Clinical Algorithm for the Management of Ipsilateral Proximal and Shaft Femur Fractures Using Single or Dual Implants.

Purpose of the study The current study had two goals: first, it compared the radiological and functional results of the ipsilateral shaft and proximal femur fractures treated by using two different methods, i.e., single implant vs dual implants. The second goal was to devise a clinical algorithm for guiding and managing such fractures. Methods This study was conducted in a level 1 trauma center and included 34 patients with concomitant ipsilateral fractures of the proximal femur and shaft of the femur. The patients were divided into two groups as per our clinical algorithm. Group I, comprising of 16 patients, were treated with a single implant like the proximal femoral nail (PFN) or proximal femoral nail antirotation (PFNA2). Group II of dual implants, comprising of 18 patients, were treated with two types of implants separately for proximal and shaft fracture. Results All patients were followed at monthly intervals up to six months, then at three monthly intervals up to one year, with a minimal follow-up of one year of every patient. On clinical evaluation by Friedman-Wyman criteria, in group I, seven patients had a fair outcome, eight patients had a good outcome, and one patient had a poor outcome, while in group II, eight patients had a fair outcome, nine patients had a good outcome, and one patient had a poor outcome. No patient developed non-union or avascular necrosis of the femoral head in any of the groups. Conclusion For concurrent ipsilateral diaphyseal and proximal femur fractures, both dual and single implants are equally effective alternatives if properly applied as per our clinical algorithm. Implant selection primarily depends on the pattern of injury, and our clinical algorithm can be a suitable guide for guiding the selection of implants.

Platelet-rich plasma as an effective biological therapy in early-stage knee osteoarthritis: One year follow up.

OBJECTIVE: PRP is produced by centrifugation of whole blood containing highly concentrated platelets, associated growth factors, and other bioactive agents which has been shown to provide some symptomatic relief in early knee osteoarthritis (OA). The principal objective of our study was to evaluate the effectiveness and safety of standardized intra-articular injection of autologous PRP in early osteoarthritis knee. METHODS: A total of 98 eligible symptomatic patients received two injections of standardized PRP 3 weeks apart. Clinical outcomes were evaluated using the VAS and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before treatment and at 6 weeks, 3 months, 6 months, and 1 year after treatment. Secondary objectives were safety (side effects), and the effect of PRP on the different grades of knee degeneration. RESULTS: There was a statistically significant improvement in mean VAS and WOMAC scores at 6 weeks, 3 months, 6 months, and slight loss of improvement at 1 year follow-up. There was also a correlation between the degree of degeneration and improvement in the mean scores. The decrease in mean pain score is more in grades 1 and 2 (early OA) than in grade 3. The intraarticular injection is safe, with no major complications. CONCLUSION: PRP is a safe and effective biological regenerative therapy for early OA Knees. It provides a significant clinical improvement in patients with some loss of improvement with time. More studies will be needed to confirm our findings.

Systematic First-Principles Configuration-Interaction Calculations of Linear Optical Absorption Spectra in Silicon Hydrides: Si2H2n (n = 1-3).

We have performed first-principles electron-correlated calculations employing large basis sets to optimize the geometries and to compute linear optical absorption spectra of various low-lying conformers of silicon hydrides: Si2H2n, n = 1, 2, 3. The geometry optimization for various isomers was carried out at the coupled-cluster singles-doubles-perturbative-triples [CCSD(T)] level of theory, while their excited states and absorption spectra were computed using a large-scale multireference singles-doubles configuration-interaction approach, which includes electron-correlation effects at a sophisticated level. Our calculated spectra are the first ones for Si2H2 and Si2H4 conformers, while for Si2H6, we obtain excellent agreement with the experimental measurements, suggesting that our computational approach is reliable. Our calculated absorption spectra exhibit a strong structure-property relationship, suggesting the possibility of identifying various conformers based on their optical absorption fingerprints. Furthermore, we have also performed geometry optimization for the selected optically excited states, providing insights into their character.

Excited States and Optical Properties of Hydrogen-Passivated Rectangular Graphenes: A Computational Study.

