Histomorphological studies were conducted to evaluate the effects of NS-Oil (NS) on ovarian toxicity induced by cyclophosphamide in female rats. The research aimed to assess the histological changes in ovarian tissue and correlate these findings with alterations in serum gonadotropin levels. The experimental design involved three (3) experimental groups treated with cyclophosphamide, NS-Oil oil, or a combination, with control group for comparison. Histological assessments of ovarian sections were performed to analyze structural integrity, follicular development, and toxicity signs, while serum samples were analyzed for estradiol, progestin levels.Cyclophosphamide administration significantly disrupted ovarian architecture, reducing follicle count and causing follicular degeneration. Conversely, NS-Oil oil treatment exhibited protective effects, restoring normal histological features and improving gonadotropin levels. Image J software, calibrated with a table micrometer, was used to measure diameters of follicles, follicular cells, and oocytes. Primary, secondary, and tertiary follicles were classified according to Oktay et al. (2017). Body weight showed no significant difference across groups, but ovarian weight decreased in cyclophosphamide-treated groups compared to controls (p < 0.05). However, ovarian weight increased dose-dependently in NS-Oil-treated groups (p < 0.05).Cyclophosphamide reduced ovarian cortex and medulla volumes (p < 0.05), while NS-Oil treatment increased these volumes (p < 0.05). Pre-antral and antral follicle counts decreased with cyclophosphamide but increased following NS-Oil treatment (p < 0.05). Atretic follicle counts decreased in both cyclophosphamide and NS-Oil-treated groups (p < 0.05). The diameters of pre-antral and antral follicles, as well as follicular cells, decreased with cyclophosphamide but increased post NS-Oil treatment (p < 0.05).These results suggest that NS-Oil may offer a therapeutic strategy to mitigate ovarian damage associated with cyclophosphamide treatment, highlighting its potential role in preserving reproductive health in patients undergoing chemotherapy. Further investigations are warranted to elucidate the underlying mechanisms of action and the efficacy of NS-Oil in clinical settings.

: The phenomenon of dark scleral spots postmortem is well-known in forensic pathology, first de-scribed by Sommers in 1833. Despite this, their presence is currently considered a nonspecific sign, and their pathogenesis has received little attention in forensic literature. In recent years, however, preliminary studies have suggested new mechanisms in their pathogenesis and links to specific types of death. This study aims to create a model for studying scleral spots using an animal model. Thirty-three sheep, already slaughtered for food, were used. After decapitation, the heads were transported to an environment with known temperature and humidity. The right eye underwent eyelid excision, while the left eye's eyelids were sutured. Continuous observation for approximately 24 hours was conducted, with brief interruptions to observe the closed eyes. Macroscopic obser-vation revealed dark scleral spots in 100% (20 out of 20) of the open eyes after an average of 240.96± 58,36 minutes. The spots did not appear in any of the closed eyes. Experimental data indicate that, despite the different location compared to human cadavers, this model serves as an excellent ex-perimental framework for studying postmortem scleral spots.

Objective: In this study, we investigated vitamin D, inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), MHR and plasma atherogenic index (PAI) and possible relationships with insulin resistance in children. Methods: A total of 210 individuals, including 96 children with insulin resistance and 114 children without insulin resistance, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. Result: NLR, PLR, SII and MHR were significantly higher in patients with insulin resistance compared to those without. Fasting insulin, PAI, HOMA-IR, HOMA- were significantly higher and QUICKI was significantly lower in patients with insulin resistance compared to those without insulin resistance. NLR, SII and MHR were lower in normal vitamin D groups than the others were (p

Background: Heart failure (HF) with preserved ejection fraction (pEF) has lacked effective 23 treatments for reducing mortality. However, previous studies have found an association between 24 statin use and decreased mortality in patients with HFpEF. The aim of this study was to analyze 25 whether statin therapy is associated with a reduction in mortality in these patients and whether the 26 effect differs according to presence or absence of ischemic heart disease (IHD). Methods: We ana- 27 lyzed data from the National Registry of Heart Failure, a prospective study including patients ad- 28 mitted for HF in Internal Medicine units nationwide. Patients with HFpEF were classified according 29 to the use of statins and differences between two groups were analyzed. A multivariate analysis 30 was performed using Cox regression to assess factors independently related to mortality. Results: 31 2788 patients with HFpEF were included, 63% of them were women with a mean age of 80.1(±7.8) 32 years. The statin-treated group (40.2%) was younger, with better functional status, and had a more 33 common diagnosis of vascular disease and lower frequency of atrial fibrillation. The most frequent 34 etiology of HF in both groups was the hypertensive one. Nevertheless, ischemic HF was more com- 35 mon in those who received statins (24.8% vs. 9.6%; p<0.001). Multivariate analysis showed lower 36 mortality at 1-year follow-up in statin-treated patients (OR:0.74; 95%CI:0.61-0.89; p=0.002). This as- 37 sociation was observed in patients without IHD (p<0.001), but not in those with IHD (p=0.11). Con- 38 clusion: Statins are associated with a decrease in total mortality in patients with HFpEF. This benefit 39 occurs mainly in those without IHD.

This paper reviews the ethical issues involved and argues that each of the usual policies for handling conscientious refusals faces serious challenges. Healthcare providers who refuse to provide medical services should be expected to explain their reasons, make prompt referrals, and bear some of the resulting costs or burdens.

Background: Dosimetric predictors of brain necrosis (BN) have not yet been established for fractionated stereotactic radiotherapy (SRT). Methods: Multivariate logistic models were developed for comprehensive analyses of dosimetric predictors in patients who received first-line fractionated SRT for brain metastases (BMs). The normal brain volume receiving a xx Gy biological dose in 2 Gy fractions (VxxGyE) was calculated from the retrieved dose-volume parameters. Results: Three-fraction SRT was delivered to 34 patients with 74 BMs (mean target volume, 4.3 cc), 5-fraction SRT to 58 with 106 BMs (15.4 cc), and 10-fraction SRT to 20 with 35 BMs (25.9 cc) according to protocols depending on the target volume (p &lt;0.001). In the 5- and 10-fraction groups, the incidence of symptomatic BN was significantly higher in patients with a larger V50GyE (odds ratio: 1.07, p &lt;0.02), V55GyE (1.08, p &lt;0.01), or V60GyE (1.09, p &lt;0.01). The incidence of BN was also significantly higher in cases with V55GyE &gt;30 cc or V60GyE &gt;20 cc (p &lt;0.05). Conclusion: In 5- or 10-fraction SRT, at least V55GyE ≤30 cc or V60GyE ≤20 cc should be maintained to lower the risk of BN.

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure and 24 hours after birth. Cerebral regional saturations of oxygen (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1+BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. 77 newborns composed the control group. PGE1 administration increased crSO2 from 47% to 50% in the PGE1 group but lower than in controls at 24 hours of life, while cFTOE remained elevated. The RI increased 24 hours after delivery (0.718 vs. 0.769; p=0.000002) due to decreased EDV (10.71 vs. 8.74; p&lt;0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO2 from 42% to 51% at 24 hours of life in the PGE1+BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusion: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period.

We report the case of a 45-year-old Caucasian man who was treated upfront with brentuximab vedotin (A) and doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) for advanced-stage classical Hodgkin's lymphoma (cHL). Right after completing the 6th cycle of induction therapy, he developed serotine fever, progressive clinical deterioration, symptomatic splenomegaly and se-vere anemia. Extensive infectious disease evaluations and serial PET scans were conducted to rule out lymphoma progression. Finally, a diagnosis of visceral leishmaniasis (VL) was performed. The patient was treated with parenteral amphotericin B, with rapid and complete resolution of clinical and laboratory abnormalities. We described this rare case of infectious complication after A+AVD delivered for cHL, and we performed a comprehensive review of the literature on the occurrence of VL in the context of non-HL and cHL, since this infection is becoming increasingly prevalent in non-tropical countries.

Invasive Candida infections represent a significant cause of morbidity and mortality in the neonatal intensive care unit (NICU), particularly among preterm and low birth weight neonates. The nonspecific clinical presentation of invasive candidiasis, resembling that of bacterial sepsis with multiorgan involvement, makes the diagnosis challenging. Given the atypical clinical presentation and the potential detrimental effects of delayed treatment, empirical treatment is often initiated in cases with high clinical suspicion. This underscores the need to develop alternative laboratory methods other than cultures, which are known to have low sensitivity and a prolonged detection time, to optimize therapeutic strategies. Serum biomarkers, including mannan antigen/anti-mannan antibody and 1,3-β-D-glucan (BDG), both components of the yeast cell wall, a nano-diagnostic method utilizing T2 magnetic resonance and Candida DNA detection by PCR-based techniques have been investigated as adjuncts to body fluid cultures and have shown promising results in improving diagnostic efficacy and shortening detection time in neonatal populations. This review aims to provide an overview of the diagnostic tools and the current management strategies for invasive candidiasis in neonates. Timely and accurate diagnosis followed by targeted antifungal treatment can significantly improve the survival and outcome of neonates affected by Candida species.

Background and Objectives: Zonulin is a molecule that has been identified as an intestinal permeability marker in recent years. Zonulin previously linked to Diabetes Mellitus, Obesity and Cardiovascular Disease but but its role in chronic kidney disease (CKD) was unclear. This study aims to investigate the relationship between Zonulin and systemic inflammation (SI), endothelial dysfunction (ED), especially renal functions, in patients with CKD. Materials and Methods: One hundred sixty-three participants were enrolled in this study. All participants were divided into two groups, patient and control groups, according to the presence of CKD (eGFR <60 mL/min/1.73m²). Results: A total of 104 patients with CKD (mean age 58.9 ±1.4) and 59 control subjects (mean age 59.0 ±1.1 ) were included, and age (p =0.934) and gender (p =0.196) were similar between the groups. In the comparison analysis, plasma zonulin levels in the CKD group (166.16 ± 53.54) were significantly higher than the controls group (143.30 ± 60.92) (p <0.001). In the correlation analysis, serum zonulin level showed positive correlation with claudin-3 (r =0.612, p <0.001), IL-6 (r =0.307,p <0.001), creatinine (r =0.313, p <0.001) and negative correlation with eGFR (r =-0.320, p <0.001) and TC (r =-0.074, p =0.047). Additionally, in linear regression analysis, zonulin level was significantly associated to eGFR, after adjustment for age and SBP (β value =-0.918, p =0.012). Conclusion: High serum zonulin levels in patients with CKD reflect increased intestinal permeability and were associated with impaired renal function. Moreover, it was thought that zonulin level could be associated with SI, but novel clinical studies were needed to elucidate its relationship with ED.

Although extracorporeal membrane ventilation offers the possibility for low frequency ventilation, protocols commonly used in patients with acute respiratory distress syndrome (ARDS) and treated with extracorporeal membrane oxygenation (ECMO) vary largely. Whether strict adherence to low frequency ventilation offers benefit on important outcome measures is poorly understood. Background/Objectives: This pilot clinical study investigated the efficacy of low frequency ventilation on ventilator free days (VFDs) in patients suffering from ARDS treated with ECMO therapy. Methods: In this single-center randomized controlled trial, 44 (70% male) successive ARDS patients treated with ECMO (aged 56 ± 12 years, SAPS III 64 (SD ± 14)) were randomly assigned 1:1 to control group (conventional ventilation) or treatment group (low fre-quency ventilation during first 72 hours on ECMO: respiratory rate 4-5/min; PEEP 14-16cm H2O; plateau pressure 23-25 cm H2O, tidal volume: < 4mL/kg). The primary endpoint was VFDs at day 28 of ECMO start. The major secondary endpoint was ICU mortality, 28-day and 90-day mortality. Results Twenty-three (52%) patients could be successfully weaned from ECMO and were discharged from intensive care unit (ICU). Twelve patients in the treatment group and five patients in the control group showed more than one VFD at day 28 after ECMO. VFDs were 3.0 (SD ± 5.5) days in the control group and 5.4 (SD ± 6) days in the treatment group (P = 0.117). Until day 28 after ECMO initiation, patients in the treatment group could be more often successfully weaned from ventilator (OR of 0.164 of 0 VFDs at day 28 after ECMO start; 95% CI 0.036-0.758; P = 0.021). ICU mortality did not differ significantly (36% in treatment group and 59% in control group; P = 0.227). Conclusions: Low frequency ventilation is comparable to conventional protec-tive ventilation in patients with ARDS treated with ECMO. However, low frequency ventilation may support weaning from invasive mechanical ventilation in patients suffering from ARDS treated with ECMO therapy.

Background: The predictive value of changes in C-reactive protein (CRP), procalcitonin and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. This study aims to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of patients admitted to the intensive care unit (ICU) with a diagnosis of pneumosepsis and pneumonia-related septic shock, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Methods: The study analyzed the demographic data, Charlson Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65 years), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores of 230 patients admitted to the ICU with a diagnosis of pneumosepsis and pneumonia-related septic shock between April 1, 2022, and December 31, 2023. The levels of CRP, procalcitonin, and leukocytes were also recorded and analyzed to assess their impact on 1-month and 3-month mortality outcomes. Results: According to multivariate logistic regression analysis, low BMI, male gender, high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p<0.05). An elevated SOFA score was associated with 1-month mortality, while advanced age was related to 3-month mortality (p<0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both 1-month and 3-month mortality cases (p<0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared to those who survived (p=0.004). Discussion: Although PCT, CRP, and leukocyte values measured at the time of admission were not significantly associated with 1-month mortality in patients with pneumosepsis or pneumonia-related septic shock, the persistent elevation and concurrent increase of these values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality.

