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Background: Chest wall deformities, though relatively uncommon in childhood and adolescence, significantly affect aesthetic perception and can impact cardiac and respiratory function. This study aims to compare individuals with pectus deformities to a healthy control group, shedding light on the condition's etiology and prognosis., Method: Conducted as a case-control study between 2020 and 2022, the research included a case group of 71 patients with pectus excavatum or pectus carinatum who were followed up at the Pediatric Cardiology outpatient clinic. The control group consisted of 80 children without chronic diseases. Researchers retrospectively reviewed patient files, recording demographic data, echocardiography findings, and serum levels of calcium, phosphate, vitamin D, and alkaline phosphatase., Results: Patients with chest wall deformities exhibited significantly lower serum levels of vitamin D, calcium, and phosphorus compared to those without deformities. Males constituted 77% of the case group, with 15.5% exhibiting abnormal echocardiogram results, with mitral valve anomalies being most prevalent., Conclusion: While pectus deformities may lead to cardiac or respiratory issues, patient concerns often center around aesthetics. Unlike typical studies focused on surgical techniques and postoperative patients, our study focused on all diagnosed patients. Findings emphasize the importance of monitoring calcium, phosphorus, and vitamin D levels in pectus patients to manage surgical risks and facilitate recovery., (© 2024. The Author(s).)

Background: The use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated., Methods: PCL nanoparticles were prepared by using the emulsion evaporation method and characterized by Zetasizer and scanning electron microscopy (SEM). The encapsulation efficiency and release profile of 2-AG were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The presence of cannabinoid receptors (CBRs) in HSCs and monocytes was detected by flow cytometry. Cell morphology and viability were assessed using transmission electron microscopy (TEM), SEM, and the WST-1 viability assay. The migration efficacy of the 2-AG and 2-AG-loaded nanoparticle delivery system on HSCs and HPSCs (TF-1a and TF-1) and monocytes (THP-1) was evaluated using a transwell migration assay., Results: The 140-225 nm PCL nanoparticles exhibited an increasing polydispersity index (PDI) after the addition of Ps and 2-AG, with a surface charge ranging from - 25 to -50 mV. The nanoparticles released up to 36% of 2-AG within the first 8 h. The 2-AG-Ps-PCL did not affect cellular viability compared to control on days 5 and 10. The HSCs and monocytes expressed CB1R and CB2R and revealed increased migration to media containing 1 µM 2-AG-Ps-PCL compared to control. The migration rate of the HSCs toward monocytes incubated with 1 µM 2-AG-Ps-PCL was higher than that of the monocytes of control. The 2-AG-Ps-PCL formulation provided a real time mobilization efficacy at 1 µM dose and 8 h time window via a specific CBR agonism., Conclusion: The newly generated and validated 2-AG-loaded PCL nanoparticle delivery system can serve as a stable, long lasting, targeted mobilization agent for HSCs and as a candidate therapeutic to be included in HSC transplantation (HSCT) protocols following scale-up in vivo preclinical and subsequent clinical trials., (© 2024. The Author(s).)

