Evaluating the effect of strontium ranelate and photobiomodulation on cementogenic and osteogenic differentiation of buccal fat pad-derived stem cells: An in vitro study.

This study aimed to analyze the impact of strontium ranelate (Str), photobiomodulation (PBM), or their combination of the proliferation, osteogenic differentiation, and cementogenic differentiation of buccal fat pad-derived stem cells. BFPdSCs were exposed to one of the following interventions: (1) PBM (660 nm), (2) PBM (660 nm) + Str, (3) PBM (880 nm), (4) PBM (880 nm) + Str, (5) Str. All study groups had significantly higher osteogenic differentiation than the control group (p < 0.05), and no significant difference existed between the 660 and 808 nm groups (p = 0.97). Compared to the Str group, 660 nm and 880 nm group samples had significantly lower osteogenic differentiation (p < 0.0001), while other groups did not show a significant difference. Regarding cementogenic differentiation, the 660 nm group showed higher values than the 808 nm group (p < 0.01). Compared with the Str group, 660 nm, 660 nm + Str, and 808 nm + Str groups showed significantly higher gene expression (p < 0.05). In the case of osteogenic differentiation, although photobiomodulation alone had a lower inducing effect than strontium ranelate, combining 808 nm diode lasers and strontium ranelate may provide the best results. Moreover, using a 660 nm diode laser and exposing stem cells to strontium ranelate can be the most effective approach to induce cementogenic differentiation.

Efficacy of Buzzy Device Versus EMLA Cream for Reducing Pain During Needle-Related Procedures in Children: A Randomized Controlled Trial.

OBJECTIVES: Several pain management tools exist but with limitations in their efficacy or applicability. The EMLA (eutectic mixture of local anesthetics) cream is currently used for pain relief for needle-related procedures; however, it needs a minimum of 30 to 45 minutes to be effective. The Buzzy is a device that generates vibrations with cold leading to quicker pain relief. Our aim was to evaluate the effect of the Buzzy device in pain and anxiety reduction compared with EMLA cream in children requiring intravenous cannulation or venepuncture. METHODS: This was a randomized clinical trial comparing pain and anxiety reduction by Buzzy device with the standard care (EMLA cream) in children aged 2 to 14 years who required blood extraction or intravenous cannulation based on their clinical needs. Eligible patients were randomized to either Buzzy device as the intervention or EMLA cream as the control. The outcome measures were the degree of pain scores and anxiety ratings at different stages of the needle-related procedures. RESULTS: A total of 300 patients with a mean age of 6.5 ± 3.1 years were enrolled. Baseline characteristics were similar between the Buzzy device and EMLA cream groups. The observed pain scores by research nurses and a parent were significantly lower in the EMLA group compared with the Buzzy device group; however, the pain scores by the self-assessment scale were not statistically significant with mean difference of -0.332, 95% confidence interval, -0.635 to -0.028 ( P = 0.062). The level of anxiety was significantly lower in EMLA compared with Buzzy device ( P = 0. 0.0001). Both staff and parents' satisfaction, success rate of cannulation, type of blood tests, and comment on the physician on the results were similar in both groups. CONCLUSIONS: Pain and anxiety relief using the Buzzy device is not as effective as EMLA cream in children requiring venepuncture. However, rapid onset of action of the Buzzy device is valuable in decreasing waiting time in a busy emergency department. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT05354739.

Experimental investigation of a high-power 1018 nm fiber laser using a 20/400 µm ytterbium-doped fiber.

A 472 W monolithic fiber laser, operating at 1018 nm by employing an active fiber with a low core/cladding diameter ratio of 20/400 µm, is reported in this paper. The slope efficiency and beam quality factor (M2) of the fiber laser are, respectively, 49.4% and 1.17. To realize the setup, the effects of the characteristics of the experimental elements-reflectivity of the output coupling fiber Bragg grating, length of the active fiber, etc.-on the output behavior of the system have been investigated. These are the highest recorded output signal power, efficiency, and beam quality factor in monolithic 1018 nm ytterbium-doped fiber lasers using fibers with a core/cladding diameter ratio of 20/400 µm.

Antibodies to extractable nuclear antigens (ENAS) in systemic lupus erythematosus patients: correlations with clinical manifestations and disease activity.