This study investigates the use of artificial intelligence (AI) and ethnobotanical knowledge to identify natural compounds with potent antiviral activity against HPV-16. Through molecular docking simulations, we evaluated the binding affinities of various essential oil components, in-cluding Apigenin, against the key antigenic determinants of HPV-16 (E6, E7 oncoproteins, and L1 major capsid protein). Apigenin exhibited strong binding affinities, particularly to E6 Oncopro-tein. To further enhance these findings, we employed an AI-driven reverse engineering approach to predict a natural compound with superior efficacy. The AI identified Luteolin, a flavonoid with additional hydroxyl groups, as a promising candidate. Comparative docking studies demon-strated that Luteolin possesses significantly stronger binding affinities to all three HPV-16 targets, surpassing the efficacy of Apigenin. This work highlights the potential of AI in accelerating the discovery and optimization of natural antiviral agents, providing a powerful tool for pharmaco-logical and ethnopharmacological screenings. Our findings suggest that AI-guided identification of natural compounds can lead to the development of more effective antiviral therapies, warranting further experimental validation and potential synthesis in laboratory settings.

Reproductive disorders are a common event in modern reproductive medicine, occurring both in spontaneous and assisted pregnancies. Studies of the molecular mechanisms of implantation disorders in thin endometrium, including the study of gene transcriptional activity, have shed light on the identification of potential biological markers of endometrial receptivity. Background/Objectives: to reveal significantly dysregulated selected genes expression between RIF and RPL patients with thin endometrium. Methods: Endometrial samples were collected in the implantation window days (LH+7 – LH+10) of the natural menstrual cycle from RIF patients (n=20) and RPL patients (n=19). Ten genes were chosen as target genes regarding their possible relations with the implantation process. Total RNA was purified, reverse-transcribed; gene expression was quantified by RT-PCR. Results: The expression of the IL-15, INFG and HPRT1 genes were significantly decreased in RIF with thin endometrium patients compared to the RPL patients (log2 fold change=0.92, p=0.023 for IL-15, log2 fold change=1.24, p=0.046 for INFG, and log2 fold change=0.579, p=0.046 for HPRT1). There were not significant differences in expression of CXCL8, CXCL1, MMP10, C4BPA, TNC, VEGFB and HAND2 genes between groups. Conclusions: decreased expression of IL-15, INFG and HPRT1 genes was found in patients with RIF with thin endometrium compared to the endometrium of women with RPL. This has practical significance for clinicians for differentiated prescription of immunomodulatory therapy in patients undergoing ART programs.

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease, and an apparent cause has not been identified. OLP is refractory to treatment, and malignant transformation has been reported. Therefore, discovering effective drugs with few adverse effects over long-term administration is crucial. In this study, we established an in vitro OLP model to investigate the effects of Cepharanthin®, an alkaloid mixture derived from Stephania cephalantha Hayata. Four alkaloids from Cepharanthin® suppressed the expression of cytokine genes at various degrees in activated T cells. However, the effect of Cepharanthin® was limited. On the other hand, Cepharanthin® and four alkaloids suppressed the expression of various cytokine genes in human oral epithelial cells when stimulated with IL-β. In the OLP model, activated T cells increased the inflammatory gene expression in the epithelial cells, while Cepharanthin® suppressed their gene expression. Anti-inflammatory effect of Cepharanthin® was observed by protein dot blot. The effects of Cepharanthin®️ might be expressed through two aspects: its effect of mildly suppressing the activation of T lymphocytes and strongly suppressing the response of epithelial cells to inflammatory stimuli. The in vitro model established in this study could be a tool for elucidating the mechanisms of OLP pathogenesis and disease persistence.

This review explores the nuanced decision-making surrounding postoperative radiotherapy for diffuse low-grade glioma (DLGG) patients, emphasizing the need for personalized treatment to balance the benefits of tumor control with the risks of long-term side effects. Radiotherapy is a cornerstone of DLGG treatment, offering significant improvements in progression-free survival, but its potential for cognitive decline and vascular lesions necessitates careful consideration of individual patient factors. The review delves into the complexities of radiotherapy timing, revealing that while early radiotherapy enhances progression-free survival, it does not significantly impact overall survival and may lead to earlier onset of cognitive decline. Conversely, delayed radiotherapy may mitigate cognitive decline but may result in shorter progression-free survival and the onset of neurological symptoms. The review advocates for a patient-centered approach, emphasizing the importance of weighing individual risks and benefits, and highlights the potential of artificial intelligence in predicting cognitive decline and the need to revisit previous research findings in light of the 2021 WHO (World Health Organization) classification update, underscoring the evolving nature of DLGG treatment and the ongoing quest for optimal therapeutic strategies.

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromo-some ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering in-sights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.

The study objective is to evaluate the reliability of the Göttingen Mini-pig (G-MP) as a large animal model for preclinical studies addressing articular cartilage treatment procedures. Second this work compared the G-MP to the domestic pig (DP) in terms of surgical anatomy, postoperative management, and follow-up period possibilities and challenges. Six G-MP and four DP underwent a two-stage surgical procedure including cartilage harvesting using a superolateral approach followed by cartilage implantation using a medial parapatellar tendon approach. The superolateral approach exposed 11% (SD ± 5) of the entire trochlea in G-MP and 20% in the DP model. The medial parapatellar tendon approach in G-MP exposed 63% (SD ± 4) of the trochlear surface and exposed 34% (SD ± 13) of the medial femoral condyle, allowing 4 trochlear lesions of 6mm of diameter and one to the medial condyle in 4 out of 6 G-MP and in all DPs. Cartilage thickness was under 1mm in G-MP compared to more than 2mm in DP. Weight-progression was + 4 kg/week in DP and + 0.2 kg/week for G-MP. The G-MP is a feasible model for cartilage research, with adequate access to the joint via the dual approach. Thus enabling 4-5 lesions of 6mm, however a thinner cartilage in the G-MP needs to be considered.

Background and objectives: Chronic Kidney Disease and Mineral Bone Disorders (CKD-MBD) are frequently associated with an increased risk of both Vascular Calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and osteocalcin (BGP), have pivotal roles both for VCs and BFs. The Vitamin K Italian (VIKI) dialysis study, highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP as compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs, beyond the beneficial effect to reduce PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age and sex-matched patients treated with Calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusion: The study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. Keywords: bone fractures; etecalcetide; hemodialysis; vascular calcification; vitamin K

Multiple Myeloma (MM), is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. Our analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2024, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, overall response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care.

Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review existing literature, and elucidate its clinicopathological characteristics, including potential therapeutic targets. Methods: We retrospectively reviewed the pathological diagnoses of 516 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLA. Results: Among the 516 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52-76 years old, and the initial FIGO stages were IC1 (2 cases) and IIIB (1 case). All cases exhibited HRP, pMMR, PD-L1 negativity (CPS&lt;1), and HER2-low expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. MLA frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). Conclusion: MLA accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. Literature also reports a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.

Chronic wounds are a major health problem because of delayed healing and cause hardships for the patient. The infection present in these wounds plays a role in delayed wound healing. Silver wound dressings have been used for decades, beginning in the 1960s with silver sulfadiazine for infection prevention for burn wounds. Since that time, there has been a large number of commercial silver dressings that have cleared FDA approval. In this review, we examine the literature involving in vitro, in vivo, and clinical studies with commercial silver dressings and attempt to glean the important characteristics of these dressings in treating infected wounds. The primary presentation of the literature is in the form of detailed tables. The narrative part of the review focuses on the different types of silver dressings, including the supporting matrix, the release characteristics of the silver into the surroundings, and their toxicity. Though there are many clinical studies of chronic and burn wounds using silver dressings that we discuss, it is difficult to compare the performances of the dressings directly because of the differences in the study protocols. We conclude that silver dressings can assist in wound healing, though it is difficult to provide general treatment guidelines.

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

Background: Knee osteoarthritis (OA) significantly affects quality of life and imposes economic burdens due to its prevalence and the disability it causes. The efficacy of current treatments is limited to alleviate the symptoms and not for regenerative purposes. This study aims to evaluate the efficacy and safety of combining hyaluronic acid (HA), human umbilical cord mesenchymal stem cells (hUC-MSCs), and synthetic human growth hormone (somatotropin) in the treatment of knee OA, assessing pain relief, functional improvement, and cartilage regeneration. Methods: A four-arm, double-blind randomized trial was conducted with 51 knees from 28 subjects, aged ≥ 50 with primary knee OA. Treatments involved are HA alone, HA with hUC-MSCs, HA with somatotropin, and a combination of all three. Efficacy was measured through the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and visual analog score (VAS) along with MRI T2 mapping of cartilage were taken on pre-implantation, 6th and 12th month. Results: All treatment arms showed improvement in VAS and WOMAC scores over 12 months, suggesting some pain relief and functional improvement. However, MRI T2 mapping showed no significant cartilage regeneration across the groups. Conclusion: While combined use of HA, hUC-MSCs, and somatotropin improved symptoms of knee OA, it did not enhance cartilage regeneration significantly. The study highlights the potential of these combinations for symptom management but underscores the need for further research to optimize these therapies for regenerative outcomes.

Intercellular adhesion molecule 1 (ICAM-1/CD54), a transmembrane glycoprotein, has been considered as one of the most important adhesion molecules during leukocyte recruitment. It is encoded by the ICAM1 gene and plays a central role in inflammation. It’s crucial role in many inflammatory diseases such as ulcerative colitis and rheumatoid arthritis are well established. Given that neuroinflammation, underscored by microglial activation, is a key element in neurodegenerative diseases such as Parkinson’s disease (PD), we investigated whether ICAM-1 has a role in this progressive neurological condition and if so, elucidate the underpinning mechanisms. Specifically, we were interested in potential interaction between ICAM-1, glial cells and ferroptosis, an iron-dependent form of cell death that has recently been implicated in PD. We conclude that there exist direct and indirect (via glial cells and T cells) influences of ICAM-1 on ferroptosis and that further elucidation of these interactions can suggest novel intervention for this devastating disease.

BACKGROUND Studies concerning multisystem inflammatory syndrome in children (MIS-C) and how those patients present to the Emergency Department (ED) are scarce. Our study sought to investigate whether abnormal laboratory values were associated with worse outcomes. METHODSThis was a retrospective case-control study from March 2020 to June 2020. Patients with MIS-C were compared to a control group. Laboratory values were compared whether admitted to PICU or not. The Pearson’s Chi-square test and Fisher’s exact test were conducted for associations. RESULTSA total of 80 patients were included in the study (41MISC, 39 control). There were significant associations between patients admitted to the PICU and neutrophilia (p = 0.03) and elevated troponin (p = 0.01). There were no significant associations between having a non-good outcome and obesity, neutrophilia, lymphopenia, or elevated troponin. When MIS-C patients were compared to the control group MISC-C patients had more obesity and elevated troponin. CONCLUSIONSPatients admitted to the PICU had more neutrophilia and elevated troponin yet had a fairly good outcome. When compared to control patients, there was a significant association with obesity and elevated troponin in the MIS-C group.

Background:Advanced heart failure is characterized by repeated hospital admissions due to recurring need for intravenous inotropes. Among the most commonly used medications used in this context, is milrinone, which increases the myocardial relaxation velocity, what is known as lusitropy. This effect is mediated by increasing cyclic AMP, which in turn switches on phospholamban activity, an enzyme promoting calcium reuptake by sarcoplasmic reticulum. The aim of this review is to shed light on oral medications that can play a similar role by alternative pathways. Main Body:Phospholamban can be as well stimulated by cGMP, the latter is known to be increased by medications which inhibit phosphodiesterase 5. Two well-established drugs can perform this action and are currently exclusively used as vasodilators, namely sildenafil and tadalafil. Another emerging hope is vericiguat, a medication that can directly stimulates guanylyl cyclase, leading to increase in cGMP. Conclusion:We speculate that the possible introduction of these oral medications is thought to replace the need for repeated hospital and intensive care admissions. This also might mean, delaying the necessity for mechanical support or transplantations, which can change the face of advanced or end-stage heart failure.

Out-of-hospital cardiac arrest (OHCA) represents a significant global public health burden, characterized by low survival and few established diagnostic tools to guide intervention. OHCA presents with a wide variety of etiologies in a heterogeneous population, posing a clinical challenge to care teams. In this review, we describe evolving research focused on diagnostic approaches to OHCA following resuscitation, including electrocardiography, coronary angiography, computed tomography, ultrasonography, and serologic biomarker assessment. These diagnostic tools have been employed in post-resuscitative efforts for diagnosing ischemic and non-ischemic cardiac, respiratory, neurologic, vascular, traumatic, and metabolic causes of arrest.