Aim: Here we present the patients whose body mass index is in the normal range and who visited with the complaint of headache. The differences in lipid profile in this group compared to healthy children and the risk factors that may be associated with this were investigated., Materials and Methods: 195 patients who applied to the Pediatric Neurology outpatient clinic with headache complaints between April 2021 and October 2022 were retrospectively examined. 201 healthy children were included as the control group. The gender, age, headache type, lipid profile blood test after at least 8 h of fasting [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and TG/HDL ratio], and body mass index (BMI) were recorded. Those patients who had a BMI range of 18.5-24.9 kg/m 2 were included in the study., Results: The study group had 195 patients; 118 girls (60.5%). The average age was 12,57 ± 3,48 years, and 114 patients (58.5%) had tension-type headaches and 81 (41.5%) had migraine-type headaches. There was no significant difference in age and gender between the two groups. Blood pressure, folate, and thyroid function tests were normal. In the lipid profile, a significant difference was observed between total cholesterol, LDL, HDL, and TG in the study group compared to the control group (p < 0.05). However, there was no difference in the TG/HDL ratio between those two groups. No significant statistical difference was observed in the lipid profile and other laboratory findings between headache types., Conclusion: In children presenting with headache complaints, which can be both worrying for families and cause significant loss of functionality, it is detectable (obviously) that headache is an important marker for dyslipidemia; even if BMI is in a normal range. The lipid profile should be seen both to control the complaint with an appropriate diet and to observe the risk of future atherosclerotic processes., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

We evaluated the short- and long-term effects of multisystem inflammatory syndrome in children (MIS-C) on their cardiovascular system. The study population consisted of 38 MIS-C patients and 55 control patients. Standard echocardiographic measurements and aortic stiffness parameters were compared between the two groups at different time points. During the standard echocardiographic examination at the time of diagnosis, mitral valve insufficiency was detected in 42% of the cases, left ventricular systolic dysfunction in 36%, aortic valve insufficiency in 3%, tricuspid valve insufficiency in 13%, and coronary artery dilatation in 31%. The ejection fraction, pulse pressure of the experimental group were significantly lower than the control group (p < 0.01, p = 0.045, respectively). When aortic stiffness parameters were compared, it was seen that the parameters increased in the experimental group and the difference was significant for aortic distensibility. (p = 0.105, p = 0.029 respectively). When comparing the experimental group's results at diagnosis and at the sixth month, there was a decrease in aortic stiffness parameters at the sixth month compared to the time of diagnosis, but the difference wasn't significant (p = 0.514, p = 0.334). However, no statistically significant difference was detected when comparing the aortic distensibility results of the experimental group with the control group at the sixth month (p = 0.667). Our results showed that many pathological echocardiographic findings detected at diagnosis in MIS-C patients returned to normal within six months. Therefore, we believe that the cardiovascular follow-up period of MIS-C cases should be at least six months., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: In this study, it was aimed to show whether Brucella infection, which causes various cardiovascular complications in children, can lead to an increase in aortic stiffness with a noninvasive method, echocardiography., Methods: Children who were diagnosed with Brucella infection and who had tachycardia, chest pain and murmur that were not related to body temperature increase during the treatment were evaluated cardiologically and had echocardiographic examination, were included in the study. Aortic strain, aortic distensibility measurement results and aortic stiffness index of the patients in the patient and control groups were calculated., Results: Our study included 53 cases with a mean age of 11.43±4.13 years in the patient group and 68 cases with a mean age of 10.16±3.61 years in the control group. We found that systolic blood pressure was lower in the patient group than in the control group (p=0.014). In the analysis of laboratory parameters, blood glucose level was found to be significantly higher in the patient group (p=0.001). In the statistical evaluation of aortic strain, aortic stiffness index and aortic distensibility measurement results between the patient and control groups, no statistically significant difference was found between the groups (p=0.287, p=0.784, p=0.208)., Conclusion: In our study, where we tried to show a new parameter that could contribute to the increase in aortic stiffness, the results showed that Brucella infection was not a factor that increased aortic stiffness in the pediatric age group., Competing Interests: No conflict of interest was declared by the authors.

