Effect of Yoga Lifestyle in Patients with Heart Failure: A Randomized Control Trial.

Background: In spite of significant advances in the management of heart failure (HF), morbidity and mortality remain high. Therefore, there is a need for additional strategies. We did a randomized clinical trial to study effect of yoga in patients with HF in terms of quality of life (QOL), left ventricle ejection fraction (LVEF), C-reactive protein (CRP), and NTproBNP. Materials and Methods: 60 patients with stable HF New York Heart Association Class II with LVEF 30%-40% were randomized into control group (CG) and yoga group (YG). CG received the guideline-based therapy and YG in addition practiced the yoga, one hour daily for 3 months. All patients were assessed for QOL, CRP, NTProBNP, and LVEF at baseline and after 3 months. Results: A significant difference was observed in all four parameters in the YG as compared to the CG (P < 0.01) after 12 weeks. QOL as assessed by Minnesota living with heart failure questionnaire score improved significantly in YG as compared to CG (10 V/s 14, P < 0.001). There was a significant improvement within YG in terms of LVEF (33.4-36.8, P = 0.001), and the percentage change in LVEF was significant between the groups (10% V/s 5%, P = 0.001). NTproBNP also significantly reduced by 69.8% from 755 to 220 Pmol/l in YG as compared to 39.3% in CG (679-406 Pmol/l). CRP decreased by 49.3% (5.36-2.73 mg/L) in YG and 35.8% (5.39-3.45 mg/L) in CG. Conclusion: The result of this pilot study suggests that addition of yoga to guideline-based therapy for HF patients significantly improves QOL, LVEF, and NTProBNP and reduces CRP level. Larger studies are needed to confirm these findings.

Arhgef5 Binds α-Dystrobrevin 1 and Regulates Neuromuscular Junction Integrity.

The neuromuscular junctions (NMJs) connect muscle fibers with motor neurons and enable the coordinated contraction of skeletal muscles. The dystrophin-associated glycoprotein complex (DGC) is an essential component of the postsynaptic machinery of the NMJ and is important for the maintenance of NMJ structural integrity. To identify novel proteins that are important for NMJ organization, we performed a mass spectrometry-based screen for interactors of α-dystrobrevin 1 (aDB1), one of the components of the DGC. The guanidine nucleotide exchange factor (GEF) Arhgef5 was found to be one of the aDB1 binding partners that is recruited to Tyr-713 in a phospho-dependent manner. We show here that Arhgef5 localizes to the NMJ and that its genetic depletion in the muscle causes the fragmentation of the synapses in conditional knockout mice. Arhgef5 loss in vivo is associated with a reduction in the levels of active GTP-bound RhoA and Cdc42 GTPases, highlighting the importance of actin dynamics regulation for the maintenance of NMJ integrity.

Coronectomies: assessment and treatment planning.

Coronectomy procedures are widely carried out in secondary care, involving the removal of the dental crown, while retaining the roots in situ. This paper defines and explains the rationale behind coronectomy. It also seeks to review the indications for referral of wisdom teeth, and how to identify high-risk wisdom teeth radiographically using two- and three-dimensional imaging. Using this information, this article aims to provide the practitioner with information on short- and long-term management of high-risk wisdom teeth and discusses coronectomy versus extraction. It also discusses the complications of coronectomy and the importance of adequate consent.

The importance of communication in the construction of partial dentures.

Removable partial dentures (RPDs) are still a very important treatment modality in general dentistry to replace missing teeth. With the increase in popularity of implants, RPDs are sometimes seen as an 'old-fashioned' treatment option and if not carefully designed can be damaging to oral tissue and aesthetically less favourable. However, there is still a significantly large cohort of patients for whom RPDs are the best option for replacement of teeth either due to a failing dentition, inappropriate anatomy or financial considerations. This article explores the importance of effective three way communication with the patient, the laboratory and the dental nurse to support the provision of reliable and predictable prosthodontic outcomes.

VEGF may contribute to macrophage recruitment and M2 polarization in the decidua.