Background: To evaluate the effectiveness of Defocus Incorporated Multiple Segments (DIMS) in slowing myopia progression in pediatric patients as a function of age. Methods: This was a non-randomized experimenter-masked retrospective controlled observational study of European individuals aged 6 -16 years with progressive myopia but no ocular pathology. We retrospectively reviewed the charts of the participants allocated to receive DIMS spectacles (Hoya® MiyoSmart®) or single vision spectacle lenses (control group). Cycloplegic spherical equivalent (SE) and axial length (AL), were measured at baseline and at 36 month follow up. The results were stratified by age into four groups: patients that wore DIMS spectacles oldest or youngest than 10 years of age (respectively, group A, 20 patients mean age 13.6±2.2 and group C, 20 patients mean age 9.0±1.2) and age-matched control groups (group B, 18 patients mean age 13.2±2.5 and group D, 22 patients mean age 8.5±0.9). Results: At 36 months, SE and AL increase resulted significantly reduced in groups A and C, respectively compared to groups B and D (p<0.05). Linear regression analysis showed a significant correlation (P<0.05) between patient age and myopia progression for SE in groups A and C, but only in group A also for AL. Groups B and D did not show any significant correlation (P>0.05). Conclusion: DIMS spectacles seem to slow myopia increase in pediatric patients, however their effectiveness results greatest in children oldest than 10 years of age. Morover our findings suggest that AL may be the more reliable parameter for evaluating myopia progression.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

Background/Objectives: Bacterial infections (BI) are a major cause of mortality in patients with alcohol-associated hepatitis (AH); however, only a few studies have investigated BI in AH in the last decade. Therefore, we aimed to assess the features and outcomes of BI in patients with AH. Methods: This observational descriptive study included patients with AH admitted to a tertiary academic hospital between 2016–2021. Clinical and complete microbiological data were recorded and complications, including acute-on-chronic liver failure (ACLF), and mortality over 90-days were compared between infected and non-infected patients. Results: Overall, 115 patients with AH were recruited and 75 had severe AH; among them, 66 started corticosteroid treatment. We identified 69 cases of BI in 44 patients; the incidence of BI at hospital discharge was 32.2%, which reached 38.2% at 90 days. The predominant infection site was the chest (35%). Among the identified bacteria (52.1%), half were gram-positive and half gram-negative. A low rate of multidrug-resistant bacteria (14%) was also noted. Infected patients during hospitalization (n=37) exhibited higher rates of hepatic decompensation and ACLF p=0.001) and lower survival (81.8% vs. 95.8%, p=0.015) than did non-infected patients (n=78). In-hospital infected patients (n=22) exhibited worse survival (72.7%) than did those infected upon admission (93.3%) or non-infected patients (94.9%) (p=0.009). Corticosteroid-treated patients displayed a nonsignificant increase in the total number of BI; however, without greater mortality. Conclusions: BI were common in our cohort of patients with AH. Patients with in-hospital infections commonly experienced serious complications, including high ACLF and death rates. Infections diagnosed upon admission were treated without affecting survival.

A major reason for failure of the immune system to detect tumor antigens (TA) is the insufficient uptake, processing, and presentation of TA by antigen-presenting-cells (APC). Immunogenicity of public and private TA of the individual patient can be markedly increased by in situ targeting of tumor cells for uptake by APC, without the need to identify and characterize the TA. This is feasible by intra-tumoral administration of alpha-gal micelles comprised of glycolipids presenting the carbohydrate-antigen “alpha-gal epitope” (Galalpha1-3Gal beta1-4GlcNAc-R). Humans produce a natural antibody called “anti-Gal” (constituting ~1% of immunoglobulins) which binds alpha-gal epitopes. Tumor injected alpha-gal micelles spontaneously insert into tumor cell membranes, so that multiple alpha-gal epitopes present on tumor cells. Anti-Gal binding to these epitopes activates the complement system, resulting in killing of tumor cells, and recruitment of multiple APC (dendritic cells and macrophages) into treated tumors by chemotactic complement cleavage peptides C5a and C3a. In this process of converting the treated tumor into personalized TA vaccine, recruited APC internalize anti-Gal opsonized tumor cells and cell membranes, process the internalized TA and transport them to regional lymph-nodes. TA peptides presented on APC activate TA specific T and B cells to proliferate and destroy metastatic tumor cells presenting the TA. Studies in anti-Gal producing mice demonstrated induction of effective protection against distant metastases of the highly tumorigenic B16 melanoma following injection of natural and synthetic alpha-gal micelles into primary tumors. This treatment was further found to synergize with anti-PD1 antibody. Phase-1 clinical-trials indicated that this immunotherapy is safe and can induce infiltration of CD4+ and CD8+ T cells into untreated distant metastases. It is suggested that in addition to converting treated metastases into autologous TA vaccine, this treatment should be considered as neo-adjuvant therapy administering alpha-gal micelles into primary tumors immediately following their detection. Such immunotherapy will convert tumors into personalized anti-TA vaccine for the period prior to their resection.

Pulmonary arterial hypertension (PAH) is a complex and devastating disease that the underlying cellular and molecular mechanisms are largely remains unknown. This study aimed to elucidate the key hub genes and pathways in PAH by bioinformatics analysis. In the current study, we performed WGCNA analysis to systematically identify the hub genes for PAH using transcriptome microarray data. From the Gene Expression Omnibus (GEO) database, one microarray dataset (GSE113439) was downloaded for this study. There were 26 samples in this data set, including 15 PHA samples and 11 normal controls. Based on weighted correlation network analysis, 11 modules were identified and the MEgreenyellow module showed a significantly positive correlation with PAH (r = 0.93, P = 1e−06). The genes in greenyellow module were mainly significantly enriched in mitophagy related pathways by KEGG analyses. Combined with the protein–protein interaction (PPI) and co-expression networks, ten hub genes were identified as candidate biomarkers for PAH in the greenyellow module, including CTNNB1, NIPBL, ROCK2, ROCK1, SCAF11, JAK1, BIRC6, KIF5B, PPP1R12A and XRN1. These hub genes might be potential targets for clinical therapy against PAH. The molecular mechanisms involved in these genes that affected the prognosis of PAH should be further validated through biological and basic studies.

Background: Anxiety disorders can be both an independent risk factor of many somatic conditions and the cause of complications of various organic disorders leading to poor prognosis. Objectives: The purpose of this study is to compare the heart rate variability (HRV) recorded both during the day and at night in patients with anxiety disorders and healthy individuals. Methods: The study was conducted on fifty consecutive outpatients with anxiety disorders who participated in intensive group psychotherapy. The diagnosis was made according to DSM-IV-TR criteria using the PSE-10 questionnaire. Out of 50 patients under study, 17 were diagnosed with panic disorder (PD) and 21 with generalized anxiety disorder (GAD). The control group consisted of 40 healthy people. The resulting three groups were compared in terms of circadian HRV using the Oxford Medilog Suprima Holter System. Results: The HRV analysis showed the nocturnal falls in the time and frequency parameters related to parasympathetic activity (rMSSD, pNN50, HF). The most unfavourable alterations were observed in the PD group, which comprised the disappearance of day vs. night amplitude of the majority of HRV parameters. Hence, the PD group was particularly susceptible to the arrhythmic events. It was noticeable that nocturnal vagotonia in the PD group was significantly lower as compared with the GAD and control group. Conclusions: The innovative aspect of the present study was to find a distinct profile of HRV with regard to the types of anxiety disorders because of the existing considerable differences between the nature of PD and GAD.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare type of vasculitis characterized by inflammation within small blood vessels or tissues that may cause damage to the lungs, heart, kidneys, and other organs. Here, we present a rare case of EGPA with cardiac involvement that presented with acute heart failure. Clinical findings: A 44-year-old woman with a history of bronchial asthma and sinusitis pre-sented with fever, shortness of breath, fatigue, unintentional weight loss, and polyarthritis. Physical examination revealed a fine basal crepitation and mononeuritis multiplex. Diagnosis: The peripheral film revealed dimorphic features, an elevated eosinophil count, low hemoglobin (Hb), and abnormally high lactate dehydrogenase levels. The cardiac enzyme levels were elevated upon admission. Cardiac magnetic resonance imaging (CMR) revealed global hypokinesia and features suggestive of myocarditis. Echocardiography showed a low ejection fraction of 25%. Thus, the patient diagnosed with EPGA and myocarditis presented with acute heart failure. Interventions: The patient was administered high-dose corticosteroids (intravenous bolus methylprednisolone 500 mg for three days, followed by 1 mg/kg of prednisolone) and cyclo-phosphamide 750 mg intravenously. Outcome: After one months, the patient showed a marked improvement in clinical and labora-tory parameters. The ejection fraction improved to 30-40%, the eosinophil count returned to normal, and the hemolytic anemia resolved. The patient was sent home with mycophenolate mofetil 1 g twice a day as maintenance therapy. Conclusion: Patients with EGPA have a higher morbidity and mortality rate when they have cardiac in-volvement. The pathophysiological mechanism of cardiac involvement in EGPA warrants con-sideration of immunosuppressive therapy in addition to standard heart failure treatment.

The diagnosis of migraine is based on clear criteria outlined in the International Classification of Headache Disorders version 3 (ICHD-3). Notably, the criteria in ICHD-3 omit the location of migraine. There are increasing reports of migraine in the facial region.(1-3) Facial presentations of migraine are not easy to diagnose as they appear in the lower 2/3rd of the face, often in the maxillary sinus region, around the ear, the upper/lower jaws and teeth.(4) Moreover, the symptomatology of these facial representations of these headaches often resembles sinusitis and dental pathology. We will review these presentations, their diagnosis and possible pathophysiology.

Objectives: The tau protein is essential for stabilizing microtubules. Changes in its phosphorylation are identified in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. The hyperphosphorylation of the tau protein is linked to various factors, including stress, which has a substantial impact on depressive illness. The present study aimed to systematically review studies that describe the association between tau protein and depression.Design: The present study used the PRISMA statement 2020 as the inclusion criterion for articles describing tau protein in individuals with depression. The exclusion criterion was the lack of comparison of tau protein levels with individuals without depression.Results: A total of 138 papers were identified, of which 21 were ultimately included. One out of every three articles included demonstrated the statistical significance of the tau protein values between the depression group and controls. Only one had an adequate sample but demonstrated results without any major significance.Conclusions: The association between tau protein and depression remains unclear. Studies with adequate sampling are necessary to answer this question.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, with 25% of patients presenting with metastases; of these, 8% have synchronous liver and peritoneal metastases. Although the concurrent presence of liver and peritoneal metastases was previously considered an absolute contraindication, the feasibility of combined surgery is now being re-evaluated. This study assesses 41 patients who underwent liver surgery for CRC metastases at our center between October 2021 and February 2024. Among these patients, 7 underwent concomitant cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) due to the presence of synchronous liver and peritoneal metastases. We employed simple linear regression to identify parameters that influenced the development of postoperative complications, classified by the Clavien-Dindo (CD) system. The statistical analysis showed only the operative time, the CRS+HIPEC procedure and the length of hospital stay as significative variables on CD outcome, while the different types of liver surgery were not significant. This study suggests that combining liver surgery with CRS+HIPEC may be beneficial for selected patients, potentially improving overall survival without a significant increase in postoperative complications. A multidisciplinary approach is essential to achieve a survival advantage without elevating morbidity rates.

Objective: To report time-loss match injuries in Portugal’s “Divisão de Honra” (Portuguese First Tier) 2022/23 season focusing on injury incidence, injury burden, anatomical region and type of injury. Methods: A cohort prospective observational study was conducted. Data was collected through an online form sent for every team medical department categorizing player position, injury type, location and severity. Injury incidence and burden were calculated per 1000-player-match-hours. Results: The overall injury incidence was 54.4 injuries per 1000 player-match-hours (CI95% 30.3-96.2). Forwards had a higher incidence comparing to backs. Lower limbs were the most affected location (52% of the injuries). Sprain/ligaments injuries were the most common type of injury followed by muscle injuries. Discussion: The injury incidence was higher than what is reported in amateur competitions and lower than professional ones. Injury severity was similar to other studies. Our study suggests a lower injury burden compared to other semi-professional and elite leagues. Further research with broader participation and training injury data is needed.

Background: The integration of unmanned aerial vehicles (UAVs), commonly known as drones, into medical logistics offers transformative potential for the transpor-tation of sensitive medical materials, such as blood samples. Traditional car transportation is often hindered by traffic delays, road conditions, and geographic barriers, which can compromise timely delivery. Methods: This study provides a comprehensive analysis comparing high-speed drone transportation with traditional car transportation under various weather conditions. Blood samples, including EDTA whole blood, Serum, Li-Heparin Plasma, and citrate plasma tubes, were transported via both methods across temperatures ranging from 4 to 20 degrees Celsius. The integrity of the samples was assessed using a wide array of analytes and statistical analyses, including Passing-Bablok regression and Bland-Altman plots. Results: The results demonstrated that drone transportation maintains blood sample integrity comparably to traditional car transpor-tation. For serum samples, the correlation coefficients (r) ranged from 0.830 to 1.000, and the slopes varied from 0.913 to 1.111, with minor discrepancies in five analytes (total bilirubin, calcium, ferritin, potassium, and sodium). Similar patterns were observed for EDTA, Lithium-Heparin, and Citrate samples, indicating no significant differences between transportation methods. Conclusions: These findings highlight the potential of drones to enhance the efficiency and reliability of medical sample transport, particularly in scenarios requiring rapid and reliable delivery. Drones could significantly improve logistical operations in healthcare by overcoming traditional transportation challenges.

