Theoretical and Experimental Aspects of Sodium Diclofenac Salt Release from Chitosan-Based Hydrogels and Possible Applications.

Two formulations based on diclofenac sodium salt encapsulated into a chitosan hydrogel were designed and prepared, and their drug release was investigated by combining in vitro results with mathematical modeling. To understand how the pattern of drug encapsulation impacted its release, the formulations were supramolecularly and morphologically characterized by scanning electron microscopy and polarized light microscopy, respectively. The mechanism of diclofenac release was assessed by using a mathematical model based on the multifractal theory of motion. Various drug-delivery mechanisms, such as Fickian- and non-Fickian-type diffusion, were shown to be fundamental mechanisms. More precisely, in a case of multifractal one-dimensional drug diffusion in a controlled-release polymer-drug system (i.e., in the form of a plane with a certain thickness), a solution that allowed the model's validation through the obtained experimental data was established. The present research reveals possible new perspectives, for example in the prevention of intrauterine adhesions occurring through endometrial inflammation and other pathologies with an inflammatory mechanism background, such as periodontal diseases, and also therapeutic potential beyond the anti-inflammatory action of diclofenac as an anticancer agent, with a role in cell cycle regulation and apoptosis, using this type of drug-delivery system.

Update on the Use of Nanocarriers and Drug Delivery Systems and Future Directions in Cervical Cancer.

Cervical cancer represents a major health problem among females due to its increased mortality rate. The conventional therapies are very aggressive and unsatisfactory when it comes to survival rate, especially in terminal stages, which requires the development of new treatment alternatives. With the use of nanotechnology, various chemotherapeutic drugs can be transported via nanocarriers directly to cervical cancerous cells, thus skipping the hepatic first-pass effect and decreasing the rate of chemotherapy side effects. This review comprises various drug delivery systems that were applied in cervical cancer, such as lipid-based nanocarriers, polymeric and dendrimeric nanoparticles, carbon-based nanoparticles, metallic nanoparticles, inorganic nanoparticles, micellar nanocarriers, and protein and polysaccharide nanoparticles. Nanoparticles have a great therapeutic potential by increasing the pharmacological activity, drug solubility, and bioavailability. Through their mechanisms, they highly increase the toxicity in the targeted cervical tumor cells or tissues by linking to specific ligands. In addition, a nondifferentiable model is proposed through holographic implementation in the dynamics of drug delivery dynamics. As any hologram functions as a deep learning process, the artificial intelligence can be proposed as a new analyzing method in cervical cancer.

Infectious Inflammatory Processes and the Role of Bioactive Agent Released from Imino-Chitosan Derivatives Experimental and Theoretical Aspects.

The paper focuses on the development of a multifractal theoretical model for explaining drug release dynamics (drug release laws and drug release mechanisms of cellular and channel-type) through scale transitions in scale space correlated with experimental data. The mathematical model has been developed for a hydrogel system prepared from chitosan and an antimicrobial aldehyde via covalent imine bonds. The reversible nature of the imine linkage points for a progressive release of the antimicrobial aldehyde is controlled by the reaction equilibrium shifting to the reagents, which in turn is triggered by aldehyde consumption in the inhibition of the microbial growth. The development of the mathematical model considers the release dynamic of the aldehyde in the scale space. Because the release behavior is dictated by the intrinsic properties of the polymer-drug complex system, they were explained in scale space, showing that various drug release dynamics laws can be associated with scale transitions. Moreover, the functionality of a Schrödinger-type differential equation in the same scale space reveals drug release mechanisms of channels and cellular types. These mechanisms are conditioned by the intensity of the polymer-drug interactions. It was demonstrated that the proposed mathematical model confirmed a prolonged release of the aldehyde, respecting the trend established by in vitro release experiments. At the same time, the properties of the hydrogel recommend its application in patients with intrauterine adhesions (IUAs) complicated by chronic endometritis as an alternative to the traditional antibiotics or antifungals.

Research on myoma in Northeastern Romania and socio-medical outcomes.