It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1. In situ hybridization was used for assessment of local VEGF expression and immunohistochemistry was used for identification and localization of CD68-positive endometrial macrophages. Macrophage migration in culture was assessed using a transwell migration assay, and the various M1/M2 phenotypic markers and VEGF expression were assessed using quantitative real-time PCR (qRT-PCR). We found dramatic increases in both VEGF levels and macrophage numbers in the decidua during early pregnancy compared to the secretory phase endometrium (non-pregnant), with a significant increase in M2 macrophage markers, suggesting that M2 is the predominant macrophage phenotype in the decidua. However, decidual samples from preeclamptic pregnancies showed a significant shift in macrophage phenotype markers, with upregulation of M1 and downregulation of M2 markers. In THP1 cultures, VEGF treatment significantly enhanced macrophage migration and induced M1 macrophages to shift to an M2 phenotype. Moreover, treatment with conditioned media from decidualized ESCs induced changes in macrophage migration and polarization similar to that of VEGF treatment. These effects were abrogated by the addition of a potent VEGF inhibitor. Together these results suggest that decidual VEGF plays a significant role in macrophage recruitment and M2 polarization, and that inhibition of VEGF signaling may contribute to the shift in macrophage polarity observed in different pregnancy disorders, including preeclampsia.

A Small Insulinomimetic Molecule Also Improves Insulin Sensitivity in Diabetic Mice.

Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic ß-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1.17µM) thus activating insulin receptor tyrosine kinase and its downstream signaling molecules resulting increased uptake of [14C] 2 Deoxy-glucose. Oral administration of dmp to streptozotocin treated BALB/c mice lowers blood glucose level and markedly stimulates glucose and fatty acid uptake by skeletal muscle and adipose tissue respectively. In db/db mice, it greatly improves insulin sensitivity through excess expression of PPARγ and its target genes i.e. adiponectin, CD36 and aP2. Study on the underlying mechanism demonstrated that excess expression of Wnt3a decreased PPARγ whereas dmp suppression of Wnt3a gene increased PPARγ expression which subsequently augmented adiponectin. Increased production of adiponectin in db/db mice due to dmp effected lowering of circulatory TG and FFA levels, activates AMPK in skeletal muscle and this stimulates mitochondrial biogenesis and bioenergetics. Decrease of lipid load along with increased mitochondrial activity greatly improves energy homeostasis which has been found to be correlated with the increased insulin sensitivity. The results obtained with dmp, therefore, strongly indicate that dmp could be a potential candidate for insulin replacement therapy.

The risks and benefits of social media in dental foundation training.

The use of social media has greatly expanded in the last decade, with widespread use of smartphones, the internet, and other multimedia to enhance learning. There is evidence to suggest that social media has a place in healthcare education, but there is limited research to suggest the effectiveness or use of it in dental foundation training. This paper discusses the risks and benefits of social media and suggests that a better understanding of social media and its role in the development and practice of newly qualified dental professionals could benefit both trainees and trainers.

The mechanical strength of side-to-side tendon repair with mismatched tendon size and shape.

Tendon transfers frequently require coaptation of two mismatched tendons. In this cadaver study, ultimate load, stiffness, and Young's modulus were measured in tendon-to-tendon attachments with mismatched donor and recipient tendons, using pronator teres (PT) to extensor carpi radialis brevis (ECRB) and flexor carpi ulnaris (FCU) to extensor digitorum communis (EDC). FCU-to-EDC attachments failed at higher loads than PT-to-ECRB attachments, but they had similar modulus and stiffness values. Ultimate tensile strength of the tendon attachments exceeded the maximum predicted contraction force of any of the transferred muscles, with safety factors of four-fold for the FCU-to-EDC and two-fold for the PT-to-ECRB transfers. This implies that size and shape mismatches should not be contraindications to tendon attachment in transfers. The strength safety factors suggest that postoperative immobilization of these transfers is unnecessary.

Povidone-iodine as a corrosion inhibitor towards a low modulus beta Ti-45Nb implant alloy in a simulated body fluid.

Povidone-iodine and various bactericidal agents used in dental procedures may affect the corrosion response of an implant/prosthesis in the oral environment. The effect of various concentrations of povidone-iodine (PI) on the corrosion behavior of a low modulus beta titanium alloy, Ti-45Nb, has been investigated in normal saline solution. The open circuit potential, electrochemical impedance spectroscopy and potentiodynamic polarization measurements have been used to assess the electrochemical response of the alloy surface on PI addition so as to effectively predict the prosthetic treatment outcome. As the concentration of PI is increased, the corrosion rate decreases, suggested by decreased R(p) values. Povidone-iodine acts as an anodic inhibitor by adsorbing on the anodic sites of the alloy. Addition of PI to a simulated body fluid such as normal saline leads to a decrease in corrosion rate of Ti-45Nb alloy.

Photodynamic therapy: a targeted therapy in periodontics.