Non-union is one of the severe complications of traumatic fracture and still no standard therapeutic recommendations currently. A total of eleven patients were treated on the lesions for non-union, after the failure of open reduction internal fixation (ORIF) or total hip replacement, by autologous conditioned serum (ACS) for one to three times monthly and followed up. Seven patients received ACS three times, three patients received it two times, and the only one who underwent total hip replacement received it once. Ten patients achieved union at the last follow-up visit, indicating the effectiveness of ACS on patients who suffered from non-union after ORIF. ACS has the potential as an alternative or adjective treatment for non-union and is worthy to be investigated further for the benefits of patients.

Ichthyosis is a genetic skin disorder marked by hyperkeratosis, pruritus, and scaling. This case study explores a potential association between ichthyosis and scalp paresthesia, a symptom not commonly linked with this dermatological condition. In a longstanding history of ichthyosis patients, we detail the therapeutic use of fluocinolone, a synthetic corticosteroid, in managing scalp paresthesia. The effectiveness of fluocinolone in reducing paresthesia episodes underscores its potential as a critical component in the symptomatic treatment of this complex interplay between skin and neurological symptoms. This case prompts a broader discussion on the need for increased awareness and education among healthcare providers regarding the diverse manifestations of ichthyosis. Enhanced understanding and recognition of these associations can lead to improved patient counseling, tailored management strategies, and, ultimately, better quality of life for individuals affected by ichthyosis.

Abstract Introduction: Long COVID (LC) affects multiple systems and has a significant health impact on patients and society. Therefore, long COVID services should address patients’ needs through a holistic assessment and monitoring of patients’ symptoms. Aim: The aim was to understand which of the symptoms were most and least likely to improve, after our rehabilitation intervention so that the rehabilitation measures in the clinic could be modified to meet patients’ needs. At the same time, we wanted to assess the feasibility of using C19-YRS ELAROS application in monitoring of LC symptoms during and after the rehabilitation clinic attendance. Methodology: In this study, a total of 50 patients who have attended long COVID rehabilitation clinic in Salford, UK; were assessed by using digitalised C19-YRS ELAROS application. A total of 100 eligible initial and final post rehabilitation assessments were analysed. Conclusion: Pain and anxiety symptoms were the two most likely symptoms to improve after intervention at LC rehabilitation clinic, whereas swallowing difficulty is least likely to improve. Issues with caring for family/ social life (symptoms affecting social role) are likely to worsen even after treatment. It is feasible to monitor and track Long COVID symptoms utilising the digitalised version of C19-YRS via the ELAROS App. This also allows the tracking of symptoms overtime.

Nowadays recurrent implantation failure (RIF) after invitro fertilization is common problem that reproductive specialists usually faced. The phenomenon of thin endometrium in RIF patients has yet not completely understood and properly treated. This study aimed to reveal significantly dysregulated selected genes expression between RIF patients with thin endometrium and fertile women. Endometrial samples were collected in the implantation window days (LH+7 – LH+10) of the natural menstrual cycle from RIF patients (n=20) and fertile women (n=14). Ten genes were chosen as target genes regarding their possible relations with the implantation process. Endometrial gene expression levels showed differences in RIF samples compared to fertile samples. The significant downregulation was observed for CXCL1 (p=0.005) and C4BPA (p=0.03) genes. There was no statistically significant difference between the RIF groups and the fertile group in the expression of 8 genes: CXCL8, HPRT1, MMP10, INFG, VEGFB, HAND2, IL15 and TNC (p&gt;0.05). The use of a combination of two markers (C4BPA + CXCL1) allows for good discrimination of RIF patients from fertile women (AUC 0.806).

Introduction Image Guided Superficial Radiation Therapy (IGSRT) is a novel technology which combines traditional superficial radiation therapy (SRT) with high resolution dermal ultrasound (HRDUS) to treat non-melanoma skin cancers (NMSC). Since development, IGSRT use has expanded dramatically in outpatient clinics. We review the IGSRT literature and state of the art operating principles in US dermatologic practices. Materials and Methods A literature search of electronic databases (Medline, Pubmed, Cochrane Library, Science Direct) combined with various authors’ published and unpublished documents, procedures and clinical experience with IGSRT were synthesized for this paper. Results Studies have demonstrated IGSRT consistently delivers high cure rates( >99%) with low complications for early stage (stage 0, I, or II) squamous cell and basal cell carcinomas. Control rates are statistically superior to non-image guided SRT and external beam radiation (XRT) as well as Mohs Micrographic Surgery(MMS). This improvement is attributed to in-vivo dermal tumor visualization via HRDUS and using an interdisciplinary approach to deliver care. IGSRT use in the dermatologic clinic for early stage NMSCs has become common practice and continues to expand. Conclusion While the safety and cosmetic benefits of SRT/XRT has been long documented, IGSRT represents a significant leap forward in efficacy (statistically significant) by adding in-vivo dermal tumor imaging. Results rival and appear on one study to surpass tumor control obtained with MMS. A contributing factor to the success may be the availability and use of an interdisciplinary team approach that includes dermatologists, radiation therapists, radiation oncologists and medical physicists. The high tumor control rates, minimal side effects, favorable cosmesis and ability to treat multiple lesions per session using IGSRT is establishing this modality as a standard first line therapy for early stage NMSCs in dermatology clinics. IGSRT may represent the most effective option for the non-surgical treatment of early stage NMSC to date.

Pneumococcal disease, caused by Streptococcus pneumoniae is the leading cause of high mortality in children worldwide. The tremendous direct cost of hospital admissions and significant indirect costs from productivity loss contributed considerably to the economic burden, with vaccination being the only efficient way against the illness. Our study aims to summarize the cost-effectiveness of the pneumococcal conjugate vaccine (PCV) implemented in the pediatric population. Employing online databases from Pubmed, Embase, and Medline, we looked for economic evaluation from 2018 until March 2024. The Incremental Cost-Effectiveness Ratios (ICER) and Quality-Adjusted-Life-Years (QALY) were the primary outcomes for measuring PCV's cost-effectiveness. A 28-item CHEERS 2022 checklist was applied to assess the quality of collected studies. Of the 16 papers found, 9/16 discussed the lower-valent vaccine (PCV13, PCV10) and 7/16 examined the higher-valent vaccine. (PCV20, PCV15). PCV13 and PCV10 required more cost and generated more QALY compared to no vaccination. Both PCV15 and PCV20 averted substantial healthcare costs and yielded greater quality of life than PCV13. Additionally, PCV20 was a dominant strategy compared to PCV15. Utilizing PCV13 is a very cost-effective option compared to not getting vaccinated. Transitioning from PCV13 to PCV20 would result in higher QALY gain and more cost-saving than switching to PCV15.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p&lt;0.001, Duncan’s new multiple range test) and their total duration (p&lt;0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p&lt;0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

Background: Hairy cell leukemia (HCL) is a rare indolent B-cell lymphoid malignancy. The majority of patients are asymptomatic and HCL is usually diagnosed incidentally during a routine blood cell counts. In symptomatic patients, typical symptoms are related to pancytope-nia and splenomegaly. In this review we present, rare clinical symptoms in patients with HCL. Methods: A literature search was conducted of PubMed, Web of Science, and Google Scholar for articles concerning hairy cell leukemia, leukemia cutis, bone lesions, neurological manifesta-tions, pulmonary symptoms, ocular manifestations, cardiac manifestation, rare symptoms. Publications from January 1980 to August 2024 were scrutinized. Additional relevant publica-ions were obtained by reviewing the references from the chosen articles. Results: Extra medul-lary and extra nodal manifestations of classic HCL are rare. However, leukemic involvement in the skin, bone, central nervous system, gastrointestinal tract, heart, kidney, liver, lung, ocular and other organs have been reported.

Unheralded cardiac arrest among previously healthy young people without antecedent illness, months or years after COVID-19 vaccination, highlights the urgent need for risk stratification. The most likely underlying pathophysiology is subclinical myopericarditis and reentrant ventricular tachycardia or spontaneous ventricular fibrillation that is commonly precipitated after a surge in catecholamines during exercise or the waking hours of terminal sleep. Small patches of inflammation and/or edema can be missed on cardiac imaging and autopsy, and the heart can appear grossly normal. This paper reviews evidence linking COVID-19 vaccines to cardiac arrest where unfortunately the majority of victims have had no antecedent clinical evaluation. We propose a comprehensive strategy for evaluating cardiovascular risk post-vaccination, incorporating detailed patient history, antibody testing, and cardiac diagnostics in the best attempt to detect abnormalities before sudden cardiac death. This approach aims to identify individuals at higher risk of cardiac events after COVID-19 vaccination and guide appropriate clinical management. It is prudent for each primary care physician to have a pre-established plan when addressing this issue in their practice.

Background and objective: Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present on the emergency department (ED) admission with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. This case report aims to bring awareness among healthcare professionals regarding the atypical presentation and introduce a potential differential diagnosis when evaluating patients with fever and back pain. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations. Case report: Here, we describe a case of primary iliopsoas abscess associated with drug-induced acute liver failure in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. She had a fever, pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever and vomiting, jaundiced skin, and sclera at the examination in ED. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, hepatocytolysis syndrome, and hyperbilirubinemia with the predominance of indirect bilirubin. We performed then abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess-like collection fused to the interfibrillar level of the left iliopsoas muscle; a diagnosis we most likely would have been missed. After that, the patient was hospitalized in the General Surgery Department, and surgery drainage of the abscess was performed. The patient's evolution was excellent; she was discharged after 11 days. Conclusions: The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency departments about this uncommon but essential diagnosis. With advancements in diagnostic tools and techniques, we aspire that more cases of iliopsoas abscess will be accurately diagnosed.

Background: Previous studies have found variable impact of the coronavirus disease 2019 (COVID-19) pandem-ic on the consumption of antimicrobial drugs in human medicine, with trends in several European countries differing between community and inpatient prescribing. Aim: This study analysed changes in the volumes and use density of antibacterial and antifungal drugs dis-pensed in acute care hospitals in Germany between 2019 and 2022. Methods: Surveillance data for the four years available from 279 hospitals, among them 272 for antifungals, were expressed as the total volumes of daily doses or as use density (daily doses per 100 patient/occupied bed days) per year and analysed descriptively, using recommended hospital-adapted daily dose definitions (RDD) and (as sensitivity analysis) WHO/ATC-defined daily dose definitions (DDD). Hospitals were stratified according to size (number of beds) and university affiliation, and location (East, West, South). Results: There were significant decreases both in the total number of patient days and antibacterial drug vol-umes in 2020 through 2022 compared with 2019. The relative changes between 2019 and 2020, 2021 and 2022 were -12.8%, -13.5%, and -13.3% for patient days, and -9.7%, -11.0%, and -10.1% for antibacterial RDD, respec-tively. Broad-spectrum betalactams, notably piperacillin-tazobactam and carbapenems, increased in volume unlike most other drug classes. The resulting antibacterial drug use density was slightly but significantly increas-ing with pooled means (and medians) of 43.3 (40.0) RDD/100 in 2019 compared to 44.8 (41.7), 44.5 (40.80), and 44.9 (41.7) RDD/100 in the years 2020 through 2022, respectively. Antifungal drug volumes and use density increased after 2019 and peaked 2021 (differences between 2019 and 2021 for total volumes +6.4%, and for pooled mean use density values +22.9%, respectively). These trends were similar in the different hospital strata and comparable when DDD instead of RDD were used. Conclusions: Similar to what has been observed in a majority of European countries the total volume of antibac-terial drug use in German acute care hospitals decreased with the pandemic without a rebound phenomenon in 2022. In association with restricted hospital capacities and presumably more immunocompromised general medi-cine patients, however, inpatient prescribing of (primarily broad-spectrum) antibacterials and of antifungal drugs increased.

Aim: Deep brain stimulation (DBS) involves implanting electrodes in specific brain areas. High-frequency Stimulation (HFS) and low-frequency Stimulation (LFS) target motor and non-motor symptoms differently. DBS is crucial in Parkinson's disease treatment for managing medication-resistant symptoms and improving quality of life. This review aims to evaluate the differential impact of high-frequency and low-frequency deep brain stimulation (DBS) on motor symptoms in Parkinson's disease (PD) patients. This systematic review adheres to PRISMA guidelines and focuses on clinical studies involving human subjects. Methods: Systematic search in electronic databases (PubMed, Google Scholar, Science Direct, Cochrane Collaboration Database of Randomized Trials) was performed to identify randomized controlled trials (RCTs) up to 13th July 2024. Results: Among 126 pooled patients from 8 RCTs, it was found that LFS significantly improved gait stability, swallowing, and verbal fluency with minimal adverse effects. Conversely, HFS was effective in reducing rigidity and tremor but was associated with potential side effects such as gait and speech impairment. Conclusion: The review highlights the nuanced effects of STN-DBS frequencies in Parkinson's treatment, suggesting high-frequency improves rigidity and tremor but may cause side effects, while low-frequency enhances gait stability and speech, necessitating further research for optimized, patient-specific therapies.