Multisystem inflammatory syndrome (MIS-C) in children is a rare complication of SARS-CoV-2 infection. Knowing the course of the affected or unaffected coronary arteries in the patients under follow-up is important in terms of defining the long-term prognosis of the disease and determining the follow-up plan. This is a multicenter and retrospective study. The data were obtained from nine different centers. Between May 2020 and August 2022, 68 of 790 patients had coronary artery involvement. One-year echocardiographic data of 67 of 789 MIS-C patients with coronary artery involvement were analyzed. Existing pathologies of the coronary arteries were grouped as increased echogenicity, dilatation and aneurysm according to Z scores, and their changes over a 1-year period were determined. The data of all three groups are defined as frequency. SPSS Statistics version 22 was used to evaluate the data. In our study, aneurysm was observed in 16.4%, dilatation in 68.7% and increased echogenicity in 13.4% of the patients. All of the patients with involvement in the form of increased echogenicity recovered without sequelae by the end of the first month. No progression to aneurysm was observed in any of the patients with dilatation. No new-onset involvement was observed in patients with previously healthy coronary arteries during the convalescent period. In addition, from the sixth month follow-up period, there was no worsening in the amount of dilatation in any of the patients. At least 94% of the patients who completed the 12th month control period returned to normal., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Due to its link with the 2019 coronavirus, the multisystem inflammatory syndrome in children (MISC) has garnered considerable international interest. The aim of this study, in which MISC patients were evaluated multicenter, and the data of the third period of the Turk-MISC study group, to compare the clinical and laboratory characteristics and outcomes of MISC patients who did and did not require admission to an intensive care unit (ICU)., Methods: This retrospective multicenter observational study was carried out between June 11, 2021, and January 01, 2022. The demographics, complaints, laboratory results, system involvements, and outcomes of the patients were documented., Results: A total of 601 patients were enrolled; 157 patients (26.1%) required hospitalization in the intensive care unit (ICU). Median age was 8 years (interquartile range (IQR) 4.5-11.3 years. The proportion of Kawasaki disease-like features in the ICU group was significantly higher than in the non-ICU group (56.1% vs. 43.2% p = 0.006). The ICU group had considerably lower counts of both lymphocytes and platelets (lymphocyte count 900 vs. 1280 cells × μL, platelet count 153 vs. 212 cells × 10 3 / μL, all for p< 0.001). C-reactive protein, procalcitonin, and ferritin levels were significantly higher in the ICU group (CRP 164 vs. 129 mg/L, procalcitonin 9.2 vs. 2.2 μg/L, ferritin 644 vs. 334 μg/L, all for p< 0.001). Being between ages 5-12 and older than 12 increased the likelihood of hospitalization in the ICU by four [95% confidence intervals (CI)1.971-8.627] and six times (95% CI 2.575-14.654), respectively, compared to being between the ages 0-5. A one-unit increase in log D-dimer (µg/L) and log troponin (ng/L) was also demonstrated to increase the need for intensive care by 1.8 (95% CI 1.079-3.233) and 1.4 times (95% CI 1.133-1.789), respectively.     Conclusion: By comparing this study to our other studies, we found that the median age of MISC patients has been rising. Patients requiring an ICU stay had considerably higher levels of procalcitonin, CRP, and ferritin but significantly lower levels of lymphocyte and thrombocyte. In particular, high levels of procalcitonin in the serum might serve as a valuable laboratory marker for anticipating the need for intensive care., What Is Known: • Lymphopenia and thrombocytopenia were an independent predictor factors in patients with MISC who needed to stay in intensive care unit. • The possibility of the need to stay in the intensive care unit in patients with MISC who had Kawasaki disease-like findings was controversial compared with those who did not., What Is New: • A one-unit increase log D dimer and log troponin was demonstrated to require for intensive care unit by 1.8 and 1.4 times, respectively. • Serum procalcitonin levels had the best performance to predict stay in the intensive care unit stay., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to present the clinical and microbiological characteristics of patients with infective endocarditis.A retrospective evaluation was made of patients diagnosed with infective endocarditis between 1995 and 2021. The clinical and laboratory characteristics of the patients were recorded together with conditions constituting a risk for the development of endocarditis, treatment, and surgical outcomes.Evaluation was made of 68 patients with a mean age of 7.3 years (3 months-17 years), diagnosed with infective endocarditis. An underlying cause of CHD was determined in 47 (69%) patients and rheumatic valve disease in 3 (4.4%). There was no structural heart disease in 18 (26%) patients of whom 13 of them had other risk factors. A causative organism was found in 41 (60%) cases, and the microorganism most often determined was viridans group streptococcus. No difference was determined between the patients diagnosed before and after 2007 in respect of the frequency of viridans streptococcus (p > 0.05). Septic emboli were seen in 18 (26%) patients, of which 17 required surgical treatments. In 5 of 11 (16.6%) patients with mortality, the agent was S. aureus . Of the total 28 (41%) patients were evaluated as hospital-acquired endocarditis. The most frequently determined agents in this group were staphylococcus epidermidis and S. aureus .Although CHDs continue to be the greatest risk factor for endocarditis, there is an increasing frequency of endocarditis in patients with no structural heart disease. Mortality rates are still high in infective endocarditis, especially in S. aureus endocarditis.

