronary intervention (PCI). The conventional group received routine nursing before and after operation. On the basis of routine nursing, systematic nursing cooperation was given in the system group. The time of opening infarct vessels, the incidence of total adverse reactions during interventional treatment, mortality, success rate of treatment, improvement of cardiac function and length of hospital stay were compared between the two groups. Results: The time of opening infarct vessel in system group was significantly better than that in routine group (P < 0.05). The total adverse reaction rate in system group was significantly lower than that in routine group (P < 0.05); The mortality of routine group was significantly higher than that of system group (P < 0.05). The success rate of system group was significantly higher than that of routine group (P < 0.05); The number of patients with improved cardiac function and length of hospital stay in system group were significantly better than those in routine group (P < 0.05). Conclusion: Good intraoperative cooperation and nursing is an important guarantee for patients with ST-segment elevation myocardial infarction, which can effectively reduce the occurrence of adverse reactions during interventional treatment, improve the success rate of treatment, and reduce the death of patients during interventional treatment.

Objective: To examine the effect of bilateral total lobectomy and unilateral total lobectomy on improving thyroid function in patients with thyroid micropapillary carcinoma treated with euthyrox. Methods: The study was conducted on 68 patients with thyroid micro papillary carcinoma treated with euthyroxwho had been surgically treated with euthyrox in our hospital between January 2018 and December 2019. On the basis of random number grouping, they were divided into control groups (n = 34, bilateral total lobectomy) and observation groups (n = 34, unilateral total lobectomy plus isthmectomy). Thyroid function, free triiodothyronine (FT3), thyroid hormone (TSH), and voice function (VHI score) of the two groups were compared.Results: In comparison to the control group, the observation group had shorter incision lengths, shorter operation times, and shorter hospital stays, as well as less intraoperative bleeding and drainage volume, and the difference was statistically significant (P < 0.05); As compared with the control group, the observation group had higher FT4 and FT3 levels as well as lower TSH levels, a statistically significant difference (P < 0.05).VHI scores of emotions, function, physiology, and other voice functions were significantly lower among the observation group than those of the control group (P < 0.05).Conclusion: A unilateral total lobectomy with adjacent isthmus resection in patients with thyroid micro papillary carcinoma can yield ideal results, accelerate the time taken for surgical rehabilitation, improve thyroid function, thereby improving voice quality, as well as improve the overall prognosis of the patient.

Introduction: Suicide is the second leading cause of death among 15 to 19-years-olds in Europe. From the beginning of COVID-19 pandemic, literature confirms a significant increase in mental health disease in children and adolescents. At Bambino Gesù Pediatric Hospital emergency department (Rome, Italy) there was a dramatic increase of suicidal attempts, and particularly a rise of suicidal jumpers. Many of these patients presented vertebral fractures. Material and Methods: This retrospective study includes all suicidal jumpers with vertebral fractures treated at our Pediatric Hospital from April 1, 2017 to March 31, 2023. We collected and compared data from three years before to three years after pandemic spreading analyzing vertebral fractures. Results: From April 1 2019 to March 31, 2020 141 cases of suicide attempt arrived at Bambino Gesù Pediatric Hospital emergency department. Five of these patients were suicidal jumpers but none had a vertebral fracture. From April 1, 2020 to March 31, 2023, 362 cases of suicide attempts arrived in the same emergency department and 19 were suicidal jumpers; 12 reported vertebral fractures and were included in this study. Mean age was 14 years. Most common level of fracture was L1. Four patients presented with preoperative neurologic impairment and two cases recovered completely. There was a transforaminal sacral fracture, a spinopelvic dissociation and an Anderson-D’Alonso C2 type II fracture. Two cases with thoracolumbar vertebral fractures were conservatively treated. Seven patients were treated by percutaneous pedicle fixation to achieve an indirect decompression and to restore a better sagittal balance. Only three patients needed an open spinal surgery by posterior approach and in two cases a posterior decompression was performed. One case with cervical fractures was treated by Halo-Vest. Conclusions: Recent literature highlights concern about the consequences of COVID-19 pandemic on pediatric population mental health. This is the first report that shows a significant increase in vertebral body fractures due to suicide jumping attempt. The comparison between three years pre and post pandemic is sufficient to demonstrate a sharp increase of these cases. This could be a new epidemiological phenomenon that could persist or even increase over time because of COVID-19 pandemic.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e. cytoskeletal and cytosolic proteins (actin, tubulin, histones), nucleic acids (mRNA, miRNA, DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, adhesion molecules). This review would be a synopsis of the actual knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, liver and kidney injuries. Current knowledge indicates that the role of exosomes in therapy of inflammation and in inflammatory diseases could be distinctive. Main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of selection of exosomes, their dosages and routes of administration, and a deeper knowledge about their biodistribution, type and incidence of adverse events and long-term effects of exosomes. In conclusion, exosomes can very promising next generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile and selective delivery systems in the future.

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symp-toms of schizophrenia. These beneficial changes might be mediated by trophic factors such as ep-idermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable an-tipsychotic treatment and thereby evaluate the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. 58 subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 grams of sarcosine (n=28) or placebo (n=30) daily. Serum EGF levels and symptom se-verity (using Positive and Negative Syndrome Scale - PANSS and Calgary Depression Scale for Schizophrenia - CDSS) were assessed at baseline, 6 weeks, and 6 months follow-up. Augmenta-tion antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time-points. Only the sarcosine group showed a significant improvement in negative symptoms, general psy-chopathology subscales, and the overall PANSS score. We found reduction of serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels.

Background and Objectives: The current study aimed to determine the impact of fasciotomy on mortality and morbidity in children and adults with crush-related AKI following the 2023 Kahramanmaraş earthquakes. Materials and Methods: The study included individuals who had suffered crush injuries after the 2023 Kahramanmaraş earthquakes and were identified as having acute kidney injury (AKI). Patients with AKI were divided into two groups based on age: those under 18 years and those over 18 years. A comparative analysis was conducted between the mortality and morbidity rates of patients who underwent fasciotomy and those who did not. Disseminated intravascular coagulopathy (DIC), sepsis, and adult respiratory distress syndrome (ARDS) have all been identified as contributors to morbidity. Results: The study was conducted with a total of 40 patients (21 males and 19 females) aged between four and 83 years. A total of 21 patients underwent fasciotomy and the patients underwent varying numbers of fasciotomy, ranging from zero to 11. The mortality rate was 12.5%, corresponding to five adult patients. No instances of mortality were reported in the paediatric cohort. The application of fasciotomy in instances of crush-induced AKI did not result in elevated levels of mortality in either the paediatric or adult demographic. Within the adult population, a substantial difference in the duration of dialysis was observed between individuals who underwent fasciotomy and those who did not. A statistically significant increase in the number of fasciotomy incisions was observed in patients diagnosed with sepsis compared with those without sepsis. The study found a significant positive correlation between the number of fasciotomy incisions and dialysis days. Conclusions: Neither adult nor paediatric patients with crush-induced AKI showed an increased risk of death after fasciotomy. The number of fasciotomy incisions significantly correlated with the development of sepsis. Despite experiencing delays in hospital admission for paediatric patients, the incidence of both crush syndrome and mortality rates among children remained relatively low.

Autoinflammatory disorders encompass a wide range of conditions with systemic and neuro-logical symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reac-tion. On the other hand, autoimmune diseases result from dysregulation of the adaptive im-mune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflam-matory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.

Background: The level of food processing has gained interest for a potential determinant of human health. The aim of this study was to assess the relation between level of food processing and prostate cancer severity. Methods: A sample of 120 consecutive patients were examined for their dietary habits assessed through validated food frequency questionnaires, their dietary intake of food groups categorized according to the NOVA classification, and the severity of prostate cancer according to the European Association of Urology (EAU) guidelines groups risk. Uni- and multivariate logistic regression analyses were performed to test the association between the variables of interest. Results: Individuals reporting higher consumption of unprocessed/minimally processed foods were less likely to have worse prostate cancer severity than lower consumers in the energy-adjusted model [odds ratio (OR) = 0.38, 95% confidence interval (CI): 1.17-0.84, P = 0.017 and OR = 0.33, 95% CI: 0.12-0.91, P = 0.032 for medium/high vs. low grade and high vs. medium/low grade prostate cancers, respectively); however, after adjusted for potential confounding factors, the association was no more significant (Table 4). A borderline association was also found between higher consumption of UPF and worse prostate cancer severity in the energy-adjusted model (OR = 2.11, 95% CI: 0.998-4.44; P = 0.051), but again the association was no more significant after adjusting for the other covariates. Conclusions: The level of food processing seems not to be independently associated with prostate cancer severity, while potentially related to other factors that need further investigation.

Pulmonary hypertension (PH) is a severe vascular complication of connective tissue diseases (CTD). Patients with CTD may develop PH belonging to different groups: 1) pulmonary arterial hypertension (PAH), 2) PH secondary to lung disease and/or hypoxia, 3) PH due to left heart disease, and 4) chronic thromboembolic pulmonary hypertension (CTEPH). PAH most often develops in systemic scleroderma (SSc), mostly in its limited variant. PAH-CTD is a progressive disease characterized by poor prognosis, therefore the early diagnosis should be established A specific treatment for PAH-CTD is currently available and recommended: prostacyclin derivative (treprostinil, epoprostenol, iloprost, selexipag), nitric oxide and natriuretic pathway: stimulators of soluble guanylate cyclase (sGC: riociguat) and phosphodiesterase 5 inhibitors (PDE5i: sildenafil, tadalafil), endothelin receptor antagonists (ERA: bosentan, macitentan, ambrisentan). Moreover, novel drugs e.g. sotatercept are intensively investigated in the clinical trials. The aim of this paper is to review the literature on the recent advances in treatment strategy and prognosis of patients with PAH-CTD.

