Refractory and Recurrent Idiopathic Granulomatous Mastitis Treatment: Adaptive, Randomized Clinical Trial.

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is mostly described as an autoimmune disease with higher prevalence among Middle Eastern childbearing-age women. This study aimed to evaluate the best treatment of choice in patients with resistant or recurrent IGM. STUDY DESIGN: Patients with established recurrent or resistant IGM who were referred to the Breast Cancer Research Center from 2017 to 2020 were randomly assigned to either one of the following treatment groups: A (best supportive care), B (corticosteroids: prednisolone), and C (methotrexate and low-dose corticosteroids). This adaptive clinical trial evaluated radiological and clinical responses, as well as the potential side effects, on a regular basis in each group, with patients followed up for a minimum of 2 years. RESULTS: A total of 318 participants, with a mean age of 33.52 ± 6.77 years, were divided into groups A (10 patients), B (78 patients), and C (230 patients). In group A, no therapeutic response was observed; group B exhibited a mixed response, with 14.1% experiencing complete or partial responses, 7.7% maintaining stability, and 78.2% experiencing disease progression. Accordingly, groups A and B were terminated due to inadequate response. In group C, 94.3% achieved complete response, 3% showed partial remission, and 2.7% had no response to therapy. Among the entire patient cohort, 11.6% tested positive for antinuclear antibodies, 3.5% for angiotensin-converting enzyme, and 12.3% for erythema nodosum. Notably, hypothyroidism was a prevalent condition among the patients, affecting 7.2% of the cohort. The incidence of common side effects was consistent across all groups. CONCLUSIONS: The most effective treatment option for patients with recurrent or resistant IGM is a combination therapy involving steroids and disease-modifying antirheumatic drugs such as methotrexate.

Effectiveness of plant-mediated synthesis of hydroxyapatite nano-particles impregnated in Pistachio oleogum resin on mineral contents of human teeth. An in-situ single-blind controlled study.

OBJECTIVES: This study aimed to synthesize and characterize an environmentally friendly nanohydroxyapatite (n-HA) and evaluate its impact on enamel mineral content when incorporated into a Pistachio oleo gum resin (Saqqez) bio-chewing gum for in-situ models. We compared the effects of this green nano-hydroxyapatite (G n-HA) with those of a commercially available synthetic nano-hydroxyapatite (S n-HA). METHODS: Various analytical techniques were employed including XRD, FESEM, FT-IR, EDX/SEM and TGA/DTA to characterize the crystallinity, size and composition of the G n-HA powder. Three chewing gum groups were formulated: (1) Saqqez gum containing 10% wt G n-HA, (2) Saqqez gum containing 10% wt S n-HA, and (3) pure Saqqez gum. In order to evaluate the impact of these chewing gums on enamel, intraoral appliances were fabricated, each containing six enamel specimens. Participants were instructed to chew the gums while wearing these appliances. The calcium (Ca+2) and phosphorus (P) levels in enamel specimens, both with and without exposure to an acid challenge, were quantified using EDX/SEM. FE-SEM was employed to capture the microstructure of the enamel surface. In terms of the statistical analysis, one-way ANOVA and Tukey's post hoc tests were utilized to compare the data, where the significance level (α) was set at 0.05. RESULTS: The characterization tests confirmed the successful synthesis of G n-HA. Furthermore, EDX/SEM analysis of the enamel specimens from the intraoral appliance revealed significant variations in calcium (Ca+2) content among the enamel specimens (P = 0.000). The S n-HA group, in particular, exhibited the highest Ca+2 content, while the pure Saqqez group displayed the lowest. Nonetheless, there was no statistically significant differences in phosphorus (P) content observed among the three groups (P = 0.27). CONCLUSIONS: Saqqez gum can be considered a wholesome natural chewing gum that serves, as a carrier for delivering remineralization agents to the tooth surfaces. This was evident in the groups containing n-HA, exhibiting elevated Ca+2 levels. It's noteworthy that G n-HA demonstrated less efficacy in enamel remineralization compared to S n-HA.