The aim was to explore possible correlations of antibodies to extractable nuclear antigens (ENA) with clinical manifestations and disease activity indices in systemic lupus erythematosus (SLE) patients. A total of 70 consecutive SLE patients (64 females) were included. Disease activity was assessed by SLE activity index (SLEDAI), and British Isles Lupus Assessment Group (BILAG). Anti-Ro/SSA correlated positively with, headache (r=0.24, p=0.04), blurring of vision (r=0.25, p=0.03) and SLEDAI (r=0.25, p=0.04) and negatively with C3 (r=-0.35, p=0.003). Anti-Ro/SSA correlated with anti La/SSB antibodies (r=0.69, p<0.001), but not with anti-DNA, anti-RNP and anti-Sm antibodies. Anti-La/SSB antibodies correlated with headache (r=0.26, p=0.03), SLEDAI (r=0.25, p=0.03) and negatively with C3 (r=-0.34, p=0.004). Anti-La/SSB did not correlate with anti-RNP or anti-Sm antibodies. Anti-Sm antibodies correlated with disease duration (r=0.34, p=0.003), 24 hours urinary proteins (r=0.31, p=0.008), SLEDAI (r=0.31, p=0.009), BILAG renal score (r=0.29, p=0.02) and negatively with age at onset (r=-0.27, p=0.02), WBCs (r=-0.29, p=0.014) and C4 (r=-0.25, p=0.049). In multivariate analyses, anti-Ro/SSA antibodies remained associated with headache, blurring of vision and C3 and anti-La/SSB antibodies remained associated with C3 and with headache. Anti-Sm antibodies were independently associated with disease duration and total SLEDAI scores, while anti-RNP antibodies remained significantly associated with BILAG mucocutaneous scores only. Antibodies to ENAs are associated with clinical aspects of SLE and may play a role in the assessment of disease activity. Insight into these ENAs may lead to new approaches to diagnostic testing, accurate evaluation of disease activity and lead to target approach for SLE.

Detailed solvent, structural, quantum chemical study and antimicrobial activity of isatin Schiff base.

The ratios of E/Z isomers of sixteen synthesized 1,3-dihydro-3-(substituted phenylimino)-2H-indol-2-one were studied using experimental and theoretical methodology. Linear solvation energy relationships (LSER) rationalized solvent influence of the solvent-solute interactions on the UV-Vis absorption maxima shifts (νmax) of both geometrical isomers using the Kamlet-Taft equation. Linear free energy relationships (LFER) in the form of single substituent parameter equation (SSP) was used to analyze substituent effect on pKa, NMR chemical shifts and νmax values. Electron charge density was obtained by the use of Quantum Theory of Atoms in Molecules, i.e. Bader's analysis. The substituent and solvent effect on intramolecular charge transfer (ICT) were interpreted with the aid of time-dependent density functional (TD-DFT) method. Additionally, the results of TD-DFT calculations quantified the efficiency of ICT from the calculated charge-transfer distance (DCT) and amount of transferred charge (QCT). The antimicrobial activity was evaluated using broth microdilution method. 3D QSAR modeling was used to demonstrate the influence of substituents effect as well as molecule geometry on antimicrobial activity.

Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma

Purpose. Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. Methods. We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. Results. We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. Conclusions. These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results (AU)

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Differential BMI1, TWIST1, SNAI2 mRNA expression pattern correlation with malignancy type in a spectrum of common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and melanoma.

PURPOSE: Melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) can be used as a unique model to identify molecular mechanisms to distinguish rarely metastatic (BCC), often metastatic (SCC) and most metastatic (melanoma) cancer. It is known that epithelial-mesenchymal transition and stemness transcription factors (TWIST1, SNAI2/SLUG, and BMI1) play an important role in metastasis and their dysregulation has been demonstrated in metastatic cancers. We hypothesized that this spectrum of cutaneous cancers (BCC, SCC, and melanoma) would be a unique cancer model system to elucidate steps toward cancer invasion and metastasis. METHODS: We evaluated the mRNA expression level of BMI1, TWIST1, and SNAI2/SLUG and studied clinicopathological features in 170 skin cancers along with normal tissue samples. RESULTS: We demonstrate downregulation of BMI1 mRNA expression in BCC samples compared with controls (p = 0.0001), SCC (p = 0.001), and melanoma (p = 0.0001) samples. Downregulation of TWIST1 mRNA expression is seen in only BCC samples compared with controls (p = 0.031). High SNAI2 mRNA expression is represented in melanoma samples compared with controls (p = 0.022) and SCC samples (p = 0.031). High mRNA expression of TWIST1 is seen in patients with positive history of cancers. Extremely low mRNA expression of BMI1 is detected in patients with positive history of cancers other than skin cancer. CONCLUSIONS: These findings provide support for the hypothesis that the spectrum of cutaneous cancers could be better understood as a series of gene dosage-dependent entities with distinct molecular events. Oncogene-induced senescence, mechanism of which is still unclear, could be one explanation for these results.

