Background/Objectives:The first attempts of posterior lumbar interbody fusion can be traced back to the 1940s, where their performance was marked by animosity due to high rates of failure. Nowadays, the use of interbody fusion involves a much more complicated consideration of factors such as global alignment, disc height, fusion rates, and operative risk, all combined at once.Our study aims to examine all these effects using Flarehawk 9 as a means of interbody fusion.Materials and methods: A total of 58 patients underwent open posterior lumbar surgery using Flarehawk 9 between September 2021 and February 2023 with a mean follow up of 1 year.The mean age was 59.8 years old ( range between 33 and 79 years old), 36 of them are males while 22 of them are females. The diagnostic groups included spinal canal stenosis (n=40), failed back surgery syndrome-revision surgery (n=5),spondylolisthesis with slip percentage 25% (n=4),recurrent herniated disc (n=7) and adjacent segment disease (n=2). Results: The majority of patients demonstrated remarkable improvement based on ODI scores.The rate of union varied based on the fused levels and whether the patients had previous surgery or not.The amount of lordosis postoperatively is increased by 2±0.4 degrees.Conclusions: Even though anterior approaches become more and more popular and advanced nowadays, posterior fusion with interbody cage still remains a safe and effective method to treat various spine surgical pathologies with optimal results.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

Aerobic vaginitis (AV) is a distinct clinical entity characterized by inflammation and abnormal vaginal microflora. Often mistaken for bacterial vaginosis, AV remains relatively unknown and underdiagnosed. AV's understanding is evolving, with some experts suggesting it may primarily be an immunological disorder, the prevalence of which ranges from 7-13% in non-pregnant women and 4.1-8.3% during pregnancy. Pregnancy can affect susceptibility to vaginal infections, leading to adverse outcomes for the woman and the newborn. This review summarizes the correlation between AV and adverse pregnancy outcomes, particularly preterm birth, the leading cause of morbidity and mortality among neonates. Improved understanding of AV's impact on pregnancy outcomes can lead to early recognition, proper management, and effective interventions. While some studies support an association between AV and preterm labor, the existing knowledge of this relationship remains limited. The evidence suggests that AV may contribute to adverse pregnancy outcomes, mainly preterm birth, but further research is needed to establish a definitive link. Further studies are needed to investigate the underlying mechanisms and clarify AV's role in premature labor. A comprehensive understanding of AV's impact on pregnancy outcomes is crucial for early recognition, appropriate management, and effective interventions.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Our results demonstrated that SWT stimulates osteoblastogenesis and increase the cell number of osteoblasts, suggesting positive regulatory effects on osteoblast differentiation. However, the effect of SWT on bone formation need further examination, since the expression of alp gene is downregulated. On the other hand, SWT appears to negatively regulate osteoclast differentiation and bone resorption, as number of osteoclasts and the expression of critical bone resorptive genes are all downregulated. Collectively, SWT might change the equilibrium of bone remodeling and increase the bone mass. Our data provided supportive evidences that this medicine formulation can be applied to treat osteoporosis or bone destructive diseases.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p<0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

Critically ill patients treated in the intensive care unit (ICU) can present many abdominal conditions that need a prompt diagnosis and timely treatment because of their general frailty. Clinical evaluation and diagnostic tools like ultrasound or CT scan are not reliable or feasible in these patients. Bedside laparoscopy (BSL) is a minimally invasive procedure that allows surgeons to assess the abdominal cavity directly in the ICU, thus avoiding unnecessary exploratory laparotomy or incidence related to intra-hospital transfer. We conducted a review of the literature to summarize the state-of-the-art of BSL. Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus databases were utilized to identify all relevant publications. Indications, contraindications, technical aspects, and outcomes are discussed. The procedure is safe, feasible, and effective. When other diagnostic tools fail to diagnose or exclude an intra-abdominal condition in ICU patients, BSL should be preferred over exploratory laparotomy.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Objective: To summarize the prevalence of PASC/Long COVID symptoms among the general population reported in published articles. This narrative review examined 21 PASC symptoms. Methods: A PubMed/manual search returned 114 articles on general PASC/Long COVID symptoms. Manuscripts were excluded if they were not research studies, didn’t report symptom prevalence, or used a pediatric population. Ninety-eight studies were selected for review and 59 met criteria for inclusion. Risk of bias was assessed with the Hoy critical appraisal tool. Results: After excluding studies with high risk of bias, meta-analysis of prevalence for 21 symptom categories ranged from 2.6-28.7% in studies based on surveys to 0.3%-7.1% in studies based on EHR data. Conclusions: PASC symptom studies are limited by variability in study design and representation of the general population. Further research is needed to effectively cluster symptoms in meaningful ways that enable focused treatment.

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

Periodontitis is a chronic inflammatory disease which results in the destruction of the tooth’ s supporting tissues and the alveolar bone resorption. The complement becomes a major link between infection and inflammatory pathology including periodontitis. Gingipians as important virulence factors of P. gingivalis have the activity of C5 convertase, could cleave C5 into fully functional C5a to activate C5aR. The above process could be blocked by the C5aR antagonist (PMX-53) to suppress local periodontal inflammation, and then achieves the purpose of treatment of periodontitis. Nanoparticles incorporated within gelatin are promising carrier system for drug delivery in recent years. This study aimed to investigate whether gelatin nanoparticles loaded with PMX-53 prevents alveolar bone resorption in miniature swines model of periodontitis. Four miniature swines were placed ligatures around the maxillary and mandibular fourth premolar and first molar on both sides for seven weeks to induce periodontitis. Then, animals were assigned randomly to four groups: minocycline-treated group, gelatin with PMX53-treated group, gelatin-treated group and a sham control group. They were treated with 1ml related drugs respectively, into gingival sulcusl for 4 times at one-week intervals. We showed that local treatments with gelatin nanoparticles loaded with PMX-53 could inhibit alveolar bone loss of periodontitis. Our study revealed that gelatin nanoparticles loaded with PMX-53 prevented alveolar bone resorption miniature swines model of periodontitis. In addition, provided proof-of-concept for local targeting of gelatin nanoparticles loaded with PMX-53 as a powerful candidate for the treatment of periodontitis.