Background: COVID-19 represents a threat for frailty patients. Objective: Investigate efficacy, safety and economic value of treatment with Molnupiravir in a cohort of fragile patients affected by COVID-19. Methods: Observational, prospective study. The data collected allowed to assess efficacy and safety of Molnupiravir in real life, compare the results with a subgroup of patients treated with Nirmatrelvir-Ritonavir and to effect a cost-effectiveness analysis. Results: In January-December 2022, 435 patients (225 males, 220 females; median age 72 years), were enrolled; 24 patients were unvaccinated, 280 patients had ≥2 risk factors. Molnupiravir appeared to give better results than the SOC both clinically and economically. In these patients in comparison with literature data or SOC, hospitalization was 2.5% vs 6.8% (p&lt;0.005), overall adverse effects 14,3% vs 30.4% (p&lt;0.0001), severe adverse effects 2.6 vs 6.9% (p&lt;0.001), thus involving a potential total savings of about € 92.954 per patient (8% of standard of care cost). Conclusions: early Molnupiravir treatment helped fragile patients who partially responded to vaccine, or with absolute contraindications to vaccination, to overcome COVID-19 without the need of hospitalization. Molnupiravir represents a clinical and economic effective treatment, avoiding disease progression in old patients suffering from multiple pathologies and taking several drugs.

Introduction: The objectives of this study were to (1) investigate the association between human blood type and COVID-19 infection in both inpatient and longitudinal populations at our institution in South Florida and (2) identify the association between blood type and severity of COVID-19 infection via presence of cellular biomarkers of severe infection in hospitalized individuals. Methods: This study consists of (1) a single-center retrospective analysis of 669 of 2,741 COVID-19 positive screened patients seen from January 1, 2020 until March 31, 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 infection and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study (“CITY”) at the University of Miami Miller School of Medicine consisting of 185 survey participants. COVID-19 outcome rates and 95% confidence intervals were calculated for each ABO blood type and Rh group using Chi-squared tests for categorical and ANOVA for continuous variables in the inpatient cohort and Chi-squared tests for the longitudinal cohort, all executed in R studio. Results: Our inpatient cohort had a mean age of 53.6 (± 17.9) years with 48% males and 52% females. When compared to patients with other blood types, those with O- demonstrated less risk of developing COVID-19 pneumonia (26.7% for O- vs. 69.2% for type A-, 56.5% for A+, 71.4% for AB+, 53.7% for B+, 51.5% for O+, p-value= 0.003 via Chi-squared test) and decreased mortality due to COVID-19 infection (17.0% mortality for O vs. 26.3% for A, 29.2% for B, p-value= 0.012 via Chi-squared test). Blood type O- demonstrated less elevated levels of LDH than did other blood types (p-value= 0.001, ANOVA) and a higher frequency of clinically accepted baseline levels of troponin (0.04 ng/mL) (p-value= 0.026, ANOVA) (Figure 1). Most of the longitudinal cohort was ABO blood grouping type O (47% (87/185)), with 33.5% type A, 14.1% B, and 5.4% AB. Most individuals were Rh positive (85.9%). There was no significant association found between COVID status (infection vs. non-infection) and ABO (Chi-squared test (3, N = 185) = 1.8, p = 0.6) or Rh (Chi-squared test (1, N = 185) = 0.16, p = 0.7) blood typing. Nearly all participants had been vaccinated (95.1% (176/185)), with a majority reporting primary vaccination with Pfizer (57.8% (107/185)), followed by Moderna (33% (61/185)), and Johnson & Johnson (4.3% (8/185)). 8 participants (4.3%) were unvaccinated. Conclusions: In an inpatient setting, blood type O sustained less risk of COVID-19 mortality and O- demonstrated less risk of developing COVID-19 pneumonia. In a longitudinal setting, there was no association found between blood type and COVID-19 severity. As the novelty of COVID-19 infection declines with time, further studies on risk-stratification by blood type are encouraged.

Drug-induced pruritus triggers a desire to scratch, thereby diminishing one’s quality of life. Certain instances of this phenomenon follow complex mechanisms of action that diverge from histamine-mediated pathways, known contributors to pruritus. However, investigations into the relationship between drugs and pruritus are limited. In this study, data mining techniques were employed to comprehensively analyze the characteristics of drugs linked to pruritus, using the FDA Adverse Event Reporting System(FAERS) Data maintained in the United States. Reports linked to pruritus demonstrated noteworthy differences in gender, age, and weight when compared with non-pruritus cases. Among the leading candidates for drugs prompting pruritus were ophthalmic drugs, systemic antibacterials, contrast media, dermatological antifungals, and dermatological preparations. Principal component analysis showed that the second principal component served as an indicator for distinguishing between onsets at mucous membranes or the skin surface. Additionally, the third principal component functioned as an indicator for categorizing administration methods as either invasive or noninvasive. Furthermore, a hierarchical cluster analysis conducted on these obtained principal components revealed the potential for classifying drugs based on the site of pruritus onset and the method of drug administration. These findings contribute to the development of targeted prevention and treatment strategies for avoiding pruritus in clinical practice.

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of the ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analysis of randomized controlled trials (RCTs), assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identify, analyzed in terms of safety/efficacy ratio and of risk of bias, and graded using Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In IVF population not at high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of GnRH antagonist may reduce the OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have shown to be promising.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC; some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and im-proved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years with histologi-cally confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP. Results: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 [18%]), HER2 (5 [18%]), MTAP (5 [18%]), and FGFR (3 [11%]). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n=12 [11.8%]), 14 months in patients with actionable GAs treated with standard therapies (n=17 [16.7%]), and 17 months in patients without actionable GAs treated with standard therapies (n=73 [71.5%]; p=0.26). The absence of liver metastases was associated with better OS (HR=0.471, p=0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. Interpretation: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.

(1) In searching for herbal alternatives for treating coccidiosis in turkeys, this trial aimed to evaluate whether minced black garlic (Allium sativa) or turmeric powder (Curcuma longa) or their combination, included in dried alginate beads, were capable of controlling clinical coccidiosis in turkey male poults. (2) Four groups of 15 twelve-day-old turkey poults per group were set and rose in this trial until the end of week six. Groups were: CTR = control untreated turkeys; GAR = turkeys fed 4% of their diet with minced garlic included in dried alginate beads; CUR = treated fed 4% powder Curcuma, also prepared as dried alginate beads; and G.C. = turkeys fed 8% of their diet with the mixture of minced black garlic plus powder Curcuma (4% of each one), entrapped in dried alginate beads. Treatments were incorporated as feed-dressing, considering their mean feed intake. (3) Results reveal that turkeys in group G.C. showed a significant decrease in oocysts per gram of feces during the first six weeks of age compared to values found in the CTR group and the other treatments. These results identify that in turkey poults, there is a statistically significant anticoccidial activity of the combination of minced garlic plus powder Curcuma, included in alginate beads and administered as 4% of their feed intake. Additionally, better productive variables were recorded for this combination compared to the other three groups (P &lt;0.05). (4) The use of vehicles specifically designed for the digestive tract of turkeys may improve the effectiveness of plant extracts for the control of coccidiosis.

Since the development of CBCT had been utilized in dentistry, the images of the CBCT can assist the surgeon to evaluate the anatomy carefully. Despite the value of the radiology evaluation, the implant procedures may require additional consideration rather than only evaluating the anatomical factors. The purpose of this study is to evaluate the predictability of using CBCT alone to plan for implant placement on the edentulous patient digitally CBCT images were analyzed by clinicians, measuring the ridge heights and widths of 4 selected implant sites in the maxillary and 2 selected implant sites in the mandibular arches for 91 patients planning for the implant-supported overdenture. (A total of 47 patients out of the 91 had completed the implant placement on the edentulous ridge, contributing to 55 upper and/or lower arches (136 dental implants). . Both predictabilities are low, implying the CBCT planning for implant placement on the edentulous ridge is not a good index and is insufficient to predict the surgical procedures as a solo method. The finding of this study indicates that digital planning by CBCT is insufficient to serve as an individual tool to predict implant procedures. Further information and evaluation must be considered for implant placement on the edentulous ridge.

Patients with neurodegenerative diseases (NDDs) are rapidly increasing all over the world. Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease (HD), frontotemporal lobar degeneration (FTLD) and many other diseases are classified as NDDs, however, no therapeutic drugs have been developed against NDDs yet. As common phenomenon, protein oligomers and aggregates (inclusion bodies) are formed in neurons, and they trigger neuronal cell death and/or axonal degeneration. We have investigated the mechanisms of NDDs, and discovered several chemicals and peptides have potential to cure NDDs. Here, we show phorbol 12-myristate 13-acetate (PMA) significantly inhibits aggregate formation and promotes neurite regeneration in human neuronal cell culture model of NDDs, FTLD and AD. We expressed R406W mutant tau protein found in FTLD patients in human neuroblastoma SH-SY5Y cells as FTLD cell culture model. These FTLD neuronal cells showed intracellular aggregate formation and impaired neurite growth. Addition of PMA to culture medium 60% suppressed aggregate formation. PMA also enhanced neurite growth to the normal level at nanomolar concentration. We cultured SH-SY5Y cells in the medium containing -amyloid (1-42) as AD cell culture model. In these cells, neurite growth was limited to less than 50% of controls by the treatment of -amyloid (1-42). Surprisingly, addition of PMA increased the number of cells with >10-fold neurite extension to seven times even in -amyloid (1-42) contained medium. Also, PMA increased the expression of several genes and proteins important for cell survival in both cell culture models. These results suggest PMA has unexpected potential for the drug development against NDDs.

Ubiquitin-Specific-peptidase 22 (Usp22) cleaves ubiquitin moieties from numerous proteins, in particular transcription factors. Recently, it was reported that Usp22 acts as negative regulator of interferon-dependent responses. In the current study, we investigated the role of Usp22 deficiency upon acute viral infection with lymphocytic choriomeningitis (LCMV) virus. We found that lack of Usp22 on bone marrow derived cells (Usp22 fl/fl Vav1-Cre mice) reduced induction of type I and II interferons. Limited type I interferon response did not influence virus replication. However, restricted expression of PD-L1 led to increased frequencies of functional virus-specific CD8+ T cells and rapid death of Usp22 deficient mice. CD8+ T cell depletion experiments revealed that accelerated CD8+ T cells were responsible for enhanced lethality in Usp22 deficient mice. In conclusion, we found that the lack of Usp22 generated a pathological CD8+ T cell response, which gave rise to severe disease in mice.