Scolicidal effect of Allium sativum flowers on hydatid cyst protoscolices.

UNLABELLED: he s OBJECTIVE: Because there is no effective and safe drug therapy for hydatid cyst, finding of some new agents especially from herbal origin with a desired scolicidal effect attracts great attention for treatment and pre-surgical use to prevent the hydatid cyst recurrence. In this study, the scolicidal effect of ultrasonic methanol extract of Garlic (Allium sativum) flower is investigated. MATERIALS AND METHODS: Protoscolices were collected aseptically from sheep livers containing hydatid cyst and were exposed to different concentrations of extract for various exposure times. The viability of protoscolices was confirmed by 0.1% Eosin staining. RESULTS: The scolicidal activity of extract at a concentration of 50 mg ml-1 was 59, 76, 81 and 86% after 10, 30, 60, and 180 min of exposure respectively. The scolicidal effect at 100 mg ml-1 was 67, 78, 85 and 98% after various exposure times, respectively. The results of this study showed that the ultrasonic extract has high scolicidal activity and might be used as a natural scolicidal agent. CONCLUSIONS: Garlic flower extracts is a potent protoscolicid and might be used in hydatid cyst treatment and pre-surgery to prevent secondary cyst recurrence.

Antidepressant activities of Feijoa sellowiana fruit.

OBJECTIVE: Many pharmacological activities have been reported for Feijoa sellowiana. The aim of present study was to investigate antidepressant activities of its leaf and fruit extracts. MATERIALS AND METHODS: Antidepressant activities of methanolic extracts were evaluated by modified forced swimming test (FST) and tail suspension tests (TST) in male Swiss albino mice. RESULTS: Extracts showed signicant antidepressant activity in both models. They shortened remarkably the immobility period in both FST and TST and exhibited a dose dependent activity (p < 0.001). Leaf extract showed better activity than fruit extract. At 800 mg kg-1, it showed far better activity than imipramine in FST (p < 0.001). Both extracts showed significantly better activity than imipramine in increasing climbing time (p < 0.001). They showed significant activity in increasing in swimming time as compared to the control group (p < 0.001). CONCLUSIONS: Our studies indicate that Feijoa showed significant antidepressant activity. It produced dose dependent effect on both models. It seems this effect is mainly mediated by inhibition of reuptake of catecholamines. These results introduced these plants as easily accessible source of natural antidepressant.

Top-Down and Bottom-Up Approaches in 3D Printing Technologies for Drug Delivery Challenges.

3-Dimensional printing (3DP) constitutes a raft of technologies, based on different physical mechanisms, that generate a 3-dimensional physical object from a digital model. Because of its rapid fabrication and precise geometry, 3DP has gained a prominent focus in biomedical and nanobiomaterials research. Despite advancements in targeted, controlled, and pulsatile drug delivery, the achievement of site-specific and disease-responsive drug release and stringent control over in vivo biodistribution, are still some of the important, challenging areas for pharmaceutical research and development and existing drug delivery techniques. Microelectronic industries are capable of generating nano-/microdrug delivery devices at high throughputs with a highly precise control over design. Successful miniaturizations of micro-pumps with multireservoir architectures for delivery of pharmaceuticals developed by micro-electromechanical systems technology were more acceptable than implantable devices. Inkjet printing technologies, which dispense a precise amount of polymer ink solutions, find applications in controlled drug delivery. Bioelectronic products have revolutionized drug delivery technologies. Designing nanoparticles by nanoimprint lithography showed a controlled drug release pattern, biodistribution, and in vivo transport. This review highlights the "top-down" and "bottom-up" approaches of the most promising 3DP technologies and their broader applications in biomedical and therapeutic drug delivery, with critical assessment of its merits, demerits, and intellectual property rights challenges.

Efficacy of cleaning tablets for removable orthodontic appliances: an in vivo pilot study.

OBJECTIVES: The purpose of this study was to test the cleaning effect of three commercially available effervescent tablet products on acrylic resin surfaces compared to water as control medium. METHODS: A total of 20 volunteers were instructed to wear a vacuum-formed maxillary splint continuously for 96 h. Each splint incorporated four resin discs in the palate area. Each of these PMMA (polymethyl methacrylate) discs was split into two specimens which were analyzed upon removing the splint after the 4-day period. One specimen per disc was analyzed uncleaned and one after cleaning, using one of the investigated tablet products according to the manufacturer's recommendations or water as control medium. The outcomes of cleaning were evaluated with the modified ortho-phthaldialdehyde (OPA) method by determining the amounts of surface protein. RESULTS: Significant differences in relative (%) protein removal were noted between all three tablet products and water, and fittydent super® was significantly more effective in removing biofilm than Kukis®. No significant differences were observed between fittydent super® and NitrAdine® Ortho&Junior™ or NitrAdine® Ortho&Junior™ and Kukis®. CONCLUSION: The modified OPA method proved to be successful in examining protein-containing contaminations on the specimens, and the effervescent products tested were more effective than pure water in removing contaminants from orthodontic appliances. These results are, however, confined to soft plaque not older than 4 days.