Prevalence and Risk Factors of Bruxism in a Selected Population of Iranian Children

ABSTRACT Objective: To investigate the prevalence of bruxism in Iranian children aged 6 to 12 years. Material and Methods: This cross-sectional study was conducted on 600 schoolchildren aged 6-12 years. The questionnaire consisted of two sections: the first section included demographic information, while the second evaluated the occurrence of bruxism. Kruskal-Wallis, Chi-Square, Fisher and Multinomial logistic regression were used. A level of p<0.05 was considered statistically significant. Results: 698 questionnaires were distributed, of which 600 participants were returned. According to Multinomial logistic regression, awake bruxism was associated significantly with the following variables: age, sequence of birth, recurrent headache, gastrointestinal disease, nasal obstruction, neurological disorder, easy child crying, sleep disorders, talking in a dream and snoring and jaw disorder. Sleep bruxism was associated significantly with age, premature birth, allergy, gastrointestinal disease, drooling, mouth breathing, nasal obstruction, oral habit, nail biting, sleep disorder, jaw disorders, and family history. Conclusion: Pre-birth and post-birth factors play an important role in the prevalence of bruxism in society. It is possible to prevent complications of bruxism by informing parents and making a timely diagnosis. Parents should be aware of this occurrence to reduce possible related factors to teeth and the masticatory system.

In vitro comparison of microleakage with two different techniques of placing stainless steel crowns on mandibular deciduous first molar teeth with decreased mesiodistal width.

Background. Stainless steel crowns (SSCs) of the opposing maxillary deciduous molar teeth are used in mandibular deciduous first molars with decreased proximal surfaces due to caries. However, the SSCs of maxillary deciduous molar teeth are different from those of the mandibular deciduous molars in terms of the occlusal surface morphology, the buccal margin, and the proximal surface contour. Therefore, it is possible to prepare the buccal and lingual surfaces to use the SSC of the lower deciduous molar teeth and compare microleakage. Methods. Eighty extracted mandibular deciduous first molars were randomly assigned to two groups. In the case group (BLP), the buccal (B) and lingual (L) surfaces were prepared in addition to the proximal (P) surface, and an SSC was placed on the mandibular first deciduous teeth. Only the proximal surface was prepared in the control (P) group, and the SSC of the opposing tooth (maxillary deciduous first molar teeth) was placed. After dissecting the teeth, the extent of dye penetration was measured. Results. The difference in microleakage on the buccal aspect between the case and control groups was significant (P=0.02); however, the difference in microleakage on the lingual aspect between the case and control groups was not significant (P=0.89). Conclusion. Microleakage at the buccal margin of the SSC of mandibular deciduous first molars was less than the maxillary deciduous first molar SSC, with no significant differences in the lingual margin.

Evaluation of the Levels of Evidence in Three Clinical Chapters in Five Editions of the Textbook Pathways of the Pulp.

Introduction: The levels of evidence (LOE) of dental education texts is critical from the educational point of view. The present study aimed to evaluate the levels of evidence of references used in three clinical chapters in the textbook Pathways of the Pulp. Material & Method: The references of three clinical chapters in the text book Pathways of the Pulp were assessed in five of its editions. The levels of evidence were ranked according to study type and the Oxford scale from 0 to 5. The chi-square test was used to compare the level of evidence between different editions of the "Retreatment," "Trauma," and "Surgery" chapters. Results: A total of 3656 references were reviewed and analyzed from the "Trauma" (928 references), "Re-treatment" (1906 references), and "Surgery" (822 references) chapters in the 1998, 2002, 2006, 2011, and 2016 editions. The percentage of the LOE 0 (no evidence) was high (>60%) in all three chapters in all editions (P<0.001). The levels of evidence had the same distribution in all editions (P=0.871). The LOE of the "Re-treatment" (P=0.044) and "Surgery" (P<0.001) chapters changed in some editions. Conclusion: The majority of references in the three clinical chapters of the book are low-level evidence. Encouragement policies for researchers to conduct studies with high LOE are necessary.

Goldenhar Syndrome in a 6-Year-Old Patient: a Case Report and Review of Literature.

Goldenhar syndrome (GHS) is a complex syndrome characterized by relation of mandibular hypoplasia, abnormality of the ear, ocular dermoid and vertebral disorders and hemi facial macrosomia. Treatment protocol depends on the patient's age and systemic clinical presentations, with a multidisciplinary method often being required. This case report describes a typical 6-year-old female patient who presented to the Department of Pediatric Dentistry, Faculty of Dentistry, University of Medical Sciences, Kerman, Iran with mandibular hypoplasia, facial asymmetry, ear tags and ocular dermoid after plastic surgery. Diagnosis was based on clinical aspects, radiology and laboratory findings. GHS is a developmental complaint that can disturb many aspects of the patient's life; therefore, immediate treatment from birth is necessary.

An Adaptive Robust Control Strategy in a Cancer Tumor-Immune System under Uncertainties.

We propose an adaptive robust control for a second order nonlinear model of the interaction between cancer and immune cells of the body to control the growth of cancer and maintain the number of immune cells in an appropriate level. Most of the control approaches are based on minimizing the drug dosage based on an optimal control structure. However, in many cases, measuring the exact quantity of the model parameters is not possible. This is due to limitation in measuring devices, variational and undetermined characteristics of micro-environmental factors. It is of great importance to present a control strategy that can deal with these unknown factors in a nonlinear model.