Aim: To improve risk stratification in early-stage endometrial cancer (EC), we performed mo-lecular classification, and L1CAM immunohistochemistry (IHC) for additional risk assessment. Method: We analyzed archival tumor tissue from 247 early-stage EC patients. POLE mutations were detected using a Droplet digital polymerase chain reaction assay and Sanger sequencing, while the mismatch repair (MMR) status was determined by MMR protein IHC and MSI test. Additionally, we conducted IHC of p53 and L1CAM. Results: The 247 ECs were categorized into four subgroups: POLE-mutated (13.0%), MMR-deficient (27.9%), p53-abnormal (8.5%), and non-specific molecular profile (NSMP, 50.6%). We further subcategorized NSMP subgroup into NSMP-L1CAMneg (44.9%) and NSMP-L1CAMpos (5.7%), which we refer to as the molecu-lar-L1CAM classification. The molecular-L1CAM classification was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (p <0.001, each). Similarly, the simplified L1CAM-p53 categorization, for practical use, remained an independent prognostic factor for RFS and OS (p <0.001, p =0.003, respectively). Conclusion: Integrating the molecu-lar-L1CAM classification or the simplified L1CAM/p53 categorization can enhance risk stratifi-cation in early-stage EC, providing valuable prognostic information to guide treatment deci-sions and improve patient outcomes.

Background: External beam radiation therapy requires a sophisticated and laborious planning procedure. To improve the efficiency and quality of the planning procedure, machine learning predictions of the dose distributions have been introduced to speed up the planning procedure and to serve as quality assurance. The most recent dose prediction models are based on deep learning U-Nets that give good approximations of the dose in 3D almost instantly. It is our purpose to train a 3D dose prediction for glioblastoma VMAT treatment and test its robustness and sensitivity for the purpose of quality assurance of automatic contouring. Methods: From a cohort of 125 glioblastoma (GBM) patients, VMAT plans were created according to a clinical protocol. The initial model was trained on a concatenated 3D U-Net. A total of 60 cases were used for training, 15 for validation and 20 for testing. The prediction model was tested for sensitivity to dose changes according to realistic contour variations. Additionally, the model was tested for robustness by exposing it to a worst-case test set containing out-of-distribution cases.Results: The initially trained prediction model had a dose score of 0.94 Gy and a mean DVH score for all structures of 1.95 Gy. In terms of sensitivity, the model was able to predict the dose changes that occurred due to the contour variations with a mean error of 1.38 Gy.Conclusions: We obtained a 3D VMAT dose prediction model for GBM with limited data, providing good sensitivity to realistic contour variations. We tested and improved the model's robustness, by targeted updating the training set, making it a useful technique for dose awareness in the contouring evaluation and quality assurance.

Background: The oral health-related quality of life (OHRQoL) assessment evaluated the impact of individual’s oral health on the patient's physical and psychosocial status. We evaluated the association between subjective OHRQoL, measured with the Oral Health Impact Profile-14 (OHIP-14) questionnaire, and unfavorable body mass index (BMI) (i.e., too high or too low) in a large population-based study on older adults from Southern Italy. Moreover, we assessed which of the seven OHIP-14 domains was most strongly associated with an unfavorable BMI. Methods: We used data on a subpopulation of the Salus in Apulia Study, including 216 older adults. BMI &lt;18.4 kg/m2 and &gt;30 kg/m2 were classified as unfavorable, values between 18.5 and 30 kg/m2 were classified as ideal. Results: Higher OHIP-14 total score increased the risk to have an unfavorable BMI [odds ratio (OR):1.08, 95% confidence interval (CI):1.01-1.15]. In the model adjusted for age, sex, education, hypertension, carbohydrate consumption, and alcohol consumption, this finding was confirmed with higher OHIP-14 total score increasing the risk to have an unfavorable BMI (OR:1.10, 95% CI:1.01-1.22), and higher age linked to a decreased risk to have an unfavorable BMI (OR:0.89, 95% CI:0.82-0.97). In a random forest regression model, the most important predictive domains/sub-scales of OHIP-14 in mean decrease Gini for unfavorable BMI were, in order of decreasing importance, physical pain, functional limitation, psychological discomfort, physical disability, social disability, psychological disability, and handicap. Conclusions: In older age, negative OHRQoL, particularly linked to the physical pain domain, increased the risk of underweight or overweight and obesity.

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, USFDA has given expedited approval to bedaquiline (BDQ), as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis but due to poor solubility desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of Bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of Bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88±2.1 nm with a zeta potential of 21.16 mV. In vitro, studies showed enhanced drug release with a high degree of stability at 25 ± 2 ºC & 60 ± 5 % and 40 ± 2 ºC & 75± 5 %. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological aims, were presently tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues, and to assess calcium antagonism in comparison to amiodarone, lidocaine, procainamide, and quinidine. All compounds, but two, compared favorably with the reference drugs. Potent antiarrhythmic activity was observed for compounds (in increasing order) 4, 1, 6 and 5. The last compound N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase of threshold of ac-arrhythmia, and being devoid of antihypertensive activity against spontaneously hypertensive rats.

Background: Obtaining adipose-derived stem cells is limited by its capacity to differentiate. Stimulation by platelet-rich fibrin appears to have the beneficial effects to accelerate differentiation. Objective: To obtain immunohistochemistry evidence of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells. Methods: We used post-test only controlled-group design. Adipose-derived stem cells were isolated and cultured until 4 passages in α-MEM culture medium. Results: GATA-4 expression increased in platelet-rich fibrin group compared with control group (68.20±6.82 vs 58.15±1.23 counts; p<0.05; 68.20±6.82 vs 52.96±2.02 counts; p<0.05). Troponin expression also increased in platelet-rich fibrin group (50.66±7.2 vs 10.73±2.39 counts; p<0.05; 50.66±7.2 vs 26.00±0.4 counts; p<0.05). Conclusion: There is an immunohistochemistry benefit of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells into cardiomyocyte-like cells.

Alopecia refers to the continuous shedding of hair from the scalp or other areas. Genetic factors are the most common of the variety of causes of alopecia. Male pattern baldness, also known as androgenic alopecia, is prevalent. Recently, the interest in hair loss treatment has increased due to the growing number of people experiencing anxiety and stress related to hair loss. Nepenthes kampotiana Lecomte is known for its anticancer effects, but its potential for preventing hair loss has not been researched. Therefore, this study focused on the hair loss prevention effects of N. kampotiana Lecomte ethanol extract (Nk-EE). The results showed that Nk-EE has a proliferative effect on human follicle dermal papilla cells and inhibited cell death. In vivo experiments using androgenic areata models showed that Nk-EE had a positive effect on a variety of biomarkers such as hair-to-skin ratio, hair type frequency, and hair thickness. The results of this study suggest that Nk-EE has the potential to be an effective treatment for androgenic alopecia.

Febrile seizure (FS), which occurs as a response to fever, is the most common seizure that occurs in infants and young children. FS is usually accompanied by diverse neuropsychiatric symptoms including impaired social behaviors; however, no causative link between FS and autism spectrum disorder (ASD) has yet been established. Here, we provide evidence linking FS occurrence with ASD pathogenesis in rats. We developed an FS juvenile rats model and found ASD-like abnormal behaviors including deficits in social novelty, repetitive behaviors, and hyperlocomotion. In addition, FS model juvenile rats showed enhanced levels of gliosis and inflammation in the hippocampal CA2 region and cerebellum. Furthermore, abnormal levels of social and repetitive behaviors persisted in adults FS model rats. These findings suggest that occurrence of FS in infants can cause behavioral endophenotypes of ASD.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten time to antibiotic administration in the Emergency Department. We retrospectively evaluated all patients above 18 years of age that were diagnosed with sepsis or severe infection in our Emergency Department between 2018 and 2020. We recorded the suspected diagnosis at time of presentation, type of referring healthcare provider and time until initiation of antibiotic treatment. Differences between groups were calculated using Kruskal-Wallis rank sum test. Of the 277 patients that were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well described outcome benefits to early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce time to antibiotic administration and improve patient outcomes.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

Chlorhexidine digluconate (CHX) has shown the ability to significantly reduce inflammation and marginal bone loss (MBL) at 1-year follow-up but limited data exists regarding its long-term efficacy in peri implant stability. The objective was to compare the long-term effects of a placebo gel (16 patients in Group A) or a 0.20% CHX gel (15 patients in Group B) used at each previous surgical and prosthetic stage. Follow-ups were conducted in 2022, investigating by biological, radiological, clinical, mechanical evaluation the long-term effects. Data were statistically analyzed. The research achieved a 96.7% implant success rate over five years, but 41.9% of patients didn't attend annual oral hygiene check-ups. The average MBL was 1.04 ± 0.39 mm, with no significant differences between the two groups. Notably, patients who attended regular periodontal check-ups experienced significantly less MBL than those who didn't (p &lt;0.05). At five years, the effects of CHX were reduced, with both groups showing moderate bone loss. The results suggest early disinfection could enhance both short and long-term outcomes. In fact, patient with initial minor MBL preserve this advantage also at 5 years of follow-up. Additionally, the data underscore the importance of annual check-ups in early detection and management of biological and mechanical complications.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications, as well as HbA1c. This cross-sectional observational study consisting of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values analyzing biochemical and body composition measurements. Shapiro-Wilk test with Lilliefors correction, non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-1 ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

Mitochondrial dysfunction has been linked to psoriasis, and may be an important underlying factor contributing to this disease. However, a precise methodology for assessing mitochondrial dysfunction has yet to be developed. One promising approach is to measure NADH autofluorescence from affected skin areas. In this study, we show that Flow Mediated Skin Fluorescence (FMSF) can be used for non-invasive assessment of mitochondrial dysfunction in psoriasis. The fluorescence level at baseline and the half-time of ischemic growth (t1/2) derived from the FMSF traces can be used for non-invasive assessment of NADH/NAD+ redox imbalance in psoriatic lesions compared to unaffected skin. These results are supported by analysis of the key FMSF parameters, Reactive Hyperemia Response (RHR) and Hypoxia Sensitivity (HS). This method not only contributes to understanding of the biochemical processes involved in the etiopathogenesis of psoriasis, but also provides a basis for identifying new drug targets and improving the treatment process.

Age-related macular degeneration (AMD) causes visual impairment in individuals >50 years of age. However, no study has investigated AMD using ultra-wide-field swept-source optical co-herence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thickness using UWF SS-OCT and compare AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare cho-roidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9–18 mm from the fovea. PNV patients were significantly younger than those with tAMD (P=0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (P<0.01) and choroidal thickness significantly correlated with age and axial length in all subfields (P<0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (P<0.05). In addition, the ratio of the posterior < 9 mm to peripheral 9–18 mm choroidal thickness in PNV was significantly greater than that in tAMD (P<0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.