In this paper, we perform large-scale electron-correlated calculations of optoelectronic properties of rectangular graphene-like polycyclic aromatic hydrocarbon molecules. Theoretical methodology employed in this work is based upon Pariser-Parr-Pople (PPP) π-electron model Hamiltonian, which includes long-range electron-electron interactions. Electron-correlation effects were incorporated using multi-reference singles-doubles configurationinteraction (MRSDCI) method, and the ground and excited state wave functions thus obtained were employed to calculate the linear optical absorption spectra of these molecules, within the electric-dipole approximation. As far as the ground state wave functions of these molecules are concerned, we find that with the increasing size, they develop a strong diradical open-shell character. Our results on optical absorption spectra are in very good agreement with the available experimental results, outlining the importance of electron-correlation effects in accurate description of the excited states. In addition to the optical gap, spin gap of each molecule was also computed using the same methodology. Calculated spin gaps exhibit a decreasing trend with the increasing sizes of the molecules, suggesting that the infinite graphene has a vanishing spin gap.

Review of Simulation in Pediatrics: The Evolution of a Revolution.

Recent changes in medical education have highlighted the importance of experiential learning. Simulation is one model that has gained significant attention in the last decade and has been widely adopted as a training and assessment tool in medical education. Pediatric simulation has been utilized to teach various skills including resuscitation and trauma management, procedural skills, and team training. It is also a valuable tool for health care educators, as it allows learners to achieve competence without putting patients at risk. Recent literature demonstrates increased retention of knowledge and skills after simulation-based training. Further research is required to improve current simulation curriculums, develop validated assessment tools, and to demonstrate improved clinical outcomes after simulation-based training. We conducted an online search of original and review articles related to simulation and pediatric medical education and provide an overview of the role and utility of simulation in pediatrics. Key PointsSimulation in pediatrics has been widely accepted and adapted as a training and assessment tool in medical education.Simulation in pediatrics has been utilized to teach various skills including resuscitation and trauma management, procedural skills, and team training.Further research is required to improve current simulation curriculums, to develop validated assessment tools, and to demonstrate improved clinical outcomes after simulation-based training.

A Comparison of Functional Outcomes After Metallic and Bioabsorbable Interference Screw Fixations in Arthroscopic ACL Reconstructions.

INTRODUCTION: Anterior Cruciate Ligament (ACL) is as one of the most frequently injured ligaments in the modern contact sports scenario. Graft fixations can be achieved during anterior cruciate ligament (ACL) reconstructions by using either bioabsorbable screws or metal screws. The objective of this study was to compare the functional outcomes after bioabsorbable and metallic interference screw fixations in arthroscopic anterior cruciate ligament reconstructions done by using hamstring grafts. MATERIALS AND METHODS: This was a prospective, randomized study. Patients in Group 1 received bioabsorbable interference screws and patients in Group 2 received metallic interference screws. Arthroscopic assisted, anterior cruciate ligament reconstructions with the use of hamstring grafts which were fixed proximally with endobuttons and distally with bioabsorbable or metallic interference screws, were undertaken. Progress in functional outcomes was assessed by using Mann Whitney U- test. Functional outcomes in the two groups were compared by using independent t-test. OBSERVATION AND RESULTS: In each group, there were statistically significant improvements in functional outcomes over successive follow-ups, which were seen on basis on Mann-Whitney U-test. The comparison of functional outcomes between the two groups, done by using independent t-test, showed no statistically significant differences between the two groups at 3 months, 6 months and 1 year of follow-up. p-value <0.05 was considered to be significant in our study. CONCLUSION: In our prospective study of comparison of functional outcomes between bioabsorbable and metallic interference screws in arthroscopic anterior cruciate ligament reconstuctions, which were evaluated by using Tegner activity scale and Lysholm knee scoring scale for a period of 1 year, no statistically significant difference was found. However, further authentication is required by doing long term studies.

Orthodontic Microimplants Assisted Intrusion of Supra-erupted Maxillary Molar Enabling Osseointegrated Implant Supported Mandibular Prosthesis: Case Reports.

Loss of mandibular molars, when not replaced in time, are usually associated with overeruption of maxillary molars. To provide prosthetic replacement for missing lower posteriors, over erupted maxillary teeth have been intruded in past with great difficulty in adults with conventional orthodontics, along with associated problems of root resorption. Currently orthodontic microimplants provide stable intraoral anchorage, allow predictable maxillary molar intrusion enabling reestablishment of functional posterior occlusion with mandibular implant supported prosthesis, thereby reducing need for prosthetic crown reduction in maxillary arch. The added advantage of microimplant is it enables use of sectional appliance in area of concern instead of full arch bracketed appliance which an adult may not accept. The case reports demonstrates, overerupted maxillary molars were intruded using orthodontic microimplants to enable prosthetic rehabilitation of mandibular dentition by osseointegrated implant supported prosthesis. The second case report also demonstrates use of CBCT scan in planning and execution.