Background: Escalating climate change concerns have prompted the healthcare sector, particularly anaesthesia, to reassess its practices to align with environmental sustainability. Anesthetic gases like desflurane, sevoflurane, and isoflurane significantly impact the environment due to their high Global Warming Potentials (GWPs) and prolonged atmospheric lifetimes. This manuscript investigates these impacts and advocates for strategies to reduce the carbon footprint of anesthetic care while maintaining patient safety. Methods: We reviewed the environmental impacts of anesthetic gases and explored various strategies for sustainable anaesthesia. These strategies include adopting anesthetics with lower GWPs, enhancing recycling and waste reduction techniques, transitioning to intravenous anaesthesia, and implementing low-flow anaesthesia methods. We also examined barriers to these strategies, such as educational gaps, technological challenges, resistance to change, and policy limitations. Results: Adopting anesthetics with lower GWPs, such as sevoflurane over desflurane, and implementing low-flow anaesthesia can significantly reduce greenhouse gas emissions. Recycling and waste reduction techniques, though challenging, offer additional environmental benefits. Transitioning to intravenous anaesthesia can eliminate the direct GWP contributions from volatile anesthetic gases. However, these strategies require comprehensive education, advocacy for research and innovation, strategic change management, and supportive policies. Conclusions: Continuous monitoring and evaluation are crucial to ensure the effectiveness of sustainable practices in anaesthesia. Establishing robust Key Performance Indicators (KPIs) and utilizing advanced analytical tools will enable the anaesthesia community to adapt and refine practices. Collaborative efforts among clinicians, policymakers, and stakeholders are essential to significantly reduce the environmental impact of anaesthesia and promote ecological responsibility within healthcare.

Recent advances in organoid technology have revolutionized cancer biology and thera-peutic interventions, offering personalized immunotherapy treatment. Organoids, three-dimensional cell cultures derived from patient tumors, accurately replicate the tumor microenvi-ronment, providing unprecedented insights into tumor-immune interactions and therapeutic re-sponses. In this literature-based study, we discuss various culture methods for the diverse appli-cations of organoids in cancer immunotherapy, including drug screening, personalized treatment strategies, and mechanistic studies. Additionally, we address the technological challenges asso-ciated with these methods and propose potential future solutions to accelerate the development of novel immunotherapeutic approaches. This review highlights the transformative potential of or-ganoid models in advancing preclinical cancer immunotherapy modeling, screening, and evalua-tion, paving the way for more effective and personalized cancer treatments.

Short-cycle therapy has proven to be a safe and effective alternative to standard everyday antiretroviral treatment for virally suppressed people living with HIV. Here we report a favorable long-term virological and immunological outcome in 12 virally suppressed people on short cycle therapy with bictegravir/emtricitabine/tenofovir alafenamide administered five days a week (Monday to Friday).

The α-Klotho protein (hereafter Klotho) is an obligate coreceptor for fibroblast growth factor 23 (FGF23). It is produced in the kidneys, brain and other sites. Klotho insufficiency causes hyperphosphatemia and other anomalies. Importantly, it is associated with chronic pathologies (often age-related) that have an inflammatory component. This includes atherosclerosis, diabetes and Alzheimer’s disease. Its mode of action in these diseases is not well understood, but it inhibits or regulates multiple major pathways. Klotho has a membrane form, and a soluble form (s-Klotho). Cytosolic Klotho is postulated but not well characterized. s-Klotho has endocrine properties that are incompletely elucidated. It binds to the FGF receptor 1c (FGFR1c) that is widely expressed (including endothelial cells). It also attaches to soluble FGF23, and FGF23/Klotho binds to FGFRs. Thus, s-Klotho might be a roaming FGF23 coreceptor, but it has other functions. Notably, Klotho (cell-bound or soluble) counteracts inflammation, and appears to mitigate related aging (inflammaging). It inhibits NF-κB and the NLRP3 inflammasome. This inflammasome requires priming by NF-κB, and produces active IL-1β, membrane pores and cell death (pyroptosis). In accord, Klotho countered inflammation and cell injury induced by toxins, damage-associated molecular patterns (DAMPs), cytokines, and reactive oxygen species (ROS). s-Klotho also blocks the TGF-β receptor and Wnt ligands, which lessens fibrotic disease. Low Klotho is associated with loss of muscle mass (sarcopenia), as occurs in aging and chronic diseases. s-Klotho counters the inhibitory effects of myostatin and TGF-β on muscle, reduces inflammation, and improves muscle repair following injury. Inhibition of TGF-β and other factors may also be protective in diabetic retinopathy and age-related macular degeneration (AMD). This review examines Klotho functions especially as related to inflammation, and potential applications.

Reducing visceral fat is an important issue for obesity prevention. We previously reported a novel dietary intervention program using “Optimized Nutri-Dense Meals” based on the nutrients described in Dietary Reference Intakes in Japan. This open-label randomized controlled trial evaluated the visceral fat reducing effect of the program. In total, 100 Japanese obese/overweight male patients were recruited and divided into a control group that continued their usual diets and a test group that consumed test meals twice per weekday for four weeks. Visceral fat area, set as the primary outcome, was significantly decreased in the test group compared with the control group. Regarding other outcomes, the occupancy levels of some gut floras and presenteeism scores were significantly increased in the test group compared with the control group. These results indicate that dietary intervention based on the Dietary Reference Intakes can prevent visceral fat accumulation and contribute to the improvement of health, without the need for completely replacing the everyday diet.

Background: Current treatment for Chronic Kidney Disease (CKD) focuses on improving manifestations and delaying progression. Nutritional approaches play a crucial role in CKD management, and various supplements have become available. Ketoanalogues of amino acids (KA), calcum citrate, and inulin have been proposed as suitable supplements, yet their widespread use has been limited due to insufficient evidence. This study aimed to generate general guidance statements on the appropriateness of these supplements through a RAND/UCLA consensus process; Methods: A RAND/UCLA consensus panel was convened to evaluate the appropriateness of these supplements in different clinical scenarios. In this study, we present a subgroup analysis focusing on a panel of eleven clinical nephrologists from among the experts; Results: Supplementation of low protein diets (LPD) and very low protein diets (VLPD) with KA was considered appropriate to reduce manifestations and delay CKD outcomes, supplementation with calcium citrate is considered appropriate to reduce CKD manifestations, and supplementation with inulin is considered appropriate to delay CKD outcomes and manage comorbidities; Conclusions: Based on a combination of clinical experience and scientific evidence , the panel reached a consensus that KA supplementation of LPD and VLPD, calcium citrate, and inulin are appropriate in patients with CKD across various scenarios.

Exogenous melatonin, a nutraceutical for maintaining a healthy sleep-wake cycle and managing sleep disorders, requires large, repeated doses due to low bioavailability and short half-life. This necessitates the development of a sustained-release formulation with a longer half-life and sustained plasma concentration. Therefore, exogenous novel 5 mg sustained-release melatonin capsules (Melatonin-SR, test product) were formulated. This open-label cross-over study compared the pharmacokinetics (maximum concentration [Cmax], time to reach Cmax [Tmax], area under the curve [AUC] and elimination half-life [t1/2]) and safety of Melatonin-SR with 5 mg immediate-release melatonin capsules (Melatonin-IR, reference product) after single-dose oral administration in healthy fasting adults. Sixteen participants (aged 18-45 years) were randomized (1:1) to receive either Melatonin-SR or Melatonin-IR in two periods with a 7-day washout period. Melatonin-SR reported lower Cmax (11446.87 pg/mL) compared to Melatonin-IR (22786.30 pg/mL). The mean Tmax of Melatonin-SR and Melatonin-IR was 1.26 h and 0.87 h, respectively. The mean t1/2 of Melatonin-SR (5.10 h) was prolonged by five-fold compared to Melatonin-IR (1.01 h). One adverse event (vomiting) was reported following administration of the Melatonin-IR. Melatonin-SR resulted in higher and sustained plasma melatonin concentrations for an extended period and was well-tolerated. Hence, Melatonin-SR may be a promising nutraceutical for maintaining healthy sleep.

Balanites aegyptiaca del. (Zygophyllaceae) is widely used in traditional medicine, both human and veterinary, throughout Africa for its many properties, including antiparasitic properties. This experimental study aims to optimise the extraction conditions of the seeds of Balanites aegyptiaca del. Aqueous maceration was carried out with mass to volume ratios of 40%, 30%, 20%, 10% and 5% and extraction times of 6, 12, 24, 36 and 48 hours. Extraction yields, phytochemical screening, saponins assay, antioxidant activities (ABTS and FRAP) and antiparasitic tests on Heligmosomoides bakeri were used to compare the different extracts. The pharmaco-chemical study generally showed that aqueous maceration gave the best results, with a mass/volume ratio of 10% after 12 hours of maceration. The yield obtained was 28.03% with a saponins content of 13.81 mg/g. The antioxidant activities were 4.25 ± 0.17µg/mL by the ABTS method and 0.739µg/mL by the FRAP method. The larvicidal activity also showed that the 10%12h extract produced 100% larval mortality from 25ug/mL. These data provide a basis for guiding the choice of extraction process parameters in producing this antiparasitic phytomedicine.

Endometrial preparation is crucial in in vitro fertilization (IVF) protocols to create optimal conditions for embryo implantation and pregnancy. Successful embryo nidation requires a receptive endometrium, which is influenced by factors such as endometrial thickness, hormonal environment, autocrine and paracrine growth factors, and the presence of resident and non-resident stem cells within the endometrium basalis. Synchronization between endometrial and embryonic development is also essential. Endometrial preparation, whether achieved through spontaneous cycles, natural cycles with minimal support, ovulation induction, or hormone replacement therapy (HRT), results from a combination of biochemical and biophysical conditions, each independent of the others. These conditions are difficult to pinpoint within a fixed period (Window of Implantation, WOI) using any specific examination due to the variability in estrogen and progesterone production rates, their metabolic clearance rates (MCR) when administered exogenously, and their metabolism when given systemically, topically, or orally. These variations also occur in different phenotypes and over different durations. Moreover, the synchronization of endometrial preparation with incomplete decidualization and the uncertain duration of the implantation window pose challenges. It is also unknown if there are compliance mechanisms similar to diapause seen in other species. This review aims to outline a clinical approach that, while not an absolute clinical recommendation due to the lack of definitive certainties, assists in understanding complementary phenomena and provides a useful orientation for clinical practice.

Histone deacetylase inhibitors (HDACis) are being recognized as a potentially effective treatment approach for peripheral T-cell lymphoma (PTCL), which is a diverse group of aggressive lymphomas with a bleak prognosis. Recent evidence has shown that HDACi are effective in treating PTCL, especially in cases where the disease has relapsed or is resistant to other treatments, and there are few available options. Several clinical trials have demonstrated that HDACi, such as romidepsin and belinostat, can elicit long-lasting positive outcomes in individuals with PTCL, either when used alone or in conjunction with conventional chemotherapy. They exert their anti-tumor actions by regulating gene expression through inhibiting histone deacetylases, which results in the halting of cell division, programmed cell death, and the transformation of cancerous T-cell, as indicated by gene expression profile studies. Importantly, besides clinical trials, real-world evidence indicated that the utilization of HDACi presents a significant and beneficial treatment choice for PTCL. However, although HDACi showed potential effectiveness, they couldn’t cure most patients. Therefore, new combination with conventional drugs as well as new targeted agents are under investigation.

The rise in precocious puberty cases can be attributed to a combination of genetic and environmental factors. Genetic factors play a significant role, with studies identifying genetic abnormalities in genes such as KISS1, KISS1R, MKRN3, DLK1, GABRA1, LIN28B, NPYR, TAC3, and TACR3, which are associated with central precocious puberty (CPP). Epigenetic factors like DNA methylation and histone modifications may mediate the relationship between genetic and environmental influences on CPP development. Environmental factors such as exposure to secondhand smoke, cesarean section, and BMI have also been linked to precocious puberty, particularly in girls, highlighting the multifactorial nature of this phenomenon. Understanding the interplay between these genetic and environmental factors is crucial in addressing the increasing prevalence of precocious puberty in children. The published literature in the past five years was systematically reviewed and summarized highlighting the interplay of genetic and environmental factors for the rise in the precocious puberty.