The oral cavity is colonized by a large number and highly diversified communities of micro-organisms. Bacterial biofilm present on tooth or root surface is a major cause of gingivitis and periodontitis. Chemical antimicrobial agents are widely used in prophylactic and therapeutic regimens for dental plaque related diseases, which are among the most common human infections. As these agents are difficult to maintain at therapeutic concentrations in the oral cavity and can be rendered ineffective by resistance development in target organisms, there is a need for an alternative antimicrobial approach. A novel approach, photodynamic therapy (PDT), could be a solution to these problems. Lethal photosensitization of many bacteria, both Gram positive and Gram negative was found in many studies. The advantage of this new approach includes rapid bacterial elimination, minimal chance of resistance development and safety of adjacent host tissue and normal microflora. Thus, the available knowledge of photodynamic therapy should encourage a more clinically oriented application of this technique.

Translocation t(2;3)(p15-23;q26-27) in myeloid malignancies: report of 21 new cases, clinical, cytogenetic and molecular genetic features.

Chromosomal rearrangements involving 3q26 either due to inversion or translocation with various partner chromosomes are a recurrent finding in malignant myeloid disorders. Typically, these chromosome aberrations contribute to ectopic expression of or to the formation of fusion genes involving the EVI1 proto-oncogene. Chromosomal translocations involving the short arm of chromosome 2 (p15-p23) and the distal part of the long arm of chromosome 3 (q26-q27) are a rare but recurrent finding in patients with myeloid malignancies, and are assumed to be part of this spectrum of disorders. Thus far, however, these translocations have been poorly studied. Here, we present 21 new cases with myelodysplasia, acute myeloid leukemia or CML in blast crisis, which upon karyotyping showed the presence of a t(2;3). Furthermore, an extensive literature review disclosed 29 additional cases. Morphological, clinical and cytogenetic assessment revealed the typical hallmarks of 3q26/EVI1 rearrangements, that is, trilineage dysplasia and dysmegakaryopoiesis, poor prognosis and additional monosomy 7. Molecular cytogenetic analysis and PCR in selected samples indicated that in most cases the translocation indeed targets the EVI1 locus. Mapping of the chromosome 2 breakpoints confirmed the initially suspected cytogenetic breakpoint heterogeneity at the 2p arm.

A novel chromosomal translocation t(3;5)(q12;p15.3) and loss of heterozygosity on chromosome 22 in a multifocal follicular variant of papillary thyroid carcinoma presenting with skin metastases.

Classic genetic rearrangements in papillary carcinoma of the thyroid involve the RET- or TRK proto-oncogenes. We report a novel chromosomal translocation t(3;5)(q12;p15.3), confirmed by fluorescence in situ hybridization, in a multifocal follicular variant of a papillary carcinoma of the thyroid in a 79-year-old woman, with skin metastases as a presenting symptom. Three years earlier, another cutaneous metastasis on her scalp was misdiagnosed as hidradenoma. Four tumour foci were recognized in the thyroid, two with a follicular variant of papillary carcinoma. To detect loss of heterozygosity, 14 chromosomes were investigated with 59 microsatellite markers. A clonal relationship was detected between the two foci of tumour in the thyroid gland containing follicular variant of papillary carcinoma and one of the skin lesions tested, all demonstrating loss of heterozygosity (LOH) in the same region of chromosome 22. Based on earlier reports, the low rate of LOH detected is in agreement with the diagnosis papillary carcinoma of the thyroid. Whole body scintigraphy performed after ablative therapy with radioiodine revealed multiple metastases in the lungs and skeleton. After repeated radioiodine therapy, thyroglobulin under thyroxine suppression became undetectable and post-therapeutic scintigraphy revealed important regression of metastases.

Monitoring of engraftment and progression of acute lymphoblastic leukemia in individual NOD/SCID mice.

