Three-dimensional volumetric evaluation of root resorption in maxillary anteriors following en-masse retraction with varying force vectors - a randomized control trial.

BACKGROUND: Root resorption in orthodontics is associated with direction and magnitude of force application as primary etiological factors. Well-controlled trials that utilize three-dimensional segmentation to detect volumetric changes in tooth structure are required to assess the quantitative nature of root resorption. OBJECTIVE: To assess the severity of root resorption (RR) during retraction of maxillary anteriors with three different force vectors (with and without skeletal anchorage) via cone-beam computed tomography (CBCT) superimpositions. TRIAL DESIGN: Three-arm parallel randomized clinical trial (RCT). MATERIALS AND METHODS: Forty-two (16 males, 26 females) patients, (17-28 years), in permanent dentition with bimaxillary protrusion were randomly allocated to three groups of 14 patients each using block randomization (1:1:1 ratio) and allocation concealment. En-masse anterior retraction post first premolar extractions was carried out with modified force vectors in the three groups based on anchorage type [Molar, Mini-implant and Infrazygomatic crest (IZC) bone screws]. Volumetric root loss and linear dimensional changes were blindly assessed on initial (T0) and final (T1, end of space closure) CBCT scans. Normality distribution of values was done using Shapiro-Wilk's test. ANOVA and Post-hoc Tukey HSD test were done to compare measurements between groups at significance levels (P < .05). RESULTS: Forty patients were analysed (14, 14, and 12 in three groups). Significant volumetric loss was noted in all groups. Central incisors demonstrated a significant reduction in IZC group (81.5 ± 21.1 mm3 ) compared to conventional (50.1 ± 26.5 mm3 ) and mini-implant groups (76.1 ± 27.6 mm3 ). Canines demonstrated a significant reduction in mini-implant group (108.9 ± 33.9 mm3 ) compared to conventional (68.8 ± 42.5 mm3 ) and IZC groups (103.1 ± 29.1 mm3 ). Regarding linear parameters, central incisors and canines revealed significant root length reduction in both skeletal anchorage groups. Lateral incisors showed no significant changes between groups. CONCLUSIONS: Intrusive force vectors generated during skeletally anchored retraction can predispose anteriors to an increased risk of resorption. Greater loss of root volume was noted in the centrals and canines when retracted with skeletal anchorage. LIMITATIONS: Small sample size and variations during CBCT acquisition. HARMS: Low-dose CBCT scans were taken at T0 and T1 treatment intervals.

Evaluation of scanning accuracy for two commercially available intraoral scanners in reproducing orthodontic bracket dimensions.

OBJECTIVE: The aim of this study was to compare the scanning accuracy of two different intra-oral scanners- MEDIT i500 and TRIOS 3 shape in reproducing orthodontic bracket dimensions. MATERIALS AND METHODS: This in vivo cross-sectional study comprised seven subjects with a full complement of permanent dentition without third molars. Complete arch scanning was carried out with two intraoral scanners, such as MEDIT i500, TRIOS 3 shape, after bonding with brackets. The control group consisted of bracket dimensions measured directly by using Vernier calipers before bonding. Bracket dimensions of three-dimensional (3D) images were measured by using OrthoAnalyzer software. The accuracy of intraoral scanning was investigated by comparing bracket dimensions among the three groups using One-way ANOVA and Post-Hoc Tukey HSD test, and by evaluating outcomes for each quadrant and an individual tooth in complete-arch scans. RESULTS: When comparing bracket dimensions of 3D images with manual measurements using a traditional Vernier caliper, MEDIT i500 showed no significant difference when compared to the control group (p>0.05) in full arch scanning as well as the quadrant and single tooth scans in complete arch scanning. TRIOS 3 shape showed a significant difference when compared to the control and MEDIT i500 group (p<0.05) for all parameters. CONCLUSIONS: MEDIT i500 showed higher accuracy and better reproduction of orthodontic bracket dimensions than TRIOS 3 shape.