An easy method of attachment to an impacted canine.

BACKGROUND: Since many years, various bonding attachments have been used as a mode of traction for surgically exposed impacted teeth. It has always been a challenge to select an attachment considering predictability of the bonded attachment, mucogingival and periodontal conditions of the overlying tissues, and additional inventory requirement. METHODS: A 0.010-in. stainless steel ligature wire with eyelets at one end and spiral twisted at the other end was made and used as an attachment to guide surgically exposed impacted canine. RESULTS: Orthodontic guided eruption of an impacted canine of a 16-year-old patient using this simple attachment with 1-year follow-up illustrates adequate amount of attached gingiva. CONCLUSIONS: Ligature wire attachment is a simple inexpensive attachment that can be custom made without any need for additional inventory, besides being more comfortable to patients.

Fluoride in groundwater: toxicological exposure and remedies.

Fluoride is a chemical element that is found most frequently in groundwater and has become one of the most important toxicological environmental hazards globally. The occurrence of fluoride in groundwater is due to weathering and leaching of fluoride-bearing minerals from rocks and sediments. Fluoride when ingested in small quantities (<0.5 mg/L) is beneficial in promoting dental health by reducing dental caries, whereas higher concentrations (>1.5 mg/L) may cause fluorosis. It is estimated that about 200 million people, from among 25 nations the world over, may suffer from fluorosis and the causes have been ascribed to fluoride contamination in groundwater including India. High fluoride occurrence in groundwaters is expected from sodium bicarbonate-type water, which is calcium deficient. The alkalinity of water also helps in mobilizing fluoride from fluorite (CaF2). Fluoride exposure in humans is related to (1) fluoride concentration in drinking water, (2) duration of consumption, and (3) climate of the area. In hotter climates where water consumption is greater, exposure doses of fluoride need to be modified based on mean fluoride intake. Various cost-effective and simple procedures for water defluoridation techniques are already known, but the benefits of such techniques have not reached the rural affected population due to limitations. Therefore, there is a need to develop workable strategies to provide fluoride-safe drinking water to rural communities. The study investigated the geochemistry and occurrence of fluoride and its contamination in groundwater, human exposure, various adverse health effects, and possible remedial measures from fluoride toxicity effects.

Biochemical and physiological changes in Fenugreek (Trigonella foenum- graecum L.) leaves during storage under modified atmosphere packaging.

Fenugreek (Trigonella foenum-graecum L.), is a highly respiring leafy vegetable enriched with many nutrients and other active ingredients such as protein, vitamin C, niacin, potassium, alkaloids, lysine and L-tryptophan as well as steroidal saponins which are beneficial for human health. Both, quantitative and qualitative losses in this vegetable can be reduced by appropriate packaging and storage techniques which have not been applied hitherto. This study was taken upon to assess the potential of macro-perforated MAP for storage of fenugreek leaves. Packages (bag area: 0.075 m(2)) made from polypropylene (PP) film (Thickness: 35 µmm) were selected for the storage studies. The leaves were packaged in macro-perforated (2 perforations, perforation diameter: 0.3 mm each, with and without mustard seeds as natural absorbents) as well as in non-perforated PP film packages with and without mustard seeds. 10 g of mustard seeds were placed inside the packages to check water accumulation. The packaged samples were stored for 6 days at 75% relative humidity (RH) at 15°C to check water accumulation, if any. Different physiological and biochemical characteristics which generally affect the post-harvest life of the produce were monitored during the storage period. Results of the study suggested that among all the treatments, packaging of fenugreek in two perforation packets with mustard seeds resulted in best maintenance of chlorophyll, ascorbic acid, phenols and aroma. Water accumulation was also consoled due to mustard seeds after 6 days of storage.

Gene set enrichment analysis unveils the mechanism for the phosphodiesterase 4B control of glucocorticoid response in B-cell lymphoma.

