Opsoclonus Myoclonus (OMS) is a rare neurological disorder which appears to be the result of an autoimmune dysfunction. It is an extremely rare condition, affecting as few as 1 in 10,000,000 people every year. It affects 2 to 3% of children. Opsoclonus Myoclonus, which manifests itself as post infectious encephalopathy, occasionally along with HIV infection, post Streptococcal infection, West Nile virus encephalitis and Rickettsial infection, most often presents as a paraneoplastic syndrome, which is especially caused by occult neuroblastoma which is commonly seen in childhood and occurs in adults in relation to breast cancer and small cell lung cancer. In this study, two adult post infectious cases which had rare manifestations, have been presented. The cases were managed by using corticosteroids.
Opsoclonus myoclonus; Paraneoplastic syndrome; Autoimmune disorder; Post infectious encephalopathy
Background: With the advent of functional appliances and orthopedic appliances the elimination and correction of skeletal and dental discrepancies has been much reduced. Most orthodontists agree that elimination of oral habits and orthopaedic treatment of class 3 malocclusion and posterior cross bites deserve treatment at an early age. Early treatment was proposed along the lines of “catch them in the young”, and “you see it, you treat it” is the main ideology of Early Orthodonticc Treatment (EOT). Furthermore, the majority of children have habits driving the malocclusion. Mouth breathing, tongue thrusting and incorrect swallowing patterns are all known causes of malocclusion and poor facial growth.
Aims: To evaluate the prevalence of dental feature that might result in malocclusion and need for early orthodontic treatment.
Settings and Design: Groups of 532 school going children were selected and complete case history was taken and were categorized based on the type of malocclusions, dental features that can predetermine need for early orthodontic treatment. Statistical analysis used.
Results: The results shows the increase in prevalence of malocclusion and the dental features that gives clues for an orthodontist to frame up his treatment modalities not just for corrective orthodontics but for also preventive and interceptive orthodontics.
Conclusion: Angle’s Class I malocclusion is most commonly seen malocclusion followed by class II division 1 malocclusion followed by Angles class II division 2 malocclusion. In angle’s class I malocclusion, incidence of crowding is more followed by proclination of anterior teeth. There is no significant difference between incidence of malocclusion in males and females. The children who needed immediate orthodontic care were more than the children who doesn’t need an orthodontic treatment. Need for increase of awareness programs is required in order to educate the people about the early orthodontic treatment.
Early orthodontic intervention; Growth modification; Malocclusion prevalence
Hypercementosis is an abnormal thickening of cementum which may be generalized or localized. Localized hypercementosis is usually characterized by nodular enlargement of apical third of root. Hypercementosis in the form of multiple cemental spikes distributed throughout the entire length of root is a very rare finding. In this article, we report such a rare manifestation of localized hypercementosis affecting right maxillary third molar in a 24-year-old male. This finding was an accidental observation following a difficult extraction procedure as the spikes were not evident in the orthopantamogram. It is imperative that every dental practitioner be aware of several presentations of hypercementosis and ensure that such an entity is considered in the differential diagnosis of difficult extraction procedures as an Intraoral Periapical (IOPA) radiograph or even an Orthopantamogram (OPG) could not differentiate the root morphology.
Hypercementosis; Localized; Cemental spikes
Ciliated hepatic foregut cysts (CHFCs) are rare congenital cysts of the liver that originate from the embryologic foregut. Despite an increase in incidence, they remain rare and several key characteristics remain poorly understood, including the range of presentation and the risk of malignant conversion. Large, symptomatic cysts and small asymptomatic, atypical cysts should be resected. We present a patient who recently underwent laparoscopic excision of a CHFC, review the literature and propose the rationale for attempting removal of these cysts through a laparoscopic approach.
Ciliated hepatic foregut cyst; foregut cyst; hepatic cyst
Eucalyptus nitens is a perennial forest tree species grown mainly for kraft pulp production in many parts of the world. Kraft pulp yield (KPY) is a key determinant of plantation profitability and increasing the KPY of trees grown in plantations is a major breeding objective. To speed up the breeding process, molecular markers that can predict KPY are desirable. To achieve this goal, we carried out RNA-Seq studies on trees at extremes of KPY in two different trials to identify genes and alleles whose expression correlated with KPY. KPY is positively correlated with growth measured as diameter at breast height (DBH) in both trials. In total, six RNA bulks from two treatments were sequenced on an Illumina HiSeq platform. At 5% false discovery rate level, 3953 transcripts showed differential expression in the same direction in both trials; 2551 (65%) were down-regulated and 1402 (35%) were up-regulated in low KPY samples. The genes up-regulated in low KPY trees were largely involved in biotic and abiotic stress response reflecting the low growth among low KPY trees. Genes down-regulated in low KPY trees mainly belonged to gene categories involved in wood formation and growth. Differential allelic expression was observed in 2103 SNPs (in 1068 genes) and of these 640 SNPs (30%) occurred in 313 unique genes that were also differentially expressed. These SNPs may represent the cis-acting regulatory variants that influence total gene expression. In addition we also identified 196 genes which had Ka/Ks ratios greater than 1.5, suggesting that these genes are under positive selection. Candidate genes and alleles identified in this study will provide a valuable resource for future association studies aimed at identifying molecular markers for KPY and growth.