Lung neuroendocrine tumors (LNETs) and gastroenteropancreatic neuroendocrine tumors (GEPNETs) are two distinct types of neuroendocrine tumors (NETs) that have traditionally been treated as a single entity despite originating from different sources. Although they share certain phenotypic characteristics and the expression of neuroendocrine markers, they exhibit differences in their microenvironment, molecular mutations, and responses to various therapeutic regimens. Recent research has explored the genetic alterations in these tumors, revealing dissimilarities in the frequently mutated genes, role of EGFR in carcinogenesis, presence of transcription factors, and immunogenicity of the tumor and its microenvironment. Spread Through Air Spaces (STAS), a phenomenon unique to lung carcinomas, appears to play a crucial role in LNET prognosis. These distinctions are also evident in the cascade response of lung and GI tract neuroendocrine tumors to somatostatin analogs, Peptide Receptor Radionuclide Therapy (PRRT), chemotherapy, and immunotherapy. Identifying similarities and differences between the two groups may im-prove our understanding of the underlying mechanisms and facilitate the development of more effective treatment strategies.

There are several well-described molecular mechanisms that influence cell growth and are relat-ed to the development of cancer. Chemokines constitute a fundamental element which are not only involved in local growth but also affect angiogenesis, tumor spread and metastatic disease. Among them, the C-X-C motif chemokine ligand 12 (CXCL12) and its specific receptor the chemo-kine C-X-C motif receptor 4 (CXCR4) have been widely studied. The overexpression in cell mem-branes of CXCR4 has been shown to be associated with the development of different kinds of his-tological malignancies, such as adenocarcinomas, epidermoid carcinomas, mesenchymal tumors or neuroendocrine neoplasms (NENs). The molecular synapsis between CXCL12 and CXCR4 leads to the interaction of G proteins and activation of different intracellular signaling pathways in both gastroenteropancreatic (GEP) and bronchopulmonary (BP) NENs conferring greater ca-pacity for locoregional aggressiveness, epithelial-mesenchymal transition (EMT) and the ap-pearance of metastases. Therefore, it has been hypothesized how to design tools that target this receptor. The aim of this review is to focus on current knowledge of the relationship between CXCR4 and NENs, with a special emphasis on diagnostic and therapeutic molecular targets.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

The aging of the population in developing and developed countries has lead to a significant increase in health burden of spinal diseases. These elderly patients often have a number of medical co-morbidities due to aging. The need for minimally invasive techniques to address spinal disorders in this elderly population group cannot be stressed enough. Minimally invasive spine surgery (MISS) has several proven benefits such as minimal muscle trauma, minimal bony resection, lesser post-operative pain, decreased infection rate and shorter hospital stay. Over the last 40 years, constant efforts are being made to develop newer techniques of spine surgery. Endoscopic spine surgery is one such subset of MISS which has all the benefits of modern MISS. Endoscopic spine surgery initially was limited only to treatment of lumbar disc herniations. With improvement in optics, endoscopes, endoscopic drills and shavers, irrigation pumps, there has been a paradigm shift. Endoscopic spine surgery can now be performed with high magnification thus allowing its application not only to lumbar spinal stenosis, but also to spinal fusion surgeries, cervical and thoracic pathology as well. There has been increasing evidence in support of these newer techniques of spine surgery. For the purpose of this review, we studied current available literature and outlined the historical evolution of endoscopic spine surgery, the various different endoscopic systems, and techniques available and the current applications of endoscopic techniques as an alternative to traditional spinal surgery.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. Defining RWD based on its original intent, which is the collection of data at the point of care for clinical purposes, can distinguish it from conventional clinical trial data. RWD can be generated using experimental designs that resemble those used in conventional clinical trials, but with several advantages, such as improved efficiency and a better balance between internal and external validity. RWD can support pharmacovigilance, insights into disease progression, and the development of external control groups. Prospective RWD collection enables evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly, patients with poor performance status (PS), hepatitis, or human immunodeficiency virus-infected patients, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

(1) Background: As part of the Scottish Governments five-year recovery plan to address the backlog in NHS care following the COVID-19 pandemic, community pharmacies in Scotland are planned to provide a Hospital Discharge Medicines Supply and Medicines Reconciliation Service. We aimed to qualitatively explore patients’ experience of this new service; (2) Method: Adult patients (≥18yrs age) who consented to participate in the Community Pharmacy Hospital Dis-charge and Medicines Reconciliation Service were invited for interview within 21 days of dis-charge from hospital. Qualitative, one-to-one, semi-structured, patient interviews were conducted by telephone and audio-recorded using Microsoft Teams®. The interview audio recordings were transcribed verbatim and underwent thematic analysis; (3) Results: 12 patients were inter-viewed, evenly split by sex and with a median age of 62 years (range; 36 to 88 years). Analysis generated main five themes; Patient Engagement, Stakeholder Communication, Practical Factors, Human Factors, and Comparative Experiences. Many of these were interdependent; (4) Con-clusions: Patients appreciated that the service ensured a quicker discharge from hospital. Good stakeholder communication, practical factors (including choice, location, and the realities of ob-taining their medication from the community pharmacy), and a pre-existing and trusted rela-tionship in their usual community pharmacy were the key factors that regulated the patient ex-perience. In the main, patients were positive about the introduction of this new service. However, a lack of previous relationship or trust with a community pharmacy, and previous experiences with medication supply problems were factors which had the potential to negatively impact on patient experiences.