PURPOSE: Resistance to glucocorticoid (GC) is a significant problem in the clinical management of lymphoid malignancies. Addressing this issue via a mechanistic understanding of relevant signaling pathways is more likely to yield positive outcomes. EXPERIMENTAL DESIGN: We used gene set enrichment analysis (GSEA), multiple genetic models of gain and loss of function in B-cell lymphoma cell lines, in vitro and in vivo, and primary patient samples to characterize a novel relationship between the cyclic AMP/phosphodiesterase 4B (cAMP/PDE4B), AKT/mTOR activities, and GC responses. RESULTS: Starting from the GSEA, we found that overexpression of the PDE4B in diffuse large B-cell lymphoma (DLBCL) impinge on the same genes/pathways that are abnormally active in GC-resistant tumors. We used genetically modified cell lines to show that PDE4B modulates cAMP inhibitory activities toward the AKT/mTOR pathway and defines GC resistance in DLBCL. In agreement with these data, pharmacologic inhibition of PDE4 in a xenograft model of human lymphoma unleashed cAMP effects, inhibited AKT, and restored GC sensitivity. Finally, we used primary DLBCL samples to confirm the clinical relevance and biomarker potential of AKT/mTOR regulation by PDE4B. CONCLUSIONS: Together, these data mechanistically elucidated how cAMP modulates GC responses in lymphocytes, defined AKT as the principal transducer of the growth inhibitory effects of cAMP in B cells, and allowed the formulation of genomics-guided clinical trials that test the ability of PDE4 inhibitors to restore GC sensitivity and improve the outcome of patients with B-cell malignancies.

Biochemical, microbiological and physiological changes in Jamun (Syzyium cumini L.) kept for long term storage under modified atmosphere packaging.

Jamun or Indian blackberry (Syzygium cumini L.) is a minor and highly perishable fruit enriched with flavonoids, essential oils, anthocyanins phenolic compounds and other antioxidants. The quantitative and qualitative losses in this seasonal fruit are tremendous and can be reduced by appropriate packaging and storage techniques which have not been applied hitherto. This study was undertaken to extend the shelf-life as well as to assess the biochemical, microbiological and physiological changes in jamun fruit under perforated and non-perforated modified atmosphere (MA) conditions. Fruits were stored under differential MA in macro-perforated (1 and 2 perforations, 0.3 mm dia. each) and non-perforated polypropylene (PP) film packages (Thickness: 35 µm, bag area: 0.036 m(2)) at 5 °C and 75% relative humidity (RH) for 23 days. Sachets containing white silica gel beads were placed inside all the packages to check water accumulation, if any. Different physiological, biochemical and microbiological characteristics which generally affect the post-harvest life of the produce were monitored during the storage period. Results of the study suggested most of the subjectively and objectively determined qualitative parameters to be retained satisfactorily under macro-perforated packaging treatments. Further, the microbiological analysis, surmised that the fruits could be stored for long term using packages with 1 macro-perforation.

Tendon xanthomas.

Tendon xanthomas usually present over the tendo Achilles and are associated with hyperlipidaemias. A brief review of xanthomas is presented.

The rGel/BLyS fusion toxin inhibits diffuse large B-cell lymphoma growth in vitro and in vivo.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL) and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-kappaB (NF-kappaB) are expected to be of therapeutic value in those tumors where NF-kappaB seems to play a unique survival role such as activated B-cell (ABC)-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-kappaB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-kappaB (IkappaB-alpha), inhibition of NF-kappaB DNA-binding activity, and accumulation of IkappaB-alpha. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-kappaB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05) in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-kappaB and are resistant to conventional chemotherapeutic regimens.

Targeting of SMAD5 links microRNA-155 to the TGF-beta pathway and lymphomagenesis.

The mechanisms by which microRNA dysfunction contributes to the pathogenesis of diffuse large B cell lymphoma (DLBCL) are not well established. The identification of the genes and pathways directly targeted by these small regulatory RNAs is a critical step to advance this field. Using unbiased genome-wide approaches in DLBCL, we discovered that the oncogenic microRNA-155 (miR-155) directly targets the bone morphogenetic protein (BMP)-responsive transcriptional factor SMAD5. Surprisingly, we found that in DLBCL a noncanonical signaling module linking TGF-beta1 signals to SMAD5 is also active. In agreement with these data, miR-155 overexpression rendered DLBCLs resistant to the growth-inhibitory effects of both TGF-beta1 and BMPs, via defective induction of p21 and impaired cell cycle arrest. In confirmatory experiments, RNAi-based SMAD5 knockdown recapitulated in vitro and in vivo the effects miR-155 overexpression. Furthermore, in primary DLBCLs, miR-155 overexpression inhibited SMAD5 expression and disrupted its activity, as defined by individual and global analyses of its transcriptional targets. Together, our data helped explain miR-155 function, highlighted a hitherto unappreciated role of SMAD5 in lymphoma biology, and defined a unique mechanism used by cancer cells to escape TGF-beta's growth-inhibitory effects.