In vitro-in vivo studies of the quantitative effect of calcium, multivitamins and milk on single dose ciprofloxacin bioavailability.

Ciprofloxacin, commonly used in India as an anti-microbial for prolonged use in chronic and non-specific indications, may affect the bioavailability of the drug. The drug prescribed is commonly taken with multivitamins, calcium and milk. A simple and reliable analytical methodology obtaining a correlation with in vivo urinary excretion studies using UV and HPLC and in vitro dissolution studies (IVIVC) has shown a significant increase in elimination rate of ciprofloxacin co-administered with multivitamins, calcium and milk. Appreciable IVIVC results proved that dissolution studies could serve as an alternative to in vivo bioavailability and also support bio-waivers.

An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related Products by RP-HPLC.

Impurity profiling has become an important phase of pharmaceutical research where both spectroscopic and chromatographic methods find applications. The analytical methodology needs to be very sensitive, specific, and precise which will separate and determine the impurity of interest at the 0.1% level. Current research reports a validated RP-HPLC method to detect and separate valacyclovir-related impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was found in the concentration range of 50-150 µg/mL. The mean recovery of impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp-E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the retention times of the impurities suggest the specificity of the method. The LOD values were 0.0024 µg/mL for Imp-E and 0.04 µg/mL for Imp-G and the LOQ values were obtained as 0.0082 µg/mL and 0.136 µg/mL, respectively, for the impurities. The S/N ratios in both cases were within the specification limits. Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances.

The Role of sentinel lymph-node biopsy in managing lip squamous cell carcinoma patients without clinical evidence of nodal metastasis.

AIM: Squamous cell carcinoma (SCC) of the lip is a common oral malignancy. Lymph node metastasis occurs lately in the natural history of the disease but it is associated with poor outcome. Sentinel lymph node biopsy (SLNB) is an option that determines the potentially affected lymph nodes especially in clinically negative-node patients. The study aims to determine the feasibility of SLNB as a reliable staging tool in N0 stage lip SCC patients. METHODS: Eighteen patients with N0 stage lip SCC were enrolled in the study. They were subjected to SLNB using the injection of the radiocolloid material and the Blue dye. The procedure was followed by bilateral supraomohyoid neck dissection in all patients. The pathological results of the harvested sentinel lymph nodes (SLNs) were compared with that of the dissection specimen in each patient. RESULTS: The patent blue dye could localize the SLN in 15/18 patients whilst the radioisotope scanning could successfully identify it in 17/18 patents. On average, 1.8 SLNs were harvested from each patient. Two of seventeen patients with identified SLNs (11.8%) have positive nodal metastases. One of them has two SLNs and the other has only one. No false negativity was reported in the study as all the excised SLNs reflected correctly the status of the lymph node basin. CONCLUSION: Sentinel lymphadenectomy is a safe and feasible procedure in managing neck of patients with node-negative lip SCC. It can accurately stage these patients. KEYWORDS: sentinel lymph node, lip, cancer.

Combination of sitaxentan and tadalafil for idiopathic pulmonary arterial hypertension following relapse on bosentan.

Sitaxentan, a highly-selective endothelin receptor antagonist (ETRA) and bosentan a non-selective ETRA are both approved for the treatment of idiopathic pulmonary arterial hypertension (iPAH). Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor used in the treatment of iPAH. Tadalafil is a long acting PDE-5 inhibitor largely unexplored for the treatment of iPAH. Following failure of monotherapy combination therapy with an ETRA and a PDE-5 inhibitor is often used, a frequently used combination being bosentan with sildenafil. We report our clinical experience in three patients with iPAH treated with a combination of sitaxentan and tadalafil, who previously discontinued bosentan. There was sustained symptomatic and haemodynamic improvement in all three patients treated with the combination. No adverse effect related to the combination treatment was noted. Sitaxentan and tadalafil, both being once a day treatments, can also possibly increase compliance.

The online Cough Clinic: developing guideline-based diagnosis and advice.