Uterine cancer is the fourth most common cancer in women. Despite various chemotherapy approaches, the desired effect has not yet been achieved. The main reason is each patient responds differently to standard treatment protocols. The production of personalized drugs and/or drug-loaded implants is not possible in today's pharmaceutical industry; 3D printers allow for the rapid and flexible preparation of personalized drug-loaded implants. However, the key point is the preparation of drug-loaded working material such as filament for 3D printers. In this study, two different anticancer (paclitaxel, carboplatin) drug-loaded PCL filaments with a 1.75 mm diameter were prepared with a hot-melt extruder. To optimize the filament for a 3D printer, different PCL M n , cyclodextrins and different formulation parameters were tried, and a series of characterization studies of filaments were conducted. The encapsulation efficiency, drug release profile and in vitro cell culture studies have shown that 85% of loaded drugs retain their effectiveness, provide a controlled release for 10 days and cause a decrease in cell viability of over 60%. In conclusion, it is possible to prepare optimum dual anticancer drug-loaded filaments for FDM 3D printers. Drug-eluting personalized intra-uterine devices can be designed for the treatment of uterine cancer by using these filaments.

Background: The aim of the study was to evaluate the clinical and diagnostic findings, treatment, and follow-up of cases of anomalous origin of coronary arteries from the pulmonary artery., Methods: Between January 1998 and June 2021, a total of 14 patients (5 males, 9 females; median age: 15 months; range, 3 to 156 months) diagnosed with anomalous origin of coronary arteries from the pulmonary artery were retrospectively analyzed. Demographic and clinical data of the patients, electrocardiographic, echocardiographic, angiographic, surgical, and follow-up findings were evaluated., Results: The most common symptoms were respiratory distress (n=6) and murmur (n=3). With the exception of three cases, all other patients were diagnosed by echocardiography in the first examination. Severe mitral valve insufficiency was detected in four patients and four other patients had moderate mitral insufficiency on echocardiography. Ejection fraction values ranged between 38 and 79%. Eleven patients underwent direct implantation of the coronary artery into the aorta, and three underwent a Takeuchi procedure. Mortality occurred in only one case. After surgery, mitral insufficiency and ejection fraction values improved. Median follow-up was 62 (range, 5 to 170) months and all patients were asymptomatic, except one who required redo surgery., Conclusion: Anomalous origin of the coronary arteries from the pulmonary artery is an uncommon congenital anomaly. Echocardiography is the main diagnostic tool. If all echocardiographic findings of the coronary anomaly are not investigated thoroughly, the diagnosis may be overlooked., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish Society of Cardiovascular Surgery.)