The most prevalent musculoskeletal disorder of childhood with unclear aetiology is Growing Pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GPs pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3-7 years. Among them 10 pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. 78 children presented GPs meeting Peterson’s criteria. Genu valgum severity was a significant factor for GPs manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33cm) and birth length or weight (smaller than 50 cm and 3000gr, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive for the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GPs appearance.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p&lt;0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p&lt;0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

Thin people who undergo implant insertion into the chest wall face a high risk of implant exposure to the external environment. Five months after an 8-year-old boy underwent implantable cardioverter-defibrillator (ICD) implantation in a subcutaneous pocket in the left anterolateral chest wall to manage long QT syndrome, ICD replacement became necessary owing to exposure risk from distal and lateral thinning of the ICD pocket. Pocket rupture and exposure would increase the risk of infection; therefore, we performed ICD removal and primary pocket closure. Two weeks later, a new suprafascial pocket was created, acellular dermal matrix (ADM) was attached to the inner wall to prevent ICD protrusion, and a new ICD was inserted. One year postoperatively, the ADM was engrafted, and no complications were observed. A thin subcutaneous layer increases the risk of ICD implantation complications. Inner wall strengthening with ADM can help prevent pocket rupture.

There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines, during e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron Paramagnetic Resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ from binding to fodipir (DPDP), and hence suggest that the previously reported CIPN protective efficacy of MnDPDP is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

Abstract: Laryngoscopy for tracheal intubation has been developed for many decades. Among various conventional laryngoscopes, videolaryngoscopes (VL) have been applied in different patient populations, including difficult airways. The safety and effectiveness of VL have been repeatedly studied in both normal and difficult airways. The superiority of VL then has been observed and is advocated as the standard of care. In contrast to laryngoscopy, the development of video-assisted intubating stylet (VS, also named as styletubation) has been noticed two dec-ades ago. Since then, sporadic clinical experiences of use have appeared in literature. In this re-view article, we presented our vast use experiences of the styletubation (more than 55,000 pa-tients since 2016). We found this technique is swift (the time to intubate: from 3 s to 10 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satis-faction and fast learning curve for the novice trainees) in both normal and difficult airway sce-narios. We therefore propose styletubation technique can be feasibly applied as universal rou-tine use for tracheal intubation.

(1) Background: Ectopic pregnancy (EP) is when fertilized ovum implanted outside of uterine cavity. The incidence was 1.5% to 2.0% of all pregnancies [1, 2]. EP decreases fertility ability [3]. This study focused on the pregnancy rate after EP and various parameters influencing pregnancy. (2) Methods: The data was extracted from National Health Insurance Research Database (NHIRD) during 2000-2013. The study group enrolled women with one EP history. Those who did not have EP was put into the control group. Chi-square/Fisher exact test was performed on category variable and t-test was used on continue variables. (3) Results: The EP group had a higher cumulative rate of conceive, 41.55% than control group, 37.14% and 1.16 times higher risk in developing pregnancy (P&lt;0.001). The conceiving rate was lower than the control group in the first 5 years, but higher than the control group in the 10th to 14th years. (4) Conclusions: The fecundability after EP is lower at the beginning, but regained after long term follow.

Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

(1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLNs assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is at stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: we described a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary to evolve through future IDEAL stage 2b (multi-center studies) and stage 3 (randomized controlled trials) studies.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Keywords: Oral health, diabetes, periodontal disease, caries, periodontitis.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p&lt;0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

The importance of frailty in older people is getting constant recognition as an important aspect both in terms of public health, as well in personal level for the appropriate management of an older person health condition. This is reflected by the continuously increasing number of research studies carried out in several settings across different countries. Sometimes this is very solid, but in other cases there is a considerable gap in terms of accurate and well grounded documentation of frailty status. This is the case in Greece, where we are missing clinically validated tools to approach frailty. We are missing frailty screening tools, such as for instance PRISMA 7, the gold standard tool of Fried criteria is somehow problematic since the question referring to physical activity originates from a questionnaire that has not been translated and validated, while Clinical Frailty Scale has been validated for the translation but not for the capacity to detect frailty. Aim of this study is to validate these tools for their accuracy to detect frailty by using a measurable index of frailty, previously proposed for use in clinical studies: the Short Physical Performance Battery (SPPB). 74 male and female participants have been evaluated for their frailty status using different tools. We observed that PRISMA 7 translation detects frailty only when one question is removed at a cut-off of ≥ 2 and indicated a sensitivity of 88.1%, and specificity of 99.9% with a good correlation with SPPB measurements (r = 0.858; p &lt; 0.001). When CFS was validated using SPPB it demonstrated a very good correlation (r = -0.838; p &lt; 0.001 respectively) as it was the case for the modified Fried Criteria (r = -0.725; p &lt; 0.001). All items demonstrated a good correlation between them. We can here propose that we can accurately assess frailty status in the community setting by using a modified version of Fried criteria, Clinical Frailty Scale translation in Greek and we can screen for frailty by using the Greek translation of PRISMA 7 only after removing the item 6 of the questionnaire.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