Chronic pancreatitis is a progressive fibroinflammatory disorder with no currently satisfactory treatment. Emerging evidence suggests an association between gut microbial dysbiosis and chronic pancreatitis. Although direct causative evidence is lacking, it is hypothesized that the gut microbiota may play a pivotal role in modulating pancreatic function via the gut-pancreas axis. Thus, modulating the gut microbiota through the administration of probiotics or prebiotics may alleviate pancreatic disorders. In this review, we first propose the potential mechanisms by which specific probiotics or prebiotics may ameliorate chronic pancreatitis, including the alleviation of small intestinal bacterial overgrowth (SIBO), facilitation of short-chain fatty acids (SCFAs) production, activation of the glucagon-like peptide 1 receptors (GLP-1Rs) in the pancreas. Since there are currently no probiotics or prebiotics used for the treatment of chronic pancreatitis, we have discussed research in other disease models that use probiotics or prebiotics to modulate pancreatic endocrine and exocrine functions and prevent pancreatic fibrosis. This provides indirect evidence for their potential application in the treatment of chronic pancreatitis. We anticipate that this research will stimulate further investigation into the gut-pancreas axis and the potential therapeutic value of probiotics and prebiotics in chronic pancreatitis.

Background: Vestibular Neuritis (VN) induces Acute Vestibular Syndrome (AVS). This study aimed to identify predictive factors of VN recovery by healing and/or compensation. Methods: In this longitudinal and prospective study, 40 patients were included. The first assessment (T0) included medical history taking (general and specific), for cardiovascular risk factors (CVRFs), a battery of diagnostic tests, bithermal caloric test (BCT), video Head Impulse Test (VHIT) and skull vibration induced nystagmus (SVIN). All patients also completed a Dizziness Handicap Inventory (DHI). All assessments were repeated 90±15 days (T3) later. Subjective criteria compensation were based on DHI total score and objective criteria compensation on the instrumental test results. Four groups of patients (A, B, C, D) were delineated by combining patients with normal vs abnormal vestibular tests and patients with normal vs abnormal DH. Results: CVRFs were associated with a poorer recovery of symptoms but not the age or BMI. Vestibular tests mainly BCT (canal paresis %), VHIT (lateral semicircular canal gain) and SVINT (nystagmus slow phase velocity) recovered within normal values in 20%, 20%, 26% of cases respectively at T3 for the 40-patient group. Conclusions: Vascular risk factors (hypercholesterolemia) are correlated with patients who do not recover their symptoms either by healing or compensation. The evolution did not show any significant difference between high or low frequency vestibular tests in patients recovering from their symptoms. However, some patients with objective recovery may continue to show persisting subjective symptoms.

The disease of transthyretin (TTR) amyloidosis (ATTR) has been known since the 1960s, and during these past 60 or so years, there has been a sustained peri-od of steady discoveries that have led to the current model of ATTR pathogene-sis. More recent research has achieved major advances in both diagnostics and therapeutics for ATTR, which are having a significant impact on ATTR patients today. Aiding these recent achievements has been the remarkable ability of cryo-electron microscopy (EM) to determine high-resolution structures of amy-loid fibrils obtained from individual patients. Here, we will examine cryo-EM structures of transthyretin amyloid fibrils to explore the structural basis of re-cent monoclonal antibody therapies for ATTR, including ALXN-2220 and Co-ramitug; as well as to point out potential applications of this approach to other systemic amyloid diseases.

Background and Objectives: Proteomics encompasses the exploration of protein composition, regulation, function, and pathways. Its influence spans diverse clinical fields and holds promise in addressing various women’s health conditions, including cancers, osteoporosis, and cardiovascular disorders. However, no comprehensive summary of proteomics and menopausal health exists. Our objective was to summarize proteomic profiles associated with diseases and disorders in peri and postmenopausal women. Materials and Methods: We conducted a comprehensive search of databases including PubMed, Google Scholar, Cochrane database, Elsevier, and ScienceDirect until 2022. A total of 253 studies were identified, 41 studies met the inclusion criteria to identify data of interest. These included study design, disease, and proteomics/proteins of significance as described by the authors. Results: The 41 studies, covered diverse areas including bone disorders (10 studies), cardiovascular diseases (5 studies), oncological malignancies (10 studies), and conditions such as obesity, nonalcoholic liver disease, the effects of hormone replacement therapy, and neurological diseases (16 studies). Results of our study indicate that proteomic profiles correlate with heart disease in peri- and postmenopausal women, with distinct sex differences. Furthermore, proteomic profiles significantly differed between women with and without osteoporosis. Additionally, patients with breast, ovarian, and endometrial cancer exhibited notable variations in proteomic profiles compared to those without these conditions. Conclusions: Proteomics has the potential to enhance risk assessment and disease monitoring in peri- and postmenopausal women. By analyzing unique protein profiles, clinicians can identify individuals with heightened susceptibility to specific diseases or those already affected by established conditions. This review suggests that there is sufficient preliminary data for proteomics in peri- and postmenopausal women for early identification of cardiovascular disease, osteoporosis, and cancers, in disease monitoring, and in tailoring individualized therapies. Rigorous validation studies involving large populations are essential before drawing definitive conclusions regarding the clinical applicability of proteomic findings.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic VSL#3 at improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and VSL#3 treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n=64) was treated with rifaximin (seven days per month for three months) followed by VSL#3, and group B (n=60) was treated with a placebo. At the beginning of the study and after three months of treatment, all patients completed NIH-CPSI and IBS-SSS questionnaires to score the severity of their urogenital and gastrointestinal symptoms, and we measured seminal plasma levels of IL-6 and IL-10 using ELISA. We defined patients who improved following the treatment as those with a ≥6-point reduction in their NIH-CPSI score or ≥50-point reduction in their IBS-SSS score. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI and IBS-SSS scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs 4.4 pg/mL) relative to baseline, whereas levels of IL-6 and Il-10 did not change in the placebo group. The co-occurrence of two clinical phenotypes (IBS-D plus IIIa prostatitis) result in increased intestinal inflammation and altered immune activation, both of which can be balanced by treatment with rifaximin and VSL#3.

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is a clinical entity characterized by the absence of significant coronary artery obstruction in epicardial arteries (&lt; 50%) on coronary angiography in the setting of acute myocardial infarction (AMI). This article aims to provide a narrative review of the pathophysiological mechanisms, diagnostic challenges, and prognosis associated with MINOCA focusing only on cases associated with myocardial ischemia but of non-atherosclerotic origin. Etiological factors, including thromboembolism, coronary artery spasm, spontaneous coronary artery dissection, coronary microvascular disease, and supply-demand mismatch are addressed. Imaging modalities such as echocardiography, advances in coronary angiography like intravascular ultrasound (IVUS) and optical coherence tomography (OCT), cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) are also analyzed. MINOCA patients have a better short-term prognosis compared to those with obstructive coronary artery disease but face significant long-term risks, underscoring the need for precise diagnosis and management strategies. Elevated inflammatory markers and specific genetic predispositions are also associated with adverse outcomes in MINOCA. This review focused on MINOCA from the pathophysiological perspective on ischemic, non-atherosclerotic causes, the diverse underlying mechanisms, the challenges in achieving accurate diagnosis, the importance of a tailored therapeutic approach and the necessity for further investigation of clinical outcomes.

Inherited cardiomyopathies are a diverse group of heart muscle diseases caused by genetic mutations that result in structural and functional abnormalities of the myocardium. Understanding genotype-phenotype correlations in these conditions is vital for personalized cardiac medicine, enabling targeted therapeutic strategies and predictive diagnostics. This review explores the major types of inherited cardiomyopathies—hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM)—and provides detailed insights into how different genetic mutations manifest as clinical features. The integration of multi-omics approaches and advanced disease modeling techniques has enhanced our ability to dissect these correlations. The review also discusses the implications of these findings for personalized medicine, including tailored therapeutic strategies, predictive diagnostics, and future research directions.

Objective: Breast cancer (BC) is the most common cause of death among females. There are many prognostic systems, the most recent of which are the molecular subtypes. Recently, it was included that thyroid disease is a favorable factor for the patients with BC and that the thyroid hormones have an effect on the disease. Thyroid stimulating hormone (TSH), however, is thought to be unrelated to the cancer aggressiveness. In the current study we aimed to examine the status of the postoperative TSH levels, as well as the impact of the thyroid disease on the cancer aggressiveness. Methods: A retrospective comparative analysis of invasive BC patients was performed between 2017 and 2019 year. 111 patients were selected. They were divided into group A (n=62) and group B (n=49), based on the presence or absence of thyroid disease, respectively. The data was processed with SPSS version 25. Results: There is a significant difference between group A and group B concerning the molecular subtypes, ki-67, and estrogen receptor. The current study supports the fact that TSH is responsible for the aggressiveness of the invasive BC and not the thyroid hormones themselves. Moreover, based on the correlation analyses calcium levels preoperatively are linked to cancer aggressiveness and could be used as future prognostic factors. Conclusion: Indeed, the thyroid disease appears to have more favorable prognosis based on the molecular subtype frequency but more emphasis in future studies should be given to the TSH and its relation to the overall survival of the patients.

Cestodes are etiological agents of neglected diseases such as echinococcosis and cysticercosis, which are major public health problems. Antiparasitic treatment relies on a small number of approved drugs, which are often only partially effective, poorly tolerated and require prolonged administration. Thus, the discovery of novel potential treatments is critical. The Stevia genus (Asteraceae) includes species that are associated with medicinal uses and are considered a source of bioactive compounds. Here, we analyzed four South American Stevia species that have previously demonstrated antiprotozoal properties. The effect of dichloromethane extracts of these species was determined by motility assays on Mesocestoides vogae, a laboratory model of cestodes. Stevia alpina showed the highest anthelmintic potential followed by S. maimarensis and S. multiaristata, while S. aristata was the least active. The sesquiterpene lactones estafietin and eupatoriopicrin were purified from S. alpina and S. maimarensis, respectively. Estafietin showed cestocidal activity, inhibiting parasite viability in a dose-dependent manner, even from the first day of incubation. Consistent with the motility effects, the extract of S. alpina and estafietin induced major alterations on the morphology of the parasite. The results of this report show that Stevia species represent a source of new molecules with potential for the treatment of neglected tropical diseases caused by cestodes.

Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (Postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe in pups on P0 and as adults on P70, and the concentration of copper (Cu) and zinc (Zn). Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin was significantly lower following ID, whereas cerebral hepcidin was virtually undetectable in all experimental groups. In conclusion, administering FDI subcutaneously to ID pregnant rats on EO normalizes cerebral Fe in the fetus, but when applied at later gestational ages, additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

99mTc is a well-known radionuclide widely used and readily available for medical imaging. Despite this, the 99mTc isotope is rarely utilized for tumour imaging due to the lack of agents that can selectively deliver it to tumours. However, the use of immunologically compatible recombinant proteins, which combine metal-binding sites and tumour-specific ligands, shows promise for utilizing 99mTc in the early detection of tumours. To illustrate this, a protein called E1b, containing a metal binding center with ELP repeats, tumour-specific ligands recognizing integrin αvβ3 and nucleolin, as well as a short Cys-rich sequence, was artificially designed. This protein was produced in E. coli and purified to homogeneity using metal-chelate chromatography. In experiments, C57Bl/6 and Balb/C mice with subcutaneously grafted lung carcinoma (LLC) or mammary gland adenocarcinoma (Ca755, EMT6, or 4T1) were used to test 99mTc-E1b selectivity and the kinetics of isotope retention. The mice were intravenously injected with approximately 80 MBq of 99mTc in complex with E1b, which had been freshly purified using gel-chromatography. The biodistribution of the labeled protein was then studied using the SPECT/CT imaging method within 24 h. The ratio of radionuclide distribution in the tumour versus the adjacent normal tissue (T/N) steadily increased over the 24-h period, reaching 15.7±4.2 for EMT6, 16.5±3.8 for Ca755, 6.7±4.2 for LLC, and 7.5±3.1 for 4T1.

Background: Respiratory syncytial virus (RSV) is a significant cause of illness in adults, especially older adults and those with underlying conditions. This study aimed to assess the incidence of RSV hospitalizations in adults and identify risk factors for hospitalization and poor outcomes. Methods: A retrospective cohort study was conducted using data from two hospitals in southern Israel from 2016-2022. We calculated incidence rates of RSV and influenza hospitalizations. Risk factors for hospitalization were analyzed using Poisson regression. We evaluated poor outcomes (death, ICU admission, or mechanical ventilation) among RSV-hospitalized patients. Results: The median annual incidence of RSV hospitalization was 28.2/100,000 population, increasing with age to 199/100,000 in those ≥75 years. Significant risk factors for RSV hospitalization included pulmonary diseases (RR 4.2, 95% CI 3.4-5.2), cardiovascular diseases (RR 3.3, 95% CI 2.6-4.2), and chronic renal failure (RR 2.9, 95% CI 2.3-3.7). Among hospitalized RSV patients, 13.9% had poor outcomes. Renal failure (RR 1.81, 95% CI 1.23-2.66), neutropenia (RR 2.53, 95% CI 1.19-5.35), neutrophilia (RR 1.66, 95% CI 1.81-2.34), and lymphopenia (RR 2.03, 95% CI 1.37-3.0) were associated with poor outcomes. Conclusions: RSV causes a substantial burden of hospitalizations in adults, particularly among older adults and those with comorbidities. Identifying high-risk groups can help target prevention and treatment strategies, including vaccination.