Aim: Multisystem inflammatory syndrome in children (MIS-C) may cause shock and even death in children. The aim of this study is to describe the clinical features, laboratory characteristics and outcome of children diagnosed with MIS-C in 25 different hospitals in Turkey., Methods: The retrospective study was conducted between 8 April and 28 October 2020 in 25 different hospitals from 17 cities. Data were collected from patients' medical records using a standardised form. Clinical and laboratory characteristics and outcomes according to different age groups, gender and body mass index percentiles were compared using multivariate logistic regression analysis., Results: The study comprised 101 patients, median age 7 years (interquartile range (IQR) 4.6-9.3); 51 (50.5%) were boys. Reverse-transcriptase polymerase chain reaction (PCR) assay was positive in 21/100 (21%) patients; 62/83 (74.6%) patients had positive serology for SARS-CoV-2. The predominant complaints were fever (100%), fatigue (n = 90, 89.1%), and gastrointestinal symptoms (n = 81, 80.2%). Serum C-reactive protein (in 101 patients, median 165 mg/L; range 112-228), erythrocyte sedimentation rate (73/84, median 53 mm/s; IQR 30-84) and procalcitonin levels (86/89, median 5 μg/L; IQR 0.58-20.2) were elevated. Thirty-eight patients (37.6%) required admission to intensive care. Kawasaki disease (KD) was diagnosed in 70 (69.3%) patients, 40 of whom had classical KD. Most patients were treated with intravenous immunoglobulin (n = 92, 91%) and glucocorticoids (n = 59, 58.4%). Seven patients (6.9%) died., Conclusion: The clinical spectrum of MIS-C is broad, but clinicians should consider MIS-C in the differential diagnosis when persistent fever, fatigue and gastrointestinal symptoms are prominent. Most patients diagnosed with MIS-C were previously healthy. Immunomodulatory treatment and supportive intensive care are important in the management of cases with MIS-C. Glucocorticoids and intravenous immunoglobulins are the most common immunomodulatory treatment options for MIS-C. Prompt diagnosis and prompt treatment are essential for optimal management., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × μL, p = 0.028; platelet count 166 vs. 216 cells × 10 3 /μL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559)., Conclusion: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD., What Is Known: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C., What Is New: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The uniqueness of paclitaxel's antimitotic action mechanism has fueled research toward its application in more effective and safer cancer treatments. However, the low water solubility, recrystallization, and side effects hinder the clinical success of classic paclitaxel chemotherapy. The aim of this study was to evaluate the in vivo efficacy and biodistribution of paclitaxel encapsulated in injectable amphiphilic cyclodextrin nanoparticles of different surface charges. It was found that paclitaxel-loaded amphiphilic cyclodextrin nanoparticles showed an antitumoral effect earlier than the drug solution. Moreover, the blank nanoparticles reduced the tumor growth with a similar trend to the paclitaxel solution. At 24 h, the nanoparticles had not accumulated in the heart and lungs according to the biodistribution assessed by in vivo imaging. Therefore, our results indicated that the amphiphilic cyclodextrin nanoparticles are potentially devoid of cardiac toxicity, which limits the clinical use and commercialization of certain polymeric nanoparticles. In conclusion, the amphiphilic cyclodextrin nanoparticles with different surface charge increased the efficiency of paclitaxel in vitro and in vivo. Cyclodextrin nanoparticles could be a good candidate vehicle for intravenous paclitaxel delivery.

Therapeutic agents used for non-small cell lung cancer (NSCLC) have limited curative efficacy and may trigger serious adverse effects. Cannabinoid ligands exert antiproliferative effect and induce apoptosis on numerous epithelial cancers. We confirmed that CB1 receptor (CB1R) is expressed in NSCLC cells in this study. Arachidonoylcyclopropylamide (ACPA) as a synthetic, CB1R-specific ligand decreased proliferation rate in NSCLC cells by WST-1 analysis and real-time proliferation assay (RTCA). The half-maximal inhibitory concentration (IC50) dose of ACPA was calculated as 1.39 × 10 -12  M. CB1 antagonist AM281 inhibited the antiproliferative effect of ACPA. Flow cytometry and ultrastructural analyzes revealed significant early and late apoptosis with diminished cell viability. Nano-immunoassay and metabolomics data on activation status of CB1R-mediated pro-apoptotic pathways found that ACPA inhibited Akt/PI3K pathway, glycolysis, TCA cycle, amino acid biosynthesis, and urea cycle and activated JNK pathway. ACPA lost its chemical stability after 24 hours tested by liquid chromatography-mass spectrometry (LC-MS/MS) assay. A novel ACPA-PCL nanoparticle system was developed by nanoprecipitation method and characterized. Sustained release of ACPA-PCL nanoparticles also reduced proliferation of NSCLC cells. Our results demonstrated that low dose ACPA and ACPA-PCL nanoparticle system harbor opportunities to be developed as a novel therapy in NSCLC patients that require further in vivo studies beforehand to validate its anticancer effect.