Background: In recent years, whole blood parameters and derivatives have been used as prognostic criteria in the course of the disease in various diseases. The prognostic nutritional index (PNI), the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR) have been adapted as an indicator of inflammation and have been widely studied to define the severity of inflammation in some diseases. The aim of this study was to evaluate the relationship between parameters such as NLR, SII, PNI, controlling nutritional status (CONUT) score, nutritional risk index (NRI) and with immunonutrition status and disease activity in patients with ischemic stroke of small vessel, large vessel and other etiologies. Methods: We retrospectively evaluated the records of 1454 consecutive ischemic stroke patients hospitalized in the emergency department of Gaziosmanpasa Education and Research Hospital from 2019 to 2023. Results: Of the 1350 SVO patients included in the study, 58.8% had small vessel, 29.3% had large vessel and 11.9% had other etiologies. There was a significant difference between the 3 etiology groups for PNI and CONUT. The median PNI was 47.03 (41.33-52.85) in the other etiology group, 35.29 (33.69-37.25) in the small vessel group, and 34.11 (30.23-36.87) in the large vessel group. The CONUT median was 5(5-6) in the small vessel group, 5(4-6) in the large vessel group and 4(4-4) in the other etiology group. In addition, CONUT and PNI were also found to be independent risk factors for death. A negative significant correlation was observed between PNI and NLR (r:-0.692), SII (r:-0.591), CONUT (r:-0.685). Significant correlations were observed between CONUT and NLR (r:0.402), SII (r:0.312). Conclusion: PNI and SII were significantly associated with disease activity. PNI, CONUT and NRI as a more accurate prognostic indicator of nutritional status in patients with ischemic stroke of small vessel, large vessel and other etiologies. NLR and SII may be important predictive markers in the course and prognosis of stroke.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

Vascular anomalies are a diverse group of abnormal blood vessel developments that can occur at birth or shortly afterward. Embolization and sclerotherapy have been utilized as a treatment option for these malformations but may cause moderate to severe pain. This study aims to evaluate the utilization of peripheral nerve blocks in opioid consumption, pain scores, and length of stay. A retrospective chart review was conducted at the UPMC Children's Hospital of Pittsburgh for all patients who underwent embolization and sclerotherapy between 2011 and 2020. Patient data was collected to compare opioid consumption, pain scores, and length of stay. Eight hundred fifty-four procedures were performed on 347 patients. The morphine milligram equivalent per kilogram mean ratio between groups was 0.9 (0.86, 0.95) with a p-value of &lt;0.001. The pain score mean ratio was –1.17 (–2.2, -0.1) and a p-value of 0.027. Length of stay had a mean ratio of 0.94 (0.4, 2) and a p-value of 0.875. By decreasing opioid consumption and postoperative pain scores, peripheral nerve blocks may have utility in patients undergoing embolization and sclerotherapy while not clinically increasing the length of stay for patients. Their use should be individualized and carefully discussed with the interventional radiologist.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

This research ventures into the critical public health challenge of childhood obesity by exploring the dynamic interplay between psychological well-being and Body Mass Index (BMI) throughout various developmental stages of childhood. It delves into how emotional regulation, attachment dynamics, and social relationships correlate with obesity from early childhood to adolescence. Highlighting key findings, such as the negative correlation between psychological resilience and higher BMI in young children, the impact of social relationships on obesity risk during pre-adolescence, and the link between adaptive emotional strategies and higher BMI in adolescents, this study brings to the fore the nuanced relationship between psychological factors and obesity. Utilizing the interdisciplinary process of bioinformatics, this research synergizes psychometric and biomedical data to unearth psychological markers critical for crafting targeted, age-appropriate interventions. This study advocates for a holistic healthcare approach, emphasizing the integration of psychological support within obesity prevention and management strategies, thereby underscoring the indispensable role of psychological factors in the fight against childhood obesity. The application of bioinformatics methods to analyze complex datasets demonstrates how collaboration across medical specialties can enrich our understanding and response to childhood obesity, contributing significantly to the development of comprehensive, bioinformatics-enhanced healthcare solutions.

The artificial intelligence (AI) refers to the science and engineering of creating intelligent machines for imitating and expanding human intelligence. Given the ongoing evolution of the multidisciplinary integration trend in modern medicine, numerous studies have investigated the power of AI to address orthopaedic-specific problems. One particular area of investigation focuses on the shoulder pathology, which is a range of disorders or abnormalities of shoulder joint, causing pain, inflammation, stiffness, weakness, and reduced range of motion. There has not yet been a comprehensive review of the recent advancements in this field. Therefore, the purpose of this review is to evaluate the current AI applications in the shoulder pathology. This review mainly summarizes several crucial stages of the clinical practice, including predictive models and prognosis, diagnosis, treatment, and physical therapy. In addition, the challenges and future development of AI are also discussed.