The hemodynamic consequences of the aortic stenosis (AS) on supraortic trunks may have a po-tential role in the diagnosis of concomitant internal carotid artery (ICA) stenosis by dampening blood flow velocity. To investigate the effect of AS on ICA blood flow we evaluated carotid and vertebral blood flow velocity indexes in patients undergoing transcatheter aortic valve implanta-tion (TAVI). Eighty-five patients admitted for endovascular treatment of a severe AS underwent supra-aortic Duplex ultrasound (DUS) examination prior and after TAVI to be enrolled in the study. Patients with other cardiac impairments that could configure a confounding factor were excluded. Pa-tients with symptomatic or severe ICA stenosis defined according to NASCET criteria were ex-cluded. Forty-five patients of a median age of 80 years met the study inclusion criteria. The peak systolic velocity (PSV) of the assessed supraortic arteries increased after TAVI: respectively common ca-rotid artery (CCA) 64 ± 17 cm/s vs 78 ± 23 cm/s, p= 0,01; ICA 68 ± 23 cm/s vs 96 ± 35 cm/s, p= 0,01; vertebral artery (VA) 45 ± 14 cm/s vs 52 ± 15 cm/s, p=0,03. Similarly, the end diastolic velocity (EDV) increased after TAVI: respectively CCA 13 ± 6 cm/s vs 15 ± 7 cm/s, p=ns; ICA 20 ± 9 cm/s vs 24 ± 9 cm/s, p= 0,01; VA 9 ± 4 cm/s vs 11 ± 4 cm/s, p=0,01. Consistently, the mean acceleration time (AC) decreased after TAVI: respectively CCA 0,17 ± 0,05 s vs 0,12 ± 0,05 s, p= 0.01; ICA 0,1 8 ± 0,05 s vs 0,12 ± 0,04 s, p= 0,01; VA 0,16 ± 0,05 s vs 0,11 ± 0,05 s, p=0,02. Severe AS significantly affects supra-aortic arteries blood flow as assessed by duplex, by de-creasing both PSV and EDV and increasing AC. This study suggests that carotid ultrasound cri-teria to assess ICA stenosis severity should be re-evaluated in larger multicenter studies to vali-date their predictive values in patients with concomitant AS.

Background: Historically, a large gender-related disparity in vascular access (AV) has been demonstrated, with a lower prevalence of women with arteriovenous fistula (AVF) compared to men and worse maturity rates. The cause of this difference is not entirely clear, although several reasons that could contribute to it have been hypothesized. The emergence of new percutaneous FAV (pFAV) systems could be an alternative for reducing these differences. Objective: The study aims to determine if there is a gender difference in the creation of AVFs using the new percutaneous systems. Material and Methods: A systematic review of the literature was conducted by searching PubMed and Google Scholar using the following terms: "percutaneous arteriovenous fistula", "endovascular arteriovenous fistula", and "hemodialysis". All clinical trials, comparative studies, and descriptive studies involving patients who underwent a pAVF were included. Results: Finally, the review includes 19 studies, comprising 14 retrospective and 5 prospective studies. Of these, 6 studies are comparative, 5 of which compare pAVF with surgically created AVFs (sAVF), and 1 comparing pAVFs performed using different systems with each other. A total of 1,269 patients were included in the review. Of the total number of patients, only 414 were women, representing 32.62%. Conclusion: The number of women included in the various studies analyzing pAVF remains very low, representing less than one-third of all patients. Although the causes of this difference are not entirely clear, several reasons have been hypothesized such as socio-economic factors, anatomical factors, or even patients' preferences. Given these results, further studies are needed to try to clarify the reasons for this gender disparity and to establish different strategies to mitigate the barriers faced by women in accessing the creation of an AVF.

Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study we aimed to investigate whether abnormal pulmonary circulatory handling of ET-1 relates to poor clinical outcomes in patients with COVID-19-induced ARDS. Plasma ET-1 levels were measured in 18 mechanically ventilated COVID-19-induced ARDS patients, with simultaneous central venous and systemic arterial blood sampling on Days 1 and 3 following ICU admission. Two age- and sex-matched non-COVID-19 control groups were also used [mechanically ventilated non-COVID-19 critically ill and ARDS patients]. On ICU admission, COVID-19-induced ARDS patients had higher systemic arterial and venous ET-1 levels compared to non-COVID-19 ARDS and critically ill patients (p< 0.05). The arterial:venous (A:V) ET-1 ratio was higher in the non-COVID-19 ARDS patients [1.06 (0.93-1.20)] compared to the other two groups (p< 0.05). The A:V ratio was 0.63 (0.49-1.02) in the COVID-19-induced ARDS patients and 0.79 (0.52-1.11) in the non-COVID-19 critically ill patients. On Day 3, the A:V ratio in all three groups was < 1. The COVID-19 patient group was then divided based on 28-day ICU mortality. Although arterial and venous levels did not differ, the A:V ratio was statistically significantly higher on ICU admission in the non-survivors [0.95 (0.78-1.34)] vs 0.57 (0.48-0.92), p= 0.027]. Measurement of ET-1 clearance via A:V plasma ET-1 levels on ICU admission may assist in predicting outcomes in COVID-19 critically ill patients.

The term ovarian rejuvenation is used for treatments aiming to reactivate ovarian function in women suffering from premature ovarian insufficiency or women with poor ovarian response following ovarian stimulation treatments. Following Bologna criteria, patients with poor ovarian response (POR) are those patients with at least one previous stimulated cycle with POR, are of advanced maternal age, and have an abnormal ovarian reserve. Patients with at least 3 failed IVF cycles due to poor ovarian response (POR) and patients with POF with amenorrhea for at least 6 months, low estradiol, and high concentrations of LH and FSH were referred for ovarian PRP treatment. Out of 190 procedures, 15 were performed using the THL as there was an inaccurate visibility by vaginal ultrasound. Under direct visualization, PRP was injected in each ovary using a 19G needle. In the 53 patients referred for IVF, an embryo transfer was possible in 40% of the started cycles (n=21); the pregnancy rate per transfer was 52% with a live birth rate of 24%. The access to the pelvis by the THL enabled a direct visualization of both ovaries allowing a correct injection. Due to maternal age, patients should be informed of the elevated risks of 40% - 50% of biochemical pregnancies or miscarriages.

Artificial Intelligence (AI) is revolutionizing head and neck cancer (HNC) care by providing innovative tools that enhance diagnostic accuracy and personalize treatment strategies. This review highlights the advancements in AI technologies, including deep learning and natural language processing, and their applications in HNC. The integration of AI with imaging techniques, genomics, and electronic health records is explored, emphasizing its role in early detection, biomarker discovery, and treatment planning. Despite noticeable progress, challenges such as data quality, algorithmic bias, and the need for interdisciplinary collaboration remain. Emerging innovations like explainable AI, AI-powered robotics, and real-time monitoring systems are poised to further advance the field. Addressing these challenges and fostering collaboration among AI experts, clinicians, and researchers is crucial for developing equitable and effective AI applications. The future of AI in HNC holds significant promise, offering potential breakthroughs in diagnostics, personalized therapies, and improved patient outcomes.

Background: Introduction of new technologies in the management of oral disease has revolutionized treatment approaches, offering less invasive options and improved patient outcomes. Among oral cavity diseases, sialolithiasis is the most common disorder of the salivary glands. It involves the formation of calculi or stones within the salivary ducts, primarily affecting the submandibular gland due to its tortuous duct and the alkaline nature of its saliva. In particular, Laser-assisted techniques have shown significant promise in enhancing the precision and safety in the management of sialolith removal. This article aims to present a case report and also explores the scientific evidence supporting these innovative methods, highlighting their benefits and limitations in clinical practice.; Methods: The research was conducted using PubMed and Scopus search engines with a combination of relevant keywords, including laser, laser-assisted, laser treatment in combination with sialolith, sialolith removal, and sialoadenectomy. Selected articles were carefully reviewed to identify studies reporting data on the effectiveness of laser-assisted sialolith removal; Results: The results of the literature review indicate a growing interest in the application of Diode Laser and CO2, with evidence suggesting improved clinical outcomes and reduced postoperative pain compared to traditional methods; Conclusions: Although lasers offer enhanced safety and reduced morbidity and bleeding, which ensures optimal visibility, their high cost and the need for specialized training are limitations. Further randomized clinical trials and longer follow-up studies are needed to better evaluate their use in sialolith removal.

Long COVID comprises persistent symptoms which extend beyond four weeks post-SARS-CoV-2 infection. The potential association between long COVID and the endorsement of COVID-19 conspiracy theories has not been explored, particularly in Arab countries where high endorsement of these theories has been reported. This study aimed to explore the association between endorsing COVID-19 conspiracy theories and the prevalence of self-reported long COVID symptoms among adults in Jordan and Kuwait in addition to other Arab countries. The study employed a cross-sectional design using an electronic self-administered survey in Arabic language. Recruitment utilized snowball sampling via social media and the survey was distributed in July 2024. The survey instrument included sections on demographic information, the history of COVID-19 infection, and vaccination status. Long COVID manifestations were assessed using a score reflecting the frequency and intensity of ten recognized long COVID symptoms with subsequent categorization into three categories: low, middle, and high. The beliefs in COVID-19 conspiracy theories were measured via a 5-point Likert scale across five items. The final study sample comprised 756 respondents, the majority of whom self-reported a history of confirmed COVID-19 diagnosis at least once (n = 493, 65.2%). The results indicated a neutral average attitude towards COVID-19 conspiracy theories (mean score = 15.18±4.64 out of 30.00). Participants with high conspiracy theories scores were significantly more likely to report high (aOR = 6.85, 95% CI: 2.90–16.13, p &lt; 0.001) and middle long COVID symptoms (aOR = 2.82, 95% CI: 1.32–6.06, p = 0.008) compared to those with lower scores. Additional predictors of higher long COVID reporting included female sex and lower self-reported household income. Frequent COVID-19 infections and hospitalizations were also associated with higher long COVID symptom reporting. The study results revealed a significant correlation between the endorsement of COVID-19 conspiracy theories and the higher frequency and magnitude of long COVID symptom reporting. The findings also highlighted the influence of sociodemographic factors and COVID-19 infection history on long COVID reporting, which suggests that public health strategies should address these factors to mitigate long COVID challenges effectively.

Previous studies found that corilagin inhibits the growth of many cancer cells. Ovarian cancer is the deadliest gynecological malignancy, but research on the effects of corilagin on ovarian cancer is limited. This experiment aims to explore the impact of corilagin on ovarian cancer A2780 cell apoptosis and its mechanism of action to evaluate the prospects of corilagin in treating ovarian cancer. Corilagin significantly affects the A2780 cell cycle, reducing the proportion of G0/G1 and G2/M phase cells and blocking them in the S phase. Corilagin at low concentrations can cause A2780 cell apoptosis, mitochondrial membrane potential decline, and calcium influx. After the cells were stained with Acridine Orange, autophagosomes were observed under a fluorescence microscope and increased with the increase in concentration. The results of transcriptome sequencing showed that the effect of corilagin could cause differential expression of apoptosis-related genes in A2780 cells and concentrated on the PI3K-AKT pathway. The qPCR results showed that the expression of genes P53 and Bax in cells increased while the expression of BCL-2 decreased. The expressions of apoptotic factors caspase-9, caspase-3, p53-upregulated modulator of apoptosis (PUMA), and cytochrome C increased after the action of corilagin, indicating that corilagin can induce cell apoptosis. Corilagin can effectively inhibit the proliferation of A2780 cells, cause cell cycle arrest, and induce cell apoptosis. Moreover, it can trigger autophagy and has in vitro antitumor effects. It is a promising drug for treating ovarian cancer through the PI3K/P53 pathway.

The fundamental goal of modern medicine is to increase human life expectancy. Currently, most of the patients in hospitals with different clinical profiles are elderly and senile subjects, with a high incidence of comorbidities, as well as concomitant age-related changes in peripheral tissues. One such change is sarcopenia, a progressive loss of muscle mass, strength, and muscle function that is associated with a high risk of adverse outcomes, leading to an increased risk of disability and death among older adults. The mechanisms of development of sarcopenia are currently being actively studied. This narrative review presents the issues of epidemiology, pathophysiology, and diagnostic criteria for sarcopenia. The relationships between sarcopenia and metabolic dysfunction-associated steatotic liver disease (MASLD) with possible promising directions for the treatment of this comorbid pathology are considered.

This study investigated the efficacy and safety of a propolis mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multi-centered randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. Results revealed that the PMEC group showed significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p&lt;0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to baseline. While clinical parameters trended towards improvement in both groups, inter-group differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

Atlas Posterior Arch Deficiency (APAD) is a rare anatomical variation of the atlas vertebra that can be detected using cone-beam computed tomography (CBCT). This study aims to evaluate the prevalence, classification, and clinical implications of APAD in an Italian cohort.

Autoimmune blistering diseases represent a group of chronic severe, disabling, potentially fatal disorders of the skin and/or mucous membranes primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality, a profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti CD-20 monoclonal antibody represents the first line of therapy for pemphigus, regardless of its severity as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab sooner or later. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory pemphigus cases are mandatory.