OBJECTIVE: The aim of this study was to develop an animal model for human acute lymphoblastic leukemia (ALL) in which the kinetics and characteristics of leukemia can be sequentially monitored in individual mice. MATERIALS AND METHODS: NOD/SCID mice were inoculated intravenously with primary ALL. Progression of leukemia was monitored throughout the development of disease by determination of absolute leukemic cell counts (LCC) in peripheral blood. RESULTS: LCC as low as 10(4) leukemic cells/mL blood could be detected. ALL cells from 5 of 5 patients engrafted, and after identification of the first leukemic cells in peripheral blood, LCC increased exponentially. Leukemic cells showed specificity of homing to spleen and bone marrow, and LCC strongly correlated with the level of leukemic engraftment in these organs throughout disease progression, demonstrating that LCC are representative for overall leukemic burden. Cytogenetic analysis of leukemic cells recovered after six successive in vivo transfers revealed no major karyotypic changes as compared to primary cells, and selection of the dominant clones was observed. This selection process was reflected by an increase in the rate of leukemic progression as compared to the first inoculation, demonstrating the accuracy with which kinetics of leukemic progression can be studied by determination of LCC. CONCLUSIONS: This model is suitable for detailed studies of kinetics and characteristics of ALL in vivo, and it may be useful for monitoring effects of novel therapeutic regimens.

Chromosome 9 alterations and trisomy 22 in central chondrosarcoma: a cytogenetic and DNA flow cytometric analysis of chondrosarcoma subtypes.

Chondrosarcomas are malignant cartilaginous tumors. Most are located in the medullar cavity (central chondrosarcoma), and a minority develop in a preexisting osteochondroma (peripheral chondrosarcoma). The authors present karyotypes for 37 central, peripheral, juxtacortical, and dedifferentiated chondrosarcomas. Using loss of heterozygosity (LOH) analysis and DNA flow cytometry, the authors previously showed that central and peripheral chondrosarcomas probably evolve by different genetic mechanisms. Peripheral chondrosarcoma is characterized by genetic instability, as was previously shown by a high percentage of LOH and a broad range in DNA ploidy. The authors now show that all peripheral chondrosarcomas tested are aneuploid, combined with many nonspecific chromosomal aberrations. Two juxtacortical chondrosarcomas showed normal chromosome numbers combined with limited structural alterations, substantiating that juxtacortical and peripheral chondrosarcomas are two clinicopathologically different entities with a different genetic background. Central chondrosarcomas were previously found to be peridiploid with limited LOH, most frequent at 9p21. In the current study, chromosome 9 was involved in five of seven central chondrosarcomas compared with only one of four peripheral chondrosarcomas. Three central tumors showed involvement of the 9pl2-22 region, suggesting an important role for chromosome 9 in the oncogenesis of central chondrosarcoma. Moreover, trisomy 22 was found in four central chondrosarcomas only.

The generation of dendritic-like cells with increased allostimulatory function from acute myeloid leukemia cells of various FAB subclasses.

To increase the immunogenicity of leukemic cells, attempts were made to generate dendritic-like antigen presenting cells (DC) from AML blasts from 14 patients with AML FAB classifications M0-M5. Leukemic cells were cultured in the presence or absence of various cytokines including GM-CSF, SCF, TNF-alpha, IL-4, and gamma-interferon. After various intervals recovery of viable cells was measured and expression of CD80, CD86, CD40, CD54, CD58, and CD11a was analyzed by flow cytometry. Functionally, DC derived from six AML samples were tested in a mixed lymphocyte response (MLR) using HLA-DR mismatched donor T cells as responder cells. Proliferation (5/14) or increased survival (7/14) of AML cells was observed in the presence of GM-CSF, SCF, and TNF-alpha. Only in the AML M2, M3, and M4 FAB subtypes proliferation was found. GM-CSF, SCF, and TNF-alpha induced morphologic changes typical for DC and increased the expression of costimulatory and adhesion molecules. No significant effect of IL-4 or gamma-interferon was observed. The day of maximal expression of these molecules varied. In cases with minor upregulation of CD80 or CD86, no further stimulation using CD40-L activation was observed. In the three cases tested, the DC-like cells retained the chromosomal abnormalities present in the original AML cells. In five out of six cases tested an increase in allostimulatory capacity was found at the day of maximal expression of costimulatory and adhesion molecules. In two patients a decrease in stimulatory capacity was found at day 7 compared with day 2 correlating with a decreased expression of these molecules. In conclusion, AML cells can be induced to increase their stimulatory capacity by upregulating costimulatory and adhesion molecules.

A DNA probe combination for improved detection of MLL/11q23 breakpoints by double-color interphase-FISH in acute leukemias.