Since first described by Dr. Tomisaku Kawasaki in 1967, the clinical diagnosis of Kawasaki disease (KD) has remained relatively unchanged. However, studies since then have suggested that diagnoses using only that original clinical criteria may lead to underdiagnosis. In this review, updated KD diagnostic methods, diagnostic methods for “atypical” KD, diagnostic pitfalls, and other differential diagnoses are discussed. Peripheral blood eosinophil showed important in distinguishing KD from febrile children. We review herein the current literature regarding new biomarkers, scoring systems, and microRNA panels that may aid in the diagnosis of KD, the importance of eosinophil and treatment updates.

Adipose tissue has acquired considerable importance due to its role in maintaining body homeostasis. Beyond storing energy, adipose tissue is essential in numerous processes of energy metabolism, food intake, endocrine and immunological functions as well as neromodulatory functions by secreting hormones that participate in the regulation of homeostasis and being responsive to soluble proteins secreted by other tissues. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favouring the secretion of deleterious adipocytokines that benefit a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases. Obesity is a disease that has increased rapidly in recent decades and is caused by environmental, hormonal, and genetic factors, which probably work in combination. Environmental factors that contribute to the increase in obesity include decreased physical activity, associated with increased screen time, increased accessibility and consumption of foods rich in fats and sugars. Weight loss should be recommended for all obese patients and overweight patients with comorbidities. For many patients who need to lose weight for medical reasons, the initial goal is to lose 5-10% of their body weight in the first 6 months. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity and in Chile, the Chilean Society of Metabolic and Bariatric Surgery led the process of adopting the adult obesity clinical practice guideline, which establishes changes in the approach to managing obesity as a chronic disease, with an emphasis on multifactorial lifestyle interventions that include dietary changes, increased physical activity, and behavioural modifications. Pharmacotherapy, medical devices, and bariatric surgery are other options for patients who need additional interventions, so the objective of this review is to know the pathophysiological mechanisms of obesity from its origin to the current treatments available for treatment.

Background: Calcaneal fractures are the most frequent traumatic injuries of the hindfoot and can cause severe disability with social and economic sequelae; since 1980 an increasing number of studies and new technologies have led to an improvement in their management and complications but treatment is still controversial. The purpose of the study to review the secondary scientific literature looking for the optimal management of calcaneal fracture; Methods: through the PubMed MEDLINE database, 4856 articles were identified; only meta-analyses and systematic reviews were included in the study. Results: 59 reviews with more than 10,000 calcaneus fractures were examined and results were divided into various topics; the majority of articles agree on the superiority of surgical versus conservative treatment; minimally invasive access to the sinus tarsi shows better results and fewer complications than traditional extended lateral access; reduction and osteosynthesis with percutaneous and/or minimally invasive techniques seem to provide better outcomes if compared to open treatments. Conclusions: The management of calcaneus fractures requires an individualized planning based on the functional demands of the patient, the type of fracture and associated injuries. New technologies and further studies may still improve the management of these lesions.

Obesity represents a worldwide epidemic disorder, increasing the overall morbidity and mortality rate. In this study we investigated the impact of obesity on peri-operative and long-term functional outcomes of Robotic assisted simple prostatectomy (RASP). Baseline flowmetry parameters and validated questionnaires’ scores were prospectively recorded. Follow-up assessments included Flowmetry and validated questionnaires. Composite outcomes (Trifecta) was defined as combination of: post-operative Q-max>15 ml/sec, IPSS score<8 and absence of complications. Pentafecta included also post-operative ejaculation persistence (MSHQ score>0) and the Erectile function maintenance (∆IEEF<6). Data were stratified by BMI (<30 or ≥30). 81 patients underwent RASP in our Institution. Baseline demographics and clinical features, questionnaires score and baseline flowmetry results were comparable between obese and non-obese cohorts. At follow-up, obese patients reported lower subjective improvement in IPSS (p=0.02) and OABQ scores (p<0.001) and higher incidence of stress incontinence requiring Duloxetin (p<0.001). Flowmetry outcomes, were also worse in this cohort (p=0.02 and p=0.03, respectively). At comprehensive outcomes assessment, obese patients had comparable Trifecta (67% vs 54%, p=0.39) and pentafecta achievement rate (p=0.76). Our prelimirary results proved that obesity is associated with worse functional outcomes (storage LUTS and incontinence rate) after RASP, but doesn’t affect trifecta and pentafecta achievement rate.

Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.

Purpose: To compare refractive prediction error (PE)s between phacotrabeculectomy and phacoemulsification. Methods: Refractive PE was defined as the difference of spherical equivalent between the predicted value using the Barrett Universal II formula and the actual value obtained at postoperative one month. Forty-eight eyes that had undergone phacotrabeculectomy (19 eyes, open-angle glaucoma; 29 eyes, angle-closure glaucoma) were matched with 48 eyes that had undergone phacoemulsification by age, average keratometry value and axial length (AL), and their PEs were compared. The factors associated with PE were analyzed by multivariable regression analyses. Results: Phacotrabeculectomy group showed a larger absolute PE compared to the phacoemulsification group (0.51 ± 0.37 Diopters vs. 0.38 ± 0.22, P=0.033). Larger absolute PE was associated with longer AL (P=0.010) and higher intraocular pressure (IOP) difference (P=0.012). Hyperopic shift (PE>0) was associated with shallower preoperative anterior chamber depth (ACD) (P=0.024) and larger IOP difference (P=0.031). In the phacotrabeculectomy group, the PE was inversely correlated with AL: long eyes showed myopic shift and short eyes hyperopic shift (P=0.002). Conclusions: Surgeons should be aware of the possibility of worse refractive outcomes when planning phacotrabeculectomy especially in eyes with high preoperative IOP, shallow ACD, and/or extreme AL.

Background: The aim of this study was to design and analyze the content validity of an instrument to assess the risk of behaviors associated with the Chemsex phenomenon since there is currently no instrument with this objective. Method: Firstly, a bank of items identified from the literature was elaborated. Secondly, 50 experts with knowledge of the Chemsex phenomenon at the national level were contacted. A Delphi group was formed with them to carry out two rounds of item evaluation (comprehension and appropriateness) using a Likert scale of 1 to 5. To assess linguistic validity, the mean score of the item comprehension scores was used. The content validity index (CVI) and Aiken's V (VdA) were calculated for each item. A minimum value of CVI and VdA of 0.6 was established to include the items in the questionnaire. Results: In the first round of evaluation, 36 experts evaluated 114 items, of which 61 were selected. In a second round, 30 experts evaluated the 61 items selected, leaving the scale finally made up of 52 items. Conclusion: A questionnaire has been designed to assess the risk of behaviors associated with the Chemsex phenomenon. The items that make up the questionnaire have shown adequate content and linguistic validity, so this instrument can be considered valid. The Delphi method proved to be a useful technique for the proposed objective.

Background and objectives: Huntington disease (HD) is characterized by motor, cognitive and psychiatric manifestations and is caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27-35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and to evaluate any differences between bipolar patients carrying normal HTT allele and patients with expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients affected by bipolar disorder type 1 and type 2. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls.

Background The prognostic value of estimated pulse wave velocity (ePWV) has been infrequently explored in high-risk patient groups. Our study aimed to evaluate the prognostic significance of ePWV among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods A total of 4,119 consecutive subjects who underwent PCI with DES (mean age, 67.1 ± 11.6 years and 33.1% were female) were retrospectively analyzed. ePWV was calculated based on the patient’s age and mean blood pressure. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke, were evaluated. Reults During a median follow-up duration of 3.51 years (interquartile range, 1.35 ~ 6.37 years), there were 746 MACE (18.1%). Multivariable analysis showed that higher ePWV was associated with higher MACE incidence (middle tertile vs. the lowest tertile: hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.81-3.42; P < 0.001; the highest tertile vs. the lowest tertile: HR, 6.18; 95% CI, 4.33-8.80; P < 0.001) The inclusion of ePWV data significantly increased the global chi-square values when added to the clinical information (from 96 to 128; P < 0.001). Conclusion ePWV demonstrated a significant association with MACE in patients who underwent DES implantation. Given its relative simplicity to calculate, ePWV could potentially serve as a valuable instrument for stratifying cardiovascular risk within this high-risk patient population.

Background: Abdominal migraine (AM) is a clinical diagnosis specified by Rome IV and ICHD III as a functional gastrointestinal disease (FGID) and a migraine associated syndrome, respectively. AM is undiagnosed and undertreated, and thus far the FDA has not approved any drug for AM treatment. We and others showed that changes in the kynurenine (KYN) pathway of tryptophan (TRP) metabolism played an important role in the pathogenesis and treatment of FIGDs. Changes in the KYN pathway were shown in migraine. Findings: Abdominal migraine reflects impairments in communication within the gut-brain axis. Treatment approaches have not been sufficiently documented and are based on experience of physicians, presenting personal rather than evidence-based practice and including efficacy of some drugs used in adult migraine. Non-pharmacological treatment of AM is aimed preventing or ameliorating AM triggers. Modulations within the KYN pathway of TRP metabolism induced by changes in TRP content in the diet, may ameliorate FGIDs and support their pharmacological treatment. Pharmacological manipulations of brain KYNs in animals have brought promising results for clinical applications. Conclusions: In conclusion, controlled placebo-based clinical trials with dietary manipulation to adjust the amount of the product of the KYN pathway of TRP metabolism are justified in children and adolescents with AM. Further preclinical studies are needed to establish details of these trials.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

(1) Background: Colon polyps are common protrusions in the colon’s lumen with potential risks of developing colorectal cancer. Early detection and intervention of these polyps are vital for reducing colorectal cancer incidence and mortality rates. This research aims to evaluate and compare the performance of three machine-learning image classification models’ performance in detecting and classifying colon polyps. (2) Methods: The performance of three machine learning image classification models, Google Teachable Machine (GTM), Roboflow3 (RF3), and You Only Look Once version 8 (YOLOV8), in the detection and classification of colon polyps were evaluated. The study used a dataset of colonoscopy images of normal colon, polyps, and resected polyps. The study assessed the models’ ability to correctly classify the images into their respective classes using precision, recall, and F1 score generated from confusion matrix analysis and performance graphs. (3) Results: All three models successfully distinguished between normal colon, polyps, and resected polyps in colonoscopy images. GTM achieved the highest accuracies: 0.99, with consistent precision, recall, and F1 scores of 1.00 for the `normal’ class, 0.97 - 1.00 for `polyps,’ and 0.97 - 1.00 for `resected polyps.’ While GTM exclusively classified images into these three categories, both YOLOV8 and RF3 extended their capabilities to detect normal colonic tissue, polyps, and resected polyps, with YOLOV8 and RF3 achieving overall accuracies of 0.84 and 0.87, respectively. (4) Conclusions: Machine learning, particularly models like GTM, shows promising results in ensuring comprehensive detection of polyps during colonoscopies.