Myomas are the most common benign uterine tumors in women of childbearing age, with an incidence of up to 77% and a major impact on women's health. The aim of our study was to provide information concerning the incidence and prevalence of myomas in the patients admitted to a tertiary referral center in Northeastern Romania. This retrospective study conducted at the Iasi 'Cuza Voda' University Hospital of Obstetrics and Gynecology (Romania) included 11,538 patients, representing all patients admitted to the gynecology department between January 2013 and December 2019. During the study interval, the number of hysterectomies (total and for myomas) had increased. The rate of laparoscopic surgery showed a small decrease (31.3% from 34%), classic therapy showed a decrease by more than 10% and the hysteroscopy rate was tripled. There are few studies in the literature that have established with accuracy the incidence of myomas. In the present study, the prevalence of hysterectomy for myomas was 54.42%. Our results are in agreement with the data in the literature, namely that 40-60% of all performed hysterectomies are for myomas. The vast majority of admissions for myomas involve a surgical procedure most commonly hysterectomy.

The added value of three-dimensional ultrasonography in uterine pathology.

The rapid development achieved over the last decades in volume rendering of ultrasound data, known as three-dimensional (3D) ultrasound technique, leads to new opportunities for refining the diagnosis in many gynaecologic conditions. The aim of the present study was to evaluate the advantages of 3D ultrasound over two-dimensional (2D) ultrasound in uterine pathology and to establish the optimal time point during the menstrual cycle to perform 3D ultrasound examination in order to achieve the maximum of useful information. A cross-sectional study on 200 patients who underwent gynaecologic 2D and 3D ultrasound examinations was performed. The addition of 3D examination to 2D ultrasound in uterine pathology provided the most useful information concerning: Congenital uterine anomalies, intrauterine devices (IUDs), adenomyosis, and submucous myomas. The findings showed that the 3D ultrasound scan is a useful tool in gynaecology, especially in cases with congenital uterine anomalies, myoma, and IUD. Although initially it was used for research purposes only, recent findings suggest its usefulness in routine ultrasound scan and the possibility of witnessing its introduction as a recommended examination procedure in the foreseeable future. Further research should be conducted in order to establish the sensitivity of 3D ultrasound in the detection of minor endometrial conditions, by correlating the imaging findings with the hysteroscopic results.

A rare complication of uterine leiomyomata: Severe haemoperitoneum caused by the rupture of an overlying subserosa variceal vein: A case report.

The rupture of a subserosa variceal vein overlying a uterine myoma is a rare complication and a less common cause of gynecologic haemoperitoneum. The literature data are scarce regarding this condition and less than 100 cases have been reported (including those occurring during pregnancy). The present case is of a 48-year-old woman, with a history of asymptomatic uterine myoma, who was hospitalised for severe abdominal pain with sudden onset and signs of hypovolemic shock. The emergency conventional imaging exams confirmed the diagnosis of uterine myoma and haemoperitoneum, but did not reveal the source of bleeding. The cause of haemoperitoneum was detected by means of emergency laparotomy. In order to obtain quick hemostasis, in the settings of a rapid deteriorating hypovolemic shock, a supracervical hysterectomy was performed. The aim of the article is to raise awareness to gynecologists regarding this extremely rare life-threatening complication of the most common benign tumor of the uterus.

A Romanian study on the impact of glypressin in laparoscopic myomectomy.

A major myomectomy-associated problem is excessive blood loss. The aim of the present study was to evaluate the effect of glypressin on blood loss during laparoscopic myomectomy (LM) in women with uterine myomas. A total of 188 women scheduled for LM for uterine myomas were divided into two groups. The one group of women (n=64) received a 5-ml intramyometrial injection of glypressin 0.2 mg/ml (glypressin group; group 1). The other group of women (n=124) (group 2) had an LM performed without any other method to reduce blood loss. The decrease in postoperative hemoglobin (Hb), hematocrit (Ht), morbidity and duration of hospital stay were assessed. The results revealed that Hb and Ht (as it was presumed) exhibited similar changes in our study. Statistically significant differences (P<0.05) were obtained between the two groups in terms of Hb and Ht; after LM both Hb and Ht were decreased. In conclusion, the impact of glypressin administration in hemorrhage control in uterine leiomyomas may establish new future perspectives, regarding its administration in gynecological hemorrhagic pathologies.

Large ovarian tumors in adolescents, a systematic review of reported cases, diagnostic findings and surgical management.