Reciprocal translocations involving the MLL gene on chromosome band 11q23 have been observed in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). In AML, identification of MLL breakpoints is an important prognostic factor. Breakpoints are clustered in an 8 kb DNA fragment (bcr) and can be detected by Southern blotting or fluorescence in situ hybridization (FISH) analysis. Our objective in this study was to design a DNA probe set that enables optimal detection of MLL rearrangements using interphase FISH. Two PAC clones, 217A21 and 167K13, spanning the MLL gene with a minimal overlap in the bcr were isolated and labeled. Twenty-seven AML/ALL patients with cytogenetic 11q23 abnormalities, seven AML/ALL patients without 11q23 abnormalities but MLL rearrangement by Southern blotting, and eight healthy donors were analyzed by FISH. We compared this double-color FISH analysis with FISH using a YAC clone (yB22B2) and with Southern blotting. The PAC probe combination detects an MLL breakpoint in all cases with MLL rearrangement detected by Southern blotting except for cases with a partial tandem duplication detected by reverse transcriptase-polymerase chain reaction (RT-PCR). FISH using the PAC probes also detected MLL breakpoints in four cases with MLL deletions telomeric to the breakpoint that could not be detected by the single probe yB22B2. This new probe set provides a reliable and rapid assay for the diagnosis of AML and ALL patients with MLL/11q23 breakpoints.

Translocations (X;10)(p22;q24) and (1;10)(q21;q11) in a follicular adenoma of the thyroid without apparent involvement of the RET protooncogene.

We report here the cytogenetic analysis of a follicular adenoma of the thyroid which revealed an abnormal clone with a t(X;10)(p22;q24) and a t(1;10)(q21;q11) together with normal cells. Fluorescence in situ hybridization (FISH) with YACs 273E3 and 344H4, which are located on 10q11.2 and are specific for the RET protooncogene, showed no abnormalities. It would therefore appear that this gene is not involved in the particular tumor, as has been reported in a number of papillary thyroid carcinomas. Several chromosomal aberrations have been suggested as been specific for follicular thyroid adenoma. However, until now, only a few such cases have been reported which involve structural abnormalities of chromosomes 10q11.2 and 10q24. We believe this to be the first report of a follicular thyroid adenoma with a t(X;10)and a t(1;10).

Ring chromosome 4 as the sole cytogenetic anomaly in a chondroblastoma: a case report and review of the literature.

Chromosome analysis of a chondroblastoma of the right distal femur in a 31-year-old male patient revealed a ring chromosome 4 in approximately one-third of the analyzed cells. The remaining cells had a normal karyotype. These findings were subsequently confirmed by fluorescence in situ hybridization (FISH) with a chromosome-4-specific library. FISH with cosmids pC847.351 (4p16.3) and cT171 (4q35) revealed that fewer than 300 kilobase pairs (kbp) are deleted. To our knowledge, ring chromosome 4 has never been reported in this type of neoplasm. There are, however, several reports of chondroblastoma with other chromosome abnormalities, but the relation of these anomalies to this tumor specifically is unclear. In this report, we also provide a review of the literature concerning cytogenetic studies in chondroblastoma. The possible significance of ring chromosome 4 in this type of tumor is discussed.

Prenatal and postnatal investigation of a case with Miller-Dieker syndrome due to a familial cryptic translocation t(17;20) (p13.3;q13.3) detected by fluorescence in situ hybridization.

We present here a case report of a fetus with a kidney anomaly and dilated occipital horns, detected initially by echoscopy at 29 weeks' amenorrhoea. After 31 weeks of gestation, the proband was born with clinical symptoms of Miller-Dieker syndrome. This was subsequently confirmed by fluorescence in situ hybridization (FISH), but not by conventional cytogenetic analysis. FISH using a cocktail of cosmids (c197-2, c197-4, c197-9) from the Miller-Dieker critical region showed a deletion of 17p13.3 in one homologue of chromosome 17. Additional FISH studies revealed a subtle 17p;20q translocation in the father, his sister, and the paternal grandmother. Hence, our patient is a carrier of an unbalanced 17;20 translocation resulting in a partial deletion of 17p and a partial trisomy 20q. Whenever kidney anomalies and dilated occipital horns are observed together with polyhydramnios during prenatal ultrasound examination, the possibility of Miller-Dieker syndrome should be suspected. In such cases, prenatal and/or postnatal chromosome studies should also include FISH analysis with the appropriate probes.

18q- and 18q+ mosaicism in a mentally retarded boy.

A mentally retarded boy was found to have an unusual chromosomal mosaicism [46,XY, del(18) (q22)/46,XY,iso psu dic(18)(q23)]. The clinical manifestations are compatible with the 18q- syndrome. The chromosome alteration was defined by high resolution banding and fluorescence in situ hybridization (FISH). A mechanism to explain the origin of the two cell lines is presented and discussed.