Urothelial cell carcinoma (UCC, bladder cancer) remains a difficult to treat malignancy with rising incidence worldwide. In the U.S., UCC is the sixth most incident neoplasm and ~90% of diagnoses are made in those &gt;55 years of age, ~four times more commonly observed in men than women. The most important risk factor for developing bladder cancer is tobacco smoking, which accounts for ∼50% of cases followed by occupational exposure to aromatic amines and ionizing radiation. The standard of care for advanced UCC includes platinum-based chemotherapy and programmed cell death (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors, administered as frontline, second-line, or maintenance therapy. UCC is highly aggressive and remains generally incurable since these cancers are associated with intrinsic and acquired drug resistance. UCC is highly lethal in the metastatic state and characterized by genomic instability, high PD-L1 expression, DNA damage-response mutations, and high tumor mutational burden. Although immune checkpoint inhibitors (ICIs) achieve long-term durable responses in other cancers, their ability to achieve similar results with metastatic UCC (mUCC) is not as well-defined. Here, we discuss the novel therapies to improve the management of mUCC.

Heart rate variability (HRV) is a measurement of the fluctuation of time between each heartbeat and reflects the function of the autonomic nervous system. HRV is an important indicator for both physical and mental status and for broad-scope diseases. In this review, we discuss how wearable devices can be used to monitor HRV, and we compare the HRV monitoring function among different devices. In addition, we have reviewed the recent progress in HRV tracking with wearable devices and its value in health monitoring and disease diagnosis. Although many challenges remain, we believe HRV tracking with wearable devices is a promising tool that can be used to improve personal health.

The practice of teaching and scientific research on cadaveric material remains crucial for medical education, especially in surgical disciplines. However, in Italy, this practice has been neglected due to legislative insufficiency and financial constraints. Although innovative methods and tools like simulators and e-learning have been adopted, direct hands-on experience with human cadavers remains irreplaceable for medical and surgical education. The absence of clear legislation governing cadaveric dissection has limited availability for teaching and research, resulting in economic burdens for universities and individuals seeking proper surgical training. To address this issue, the Law No. 10/2020 and the recent implementing decree were introduced in Italy, providing detailed legislation on the donation of bodies for educational and research purposes. The law emphasizes the importance of respecting the donor's specific choices and aligns with constitutional principles promoting culture, research, and health protection. However, some critical issues related to consent procedures, duration of body availability, and preservation of anatomical parts remain. Additionally, the law's dissemination among the population needs improvement. Future optimization could include allowing donors to choose the timing of body donation and considering different timeframes for body availability. Furthermore, the implementation of consent procedures could be simplified to increase donations. The law should also address the need for appropriate reception centers and allocate resources for effective dissemination. Despite these challenges, Law No. 10/2020 represents a significant step forward in enhancing medical-surgical training, scientific research, and the overall quality of patient care in Italy.

Postoperative adhesive arachnoiditis is an inflammatory response of the spinal leptomeninges that occurs after surgery, resulting in scar formation in the avascular nature of the arachnoid layer. Clinical manifestations of this condition include pain, sensory deficits, motor dysfunction, reflex abnormalities, and bladder/bowel impairments. In MRI scans, the signs of postoperative adhesive arachnoiditis can vary, but some specific indicators can assist surgeons in locating the lesion and planning surgical interventions more accurately. In this report, we reported a 37-year-old man with postoperative adhesive arachnoiditis after two surgeries for Chiari I malformation, demonstrating that the gradually-forming the delta cord sign with sequential syringomyelia. During the intraoperative examination, we identified the presence of the delta cord sign, which was formed by an arachnoid scar that was tethering the dorsal spinal cord to the dura. This discovery allowed us to precisely pinpoint the location of the arachnoid scar, thereby providing valuable guidance to avoid any unnecessary exploration of innocent structures during the procedure. Other localization signs were also reviewed.

Immune checkpoint blockade therapy has shown successful clinical outcomes in multiple human cancers. In dogs, several types of tumors resemble human tumors in many respects. Therefore, several groups have developed the anti-dog programmed cell death ligand 1 (dPD-L1) monoclonal antibodies (mAbs) and showed efficacy in several canine tumors. To examine the abundance of dPD-L1 in canine tumors, anti-dPD-L1 diagnostic mAbs for immunohistochemistry are required. In this study, we immunized the peptide in the dPD-L1 intracellular domain, and established anti-dPD-L1 mAbs, L1Mab-352 (mouse IgG1, kappa) and L1Mab-354 (mouse IgG1, kappa). In enzyme-linked immunosorbent assay, L1Mab-352 and L1Mab-354 showed high binding affinity to the dPD-L1 peptide, and the dissociation constants (KD) were determined as 6.9 ×10-10 M and 7.2 ×10-10 M, respectively. Furthermore, L1Mab-352 and L1Mab-354 were applicable for the detection of dPD-L1 in immunohistochemical analysis in paraffin-embedded dPD-L1-expressed cells. These results indicated that L1Mab-352 and L1Mab-354 are useful for detecting dPD-L1 in immunohistochemical analysis.

Intra-abdominal pressure (IAP) elevation during capnoperitoneum can cause adverse cardiovascular and respiratory effects. This study aimed to determine if a sequentially increased IAP affects cardiovascular and respiratory variables in anesthetized dogs and evaluate the effects of constant rate infusion of dexmedetomidine (Dex) on cardiovascular and respiratory variables with increased IAP. Five dogs were anesthetized, instrumented, and the Veress needle was equipped to adjust the IAP using a carbonic anhydrase insufflator. Stabilization was conducted for 1 h, and physiological variables were measured in IAPs of 0, 5, 10, 15, and 20 mmHg and after desufflation. After the washout period, the dogs underwent similar procedures along with constant rate infusion of dexmedetomidine. Cardiovascular effects of increased IAP up to 20 mmHg were not significant in healthy beagle dogs and those administered with dexmedetomidine. In the control group, the arterial pressure slightly increased, but not statistically significant, at an IAP of 20 mmHg compared with that at baseline (mean arterial blood pressure, p = 0.399; systolic arterial blood pressure, p = 0.293; diastolic arterial blood pressure, p = 0.141). When comparing the control and dexmedetomidine groups, overall significant effects of dexmedetomidine were noted on heart rate, cardiac output, and systemic vascular resistance during the experiment. Respiratory effects were not affected by abdominal insufflation when compared between different IAPs and between the two groups. Overall, an increased IAP of until 20 mmHg did not significantly affect cardiovascular and respiratory variables in both control and dexmedetomidine groups. This study suggests that dexmedetomidine infusion administration is applicable in laparoscopic procedures in healthy dogs.

Licochalcone H (LCH), a regioisomer of licochalcone C derived from the root of Glycyrrhiza inflata. CRC treatment has always been challenged by the development of resistance. We investigated the antiproliferative activity of LCH in oxaliplatin (Ox)-sensitive and -resistant CRC cells. LCH significantly inhibited cell viability and colony growth in both Ox-sensitive and Ox-resistant CRC cells. We found that LCH decreased epidermal growth factor receptor (EGFR) and AKT kinase activities and related activating signaling proteins including phospho (p)-EGFR and pAKT. A computational docking model indicated that LCH may interact with EGFR, AKT1, and AKT2 at the ATP-binding sites. LCH induced ROS generation, as verified by N-acetyl-L-cysteine (NAC) treatment, and increased the expression of the ER stress markers. LCH treatment of CRC cells induced depolarization of MMP and increased. Multi-caspase activity was induced by LCH treatment and confirmed by Z-VAD-FMK treatment. LCH increased the number of subG1 cells and arrested the cell cycle at the G1 phase. LCH inhibits the growth of Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, and inducing ROS generation and ER stress-mediated apoptosis. Therefore, LCH could be a potential therapeutic agent for improving not only Ox-sensitive but also Ox-resistant CRC treatment.

Aim The use of prophylactic antibiotics prior to colorectal surgery reduces surgical site infections. Cefazolin and metronidazole is a standard regimen. Ampicillin-sulbactam may be an alternative, but the data are limited. We compared the efficacy of ampicillin-sulbactam with cefazolin and metronidazole as prophylactic antibiotics. Methods Patients who underwent colorectal surgery at Inha University Hospital between 2010 and 2020 were treated prophylactically with cefazolin and metronidazole or ampicillin-sulbactam, and observed for 30 days following surgery. The primary outcome was surgical site infections. Secondary outcomes were deep/organ infections and the need for drainage. Results SSIs occurred in 2.6% (17/646) of the ampicillin-sulbactam group and was not inferior to the occurrence in the cefazolin and metronidazole group (3.8%, 21/556). There was no significant difference between the two groups in the secondary outcomes. Conclusion Compared with the cefazolin and metronidazole combination, the ampicillin-sulbactam group is non-inferior as a preoperative prophylactic antibiotic regimen for colorectal surgery.

Lycopene is a compound of colored origin that shows strong antioxidant activity. The ability to neutralize free radicals by lycopene is the basis of its pro-health effect, including the ability to inhibit the development of many civilization diseases. Therefore, this study focuses on the importance of the antioxidant effect of lycopene in inhibiting the development of such diseases as cardiovascular diseases, diseases of the etiology of etiology, diseases within the nervous system.