The purpose of this study was to analyze the published cases regarding large ovarian masses in adolescents, in order to find useful clinical implications for the diagnosis and management of the condition. The methodology employed a systematic review of reported cases of large/giant ovarian tumor in adolescence. The main objective was to assess the imagery findings, histology of the tumor, and the type of surgery performed. Our study included 58 patients with the tumor diameters ranged between 11 and 42 cm, with a median value of 22.75 cm and a mean diameter of 24.66 ± 8.50 cm. The lesions were benign in 47 cases (81%), borderline in 2 cases (3.4%), and malign in 9 cases (15.6%). We found no statistically significant difference (p > 0.05) between the size of the tumors and the ovarian markers levels. At the same time, a statistically significant difference was identified (p=<0,001) between elevated levels of the serum markers and the malignant tumor type (OR = 12.45; CI95 = 2.55-94.77). The main types of surgery performed were cystectomy (35 cases), oophorectomy (4 cases), salpingo-oophorectomy (18 cases). Open laparotomy was performed in 46 cases on tumors with a median diameter of 25 ± 8.8 cm, while laparoscopy was done in 12 cases on tumors with a median diameter of 23.7 ± 7.6 cm. For optimal surgical management, it is advisable to assess first the imagery findings and tumor markers. Then, the laparoscopic approach should be considered as a feasible option, especially in cases where there are no predictive factors for a malign disease.

A Theoretical Model for Release Dynamics of an Antifungal Agent Covalently Bonded to the Chitosan.

The aim of the study was to create a mathematical model useful for monitoring the release of bioactive aldehydes covalently bonded to the chitosan by reversible imine linkage, considered as a polymer-drug system. For this purpose, two hydrogels were prepared by the acid condensation reaction of chitosan with the antifungal 2-formyl-phenyl-boronic acid and their particularities; influencing the release of the antifungal aldehyde by shifting the imination equilibrium to the reagents was considered, i.e., the supramolecular nature of the hydrogels was highlighted by polarized light microscopy, while scanning electron microscopy showed their microporous morphology. Furthermore, the in vitro fungicidal activity was investigated on two fungal strains and the in vitro release curves of the antifungal aldehyde triggered by the pH stimulus were drawn. The theoretical model was developed starting from the hypothesis that the imine-chitosan system, both structurally and functionally, can be assimilated, from a mathematical point of view, with a multifractal object, and its dynamics were analyzed in the framework of the Scale Relativity Theory. Thus, through Riccati-type gauges, two synchronous dynamics, one in the scale space, associated with the fungicidal activity, and the other in the usual space, associated with the antifungal aldehyde release, become operational. Their synchronicity, reducible to the isomorphism of two SL(2R)-type groups, implies, by means of its joint invariant functions, bioactive aldehyde compound release dynamics in the form of "kink-antikink pairs" dynamics of a multifractal type. Finally, the theoretical model was validated through the experimental data.

Transradial Embolization, an Underused Type of Uterine Artery Embolization Approach: A Systematic Review.

Background and Objectives: The most utilized approach for the embolization of uterine arteries is the transfemoral path. However, the transradial approach (TRA) has been gaining popularity among cardiologic interventions in the last years but only few studies have shown its applicability in uterine myoma treatment. The objective of this paper is to assess the feasibility, safety and efficacy of TRA when compared with the transbrachial, transulnar or transfemoral approach (TFA) for uterine arteries embolization (UAE). Materials and methods: A systematic review of the literature that analyzes the TRA for UAE it was carried out, in order to assess its safety and effectiveness. It was systematically searched the literature (Google Scholar, PubMed/MEDLINE, Cochrane Library and Embase) using the words ''uterine artery embolization''/''uterine embolization'' and ''transradial''/''radial''. All the relevant papers published until March 2020 were retrieved and analyzed. Results: Ten studies were considered eligible for this topic. TRA is a comparable method with TFA for uterine artery embolization. Conclusions: These studies allowed us to conclude that TRA is as safe and efficient as TFA. Its advantages include few complications, shorter hospitalization period, and rapid mobilization but a steeper learning curve has the disadvantage of a longer learning curve compared to TFA. Yet, these findings are built on few reports and more research is needed.

Logistic models and artificial intelligence in the sonographic assessment of adnexal masses - a systematic review of the literature.

Adnexal masses are common, yet challenging, in gynecological practice. Making the differential diagnosis between their benign and malignant condition is essential for optimal surgical management, but reliable pre-surgical differentiation is sometimes difficult using clinical features, ultrasound examination, or tumor markers alone. A possible way to improve the diagnosis is using artificial intelligence (AI) or logistic models developed based on compiling and processing clinical, ultrasound, and tumor marker data together. Ample research has already been conducted in this regard that medical practitioners could benefit from. In this systematic review, we present logistic models and methods using AI, chosen based on their demonstrated high performance in clinical practice. Although some external validation of these models has been performed, further prospective studies are needed in order to select the best model or to create a new, more efficient, one for the pre-surgical evaluation of ovarian masses.