Targeting a conserved pocket (n-octyl-ß-D-glucoside) on the dengue virus envelope protein by small bioactive molecule inhibitors.

Dengue virus enters the cell by receptor-mediated endocytosis followed by a viral envelope (DENVE) protein-mediated membrane fusion. A small detergent molecule n-octyl-ß-D-glucoside (ßOG) occupies the hydrophobic pocket which is located in the hinge region plays a major role in the rearrangement. It has been reported that mutations occurred in this binding pocket lead to the alterations of pH threshold for fusion. In addition to this event, the protonation of histidine residues present in the hydrophobic pocket would also impart the conformational change of the E protein evidence this pocket as a promising target. The present study identified novel cinnamic acid analogs as significant blockers of the hydrophobic pocket through molecular modeling studies against DENVE. A library of seventy-two analogs of cinnamic acid was undertaken for the discovery process of DENV inhibitors. A Molecular docking study was used to analyze the binding mechanism between these compounds and DENV followed by ADMET prediction. Binding energies were predicted by the MMGBSA study. The Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. The compounds CA and SCA derivatives have been tested against HSV-1 & 2 viruses. From the computational results, the compounds CA1, CA2, SCA 60, SCA 57, SCA 37, SCA 58, and SCA 14 exhibited favorable interaction energy. The compounds have in-vitro antiviral activity; the results clearly indicate that the compounds showed the activity against both the viruses (HSV-1 & HSV-2). Our study provides valuable information on the discovery of small molecules DENVE inhibitors.Communicated by Ramaswamy H. Sarma.

Plant Based Natural Products as Quorum Sensing Inhibitors in E. Coli: A Critical Review.

The existence of multidrug-resistant (MDR) E. coli (superbugs) is a global health issue confronting humans, livestock, food processing units, and pharmaceutical industries. The quorum sensing (QS) controlling ability of the E. coli to form biofilms has become one of the important reasons for the emergence of multidrug-resistant pathogens. Quorum signaling activation and formation of biofilm lead to the emergence of antimicrobial resistance of the pathogens increasing the therapy difficult for treating bacterial diseases. There is a crucial need, therefore, to reinforce newer therapeutic designs to overcome this resistance. As the infections caused by E. coli are attributed via the QSregulated biofilm formation, easing this system by QS inhibitors is a possible strategy for treating bacterial diseases. Plant based natural products have been reported to bind to QS receptors and interrupt the QS systems of pathogens by inhibiting biofilm formation and disrupting the formed biofilms, thus minimizing the chances to develop a resistance mechanism. The present report reviews critically the QS capability of E. coli to form biofilms leading to multidrug resistant pathogens and the investigations that have been carried out so far on plant acquired natural products as QS inhibitors.

Distinct Modulation of Wild-Type and Selective Gene Mutated Vitamin D Receptor by Essential Polyunsaturated Fatty Acids.

Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor's (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of evidence reports that selective long chain polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to transcriptional activation. We, therefore, hypothesize that selective PUFAs would modulate the dynamics and kinetics of VDRs, irrespective of the deficiency of vitamin-D. The spatial arrangements of the selected PUFAs in VDR active site were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR (PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.

Novel HDAC8 inhibitors: A multi-computational approach.

Abnormal HDAC function triggers irregular gene transcription that hampers the essential cellular activities leading to tumour activation and progression. HDAC inhibition has, therefore, been reported as a potential target for cancer treatment. In the present study, a sequential computational framework was carried out to discover newer lead compounds, namely HDAC8 inhibitors for cancer therapy. Pharmacophoric hypotheses were generated based on hydroxamic acid derivatives reported earlier for HDAC inhibition. The model AAADR.122, demonstrated statistical significance (r2 = 0.93, Q2 = 0.81) and proved robust on validation with a cross-validated correlation coefficient of 0.89. It was utilized to arrive at novel hits through a virtual screening workflow. The specificity of the process was enhanced further by analysing the crucial interactions of the ligands with key catalytic residues, achieved by induced fit docking (PDB ID: 1T64). On assessment, the filtered leads displayed optimal drug like features. Investigations using density functional theory (DFT) also facilitated the recognition of molecular spots in the leads beneficial for HDAC8 interaction. Overall, two leads were proposed for HDAC8 inhibition with potential anti-cancer activity.