Microbiological control of dental pathologies presents a significant clinical challenge for dental surgeons, particularly considering drug-resistant microorganisms. To address this issue, Antimi-crobial Photodynamic Therapy (PDT) has emerged as an effective and complementary technique for microbial reduction. This therapy involves the application of a photosensitizer dye (PS) either topically or systemically, followed by exposure to low-power lasers with appropriate visible light wavelengths. PDT has found a valuable place in dentistry across various specialties, including surgery, periodontics, endodontics, dentistry, implantology, orthodontics, and pediatrics. In the realm of pediatric dentistry, managing microorganisms during dental treatments has become a major challenge.This article reviews the evidence supporting the potential of photodynamic therapy in combating bacteria, fungi, and viruses, with a particular focus on areas such as endodontics, restoration in deciduous teeth, implantology, and periodontics for bacterial control. Additionally, PDT has shown promise in stomatology, specifically in the treatment of mucositis and herpes. Considering its promising results and ease of application, photodynamic therapy presents an in-teresting alternative for clinical practice. However, it is important to note that specific protocols must be followed for each application, encompassing the type of photosensitizer, concentration, pre-irradiation time, light type, wavelength, energy, power, and mode of light delivery. Researchers have been steadily refining these protocols to facilitate PDT's integration into clinical practice.

Low nasal nitric oxide (nNO) is a typical feature in Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases such cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma and urine by validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p &lt; 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p &lt; 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p &lt;0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.

Background: To our knowledge, the sudden onset of symptomatic pulmonary hypertension after COVID-19 vaccination has not been described. Both cases presented here resulted in functional limitations and likely permanent organ damage. Case Summary: We report two cases of acute onset pulmonary hypertension in previously healthy adult males within three weeks of receiving the second dose of the Pfizer (BNT162b2) mRNA COVID-19 vaccine from different lots. Both patients experienced the sudden onset of severe fatigue and dyspnea on exertion with negative COVID-19 PCR testing. The diagnosis was made by serial transthoracic echocardiography in the first case and by both transthoracic echocardiography and right heart catheterization in the second. Discussion: Pulmonary hypertension is a serious disease characterized by damage to lung vasculature and restricted blood flow through narrowed arteries from the right to left heart. The onset of symptoms is typically insidious, progressive and incurable, leading to right heart failure and premature death. The World Health Organization (WHO) classifies pulmonary hypertension into 5 categories and recently re-defined as a resting mean pulmonary artery pressure greater than 20 mmHg. Sudden onset pulmonary hypertension would only be expected in the settings of surgical pneumonectomy or massive pulmonary emboli with compromise of at least 50% of the lung vasculature.

(1) Background: This study aimed to evaluate the role of cervical pessary for preventing preterm birth in singleton pregnant women with a cervical length (CL) ≤25 mm and a uterocervical angle (UCA) ≥95o and ≥105o. (2) Methods: A quasi-experimental study was conducted on 225 singleton pregnant women with a gestational age of 16+o-23+6 weeks and transvaginal ultrasound CL measurements ≤25 mm, whose pregnancy was man-aged at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, from September 2020 to September 2022. Participants were allocated into two groups: prophylactic treatment with progesterone (123 pregnant women) and combined with a cervical pessary (102 pregnant women). The UCAs measured via transvaginal ultrasound by a single sonographer were divided into groups with UCA measurements ≥95o and ≥105o. The gestational age at birth was classified into full-term and preterm <37 weeks and <34 weeks. A binary regression model assessed the association between CL, UCA, and pre-term birth outcomes. The difference was statistically significant, with p<0.05. (3) Results: There was no statistically significant difference in the rate of preterm birth <37 weeks and <34 weeks between the two groups (16.3% vs. 11.8% and 6.5% vs. 4.9%, p>0.05). The probability of preterm birth <37 weeks in the group of pregnant women with a UCA ≥95o treated via cervical pessary plus progesterone decreased by 60.6%, OR (95% CI) of 0.394 (0.165-0.941), p<0.05. In the group of pregnant women with a UCA ≥105o, there was a significant association in the group of progesterone treatment combined with a cervical pessary, with the lower rate of PTB <37 weeks and <34 weeks, with OR (95% CI) of 0.028 (0.005-0.146), p<0.001, and 0.141 (0.030-0.664), p<0.05, respectively. (4) Conclusion: The results of this study suggest that cervical pessary is beneficial to the prevention of preterm birth in singleton pregnant women with an obtuse uterocervical angle. Further randomized studies among pregnant women with obtuse uterocervical angles will be needed to clarify the role of a cervical pessary in preventing preterm birth.

Background: Recent advances allow the usage of Augmented Reality (AR) for many medical procedures. We perform different AR-assisted knee surgery techniques using optical surgical navigation with ArUco-type artificial marker sensors. Our study aimed to evaluate the system’s accuracy using an in vitro protocol. We hypothesised that the system’s accuracy was equal to or less than 1mm and 1° for distance and angular measurements, respectively. Methods: Our research was an in-vitro laboratory with a 316 L steel model. We evaluated absolute reliability according to the Hopkins criteria with seven independent evaluators. Each observer measured the thirty palpation points and the trademarks to acquire direct angular measurements on three occasions separated by at least two weeks. Results: The accuracy of the system to assess distances had a mean error of 1.203mm and an un-certainty of 2.062, and for the angular values, a mean error of 0.778° and an uncertainty of 1.438. The intraclass correlation coefficient was for all intra-observer and inter-observer almost perfect or perfect. Conclusions: The mean error for the distance’s determination has been statistically larger than 1mm (1.203mm) but with a trivial effect size. The mean error assessing angular values was sta-tistically minor than 1°. Our results are similar to those published by other authors in accuracy analyses of AR systems.

Background and objectives: Thoracolumbar fracture – dislocations (AO type C) are rare injuries that occur due to very high-energy trauma, and the result is transitional and rotational instability of the spinal column and neurological impairment. Several reduction maneuvers have thus far been published, each of which can be of use in certain specific situations. We developed a novel modification to the previously described reduction technique. Materials and methods: This is a retrospective review of the management of thoracic AO type C fracture-dislocations managed with a modified novel reduction technique. The success of the reduction and intraoperative iatro-genic complications such as dural tear and screw pull out were the outcomes analyzed. Results: A total of 4 cases were successfully reduced with this novel reduction technique. We did not note any complications such as a dural tear or screw failure with this modified novel reduction tech-nique. Conclusion: The novel modification to the reduction technique employed in the management of thoracic fracture-dislocations resulted in a successful reduction without the risk of iatrogenic complications due to the reduction maneuver.

This scoping review aims to identify the available evidence concerning the clinical and psychosocial impacts of the communication of oral potentially malignant disorders (OPMDs), and to map and analyze knowledge gaps regarding truth-telling about risk factors, malignant transformation, treatment, and follow-up approaches. Search strategy was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Each publication involved a different study design, study population, types of OPMDs, and results on the important aspects of the professional-patient communication about the diagnosis of OPMDs. Although specific protocols on OPMDs communication have not yet been reported, there is an elevated interest on this topic since the strategies and skills on professional communication could provide better clinical outcomes to the patients. A list of recommendation strategies on how to communicate an OPMD diagnosis is proposed; however, future studies are still needed to design specific communication protocols for OPMD.

Myxoid endometriosis is a rare entity that is part of the histological changes that can occur in endometriosis. It is extremely important that the pathologist has knowledge of the histological guidelines for the morphological recognition of this entity, as well as the histochemical and immunohistochemical techniques that will support the diagnosis. Define the morphological characteristics of myxoid endometriosis. In the present work we propose diagnostic approach guidelines, as well as the main differential diagnoses with the use of special histochemical techniques and immunohistochemical reactions to recognize this entity.

In recent years, the number of open preservation surgeries for treatment of laryngeal Cancer has increased. The purpose of this surgery is to avoid the highly mutilating intervention of a total laryngectomy (TL) and to maintain laryngeal function while ensuring oncological radicality. The aim of this study was to assess the oncologic results of OPHL I and II and to identify prognostic factors that could impact patient survival and local failure rates. This study was conducted on 182 patients with laryngeal squamous cell carcinoma treated with OPHLs between 2005 and 2015. The survival rates of a group of patients treated with TL between 2004 and 2014 were taken into con-sideration to compare survival outcomes. The DSS in pT2 and pT3 tumors in relation to the type of surgery showed no statistically significant difference between OPHLs and TL (p=0.54 and p=0.63 respectively). The 5-years T-recurrence free survival showed that pT4 tumors, perineural/vascular positive invasion and OPHL IIb + ARY treated tumors were associated with a higher risk of tumor recurrence (p<0.0001, p=0.0005 and p=0.016 respectively). OPHLs represent an excellent alterna-tive to TL considering the characteristics of the tumor and the general conditions of the patient.

In order to provide a new direction for the diagnosis and treatment of gastric cancer, the differentially expressed blood-based miRNAs in gastric carcinoma were obtained and analyzed from the datasets GSE113486, GSE112264 and GSE113740 by the SangerBox, the miRNA - target genes prediction, GO and KEGG functional enrichment analyses with DAVID 6.8, and the STRING database with Cytoscape, respectively. The correlation between the key miRNAs expression and the prognosis and diagnostic value of gastric cancer patients were detected by survival prognosis and ROC curve. QRT-PCR was used to detect the possible key miRNAs expression in human blood species. The dataset GSE108307 which shows the miRNAs affected by H. pylori infection was analyzed by GEO2R. The expression level of CagA and the clinically used gastric cancer markers were detected in human blood species for contrast. Five key blood-based miRNAs were determined, including hsa-miR-124-3p, hsa-miR-125a-3p, hsa-miR-29b-3p, hsa-miR-4276, and hsa-miR-575.The detection in human blood species as well as the cross analysis with H. pylori infection and clinically used markers expression suggested the importance and efficacy of the specific miRNAs in the early diagnosis and monitoring of gastric carcinoma. The study identified potential novel blood miRNA biomarkers of gastric cancer by bioinformatics and human blood species detection, which may give a new possibility of the important biomarkers for the diagnosis and prognosis of gastric cancer.

Introduction: Postoperative epidural hematomas of the cervical and thoracic spine can pose a great risk of rapid neurological impairment and sometimes require immediate decompressive surgery. Case Report: We present the case of a young patient operated on for stabilization of a two-level thoracic vertebra fracture who developed total paralysis due to an epidural hematoma postoperatively. The course of epidural hematoma was quickly reversed with the help of a con-servative technique that prevented revision surgery. The patient regained complete neurology on follow-up without any recurrent episodes. Conclusion: There is a role of similar maneuvers as described in this case to be employed in the management of postoperative epidural hematomas. However, prolonged watchful waiting should still be discouraged, and patients should remain ready for revision surgery if there are no early signs of rapid recovery.