Introduction: Birth Asphyxia is a severe condition that includes many potential pathways of occurrence both in utero and during childbirth. We aimed to identify and describe specific macroscopic and microscopic placental injuries in birth asphyxia to serve as a quick tool to stratify a newborn’s potential further evolution, as hypoxic-ischemic encephalopathy can be responsible for neonatal death or severe neurologic sequelae further compromising the affected persons’ quality of life. Materials and methods: We conducted an observational prospective study over 3 years. 62 patients diagnosed with birth asphyxia which had placental histopathological examination performed were enrolled. The control group consisted of 69 term newborns that required neonatal intensive care for at least three days, in the same period, for any other reason and that also had available placental exams. In our study, placental histopathological lesions identified in birth asphyxia have been classified according to Amsterdam Criteria. Results: We analysed data gathered from both groups by applying specific statistical tests for each type of variable and hypothesis. Thus, umbilical cord abnormalities were associated with hypoxic-ischemic encephalopathy in a statistically significant manner when comparing the birth asphyxia group of newborns with the control group. Also, we identified a high statistical level of significance for maternal and fetal vascular malperfusion and the occurrence of hypoxic-ischemic syndrome when comparing the two groups (p = .00). Conclusion: The macroscopic and microscopic placental examination can provide important information on the evolution of the disease in selected newborns according to the identified lesions.

Background: Early postoperative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ oedema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing the anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-Flow-Oxygen-Therapy(HFOT) is a noninvasive O2 support method providing humidification, warmed air, Positive-End-Expiratory-Pressure(AIRVO2). No data exist about HFOT use to prevent early complications after laryngo-tracheal surgery. Methods: Between Sept.2020-Sept.2022, 107 consecutive patients underwent laryngo-tracheal surgery received HFOT(Group A). Data and long-term results were compared with those of 80 patients operated between Sept.2018-Aug.2020(Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24-48 hours after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. Control group(B) presented “delayed” reintubation in 37% (p= 0.027), Intensive Care Unit admission in 67%(p=0.005) and longer hospital stay(p=0.001) compared to HFOT group(A). Minor complications rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of HFOT group, without a statistically significant difference (p=0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limit of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admission and hospital stay.

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers' pain can be complemented by knowledge of patient pain behavior, pain catastrophizing thoughts, anxiety, and mood level. Two hundred two patients completed the study: 56.4% female, 89.6% White, 5.4% Black, and 5% other race. Patient ages ranged from 11 to 17 years (mean = 13.8, SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r=0.56) have a high level of agreement, and teenagers and nurses (r=0.47) have a moderate level of agreement on pain scores (p &lt;0.05). The correlation between patient APBQ (Adolescent Pain Behavior Questionnaire) and teenager VAS (Visual Analog Scale ) and between nurse APBQ and teenager VAS, while statistically significant (p &lt; 0.05), is weaker (r range = 0.14-0.17). There is a moderate correlation between teenagers' pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range= 0.26 – 0.39; p &lt;0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. The role of dysfunctional mitochondria in psychopathology is well-established, however, the association of these organelles with sleep physiology is novel. Indeed, reducing neuronal oxidative stress by importing mitochondria from astrocytes, may be the purpose of human slumber. This model may explain mitochondrial dysfunction during anesthesia as well as in the rare genetic disease, fatal familial insomnia. In this narrative review, we focus on the salience network of the brain, a common denominator for insomnia, neuropsychiatric and neurodegenerative disorders. We also discuss mitochondria-protecting strategies, including membrane lipid replacement, natural and synthetic phenazine and phenothiazine derivatives.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including Notch1 pathway in HCC. In our study, we found that Notch1 was highly expressed in HCC especially in large HCC. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 than that in HepG2. HBx activated Notch1 pathway in HepG2.2.15. Repression of HBx and Notch1 pathway attenuated the growth of HepG2.2.15. Notch1, ERK and AKT pathways were inhibited after a γ-secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and phosphatase and tensin homolog (PTEN) were up-regulated after the γ-secretase inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that Hes1 repressed the promoters of DUSP1 and PTEN and this was reverted by γ-secretase inhibitor treatment. Western blotting demonstrated that DUSP1 dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we reported a link among HBx, Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which influenced HCC cell survival and could be a therapeutic target for HCC.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

Peritoneal dialysis (PD) is a home-based efficacious modality for replacement of renal function in end-stage kidney failure patients but is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of long-term morpho-functional peritoneal changes eventually resulting in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile proves quite difficult. New approaches targeting the composition of the PD solution include replacement of glucose with other osmotic agents and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include infusion of mesenchymal cells or the administration of orally active agents. In the present article we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

Introduction: This study aims to elucidate the clinical diagnostic value of S100 Calcium Binding Protein beta (S100B) in epilepsy, a topic of ongoing debate among European and Asian epilepsy research centres.Methods and analysis: A structured long-term research plan was developed, comprising three phases. Phase one involves observational studies investigating the correlation between S100B levels in serum or cerebrospinal fluid and epilepsy. Phase two integrates observational and randomised controlled data to establish baseline S100B levels across diverse epilepsy demographics, underpinning the predictive value of S100B for epilepsy. Phase three focuses on randomised controlled trials to evaluate the diagnostic accuracy of S100B as an epilepsy biomarker.Ethics and dissemination: All enrolled patients will provide written consent. The ethics committee of the Second People’s Hospital of Gansu Province, Affiliated Hospital of Northwest Minzu University, China, approved the study (GSSEY2022-KY009-01).Registration: The study is registered with PROSPERO (CRD42023425431).