Bovine serum albumin binding study to erlotinib using surface plasmon resonance and molecular docking methods.

Bovine serum albumin (BSA) is the most abundant protein in the blood circulation and it is commonly used for drug delivery in blood. Therefore, we aim to study BSA interaction with erlotinib as an anticancer drug using surface plasmon resonance (SPR) and molecular modeling methods under physiological conditions (pH = 7.4). BSA immobilized on carboxymethyl dextran hydrogel Au chip (CMD) after activation with N-hydroxysuccinimide and N-ethyl-N-(3-diethylaminopropyl) carbodiimide and then the erlotinib binding to BSA at different concentrations was evaluated. Increasing of erlotinib concentration led to dose-response sensorgrams of BSA. The amount of equilibrium constant (KD) at 25 °C (4.25 × 10-9) showed the high affinity of erlotinib to BSA. Thermodynamic parameters were attained at four different temperatures. The positive value of enthalpy and entropy showed that hydrophobic forces play major role in the interaction of erlotinib with BSA. Besides, the positive value of Gibbs free energy demonstrated that the interaction of erlotinib with BSA was nonspontaneous and enthalpy driven and the complexion of drug were dependent on endothermic process. According to the molecular docking study, the most favorable binding sites of erlotinib on the BSA were subdomain IIIA and IB. Moreover, molecular docking study results showed that hydrogen binding has a role in intermolecular force that stabilize erlotinib-BSA complex.

Comparing the conventional 15 cm and the C-length approaches for central venous catheter placement.

Introduction: The present guidelines recommend placing the catheter tip in the superior vena cava (SVC) above the pericardial cephalic reflection. The aim of this study was to compare the accuracy of two different approaches in locating the tip of the Central venous catheter (CVC) at the suggested vascular zone. Methods: This was an interventional study on two hundred patients undergoing Coronary artery bypass surgery (CABG) operation who required a central venous cannulation. They were randomly assigned into two groups. In the first group catheter placement was applied through using the conventional 15 cm method. In the second group a C-length method was applied for measuring the depth of catheter tip placement from the preoperative chest radiographs. For statistical analysis Chi-square test and T-test were used. Results: In the first group (15 cm) 100% of the patients had their catheters placed below the C-line (Carina line) and the average distance between the catheter tip and the C-line was +4.22±2.10 cm. In the second (C-Length) group 52% of the catheters were below C-line with an average distance of +0.77±0.5 cm. There was a meaningful difference between the two groups in respect to the catheter location depth and zone of placement (P<0.001). Conclusion: The C-Length approach in comparison to the conventional 15 cm approach resulted in a considerable higher number of catheters above the recommended C-line, thus it can provide a more reliable and safe mode for CVC placement in the SVC.

Effects of rosmarinic acid on acetaminophen-induced hepatotoxicity in male Wistar rats.

CONTEXT: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects. OBJECTIVE: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated. MATERIALS AND METHODS: Male Wistar rats were pretreated with RA (10, 50 and 100 mg/kg, i.g.) for one week. On day 7, rats received APAP (500 mg/kg, i.p.). Then aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, malondialdehyde (MDA), glutathione (GSH), total antioxidant capacity (TAC), glutathione S-transferase (GST), cytochrome CYP450 and histopathological changes were determined. RESULTS: APAP-induced oxidative stress in liver by a significant increase in the level of MDA (7.6 ± 0.21 nmol/mg) as well as a decrease in the contents of TAC (1.75 ± 0.14 µmol/g), GSH (1.9 ± 0.22 µmol/g) and GST) 3.2 ± 0.28 U/mg). RA treatment decreased MDA (4.32 ± 0.35 nmol/mg) but increased the contents of TAC (3.51 ± 0.34 µmol/g), GSH (3.42 ± 0.16 µmol/g) and GST (5.71 ± 0.71 µmol/g) in APAP group. RA 100 mg/kg decreased ALT (91.5 ± 1.5 U/L), AST (169 ± 8.8 U/L) and CYP450 (3 ± 0.2 nmol/min/mg) in APAP group. Histologically RA attenuated hepatic damage by decreasing necrosis, inflammation, and haemorrhage in liver sections of APAP group. DISCUSSION AND CONCLUSIONS: This is the first report that oral administration of RA dose-dependently elicited significant hepatoprotective effects in rats through inhibition of hepatic CYP2E1 activity and lipid peroxidation. RA-protected hepatic GSH and GST reserves and total tissue antioxidant capacity.