Fabrication and Characterization of Hybrid Sponge for Healing of Infectious Burn Wound.

Burn is the fourth most common type of trauma worldwide. It often creates a third degree to fourth degree burn wound in the victims of accident. Hence a study was undertaken to fabricate hybrid sponge with biopolymers, silver nano particle and phytochemical constituents to accelerate wound healing. Antimicrobial susceptibility of wound isolates was evaluated by disc diffusion method. The silver nano particle was synthesized using the extracts of clove bud. The size of silver nano material ranged from 59-98 nm. The sponge was fabricated by freeze drying and its swelling property was evaluated. In the present study, 82.3% of the swelling of the sponge was observed within 20 minutes. The efficiency of sponge in healing infectious burn wound was assessed in rats. On the 20(th) day, 96.92% of wound was healed in sponge dressing and 58.2% in silverex treated rats. Thus, the study proved that the sponge accelerated the healing rate. Recent patents on the formulation of antimicrobial dressings and sponge have also been discussed in this paper.

Emergency surgical retrieval of a migrated left atrial appendage occlusion device.

Although the initial results of patients who have had left atrial appendage (LAA) occlusion devices implanted have been promising, there have been associated complications requiring surgical intervention. We report a case of a LAA occlusion device migrating into the left ventricle requiring cardiac surgery to retrieve it.

Lysine requirements of healthy adult Indian subjects, measured by an indicator amino acid balance technique.

BACKGROUND: In an earlier study, using a modification of the indicator amino acid oxidation approach, we concluded that the 1985 FAO/WHO/UNU-proposed lysine requirement of 12 mg x kg(-1) x d(-1) is likely inadequate to maintain body amino acid homeostasis in apparently healthy south Asian subjects and that our proposed requirement of 30 mg x kg(-1) x d(-1) is more appropriate. OBJECTIVE: We assessed the lysine requirement in a similar population by using 4 test lysine intakes (12, 20, 28, and 36 mg x kg(-1) x d(-1)) with an indicator amino acid balance approach. DESIGN: Sixteen healthy male Indians were studied during each of 2 randomly assigned 8-d L-amino acid diets that supplied either 12 and 28 or 20 and 36 mg lysine. At 1800 on day 8, a 24-h intravenous [(13)C]leucine tracer-infusion protocol was conducted to assess leucine oxidation and daily leucine balance at each lysine intake. RESULTS: Mean 24-h leucine oxidation rates decreased significantly (P = 0.005) across different lysine intakes and were 104.1, 97.8, 87.3, and 87.3 mg x kg(-1) x d(-1) at intakes of 12, 20, 28, and 36 mg x kg(-1) x d(-1), respectively; mean 24-h leucine balances were 3.3, 9.1, 19.7, and 20.7 mg x kg(-1) x d(-1), respectively (P = 0.015, mixed-model analysis of variance). Oxidation and balances differed significantly between the lower and higher lysine intakes but were not significantly different between the 12- and 20-mg and 28- and 36-mg test intakes. Two-phase regression analysis indicated a mean breakpoint at 29 mg lysine x kg(-1) x d(-1) in the relation between lysine intake and leucine oxidation or balance. CONCLUSION: We propose a mean lysine requirement of 30 mg x kg(-1) x d(-1) for healthy Indian adults, which is the same amount we proposed previously for Western populations.

Kinetics of L-[1-(13)C]leucine when ingested with free amino acids, unlabeled or intrinsically labeled casein.