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

To explore the relevant factors that affect the efficacy of consciousness-regaining therapy (CRT)for prolonged disorder of consciousness(pDOC),a retrospective analysis was conducted on the case data of 114 patients with pDOC admitted to department of functional neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022. Basic information on the cases,data on pDOC disease assessment, consciousness-regaining therapy methods, and efficacy evaluation were collected. A total of 114 patients were grouped and compared based on the efficacy at the end of treatment. Among them, there were 61 cases in the ineffective group and 53 cases in the effective group. There was no statistically significant difference (P&gt;0.05) between the two groups in terms of gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of consciousness-regaining therapy , and duration of consciousness-regaining therapy(P&gt;0.05). However, there were statistically significant differences (P&lt;0.05) in terms of secondary hydrocephalus, , consciousness-regaining therapy methods, CRS-R grading before treatment, and GOSE score at 6 months after treatment. Binary logistic regression analysis showed that the type of therapy (OR=0.169, 95% CI: 0.057-0.508) was a related factor affecting the efficacy of consciousness-regaining therapy (P&lt;0.05).Compared with non-invasive therapy, personalized awakening therapy using various invasive consciousness-regaining therapy methods can help improve the efficacy of therapy for pDOC.

Objective: The aim of this in vitro study was to evaluate the accuracy of resin-based fixed dental restorations, namely veneers, single crowns, and four-unit fixed partial dental prosthesis (FPDs) using two different 3D printers and polymer-based materials. Materials and Methods: A standard maxillary polyurethane jaw model containing prepared teeth was scanned using an intraoral scanner. The generated STL data were used to design the restorations virtually using CAD software. Two 3D printers were utilized for the provisional digital light processing and stereolithography for the castable resin patterns. Each printer produced 10 specimens of each type of restoration, for a total of 80 restorations. The 3d-printed restorations were then 3D scanned using the same intraoral scanner and evaluated for external and internal dimensional accuracy in terms of trueness and precision. A one-way ANOVA and Two-sample T-Test were implemented to compute the precision (variability between groups) and trueness (with the designed CAD model). A level of statistical significance of p-Value

This study aimed to determine shifts in microbial populations regarding richness and diversity from daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48 years. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity, which is similar to the sampling performed for COVID-19 testing, with only very slight discomfort, if any. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

With an increase in proportion of elderly patients, the global burden of spinal disease is on the rise. Likewise, there has been an increasing trend in the number of spine surgeries being performed worldwide. As we know, rehabilitation following spine surgery is critical for optimal recovery. However, current literature lacks consensus regarding the appropriate post operative rehabilitation protocol. The goals of rehabilitation after lumbar spine surgery are to improve physical and psychosocial function and may include multiple modalities such as physical therapy, cognitive behavioral therapy, specialized instruments, and instruction to be followed during activities of daily living. In recent years, not only are a greater number of spine surgeries being performed, various different techniques of lumbar spine surgery and spinal fusion have emerged. Physical therapy programs need to be curated after assessing the functional status of the patient by using various patient reported outcome measures and taking into consideration the technique of spinal fusion used and the muscle groups involved in these surgeries. By doing so it is possible to assess the level of functional impairment and then specifically target strengthening of those muscle groups affected by surgery whilst also improving impaired balance and allowing return to activities of daily living. We reviewed available literature pertaining to the history of spinal rehabilitation, the popular patient reported outcome measures used and different rehabilitation methods with the purpose of summarizing the current guidelines for postoperative rehabilitation after spine surgery and to introduce the rehabilitation after lumbar surgeries that we provide at our hospital.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adher-ence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity mediated by the production of reactive oxygen species. This study investigates the in vitro effect of the combination of blue light (448 nm) and red light (645 nm) with terbinafine on the cell viability of human keratinocytes and the production of reactive ox-ygen species. The combination of terbinafine and blue light exhibits a synergistic effect on the production of reactive oxygen species and a significant increase in the expression of superoxide dismutase (SOD), an enzyme involved in the reduction of superoxide ions (O2-) and the genera-tion of hydrogen peroxide (H2O2). Such effect could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity, and shorten their duration.

Tinea incognito is a kind of skin infection that is caused by a fungus which has been changed by the use of topical or systemic steroids or other immunosuppressive medications. This alteration in the typical clinical presentation of the infection makes it difficult to diagnose for general practitioners and dermatologists. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. This condition can affect individuals of all ages and genders, but it is more common in children. Tinea incognito is a type of fungal skin infection that can present with various and non-specific clinical features, such as sudden onset of itching in an area that was previously unaffected, making it challenging to differentiate from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves stopping the use of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for suspecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures. The therapy utilized in published studies is also reviewed.

Our aim was to determine the secondary antibody deficiency profiles of patients in a mesoregion of São Paulo state, Brazil, focusing on infectious diseases. Demographic characteristics, clinical and laboratory data were obtained from electronic files; infections were classified as organ-specific and graded as mild, moderate, life-threatening, and fatal. Non-Hodgkin lymphoma (NHL) accounted for 30% of patients, nephrotic syndrome (NS) 25%; chronic lymphocyte leukemia 20%, and multiple myeloma 15%. Patients with NS were younger than those in other groups, and hypo-γ-globulinemia was detected in 94.1%, IgG <400 mg/dL in 60.0%, IgA <40 mg/dL in 55.0%, and CD19 <20 cells/mm³ in 30.0%. One hundred and one infections were found; 82.1% were classified as mild or moderate, 7.9% as life-threatening, and 1.9% as fatal. Respiratory tract infections were more prevalent (41.5%), and pneumonia accounted for 19.8%. Lower levels of infections were found in patients with NS compared with NHL (P=0.0001). Most patients progressed to hypo-γ-globulinemia and secondary antibody deficiency after treatment with immunosuppressants, and mild and moderate infections were predominant. These therapies are increasing in patients with different diseases, therefore monitoring hypo-γ-globulinemia and infections may help to identify patients at high risk for severe complications, antibiotic prophylaxis or treatment, and immunoglobulin replacement