In the title compound, C26H19BrN2O5S, the carbazole tricycle is essentially planar, with the largest deviation being 0.126 (3) Å for the C atom connected to the nitrophenyl group. The carbazole moiety is almost orthogonal to the benzene rings of the adjacent phenylsulfonyl and nitrophenyl groups, making dihedral angles of 85.43 (15) and 88.62 (12)°, respectively. The molecular conformation is stabilized by two C—H⋯O hydrogen bonds involving the sulfone group, which form similar six-membered rings. In the crystal, molecules symmetrically related by a glide plane are linked in C(6) chains parallel to  by C—H⋯O hydrogen bonds formed with the participation of the nitro group. The chains are reinforced by additional C—H⋯π interactions.
Tick salivary glands produce complex cocktails of bioactive molecules that facilitate blood feeding and pathogen transmission by modulating host hemostasis, pain/itch responses, wound healing, and both innate and adaptive immunity. In this study, cutaneous responses at Dermacentor andersoni bite-sites were analyzed using Affymetrix mouse genome arrays and histopathology at 12, 48, 96 and 120 h post- infestation (hpi) during primary infestations and 120 hpi during secondary infestations. The microarray data suggests: (1) chemotaxis of neutrophils, monocytes, and other cell types; (2) production and scavenging of reactive oxygen species; and, (3) keratin- based wound healing responses. Histological analysis supported the microarray findings. At 12 hpi, a mild inflammatory infiltrate was present in the dermis, especially concentrated at the junction between dermal connective tissue and underlying adipose tissue. A small lesion was located immediately under the hypostome and likely represents the feeding “pool.” Surprisingly, at 48 hpi, the number of inflammatory cells had not increased from 12 hpi, perhaps mirroring the reduction in gene expression seen at this time point. The feeding lesion is very well defined, and extravasated erythrocytes are readily evident around the hypostome. By 96 hpi, the inflammatory infiltrate has increased dramatically and the feeding lesion appears to have moved deeper into the dermis. At 120 hpi, most of the changes at 96 hpi are intensified. The infiltrate is very dense, the epidermis is markedly thickened, the feeding lesion is poorly defined and the dermal tissue near the hypostome appears to be loosing its normal architecture. In conclusion, during D. andersoni feeding infiltration of inflammatory cells increases across time concurrent with significant changes in the epidermal and dermal compartments near the feeding tick. The importance of changes in the epidermal layer in the host response to ticks is not known, however, it is possible the host attempts to “slough off” the tick by greatly increasing epithelial cell replication.
tick; tick feeding; tick saliva; Immunomodulation; Dermacentor andersonii
Configuring high quality care for the rapidly increasing number of people with type 2 diabetes (T2D) is a major challenge worldwide for both providers and commissioners. In the UK, about two thirds of people with T2D are managed entirely in primary care, with wide variation in management strategies and achievement of targets. Pay for performance, introduced in 2004, initially resulted in improvements but disparities exist in ethnic minorities and the improvements are levelling off. Community based, intermediate care clinics for diabetes (ICCDs) were considered one solution and are functioning across the UK. However, there is no randomised trial evidence for the effectiveness of such clinics.
Trial Design, Methods and Findings
This is a cluster-randomised trial, involving 3 primary care trusts, with 49 general practices randomised to usual care (n = 25) or intervention (ICCDs; n = 24). All eligible adult patients with T2D were invited; 1997 were recruited and 1280 followed-up after 18-months intervention. Primary outcome: achievement of all three of the NICE targets [(HbA1c≤7.0%/53 mmol/mol; Blood Pressure <140/80 mmHg; cholesterol <154 mg/dl (4 mmol/l)]. Primary outcome was achieved in 14.3% in the intervention arm vs. 9.3% in the control arm (p = 0.059 after adjustment for covariates). The odds ratio (95% CI) for achieving primary outcome in the intervention group was 1.56 (0.98, 2.49). Primary care and community clinic costs were significantly higher in the intervention group, but there were no significant differences in hospital costs or overall healthcare costs. An incremental cost-effectiveness ratio (ICER) of +£7,778 per QALY gained, indicated ICCD was marginally more expensive at producing health gain.
Intermediate care clinics can contribute to improving target achievement in patients with diabetes. Further work is needed to investigate the optimal scale and organisational structure of ICCD services and whether, over time, their role may change as skill levels in primary care increase.
ClinicalTrials.gov NCT00945204; National Research Register (NRR) M0014178167.