Rational combined targeting of phosphodiesterase 4B and SYK in DLBCL.

Identification of rational therapeutic targets is an important strategy to improve the cure rate of diffuse large B-cell lymphoma (DLBCL). We previously showed that inhibition of the phosphodiesterase 4B (PDE4B) unleashes cyclic-AMP (cAMP) inhibitory effects toward the PI3K/AKT pathway and induces apoptosis. These data raised important considerations as to which upstream regulators mediate cAMP inhibition of PI3K/AKT, and how identifying this signaling route could be translated into clinical initiatives. We found that in normal and malignant B cells, cAMP potently inhibit the phosphorylation and activity of the tyrosine kinase SYK. Using genetic models of gain- and loss-of-function, we demonstrated the essential role for PDE4B in controlling these effects in DLBCL. Furthermore, we used a constitutively active SYK mutant to confirm its central role in transducing cAMP effects to PI3K/AKT. Importantly, given SYK credentials as a therapeutic target in B-cell tumors, we explored the role of PDE4B in these responses. In multiple DLBCL models, we found that genetically, hence specifically, inhibiting PDE4B expression significantly improved the efficacy of SYK inhibitors. Our data defined a hitherto unknown role for cAMP in negatively regulating SYK and indicate that combined inhibition of PDE4B and SYK should be actively pursued.

Copy number abnormalities, MYC activity, and the genetic fingerprint of normal B cells mechanistically define the microRNA profile of diffuse large B-cell lymphoma.

MicroRNA (miRNA) deregulation contributes to cancer pathogenesis. However, analysis of miRNAs in diffuse large B-cell lymphoma (DLBCL) has been hindered by a focus on cell lines, limited number of miRNAs examined, and lack of copy number data. To address these restrictions, we investigated genomewide miRNA expression and copy number data in 86 DLBCLs. Permutation analysis showed that 63 miRNAs were recurrently disrupted in DLBCL, including highly expressed oncomirs not previously linked to chromosomal abnormalities. Further, using training and validation tumor groups, we defined a collection of miRNAs that robustly segregates DLBCLs into 3 subsets, which are independent of the cell-of-origin classification, extent of T-cell infiltrate, and tumor site. Instead, these unique miRNA-driven DLBCL subgroups showed markedly different MYC transcriptional activity, which explained the dominance of miRNAs regulated by MYC in their expression signatures. In addition, analysis of miRNA expression patterns of normal B cells and integration of copy number and expression data showed that genomic abnormalities and the genetic fingerprint of nonmalignant cells also contribute to the miRNA profile of DLBCL. In conclusion, we created a comprehensive map of the miRNA genome in DLBCL and, in the process, have uncovered and mechanistically elucidated the basis for additional molecular heterogeneity in this tumor.

Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma.

MicroRNAs (miRNAs) attenuate gene expression by pairing to the 3'UTR of target transcripts inducing RNA cleavage or translational inhibition. Overexpression of microRNA-155 (miR-155), measured either at the primary (BIC gene) or mature transcript level, was recently described in diffuse large B-cell lymphomas (DLBCL). These studies have been limited in size, however, and have not attempted to link miR-155 expression to that of putative target genes. To start to address these issues, we examined a collection of 22 well-characterized DLBCL cell lines. The expression of miR-155 is heterogeneous in these cell lines and associates with NF-kappaB activity. We found that the expression of the primary miR-155 transcript reliably reflects that of the functional mature miR-155. Because many gene array platforms include probe sets for the primary miR-155 sequences, these findings allowed us to confidently examine large array-based expression datasets of primary DLBCLs in the context of miR-155 levels. Our investigation revealed that miR-155 expression segregates with specific molecular subgroups of DLBCL and it is highest in activated B-cell (ABC)-type lymphomas. These tumors are characterized by constitutive activation of NF-kappaB signals, which supports the data derived from our cell lines. More importantly, using supervised learning algorithms, we identified a robust gene signature driven by the differential expression of miR-155. These profiles contained several gene markers, including predicted targets, consistently downregulated in tumors expressing high levels of miR-155. Our data start to unveil the genome-wide effects of miR-155 expression in DLBCL and indicate the utility of this strategy in the identification and validation of miRNA target genes.