Cyclodextrin-based nanosponges (CD-NS) are considered as safe and biocompatible systems for removing toxic molecules from the body. Rapid removal of toxic molecules that are formed in the body from certain food constituents, is relevant especially for patients affected by chronic kidney disease. Within the scope of this study, innovative cyclodextrin polymers were synthesized to form nanosponges able to remove indole, before it could form the toxic indoxyl sulfate in the body. Furthermore, in vivo studies were carried out using the two optimal CD-NS formulations by assessing physicochemical properties, stability, indole adsorption capacity and in vitro cytotoxicity. NS prepared from β-cyclodextrin cross-linked with toluene diisocyanate was found to be the most effective NS with an in vitro indole adsorption capacity of over 90%. In addition, this derivative was more stable in gastrointestinal media. Animal studies further revealed that oral CD-NSs did not tend to accumulate and damage gastrointestinal tissues and are excreted from the GI tract with minimal absorption. In conclusion, this study suggests that CD-NS formulations are effective and safe in removing toxic molecules from the body. Their potential use in veterinary or human medicine could reduce dialysis frequency and avoid hepatic and cardiac toxicity avoiding the indole formation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

As research progresses on personalized medicines, it is clear that personalized and flexible formulations can provide effective treatment with reduced side effects especially for diseases like cancer, characteristic of high patient variability. 2D and 3D printers are frequently reported in the literature for the preparation of pharmaceutical products with adjusted dose and selected drug combinations. However, in-depth characterization studies of these formulations are rather limited. In this paper, ex vivo and mechanical characterization studies of antiviral and anticancer drug printed film formulations designed for personalized application were performed. Effects of the printing process with pharmaceutical formulations such as paclitaxel (PCX):cyclodextrin (CD) complex or cidofovir (CDV) encapsulated into poly(ethylene glycol)-polycaprolactone (PEG-PCL) nanoparticles on the films were evaluated through a series of mechanical characterization studies. Inkjet printing process was found to cause no significant change in the thicknesses of the film formulations, while mechanical strength and surface free energy increased and nano-sized voids in the film structure decreased. According to the mechanical characterization data, the unprinted film had maximum force (F max ) value of 15.6 MPa whereas F max increased to 43.8 MPa for PCX:CD complex printed film and to 37.7 MPa for the antiviral CDV-PEG-PCL nanoparticle printed film. In the light of ex vivo findings of sheep cervix-uterine tissue, bioadhesive properties of film formulations significantly improved after inkjet printing with different drug formulations. It has also been shown that the anticancer formulation printed on the film was maintained at the cervix tissue surface for >12 h. This study has shown for the first time that inkjet printing process does not adversely affect the mechanical properties of the bioadhesive film formulations. It has also been shown that durable bioadhesive film formulations for personalized dosing can be prepared by combining nanotechnology and inkjet printing., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Personalized medicine is an important treatment approach for diseases like cancer with high intrasubject variability. In this framework, printing is one of the most promising methods since it permits dose and geometry adjustment of the final product. With this study, a combination product consisting of anticancer (paclitaxel) and antiviral (cidofovir) drugs was manufactured by inkjet printing onto adhesive film for local treatment of cervical cancers as a result of HPV infection. Furthermore, solubility problem of paclitaxel was overcome by maintaining this poorly soluble drug in a cyclodextrin inclusion complex and release of cidofovir was controlled by encapsulation in polycaprolactone nanoparticles. In vitro characterization studies of printed film formulations were performed and cell culture studies showed that drug loaded film formulation was effective on human cervical adenocarcinoma cells. Our study suggests that inkjet printing technology can be utilized in the development of antiviral/anticancer combination dosage forms for mucosal application. The drug amount in the delivery system can be accurately controlled and modified. Moreover, prolonged drug release time can be obtained. Printing of anticancer and antiviral drugs on film seem to be a potential approach for HPV-related cervical cancer treatment and a good candidate for further studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cyclodextrins are cyclic oligosaccharides obtained by enzymatic digestion of starch. The α-, β- and γ- cyclodextrins contain respectively 6, 7 and 8 glucopyranose units, with primary and