Migratory flows and international travel are triggering an increase in imported cases of schistosomiasis in non-endemic countries, with serology being the recommended method for screening migrants. The present study aims to evaluate, for the first time, the LAMP technique on patients’ urine samples for the diagnosis of imported schistosomiasis in a non-endemic area in comparison to a commercial immunochromatographic test and microscopic examination of feces and urine. A prospective observational study was conducted in sub-Saharan migrants attending at the Tropical Medicine Unit, Almería, Spain. For schistosomiasis diagnosis, serum samples were tested using an immunochromatographic test (Schistosoma ICT IgG-IgM). Stool and urine samples were examined by microcopy. Urine samples were evaluated by combining three LAMP assays for the specific detection of Schistosoma mansoni and S. haematobium, and an assay for the genus Schistosoma. To evaluate the diagnostic accuracy of Schistosoma-LAMP in comparison to microscopy and Schistosoma ICT IgG-IgM test, a Latent Class Analysis (LCA) was performed. A total of 115 patients were included; 21 patients (18.3%) were diagnosed with schistosomiasis confirmed by microscopy, with S. haematobium being the most frequent species identified (18/115; 15.7%). The Schistosoma ICT IgG-IgM test resulted 100% positive and Schistosoma-LAMP was 61.9% positive, reaching as high as 72.2% for S. haematobium. The sensitivity and specificity estimated by LCA, respectively, were: 92% and 76% for Schistosoma ICT IgG-IgM, 68% and 44% for Schistosoma-LAMP and, 46% and 97% for microscopy. The Schistosoma-LAMP technique presented a higher sensitivity than microscopy for the diagnosis of imported urinary schistosomiasis, which could improve the diagnosis both in referral centers and in centers with limited experience or scarce resources and infrastructure.

Pancreatic alterations like inflammation and insulin resistance accompany hypothyroidism. Molecular iodine (I2) exerts antioxidant and differentiation actions in several tissues, and the pancreas is an iodine-uptake tissue. We analyzed the effect of two oral I2 doses on pancreatic disorders in a model of hypothyroidism for 30 days. Adult female rabbits were divided into the following groups: control, moderate oral dose of I2 (0.2 mg/kg, M-I2), high oral dose of I2 (2.0 mg/kg, H-I2), oral dose of methimazole (MMI; 10 mg/kg), MMI+M-I2, and MMI+H-I2. Moderate or high I2 supplementation did not modify circulating metabolites or pancreatic morphology. The MMI group showed circulating reductions of thyroxine (T4) and triiodo-thyronine (T3), moderate glucose increments, and significant increases in cholesterol and low-density lipoproteins. Acinar fibrosis, high insulin content, lipoperoxidation, and over-expression of GLUT4 were observed in the pancreas of this group. M-I2 supplementation normalized the T4 and cholesterol, but T3 remained low. Pancreatic alterations were prevented, nuclear factor erythroid-2-related factor-2 (Nrf2), antioxidant enzymes, and peroxisome proliferator-activated receptor gamma (PPARG) maintained their basal values. In MMI+H-I2, hypothyroidism was avoided, but pancreatic alterations and low PPARG expression remained. In conclusion, M-I2 supplementation reestablishes thyronine synthesis and diminishes pancreatic alterations, possibly related to Nrf2 and PPARG activation.

The COVID-19 pandemic has caused unprecedented challenges in the care of children with cerebral palsy (CP) and other neuromuscular complex chronic conditions (NCCC). The purpose of this study was to explore the direct impact of the COVID-19 pandemic on healthcare delivery. From May to August 2020, medical professionals caring for CP and NCCC patients across multiple countries and disciplines completed a self-administered cross-sectional survey comparing practices before and during the COVID-19 pandemic. Of the 79 healthcare workers from 8 countries who participated—predominantly pediatric orthopedic surgeons (32%), pediatricians (30%), and pediatric physiatrists (23%)—most felt that caring for NCCC patients during the pandemic presented with unique difficulties and reported a significant decrease in in-person NCCC clinic volume (p<0.001), multidisciplinary appointments (p<0.001), surgical cases (p=0.005), and botulinum toxin/phenol injections. Most providers affirmed that institutional guidelines for perioperative emergent/urgent and elective procedures, workplace settings, and technology were modified to accommodate the ongoing public health crisis. Usage of telemedicine significantly increased for NCCC patient visits (p<0.001). During the COVID-19 pandemic, many children with NCCC lost access to routine, multidisciplinary care. Telemedicine became an integral part of communication and management. In the setting of the COVID-19 pandemic and threat of future healthcare disruptions, these data lay the foundation for trending the evolution of healthcare delivery and accelerating best practice guidelines for children with CP and NCCC.

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

Crohn's disease is a non-specific inflammatory bowel disease, which is a chronic condition that affects the ileum and/or large intestine. At the same time, it can also involve any other part of the human body, that is, from the mouth to the anus. The symptoms are very bothersome and cause a significant reduction in quality of life and sometimes even crippling permanent damage to the gastrointestinal tract, which requires enteral or parenteral nutrition for life. The purpose of this study was to investigate tissue metalloproteinases as markers of recurrent Crohn's disease. The experimental groups included 31 patients and 10 patients with normal Crohn's disease, ranging in age from 23-70 years, with a mean age of 40.4. Collected tissues were frozen and then fragmented tissues were homogenized with Ripa Lysis buffer on ice. The supernatant was collared and four metalloproteinases - MMP 3, MMP 7, MMP 8 and MMP 9 - were an-alized by Enzyme-linked Immunosorbent Assay using SEA101HU, SEA102Hu, SEA103Hu and SEA553Hu kits (Cloud-Clone Corp., Kata, TX, USA). All chemical analyses were performed in triplicate. Metalloproteinase content was expressed as mean ± standard deviation. Metalloproteinase 3 and metalloproteinase 8) significantly influenced the possibility of Crohn recurrence

(1) Background: To fight for COVID-19 pandemic, immunity against SARS-CoV-2 should be achieved not only through natural infection but also vaccination. Controversies exist about the effect of COVID-19 vaccination on previously infected persons; (2) Methods: A prospective cohort was undergone to collect sera from unvaccinated survivors and vaccinated persons--with and without COVID-19 pre-infection. The sera were analyzed for the anti-Receptor Binding Domain (RBD) titers by ELISA and for the capacity to neutralize the pseudovirus of the Wuhan-Hu-1 strain by luciferase assays; (3) Results; Neither the antibody titers nor the neutralization capacity was significantly different between the three groups. However, the correlation between the antibody titers and the percentage of viral neutralization derived from sera of unvaccinated survivors was higher than that from vaccinated persons with pre-infection (Spearman correlation coefficient (r) = -0.8558; 95% CI, -0.9259 to -0.7288), p &lt;0.0001 vs -0. 581; 95% CI, -0.7679 to -0.3028; p = 0.0002, respectively), indicating the capacity to neutralize the virus is better among the unvaccinated individuals. (4) Conclusions: Vaccines induced anti-RBD titers as high as the natural infection with lower neutralization capacity, and it did not boost the immunity in pre-infected persons.

The development of sarcopenia in the elderly is associated to many potential factors and/or processes, that impair the renovation and the maintenance of skeletal muscle mass and strength as ageing progresses. Among them, a defect by skeletal muscle to respond to anabolic stimuli is to be considered. Common anabolic stimuli/signals in skeletal muscle are hormones (insulin, growth hormones, IGF-1, androgens, β-agonists such epinephrine), substrates (amino acids as protein precursors on top, but also glucose and fat, as source of energy), metabolites (such as β-agonists and HMB), some cytokines, various biochemical/ intracellular mediators), physical exercise, neurogenic and immune-modulating factors, etc. Each of them may exhibit a reduced effect upon skeletal muscle as ageing progresses. In this review article, we will concisely overview the effects of anabolic signals on muscle metabolism, as well as currently available evidence of a resistance, at skeletal muscle level, to any of the above-mentioned anabolic factors, from both in vitro and in vivo studies.

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

Bilateral recurrent nerve damage following total thyroidectomy in thyroid surgery represents severe complications. These complications have almost low incidence thanks also by using the Nerve Intraoperative Monitoring. The aim of this observational retrospective study is to evaluate the inception mode and the recovery time for different clinical laryngeal pictures that arise from this surgery. We enrolled 25 patients with bilateral vocal folds mobility deficit between October 2017 and October 2022, diagnosed in ENT Unit of University of Campania “L. Vanvitelli”, out of a total of 1417 patients undergoing total thyroidectomy. The 25 patients (23F,2M) aged from 24 to 78 years old (average age 51.7) presented a bilateral vocal folds motility deficit (occurring in about 0.1% of cases). All patients underwent 9 months diagnostic/therapeutic process, which started approximately 30 days after thyroid surgery. There are several outcomes of these complications with functional laryngeal defects being mainly related to respiratory and phonatory activities. These clinical manifestations evolve in different ways within a context of a wide range of possibilities, from spontaneous bilateral or monolateral recovery to functional or surgical restoration. This study allowed the acquisition of useful information about prognostic indications and an adequate therapeutic process, based on the specific clinical characteristics.

To compare the quality of low-energy VMIs obtained with three DECT platforms according to phantom diameter. Three sections of the Mercury Phantom 4.0 were scanned on two generations of split-filter CTs (SFCT-1st and SFCT-2nd) and on one Dual-source CT (DSCT). Noise power spectrum (NPS), task-based transfer function (TTF) and detectability index (d’) were assessed on VMIs from 40 to 70keV. Highest noise magnitude values were found with SFCT-1st and noise magnitude was higher with DSCT than with SFCT-2nd for 26-cm (10.2±1.3%) and 31-cm (7.0±2.5%), and the opposite for 36-cm (-4.2±2.5%). The highest average NPS spatial frequencies and TTF values at 50% (f50) values were found with DSCT. For all energy levels, f50 values were higher with SFCT-2nd than SFCT-1st for 26-cm (3.2±0.4%) and the opposite for 31-cm (-6.9±0.5%) and 36-cm (-5.6±0.7%). The lowest d’ values were found with SFCT-1st. For all energy levels, d’ values were lower with SFCT-2nd than with DSCT for 26-cm (-6.2±0.7%), similar for 31-cm (-0.3±1.9%) and higher for 36-cm (5.4±2.7%). In conclusion, compared to SFCT-1st, SFCT-2nd exhibited lower noise magnitude and higher detectability values. Compared with DSCT, SFCT-2nd had lower noise magnitude and higher detectability for the 26-cm but the opposite was true for the 36-cm.