In two groups of five adults, each adapted to two different dietary regimens for 6 days, the metabolic fate of dietary [1-(13)C]leucine was examined when ingested either together with a mixture of free amino acids simulating casein (extrinsically labeled; condition A), along with the intact casein (extrinsically labeled; condition B), or bound to casein (intrinsically labeled; condition C). Fed state leucine oxidation (Ox), nonoxidative leucine disposal (NOLD), protein breakdown, and splanchnic uptake have been compared using an 8-h oral [1-(13)C]leucine and intravenous [(2)H(3)]leucine tracer protocol while giving eight equal hourly mixed meals. Lower leucine Ox, increased NOLD, and net protein synthesis were found with condition C compared with condition A (19.3 vs. 24.9; 77 vs. 55.8; 18.9 vs. 12.3 micromol. kg(-1). 30 min(-1); P < 0.05). Ox and NOLD did not differ between conditions B and C. Splanchnic leucine uptake calculated from [1-(13)C]- and [(2)H(3)]leucine plasma enrichments was between 24 and 35%. These findings indicate that the form in which leucine is consumed affects its immediate metabolic fate and retention by the body; the implications of these findings for the tracer balance technique and estimation of amino acid requirements are discussed.

Surgical management of right atrial myxomas. A 15 year experience with review of the literature.

BACKGROUND: A retrospective study to evaluate the clinical symptoms, signs, investigations, surgical technique and follow-up of an uncommon cardiac tumour. METHODS: Experimental design and setting: this retrospective study was carried out in a tertiary care hospital in South India on patients treated from 1981 to 1996. Duration of follow-up has been for a maximum period of 9.5 years. PARTICIPANTS: all patients who were diagnosed to have right atrial myxoma were included in this study. There were seven patients (4 males, 3 females) with ages ranging from 16 to 52 years. INTERVENTIONS: six of these patients underwent complete excision. One patient who presented with SVC obstruction had locally invasive tumour and only a biopsy was done. In order to reduce the risk of intraoperative pulmonary embolism in the last two cases, we crossclamped the pulmonary artery as soon as cardiopulmonary bypass was initiated. RESULTS: There was one postoperative death due to refractory right ventricular failure (14.3%). Four patients have been followed-up for a mean of 40.7 months. All of them are free of recurrence and most of them are asymptomatic. CONCLUSIONS: Right atrial myxoma is a rare usually benign cardiac tumor whose definitive diagnosis is made on the basis of 2D echocardiography. The crucial aspects of surgery are measures for prevention of intraoperative embolism, en-bloc excision of the tumour with a wide cuff of normal tissue and inspection of all four chambers in order to avoid missing tumour emboli or an occasional multicentric lesion. Patients with myxomatous emboli into the pulmonary artery require simultaneous pulmonary embolectomy.

Twenty-four-hour intravenous and oral tracer studies with L-[1-13C]-2-aminoadipic acid and L-[1-13C]lysine as tracers at generous nitrogen and lysine intakes in healthy adults.