The aim of the present study was make chronic cough guidelines more practical and user friendly by developing an internet-based interactive diagnostic questionnaire for chronic cough. A prospective cohort study of chronic cough sufferers was conducted in the UK, following European Respiratory Society guidelines for the diagnosis and management of chronic cough. Depending on the response to 16 specific questions, the medical condition responsible for the patient's chronic cough was ascertained according to a predetermined diagnostic algorithm designed to differentiate the three common causes of chronic cough. Appropriate advice and treatment recommendations were then provided. 8,546 adults with chronic cough completed the Cough Clinic diagnostic questionnaire. 46.1% were suggested to have reflux, 38.7% asthma and 15.2% rhinitis. Participants found the website easy to use (94%), the advice helpful (73%) and that it helped them to communicate with their general practitioner better (60%), and 62% reported taking the recommended treatment. The Cough Clinic, an internet-based diagnostic site for chronic cough, had a large uptake by chronic cough sufferers in the UK. Almost half were diagnosed as having reflux as the probable cause of their chronic cough. Internet diagnosis by expert algorithm provides a novel mechanism for patients to access guideline-recommended therapies and enhances dialogue between patients and physicians.

Classification techniques with minimal labelling effort and application to medical reports.

There are a number of approaches to classify text documents. Here, we use Partially Supervised Classification (PSC) and argue that it is an effective and efficient approach for real-world problems. PSC uses a two-step strategy to cut down on the labelling effort. There are a number of methods that have been proposed for each step. An evaluation of various methods is conducted using real-world medical documents. The results show that using EM to build the classifier yields better results than SVM. We also experimentally show that careful selection of a subset of features to represent the documents can improve performance.

Anatomical study of lateral circumflex femoral arterial system for the anterolateral thigh flap.

AIM: The aim of this study was to increase anatomical knowledge of anterolateral thigh (ALT) flap, vascular system nourishing the flap. METHODS: Forty thighs of 20 male cadavers of Iranian origin were examined. A total of 189 perforators were identified, mainly as musculocutaneous perforators (89.9%), usually in the middle third of the thigh and arising from the descending branch of the lateral circumflex femoral artery (DLCFA). RESULTS: The mean length of superior and inferior pedicles was 9.2 cm and 4.23 cm, respectively. The caliber of the descending artery and one of its accompanying veins was averagely 2.8 and 3.0 mm, respectively. In 85% of the ALT flaps, the DLCFA connected with the lateral superior genicular artery (SGA). CONCLUSION: These findings suggest that the number of septocutaneous is less than that of the musculocutaneous perforators in the ALT region. This new consideration of ALT flap perforators makes it possible to elevate a vital flap in a greater number of cases, but it requires a longer and more difficult surgical technique to dissect perforators through the muscles. The distally based ALT flap is a good option for coverage of soft-tissue defects around the knee. Additionally, a potentially supercharged ALT flap may be applied in respect to the superior and inferior pedicles.

Kinetics of decolorization of an azo dye in UV alone and UV/H(2)O(2) processes.

The decolorization of C.I. Acid Red 27 (AR27), a monoazo anionic dye, was studied in the ultraviolet radiation (UV) alone and UV plus hydrogen peroxide (UV/H(2)O(2)) processes. The experimental results indicated that the kinetics of both oxidation processes fit well by pseudo-first order kinetics. The reaction rate was sensitive to the operational parameters and increased with increasing H(2)O(2) concentration and light intensity. The reaction orders of H(2)O(2) concentration and light intensity in both processes were obtained with linear regression method. A regression model was developed for pseudo-first order rate constant (k(ap,UV/H(2)O(2))) as a function of the Cconcentration and UV light intensity. (k(ap,UV/H(2)O(2)))=(2 x 10(-4)I(0.75)(0) + k(3)I(1.38)(0)[H(2)O(2)](n)(0))phi(AR27). As a result of two opposing effects of H(2)O(2) concentration at low and high concentrations, n has a value of 0.49 and -0.39 and k(3) has a value of 3 x 10(-4) and 0.1 for the regions of 0 mg l(-1) < [H(2)O(2)](0) < 650 mg l(-1) and 650 mg l(-1) < [H(2)O(2)](0) < 1500 mg l(-1)1, respectively. PhiAR27 is the initial dye concentration correlation index for developing of model for different initial concentrations of AR27. This rate expression can be used for predicting k(ap,UV/H(2)O(2) at different conditions in UV alone and UV/H2O2 processes. The results show that UV alone cannot be an efficient method for decolorization of AR27 in comparison with UV/H(2)O(2) process, therefore the first term of the model can be neglected.