secondary hydroxyl groups located on the narrow and wider rims of a truncated cone shape structure. Such structure is that of a hydrophobic inner cavity with a hydrophilic outer surface allowing to interact with a wide range of molecules like ions, protein and oligonucleotides to form inclusion complexes. Many cyclodextrin applications in the pharmaceutical area have been widely described in the literature due to their low toxicity and low immunogenicity. The most important is to increase the solubility of hydrophobic drugs in water. Chemically modified cyclodextrin derivatives have been synthesized to enhance their properties and more specifically their pharmacological activity. Among these, amphiphilic derivatives were designed to build organized molecular structures, through selfassembling systems or by incorporation in lipid membranes, expected to improve the vectorization in the organism of the drug-containing cyclodextrin cavities. These derivatives can form a variety of supramolecular structures such as micelles, vesicles and nanoparticles. The purpose of this review is to summarize applications of amphiphilic cyclodextrins in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important amphiphilic cyclodextrin applications in the design of novel delivery systems like nanoparticles., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Brain tumors are the most common tumors among adolescents. Although some chemotherapeutics are known to be effective against brain tumors based on cell culture studies, the same effect is not observed in clinical trials. For this reason, the development of drug delivery systems is important to treat brain tumors and prevent tumor recurrence. The aim of this study was to develop core-shell polymeric nanoparticles with positive charge by employing a chitosan coating. Additionally, an implantable formulation for the chemotherapeutic nanoparticles was developed as a bioadhesive film to be applied at the tumor site following surgical operation for brain glioma treatment. To obtain positively charged, implantable nanoparticles, the effects of preparation technique, chitosan coating concentration and presence of surfactants were evaluated to obtain optimal nanoparticles with a diameter of less than 100 nm and a net positive surface charge to facilitate cellular internalization of drug-loaded nanoparticles. Hydroxypropyl cellulose films were prepared to incorporate these nanoparticle dispersions to complete the implantable drug delivery system. Results: The diameter of core-shell nanoparticles were in the range of 70-270 nm, depending on the preparation technique, polymer type and coating. Moreover, the chitosan coating significantly altered the surface charge of the nanoparticles to net positive values of +30 to +50 mV. The model drug docetaxel was successfully loaded into all particles, and the drug release rate from the nanoparticles was slowed down to 48 h by dispersing the nanoparticles in a hydroxypropyl cellulose film. Cell culture studies revealed that docetaxel-loaded nanoparticles cause higher cytotoxicity compared to the free docetaxel solution in DMSO. Conclusion: Docetaxel-loaded nanoparticles dispersed in a bioadhesive film were shown to be suitable for application of chemotherapeutics directly to the action site during surgical operation. The system was found to release chemotherapeutics for several days at the tumor site and neighboring tissue. This can be suggested to result in a more effective brain tumor treatment when compared to chemotherapeutics administered as an intravenous bolus infusion.

Purpose: Celiac disease (CD) is a chronic, inflammatory autoimmune disorder caused by intolerance to ingested gluten. Increased frequency of CD has been reported in occipital lobe epilepsy. The aim of the present study is to investigate the frequency of CD among children followed up due to epilepsy and diagnosed with epileptic activity in the occipital lobe in at least one electroencephalography (EEG) test., Methods: For this research, 90 pediatric epilepsy patients with epileptic activity in the occipital lobe were enrolled in the study group, while the control group comprised of 100 healthy children. In addition to the EEG examination, tissue transglutaminase (tTG) antibody was determined on duodenal biopsy., Results: None of the healthy children in the control group was positive in terms of the tTG antibody test used to scan CD. In the group with epileptic activity in the occipital lobe, two patients out of 90 were tTG antibody positive. The seroprevalence was 1/45 (2.22 %) in this group. These two patients were diagnosed with CD based on the endoscopic duodenal biopsy. In these patients, the seizures were uncontrollable through monotherapy., Conclusions: Our results showed that the prevalence of CD is observed to be higher than the normal population among the patients with occipital lobe epilepsy. This type of seizure disorder seems to be more resistant to monotherapy, compared with other types of occipital epilepsy. Therefore, screening for CD is recommended in children with resistant epileptic activity in the occipital lobe.