BACKGROUND: This is a continuation of investigations of the relations between amino acid kinetics and amino acid dietary requirements in healthy adults. OBJECTIVE: The aim was to investigate the 24-h pattern and rate of the metabolism of an L-[1-13C]-2-aminoadipic acid ([13C]AAA) tracer and of whole-body L-[1-13C]lysine ([13C]lysine) oxidation and balance in healthy, young adults receiving a generous intake of lysine. DESIGN: Thirteen healthy adults were given an adequate, L-amino acid-based diet supplying 77 mg lysine x kg(-1) x d(-1) for 6 d before the tracer studies. Two subjects received [13C]AAA intravenously and 2 received it orally; 3 subjects received [13C]lysine intravenously and 6 received it orally. We measured 13CO2 output, plasma [13C]AAA and [13C]lysine enrichment, and urinary [13C]AAA. RESULTS: [13C]AAA oxidation was estimated to be higher after the orally administered than after the intravenously administer tracer; plasma [13C]AAA was similar to urinary [13C]AAA. Whole-body lysine oxidation showed a rhythm that was induced by meal feeding. The intravenous [13C]lysine tracer gave mean estimates of lysine balances (lysine intake minus oxidation) that apparently were too low (-15.7 mg x kg(-1) x d(-1)) or too high (16.6 mg x kg(-1) x d(-1), P < 0.05 from zero balance) on the basis of urinary [13C]AAA or plasma [13C]lysine estimates of oxidation, respectively. For the orally administered tracer and plasma [13C]lysine enrichment, the mean balance was slightly positive (8.7 mg x kg(-1) x d(-1), P < 0.05 from zero). CONCLUSIONS: Use of urinary [13C]AAA as an index of the enrichment of the precursor pool did not appear to significantly improve the estimate of the fasting and feeding components of daily lysine balance. For estimates of daily, whole-body lysine oxidation, we propose use of plasma [13C]lysine with a 24-h, orally administered tracer protocol.

Moderate exercise at energy balance does not affect 24-h leucine oxidation or nitrogen retention in healthy men.

Short-term metabolic experiments have revealed that physical exercise increases the oxidation of leucine, which has been interpreted to indicate an increased requirement for dietary protein in physically active subjects. Because it may be inaccurate to extrapolate measurements of amino acid oxidation made over a few hours to the entire day, we have carried out a continuous 24-h intravenous [1-13C]leucine/[15N]urea tracer study in eight healthy adult men. Their diet supplied 1 g protein.kg-1.day-1, and exercise (mean maximal O2 consumption 46%) was for 90 min during the 12-h fast and 12-h fed periods of the day. Subjects were adapted to the diet and exercise regimen for 6 days. Then, on day 7, they were dressed in the University of Uppsala energy metabolic unit's direct calorimeter suit, were connected to an open-hood indirect calorimeter, and received the tracers. Exercise increased leucine oxidation by approximately 50 and 30% over preexercise rates for fast and fed periods, respectively. This increase amounted to approximately 4-7% of daily leucine oxidation. Subjects remained in body leucine equilibrium (balance -4.6 +/- 10.5 mg.kg-1.day-1; -3.6 +/- 8.3% of intake; P = not significant from zero balance). Therefore, moderate exercise did not cause a significant deterioration in leucine homeostasis at a protein intake of 1 g.kg-1.day-1. These findings underscore the importance of carrying out precise, continuous, 24-h measurements of whole body leucine kinetics; this model should be of value in studies concerning the quantitative interactions among physical exercise, energy/protein metabolism, and diet in humans.

Multicentric reticulohistiocytosis masquerading as lepromatous leprosy.

A 23-year old male presented for evaluation of skin coloured, non-scaly, asymptomatic papulonodules of sizes varying from 0.5 cm to 2 cm of 4 years duration distributed all over the body including the ears. The plaques present on the face gave the appearance of a 'leonine facies'. Clinically mistaken for lepromatous leprosy in reaction the patient was treated with antileprosy and anti-inflammatory drugs in 3 other centres for months with no improvement. Systemic involvement included painful swelling of both knee joints, pericardial effusion episcleritis and enlarged liver. Negative slit smears for AFB from the nodules repeatedly and the histology of one on the skin nodules clinched the diagnosis of multicentric reticulohistiocytosis. The case is reported not only for its rarity, and varying clinical lesions simulating lepromatous leprosy but also to alert the leprologists to avert unreasonable delay in diagnosis.

Cutaneous Metastases in Bronchogenic Carcinoma (five Case Reports).

Five, cases of cutaneous metastases from bronchogenic car are reported for their rartty and clinical interest. In 3 cases the histopathology showed an adenocarcinomatous deposit; in the remaining 2 cases, the histopathology showed a squamous cell carcinomatous deposit. Only 1 of the 5 patients was a female.