Background: Telemonitoring systems in cardiology have shown potential in improving chronic cardiovascular disease (CVD) management. This study aims to evaluate the impact of telemonitoring, mainly through mobile applications, on patient outcomes such as self-care, blood pressure control, quality of life, and hospitalization. Methods: We systematically reviewed studies assessing telemonitoring methods for patients with chronic CVD. The analysis included studies from various geographic regions and healthcare settings, focusing on qualitative outcomes without performing a meta-analysis. Results: Telemonitoring was found to aid in maintaining blood pressure and significantly enhance self-care abilities. Improvements in quality of life were observed in some studies, though results varied. Most studies indicated telemonitoring could effectively manage blood pressure and reduce hypertension-related complications. However, the heterogeneity of interventions and outcomes measured across trials posed challenges for a comprehensive meta-analysis. Conclusions: Integrating telemonitoring systems into routine care can significantly improve disease management and patient outcomes for chronic CVD patients. Future research should standardize telemonitoring interventions and outcome measures, conduct long-term studies, and evaluate the cost-effectiveness of these systems. Greater blindness in future randomized controlled trials and more studies on atrial fibrillation are also necessary. Significant potential exists for telemonitoring to improve patient outcomes and assist in managing chronic illnesses.

Lotions with or without 28% ascorbyl glucoside arginine complex (AGAC) were applied twice daily for 24 weeks in a double‐blind half‐face study of 27 Japanese females with solar lentigos (SLs). Pigmentation scores were evaluated using a photo‐scale and skin colors were assessed using a color difference meter and a Mexameter. Treatment with the test lotion elicited a significant decrease in pigment scores at 24 weeks compared to week 0; with a significant decrease in pigment scores at 24 weeks compared to the placebo lotion‐treated SLs. In the test lotion‐treated SLs; the L values and melanin index (MI) significantly (p<0.0001) increased and decreased; respectively; at 12 and 24 weeks of treatment compared to week 0. Comparisons of increased L (△L) values or decreased MI (△MI) values between test and placebo lotion‐treated SLs demonstrated that the test lotion‐treated SLs had significantly higher △L or △MI values than the placebo lotion‐treated SLs both at 12 and 24 weeks of treatment. The sum of our results strongly indicates that AGAC is distinctly effective in ameliorating the hyperpigmentation levels of SLs at a visibly recognizable level by the subjects without any hypo‐pigmenting effects or skin irritation.

We analyzed data of pediatric invasive fungal diseases of the central nervous system (CNS-IFDs) reported by five of total eight Pediatric Hematology-Oncology Departments in Greece for 15 years (2007-2022). A total of twelve patients (11 boys, median age: 9.5yrs range: 2-16) were reported suffering from CNS-IFDs. Underlying malignancy was acute lymphoblastic leukemia in 9/12, and acute myeloid leukemia, Ewing sarcoma and rhabdomyosarcoma in one each. Eleven patients presented with CNS-related symptoms (i.e seizures, headache, cerebral palsy, ataxia, hallucination, seizures, blurred vision, amaurosis). All patients had pathological MRI findings. Multifocal fungal disease was observed in 6/12 patients. Nine proven and three probable CNS-IFD cases were diagnosed. Causative pathogens in proven cases were Aspergillus spp. and Candida albicans (n=2 each), Mucor spp., Rhizopus arrhizus, Absidia spp., Fusarium oxysporum and Cryptococcus neoformans (n=1 each). Causative pathogens in probable cases were Aspergillus spp. (n=2) and Candida spp. (n=1). All patients received appropriate antifungal therapy (median duration: 69.5 days, range 19-364). Two patients underwent additional surgical treatment. Six patients admitted to ICU due to complications. Three patients (25%) died, two due to IFD and one due to underlying disease. Early recognition and prompt intervention of CNS-IFDs may rescue the patients and improve overall survival.

Introduction: Errors are very common in medical practice —and in particular in the healthcare of patients with inflammatory bowel disease (IBD); however, most of them can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to the problem will consist in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation in each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, the elderly patient, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it would be desirable following IBD patients in specialized units, which is undoubtedly associated with higher quality healthcare and a lower likelihood of errors in managing these patients.

Treatment of HIV-associated lymphoma (HIV-Ly) with autologous stem cell transplantation (ASCT) has shown a surprisingly low relapse rate in several series. The aim of this study was to compare the clinical outcomes of HIV-Ly and lymphomas of the general population receiving ASCT. We compared two series of consecutive HIV-positive and HIV-negative patients, based on a 1:1 propensity score analysis, matching for age, sex, histology, disease status and prior therapies. We identified 44 patients in both groups. All HIV-positive patients received combination antiretroviral therapy (cART). With a median follow-up of 51 months, PFS was significantly higher in HIV-positive patients (4-years PFS 81% and 51%, in HIV-positive and HIV-negative patients, respectively, p=0.027). Four-year OS was 81% for HIV-positive and 67% in HIV-negative patients (p=0.15). The relapse rate was significantly higher in HIV-negative patients (36% vs 23%) (p=0.04). Our results clearly show that ASCT is an effective curative option for HIV-Ly, with better PFS and lower relapse rate compared to uninfected patients. A favourable effect of ASCT on HIV infection and immune system recovery, potential off-target effects of cART or other yet unknown factors may account for this observation.

(1) Background: better mechanistic understanding of desmosome disruption and acantholysis in Grover disease (GD) may improve management of this disease. Recent molecular studies highlighted promising pathways to be explored, by directly comparing GD and selected features of associated skin diseases. The association between GD and cutaneous keratinocyte carcinomas, the most prevalent non-melanoma skin cancers (NMSC), is not completely characterized. (2) Objective: To review the medical literature regarding GD-associated cutaneous keratinocyte cancers, focusing on molecular features, pathophysiological mechanisms and disease associations, to help guide future research and patient management. (3) Result: GD has been associated with a variety of skin conditions, but its association with skin cancers has been rarely reported. Between 1983 and 2024 only 9 scientific papers presented data supporting this association. Interestingly, we found that GD may mimic multiple NMSCs, as few authors reported GD cases misdiagnosed as multiple cutaneous squamous cell carcinomas for more than 4 years, or the presence of superficial basal cell carcinoma–like areas associated with focal acantholysis. (4) Conclusions: (a) GD may be an imitator of multiple NMSCs and (b) the relationship between GD and NMSCs may reveal promising pathways for the mechanistic understanding of desmosome disruption and acantholysis in GD and may even lead to its reclassification as a distinctive syndrome.

Reducing levels of low-density-lipoprotein-cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk, and with LDL-C above 70 mg/dl. They were randomly divided in two groups: bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group including patients who doubled the dose of statin. At 12-weeks, BA group presented a greater significant decrease of LDL-C compared to ST group (-22.9% vs 7.5% p 0.002). Total-cholesterol decreased significantly in the BA group compared to ST (-14.8% vs-4.7% ; p 0.013) No significant between-groups changes in HDL and triglycerides occurred. At 12 weeks the number of patients who reached LDL-C lower than 70 mg/dl was 38 (63%) in the BA group versus 22 (37%) in the ST group (between group p 0.034). In the BA group the LDL lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of Bempedoic acid to statin/ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C. levels and increased the number of patients reaching the LDL-C goal.

The COVID-19 pandemic has underscored the intricate interplay between viral infections and opportunistic bacterial pathogens such as Klebsiella pneumoniae. K. pneumoniae harbors various antibiotic resistance determinants like extended-spectrum and plasmid-mediated AmpC β-lactamases and carbapenemases. In the two years following the pandemic, carbapenemase producing K. pneumoniae isolates obtained routinely in outpatient and inpatient setting demonstrated similar resistance patterns which prompted research. The aim was to compare and subsequently analyze carbapenem-resistant hospital and outpatient’s K. pneumoniae isolates’ resistance mechanisms, traits and molecular epidemiology, following the COVID-19 pandemic. Disk diffusion and broth dilution method were the methods of choice to determine antibiotic susceptibility. β-lactamases were screened by phenotypic methods and confirmed with PCR. In total 113 isolates were analysed. Resistance to amoxicillin-clavulanate and ertapenem was confirmed in all strains. High resistance rates (over 90%) were observed for extended-spectrum cephalosporins, and ciprofloxacin. OKNV testing and PCR detected OXA-48 in 106, NDM in 7 and KPC in only one isolate. ESBLs accompanied carbapenemases in 103 isolates. Carbapenem resistance in K. pneumoniae is becoming a global problem, hence careful monitoring of its resistance traits is of utmost importance in order to combat the arising threat. OXA-48 seems to continue predominating in the turbulent period after pandemic.

This in vitro study aimed to analyze the surface roughness (Ra) and color stability (ΔEab, ΔE00) following simulated mechanical brushing, and to evaluate the microtensile (μTBS) to dentin of Self Adhering Resin Flowable (SARF). The selected materials were Constic, Yflow AS, and Tetric N flow (TNF/control). Thirty composite resin cylinders were fabricated for surface property evaluation. Ra and color were assessed both before and after simulated brushing. The thresholds of 50:50% perceptibility and acceptability of color difference of the evaluated resins were assessed. For μTBS analysis, fifteen molars were selected, sectioned to expose flat dentin surfaces, and restored according to manufacturers' instructions. Subsequently, they were sectioned into sticks for microtensile testing. Statistically significant differences in Ra among the groups, with Constic exhibiting the highest Ra value (p < 0.05), while Yflow AS showed the lowest Ra value. No statistically significant difference in color was observed among the groups (p > 0.05). The 50:50% perceptibility and acceptability thresholds set at 1.2 and 2.7 for ΔEab and 0.8 and 1.8 for ΔE 00. All the results fell within the acceptable limits. The mean μTBS values of Constic, Yflow AS, and TNF were 10.649 MPa, 8.170 MPa, and 33.669 MPa, respectively. The study revealed increased Ra and comparable color stability among all tested composite resins after abrasion. However, SARF exhibited lower μTBS compared to conventional using an adhesive system.

Glioblastoma (GBL) is one of the more malignant primary brain tumors, currently treated by a multimodality strategy including surgery, radio- and chemotherapy, mainly consisting of Temozolomide(TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival <2 years. The identification of natural molecules having strong anti-tumor activity, led to combine these compounds with conventional chemotherapeutic agents, developing protocols of integrated anticancer therapies. Curcumin (CUR), Resveratrol (RES), and its glucoside Polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies demonstrated that the combination of these natural products was more cytotoxic than the single compound alone in different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To deepen some mechanistic aspects of these results, we investigated if the pretreatment with a combination of CUR+PLD, can improve TMZ cytotoxicity on GBL cells, by analyzing the effects on cell cycle, viability and morphology, on proteins related to cell proliferation, differentiation, apoptosis or autophagy, and on actin network. Cell viability was assessed by MTT or by the cell counter CytoSmart. CalcuSyn software was used to study the CUR+PLD synergism. Morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western Blot. Flow cytometry was used for cell cycle, autophagic flux, and apoptosis analyses. The results obtained provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating antitumor agents such as TMZ, also in drug-resistant GBL cells, through their abilities to affect survival, differentiation, and tumor invasiveness.

Underreporting is the main limitation of the spontaneous reporting systems. This study aims to reduce underreporting enhancing public participation in vaccinovigilance through an SMS-based reporting system integrated with electronic immunization registries (IRs). Using the VigiVax software, parents of vaccinated children aged 2 years or younger received a single SMS inquiry about adverse events following immunization (AEFI). Responses were collected, validated by health operators and integrated with the information on IRs. AEFI reports were automatically submitted to the Italian Pharmacovigilance system. Among 254,160 SMS messages sent, corre-sponding to 451,656 administered doses (AD), 71,643 responses were collected (28.2% response rate), 21,231of them (8.3%) reporting an AEFI. After seriousness assessment based on clinical criteria, 50 reports (0,24%) were classified as serious. Among these, causality assessment identi-fied 31 reports at least potentially related to the vaccination (RR: 6.86/100,000 AD). Febrile seizures following MMRV vaccination accounted for 11 of these 31 cases, with an incidence of 32 per 100,000 AD. No fatal outcomes were reported. Our findings support the highly favorable risk profile of pediatric vaccinations and the possibility to improve spontaneous reporting through the integration of digital technologies.

A superparamagnetic graphene oxide based drug carrier Fe3O4@SiO2/N–rGO was prepared through surface modification, material doping, and composite methods. This carrier has a large number of active sites, suitable for loading anticancer drugs, It can increase the drug load. Currently, the widely used drug in clinical use is epirubicin hydrochloride (EPI). The graphene based complex has a pH sensitive property and exhibits a pH sensitive property at pH=4.3. The release efficiency (RE) is 77.4%, making it suitable for drug release in cancerous acidic liquids. The physicochemical properties of drug carriers were studied using X–ray diffraction, Raman spectroscopy, and Fourier transform infrared spectroscopy. Electrochemical signals confirm that the anticancer drug EPI acts on the graphene plane through hydrogen bond interactions and π – π stacking.