Photodynamic N-TiO2 Nanoparticle Treatment Induces Controlled ROS-mediated Autophagy and Terminal Differentiation of Leukemia Cells.

In this study, we used nitrogen-doped titanium dioxide (N-TiO2) NPs in conjugation with visible light, and show that both reactive oxygen species (ROS) and autophagy are induced by this novel NP-based photodynamic therapy (PDT) system. While well-dispersed N-TiO2 NPs (≤100 µg/ml) were inert, their photo-activation with visible light led to ROS-mediated autophagy in leukemia K562 cells and normal peripheral lymphocytes, and this increased in parallel with increasing NP concentrations and light doses. At a constant light energy (12 J/cm2), increasing N-TiO2 NP concentrations increased ROS levels to trigger autophagy-dependent megakaryocytic terminal differentiation in K562 cells. By contrast, an ROS challenge induced by high N-TiO2 NP concentrations led to autophagy-associated apoptotic cell death. Using chemical autophagy inhibitors (3-methyladenine and Bafilomycin A1), we confirmed that autophagy is required for both terminal differentiation and apoptosis induced by photo-activated N-TiO2. Pre-incubation of leukemic cells with ROS scavengers muted the effect of N-TiO2 NP-based PDT on cell fate, highlighting the upstream role of ROS in our system. In summary, PDT using N-TiO2 NPs provides an effective method of priming autophagy by ROS induction. The capability of photo-activated N-TiO2 NPs in obtaining desirable cellular outcomes represents a novel therapeutic strategy of cancer cells.

Sclerostin and skeletal health.

Sclerostin is a cysteine-knot glycoprotein product of the SOST gene, predominately expressed by osteocytes, that is a regulator of osteoblastic bone formation. When sclerostin binds to its low-density lipoprotein receptor-related proteins 5 and 6 on the cell membrane of osteoblasts, it inhibits canonical Wnt/ß-catenin signaling and reduces osteoblastic bone formation. Sclerostin was first identified in the study of two rare autosomal recessive disorders, sclerosteosis and van Buchem disease, which are associated with absent or reduced levels of sclerostin. Although homozygote patients with these disorders have serious adverse clinical consequences due to excessive bone growth, heterozygote patients have a normal phenotype, high bone mass, and very low risk of fractures. This has led to the concept that downregulation of sclerostin might be effective in the treatment of osteoporosis. Several humanized monoclonal antibodies to sclerostin, including romosozumab and blosozumab, are now in clinical development. Preliminary data show that these agents result in a transient increase in bone formation markers, a sustained decrease in bone resorption markers, and a robust increase in bone mineral density. If any of these agents are found to reduce fracture risk with a favorable safety profile, it will expand the options for osteoanabolic therapy for patients at high risk for fractures.

Conjugated estrogens combined with bazedoxifene: the first approved tissue selective estrogen complex therapy.

Menopausal therapy with a tissue selective estrogen complex combines estrogens with a selective estrogen receptor modulator, with the goal of blending the desirable effects of estrogens on menopausal symptoms and bone with the tissue selective properties of a selective estrogen receptor modulator. The first tissue selective estrogen complex to receive regulatory approval is a combination of conjugated estrogens (CE) with bazedoxifene (BZA). Clinical trials with CE/BZA in postmenopausal women have shown improvement in vasomotor symptoms, vulvo-vaginal atrophy, and bone mineral density, without stimulation of the endometrium or breast tissue, with a generally favorable safety and tolerability profile. CE/BZA represents a new approach to the management of menopausal symptoms in women with a uterus.

Acute and chronic exposure of chick embryo to ethanol alters brain neurosteroid levels.

Neurosteroids are modulators of neuronal function that may play important role in brain maturation. The aim of the present investigation was to study the effect of prenatal exposure to acute and chronic ethanol on brain progesterone, estradiol, and testosterone concentration on 10th and 15th days following egg incubation. Eggs were exposed to ethanol at 10 % in chronic treatment and 70 % in acute treatment. Progesterone, estradiol, and testosterone were assayed by radioimmunoassay method. It was shown that brain progesterone level was significantly decreased (P < 0.05) in chronic ethanol group on embryonic day 10, but it was significantly decreased (P < 0.05) in acute and chronic groups on embryonic day 15. Brain estradiol level was significantly increased (P < 0.05) in chronic ethanol group on embryonic day 10, and it was decreased (P < 0.05) in acute and chronic groups of ethanol on embryonic day 15. Brain testosterone was significantly increased (P < 0.05) in acute and chronic ethanol-exposed groups on embryonic days 10 and 15. Our observations suggest that ethanol may modulate neurosteroid synthesis in the brain.