The forehead and temporal region are a frequent area of skin cancer development. After tumor removal, reconstruction must be performed maintaining the frontal-temporal line of the scalp and the symmetry of the eyebrows, trying to hide the scars in these marks or in natural folds and wrinkles. Second wound healing and skin grafts generally do not produce an acceptable cosmetic result. When direct closure is not possible, the technique of choice is skin flaps. In the midfrontal line, continuation of the glabella, there is a remnant of skin to be used as a donor area for local flaps; similarly, it occurs in the preauricular cheek, which can move towards the temple. In addition to the classic advancement and rotation flaps, the frontalis myocutaneous transposition flap is an excellent technique for closing defects which are wider than higher on the forehead. Its design is very versatile and can be done between the two pupil lines at different heights depending on the location of the defect. On the other hand, the preauricular skin advancement flap with an infralobular Burow's triangle is also an excellent option for reconstructing tumors in the temporal area.

Systemic sclerosis (SSc) is a progressive autoimmune disorder that mainly affects the skin. There are other clinical manifestations as renal, pulmonary, cardiovascular, and gastrointestinal tract involvements. Based on the skin involvement there are two subtypes of SSc, as limited cutaneous SSc (lSSc) which involves the acral part of the body and diffuse cutaneous SSc (dSSc) resulting in significant skin thickening of the body. The lSSc has usually moderate internal organ manifestations, except for the late-onset pulmonary arterial hypertension (PAH) mainly appearing in this form. In dSSc the severity of the organ manifestations or failure is more intensive such as scleroderma renal crisis (RSC), interstitial lung disease (ILD), myocardial fibrosis, and chronic gastrointestinal dysmotility with consequent malabsorption

Pancreatic ductal adenocarcinoma (PDAC) is a ravaging disease whose poor prognosis requires a more detailed understanding of its biology to foster the development of effective therapies. The unsatisfactory results of treatments targeting cell proliferation and its related mechanisms suggested to rather focus on the inflammatory tumor microenvironment (TME). Here, we discuss the role of cancer secreted proteins in the complex TME tumor-stroma crosstalk, to sched lights on druggable molecular targets for the development of innovative, safer and more efficient therapeutic strategies.

Postural instability (PI) in Parkinson’s disease (PD) exposes patients to increased risk of falls (RF). Although dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF are not clear. PI and RF were assessed by a stabilometric platform in 6 advanced PD patients. Patients were evaluated on and off dopaminergic medication and four DBS conditions: bilateral-DBS, DBS of the more- or less-affected side and DBS-off. Dopaminergic medication alone worsened PI and RF, DBS alone worsened RF, and no medication/DBS combination produced an improvement in postural control with respect to the OFF-medication/DBS-off condition. When ON-medication, PI and RF significantly improved after turning the DBS on, regardless of medication condition. Among DBS conditions, bilateral-DBS provided the maximal improvement of PI and RF when ON medication, and minimal worsening of PI and RF when OFF medication, whereas patients performed worse when in most-affected side DBS condition. These results can help in developing the best therapeutic strategy for postural disorders in patients with advanced PD.

Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its clinical application, including the shortage of organ donations, the quality of donated organs, injury during organ preservation and reperfusion, primary and chronic graft dysfunction, acute and chronic rejection, infection, and carcinogenesis in post-transplantation patients. Acute and chronic inflammation and cell death are two major underlying mechanisms for graft injury. Necroptosis is a type of programmed cell death involved in many diseases and has been studied in the setting of all major solid organ transplants, including the kidney, heart, liver, and lung. It is determined by the underlying donor organ conditions (e.g., age, alcohol consumption, fatty liver, hemorrhage shock, donation after circulatory death, etc.), preservation conditions and reperfusion, as well as allograft rejection. Specific molecular mechanisms of necroptosis have been uncovered in the organ transplantation setting, and potential targeting drugs have been identified. We hope this review article will promote more clinical research to determine the role of necroptosis and other types of programmed cell death in solid organ transplantation to alleviate the clinical burden of ischemia-reperfusion injury and graft rejection.

Neuromonitoring of the efferent nerve impulses transmission in the spinal cord tracts during surgical scoliosis treatment makes it possible to assess whether the functional status is deteriorating, affecting the procedure's safety. Is there any relationship between pre- and intraoperative motor evoked potentials recordings and does idiopathic scoliosis (IS) surgical correction improve directly the spinal efferent transmission? This study aimed to compare the results of surface recorded electromyography (EMG), electroneurography (ENG, M and F-waves), and especially motor evoked potentials (MEP) from tibialis anterior (TA) muscle bilaterally in 353 girls with the right idiopathic scoliosis (types 1A-4C according to Lenke classification). It has not yet been documented whether the results of MEPs recordings induced by transcranial single magnetic stimulus (TMS, pre – and postoperatively) and trains of electrical stimuli (TES; intraoperatively in T0-before surgery, T1 – after pedicle screws implantation, T2 – after scoliosis curvature distraction and derotation following two rods implantation) can be compared for diagnostic verification of improvement of the spinal neural transmission. The study also attempted to determine whether the constant level of optimal anesthesia during the certain surgical steps of scoliosis treatment affects the parameters of MEPs recorded during neuromonitoring procedures. No neurological deficits have been observed postoperatively. Values of amplitudes but not latencies in MEPs recordings evoked with TMS in IS patients compared before and after surgery indicated a slight improvement in the efferent transmission of neural impulses within the fibers of the spinal tracts postoperatively. Results of all neurophysiological studies in IS patients were significantly asymmetrical and recorded worse on the concave side, suggesting greater neurological motor deficits at p=0.04. This asymmetry had been significantly reduced following IS surgery. The surgeries in IS patients brought significant improvement (p=0.04) in parameters of amplitudes of sEMG recordings, however reflecting still the consequences of the neurogenic injury of TA muscle motor units. ENG studies results indicated the symptoms of the axonal type injury in peroneal motor fibers improved only on the concave side at p=0.04 in parallel with the significant improvement of F-waves parameters, which suggests that surgeries might result in the lumbar ventral roots decompression. There were not detected significant differences in amplitudes or latencies of MEPs induced with TMS or TES comparing the parameters recorded preoperatively (one day before surgery) and intraoperatively in T0. The amplitudes of TES evoked MEPs increased gradually at p=0.04 in the subsequent periods (T1 and T2) of observation. The significant reduction of MEPs latency at p=0.05 was observed only at the end of the IS surgery. Studies on the possible connections between the level of anesthesia fluctuations and the required TMS stimulus strength, as well as the MEPs amplitude changes measured in T0-T2 revealed lack of relationships. It is not likely that they could be the factors influencing the efferent transmission in spinal pathways beside the surgical procedures. Considering that MEPs amplitude parameter reflects the number of axons excited from the motor cortex and transmitting the efferent impulses via spinal descending tracts in the white matter, pre- (TMS evoked) and intraoperative (TES evoked) recordings are reliable for evaluating the patient’s neurological status before and during surgical scoliosis correction procedures. The results of this study indicate an agreement between preoperative and early-intraoperative evaluations with these both diagnostic methods. An increase of MEPs amplitude parameters recorded on both sides after scoliosis surgery proves immediate improvement of the total efferent spinal cord transmission. Considering comparative pre- and postoperative sEMG and ENG recordings it can be concluded that surgeries might directly result in the additional lumbar ventral roots decompression. Our results of the tests on the possible variability of the anesthesia level on the parameters of intraoperative recorded MEPs show no clear relationships. We can conclude that MEPs parameters changes are determined by the surgery procedures during neuromonitoring, not the anesthesia conditions if they are kept stable, which influences a decrease in the number of false-positive neuromonitoring warnings. Further studies on a larger population of patients with long-lasting observation postoperatively are required to confirm the presented conclusions on the direct influences of scoliosis surgery on improvement of the motor function in patients with IS.

Tyrosine Kinase Inhibitors work by blocking the tyrosine kinases responsible of the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patient and most of them were paediatrics. The 82.4% of patients were men; however, sex-related differences in drugs pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated: as patients ages increased, drug levels decreased. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that Therapeutic Drug Monitoring is a useful method for adjusting a patient treatment schedule depending on drug concentrations in biological fluids. The use of Therapeutic Drug Monitoring in conjunction with Tyrosine Kinase Inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, Tyrosine Kinase Inhibitors Therapeutic Drug Monitoring classification needs to be refined in terms of factors like sexes and ages.

Psoriasis is nowadays recognized as a multifactorial systemic disease with complex and still not fully understood pathogenesis. In psoriatic patients the increased cardiovascular disease (CVD) risk and frequent comorbidities like obesity are observed. The aim of this study was to investigate differences in miRNA (miR-22-3p, miR-133a-3p, miR-146a-5p, miR-369-3p and Let-7b-5p) involved in CVD risk among psoriatic patients with overweight/obesity and with normal weight. The study comprised 28 male psoriatic patients and 16 male healthy controls. miRNA isolated from peripheral blood mononuclear cells was reverse-transcribed and RT-qPCR was performed. We have found the decreased levels of miR-22, miR-133a, miR-146a, and miR-369 among the psoriatic patients. There was a statistically significant difference in miR-22 and miR-146a levels between psoriatic patients with overweight/obesity and with normal weight. There were positive correlations between miR-22 and miR-146a levels and psoriatic arthritis (PsA) in psoriatic patients with normal weight and between miR-133a level and PsA in the overweight/obese patients. The decreased levels of selected miRNA are consistent with their levels observed in CVD indicating their impact in the CVD risk in psoriatic patients. miR-22 and miR-146 may be recognized as one of the contributing factors in the obesity-CVD-psoriasis network.

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blind, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3,100 median cell-culture infectious dose [CCID50] measles, ~4,300 CCID50 rubella); high dose MR-HD-MAPs (~9,300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1,000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8°C for at least 24 months. When MR HD-MAPs stored at 2–8°C for 24 months were transferred to 40°C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates at day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7% respectively for measles and 37.5%, 25.0% and 35.7% respectively for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.