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

Although researchers have proposed various indentation size effect (ISE) models, these models often involve different form and number of parameters that can make our wonder which is the best in existed ISE models. Three types of ISE test data, namely, normal ISE, reverse ISE and transition of normal to reverse ISE, are used to evaluate the sixteen ISE models. The comparatively study indicates that H-J, N-G-Fs, N-G-H, N-G-A and N-G-Qs models can accurately predict the normal ISE. The reason for this is that the friction stress that is not related to dislocation activities or the indentation size effect of plastic zone has been introduced into these models. Therefore, these two factors should be considered in future ISE models. The sixteen ISE models are originally proposed to describe the normal ISE of different materials. However, to our surprise, some of these models are able to capture the reverse ISE and the transition of normal to reverse ISE of different materials. The determination coefficients (DC) of the sixteen ISE models are also determined for different materials. For reverse ISE, the highest DC value for NiCSi, TC4 and PED Ni are given by the EXP, N-G-Fs and N-G-A models, respectively. For the transition of normal to reverse ISE, the N-G-YC, N-G-Fs, and N-G-H models produce the maximum DC for ZrO2, Cu and Y2O3-ZrO2, respectively. Moreover, the mean DC of the N-G-Fs model is the maximum among the sixteen ISE models, followed by the N-G-H model, but they cannot accurately predict the reverse ISE. Therefore, the N-G-Fs and N-G-H models should be further modified to accurately predict the reverse ISE.

Infection with human immunodeficiency virus (HIV) and induced acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst the HAART regimens, darunavir and atazanavir in terms of protease inhibitors, tenofovir disoproxil fumarate, nevirapine or rilpivirine in terms of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors respectively, and especially integrase inhibitors, have demonstrated the most favorable lipid profile emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

The performance of the presurgical test (preSurg) for temporal lobe epilepsy (TLE) was evaluated via video-electroencephalography (VEEG), electroencephalography (EEG), 99mTc-HmPAO single-photon emission tomography (SPECT) and 1.5 T magnetic resonance imaging (MRI) in a group of 112 men (37.0 ± 1.1 years) and 106 women (39.7 ± 1.1 years) operated on for TLE. The epileptic zone (EZ) was adequately identified to determine whether the patient reached an Engel I grade (EI) at least one year postop. Accuracy was evaluated by the coefficient α, ranging from 3 (when result = EZ) to 2 (result in the same hemisphere as the EZ), 1 (noninformative result) or 0 (EZ in the contralateral hemisphere). The simplicity of diagnosis was defined as the number of preSurg surgeries needed to identify the EZ. EI was obtained in 85.8% of patients even though 42.2% of patients had noninformative MRI results. For preSurg α was (mean ± SEM) = VEEG (2.83 ± 0.04) &gt; MRI (2.14 ± 0.08) &gt; EEG (1.87 ± 0.09) &gt; SPECT (1.71 ± 0.09). The accuracy (combination of sensitivity and specificity) was calculated as follows: VEEG (0.797) &gt; MRI (0.518) &gt; EEG (0.446) &gt; SPECT (0.360). The likelihood positive ratio was greater, and the likelihood negative ratio was lower for VEEG. The most relevant factor for the regression model was VEEG (3.106) &gt; MRI (2.558) &gt; EEG (1.905), and the factors were not significantly related to SPECT. EZs in EI patients with low simplicity were identified mainly by VEEG. A very good postoperative outcome can be obtained even in TLE patients with no lesions on MRI. The VEEG is the most reliable preSurg test and may be the only reliable test for patients with very low simplicity (i.e., difficult).single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Background: Assessing the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and designing a personalized clinical pathway to reduce bone loss, in an Italian research hospital. Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. Results: During the first year of the new diagnostic therapeutic assistance pathway execution, an 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since prescription of endocrine therapy) were shown, thus increasing patients’ compliance. Conclusion: Case managers and bone health specialists in this context can improve patients’ adherence to therapies and bone health, helping physicians to expand their collaboration.

Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialised multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains, developed in 2018 and validated in 2023, to identify the level of complexity in patients with advanced cancer. Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. Method: An observational, prospective, multicentre study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were: a) instability ratio (IR), defined as the probability of level change or death; b) emergency department visits; c) days of hospitalisation; d) hospital death; e) survival. All variables were analysed monthly according to the level of complexity assigned at the baseline visit. Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p

Background: Microscopic examination of acid-fast stained sputum smears for detecting mycobacterial acid-fast bacilli (AFB) remains the most economical and readily available method for laboratory diagnosis of tuberculosis (TB). However, this conventional approach has limitations, including low sensitivity and labor-intensive procedures. Methods: An automated microscopy system incorporating artificial intelligence (AI) and machine learning for AFB identification was evaluated. The study was conducted at an Infectious Disease Hospital in Jiangsu Province, China, utilizing an intelligent microscope system (TB-Scan, Wellgen Medical, Kaohsiung). A total of 1,000 sputum smears were included in the analysis, with the system capturing digital microscopic images and employing an image recognition model to automatically identify and classify AFB. Referee technicians provided the gold standard for discrepant results. Results: The automated system demonstrated an overall accuracy of 95.00% (950/1,000), sensitivity of 91.24% (177/194), and specificity of 95.91% (773/806). Notably, the system identified 21 smears as positive that were previously reported as negative, with referee technicians confirming 17 of these as true positive and retracting the test results accordingly. Recalculating the performance, the accuracy increased to 96.70% (967/1,000), sensitivity to 91.94% (194/211), and specificity to 97.97% (773/789), with a false negative rate of 8.06% (17/211) and a false positive rate of 2.03% (16/789). Conclusions: The incorporation of AI and machine learning into an automated microscopy system demonstrated the potential to enhance the sensitivity and efficiency of AFB detection in sputum smears compared to conventional manual microscopy. This approach holds promise for widespread application in TB diagnostics and potentially other fields requiring labor-intensive microscopic examination.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Hereditary polyposis syndromes are rare but potentially devastating conditions which require multidisciplinary care from an early age. Societal guidelines serve as the framework for disease diagnosis, surveillance and treatment. Guidelines are based on expert opinion and ideally are evidence-based; however, recommendations may vary among different societies and can result in discordant care. This paper aims to summarize key differences in management based on societal guidelines for pediatric polyposis syndromes and identify some of the factors which may contribute to divergence in care.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. In addition, tadalafil protected cerebral nerve development in FGR offspring. The clinical trials we have conducted to date, including a case–control study, a phase I trial, and a phase II trial, have indicated the efficacy of tadalafil in prolonging pregnancy, as well as a good safety profile for fetuses and neonates. The number of fetal, neonatal, and infant deaths was significantly lower in those receiving tadalafil treatment group than that in controls, and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. The mechanism, at the functional protein level, of the resistance to therapy of TCL has not yet been well clarified. To comprehensively clarify the mechanism, we first reviewed the literature, as mentioned in the Introduction section, on 22 types of representative functional proteins reported as being potentially associated with treatment resistance, mainly in hematologic tumors. Next, we retrospectively analyzed the tumor cell expressions of these 22 functional proteins in 16 randomly selected patients with TCL who had received CHOP (cyclophosphamide, hydroxyl doxorubicin, oncovin, and prednisolone) therapy as first-line treatment. As a result, we propose a new three-group prognostic classification of TCL (the TCL Urayasu Classification) based on the mechanism of resistance to treatment of these tumors. The study subjects included 7 patients (44%) with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 6 patients (38%) with angioimmunoblastic T-cell lymphoma (AITL), and 3 patients (19%) with anaplastic large T-cell lymphoma (ALCL). Immunohistochemistry was performed in paraffin-embedded tumor tissue sections prepared from these patients as antigens using antibodies against the 22 previously reported treatment-resistance-related proteins to determine the tumor cell expression statuses of these proteins. Log-rank test was performed to compare the overall survival (OS) after CHOP therapy of the patients showing positive and negative immunostaining for these proteins, as well as among patients grouped based on other factors. Overall, the median OS of the TCL patients was about 33.5 months. When compared by the disease type, the prognosis was found to be worse in the order of ALCL, AITL, and PTCL. A multivariate analysis showed that expression of glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with shortened survival. No significant difference was observed for the conventional poor prognostic factors: high-risk International Prognostic Index (IPI) and high-risk Prognostic Index for peripheral T-cell lymphoma, unspecified (PTCL-U) (PIT). However, when GRP94 was combined with six other factors, listed below, as survival-shortening factors, significant differences were observed. The 6 factors were 1) programmed cell death-ligand 1 (PD-L1) and 2) programmed cell death 1 (PD-1), which are involved in immune surveillance; 3) aldo-keto reductase family 1 member C3 (AKR1C3), which is an enzyme that inactivates HO (hydroxyl doxorubicin [H] and oncovin [O]) of CHOP; 4) P53, a tumor suppressor; 5) Glucose-regulated protein 78 (GRP78), an ER stress protein; 6) thymidine phosphorylase (TP), which is an enzyme involved in thymidine catabolism. Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (group with a relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (group with a poor prognosis): GRP94-positive, plus expression of 2 of the 6 aforementioned factors (n = 5; median OS, 25 months; p > 0.05); and Group 3 (group with a very poor prognosis): GRP94-positive, plus expression of at least 3 of the 6 aforementioned factors (n = 5; median OS, 10 months; p < 0.01). Thus, the TCL Urayasu prognostic classification is a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. Accumulation of more cases and further analyses are expected in the future to enable clinical application, such as use of a stratified treatment approach and treatment using inhibitors.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

VITEK MS PRIME (bioMerieux), a newly developed Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, alongside VITEK PICKME Pen (PICKME), offers easy sample preparation for bacteria and yeast. VITEK MS PRIME also offers two software platforms for filamentous fungi: the IVD database and the RUO database. Our study evaluated its identification agreement on 320 clinical isolates of bacteria and yeasts, comparing PICKME and traditional wooden toothpick sampling techniques against ASTA Mi-croIDSys Elite results. Additionally, we assessed the IVD (v3.2) and SARAMIS (v4.16) RUO data-bases on 289 filamentous fungi against molecular sequencing. The concordant rates for spe-cies-level identification of bacteria and yeasts were about 89.4% (286/320) between the PICKME and wooden toothpick, about 83.4-85.3% between VITEK MS PRIME and ASTA MicroIDSys Elite. Retesting with PICKME improved concordance to 91.9%. For filamentous fungi, species-level identification reached 71.3% with the IVD database and 85.8% with RUO, which significantly enhanced basidiomycetes' identification from 35.3% to 100%. Some strains in the IVD database, like Aspergillus vesicolor, Exophiala xenobiotica, and Nannizzia gypsea failed to be identified. VITEK MS PRIME with PICKME offers reliable and efficient microorganism identification. For fila-mentous fungi, combining the use of the RUO database can be beneficial, especially for basidi-omycetes.