Data suggest that clinical applications of human induced pluripotent stem cells (hiPSCs) will be realized. Nonetheless, clinical applications will require hiPSCs that are free of exogenous DNA and that can be manufactured through Good Manufacturing Practice (GMP). Optimally, derivation of hiPSCs should be rapid and efficient in order to minimize manipulations, reduce potential for accumulation of mutations and minimize financial costs. Previous studies reported the use of modified synthetic mRNAs to reprogram fibroblasts to a pluripotent state. Here, we provide an optimized, fully chemically defined and feeder-free protocol for the derivation of hiPSCs using synthetic mRNAs. The protocol results in derivation of fully reprogrammed hiPSC lines from adult dermal fibroblasts in less than two weeks. The hiPSC lines were successfully tested for their identity, purity, stability and safety at a GMP facility and cryopreserved. To our knowledge, as a proof of principle, these are the first integration-free iPSCs lines that were reproducibly generated through synthetic mRNA reprogramming that could be putatively used for clinical purposes.
Protein crystals were vitrified using high-pressure freezing in their mother liquor at 210 MPa and 77 K without cryoprotectants or oil coating. The method was successfully applied to photosystem II, which is representative of a membrane protein with a large unit cell and weak crystal contacts.
High-pressure freezing (HPF) is a method which allows sample vitrification without cryoprotectants. In the present work, protein crystals were cooled to cryogenic temperatures at a pressure of 210 MPa. In contrast to other HPF methods published to date in the field of cryocrystallography, this protocol involves rapid sample cooling using a standard HPF device. The fast cooling rates allow HPF of protein crystals directly in their mother liquor without the need for cryoprotectants or external reagents. HPF was first attempted with hen egg-white lysozyme and cubic insulin crystals, yielding good to excellent diffraction quality. Non-cryoprotected crystals of the membrane protein photosystem II have been successfully cryocooled for the first time. This indicates that the presented HPF method is well suited to the vitrification of challenging systems with large unit cells and weak crystal contacts.
high-pressure freezing; cryocooling
A large fraction of non-small cell lung cancers (NSCLC) are dependent on defined oncogenic driver mutations. Although targeted agents exist for EGFR- and EML4-ALK-driven NSCLC, no therapies target the most frequently found driver mutation, KRAS. Furthermore, acquired resistance to the currently targetable driver mutations is nearly universally observed. Clearly a novel therapeutic approach is needed to target oncogene driven NSCLC. We recently demonstrated that the basic helix-loop-helix transcription factor Twist1 cooperates with mutant Kras to induce lung adenocarcinoma in transgenic mouse models and that inhibition of Twist1 in these models led to Kras-induced senescence. In the current study, we examine the role of TWIST1 in oncogene driven human NSCLC. Silencing of TWIST1 in KRAS mutant human NSCLC cell lines resulted in dramatic growth inhibition and either activation of a latent oncogene-induced senescence program or in some cases, apoptosis. Similar effects were observed in EGFR mutation driven and c-Met amplified NSCLC cell lines. Growth inhibition by silencing of TWIST1 was independent of p53 or p16 mutational status and did not require previously defined mediators of senescence, p21 and p27, nor could this phenotype be rescued by overexpression of SKP2. In xenograft models, silencing of TWIST1 resulted in significant growth inhibition of KRAS mutant, EGFR mutant and c-Met amplified NSCLC. Remarkably, inducible silencing of TWIST1 resulted in significant growth inhibition of established KRAS mutant tumors. Together these findings suggest that silencing of TWIST1 in oncogene driver dependent NSCLC represents a novel and promising therapeutic strategy.
TWIST1; OIS; KRAS; NSCLC; EGFR
Introduction: Three-dimensional control throughout the orthodontic treatment is essential for uncompromised results. Mini screws introduced for orthodontic anchorage has given the clinician an option of absolute three dimensional control. The purpose of this study was to compare and measure the vertical control and torque control of incisors and molar during enmass retraction with titanium microimplants and conventional molar anchorage.
Material and Methods: Twenty patients were selected with extraction of all first premolars and bonded with 0.022″ slot MBT system. After aligning and leveling, all subjects were placed with 0.019″ X 0.025″ posted SS wire with standardized torquing curve. The 20 subjects were randomly divided into 2 groups consisting of 10 each (Group A & Group B). Group A subjects, implants were placed and Group B formed the control group. Retraction was carried out using NiTi closed coil springs. The assessment of the vertical and torque control of incisors and tipping and vertical control of molars was done by radiographic method using lateral cephalogram taken before and after retraction.
Results: The torque control of incisors, P11 value in group A and B indicated no significant difference. The molar tip, P12 value in group A indicated that there was distal tipping of molars while the P12 in group B indicated mesial tipping. On vertical plane P21, P22 and P23 values in Group A indicated that there was intrusion of incisors and molars while value in Group B indicated extrusion of incisors and molars.
Conclusion: Three dimensional control is better in the implant group compared to the non implant group. Therefore the implant group definitely has citied advantages over conventional method.
Mini Screw Implant; Vertical control; Torque control; Three-dimensional control
In the title compound, C28H22N2O8S, the carbazole ring system is roughly planar, with a maximum deviation of 0.084 (3) Å for the C atom connected to the 4,5-dimethoxy-2-nitrophenyl ring. The dihedral angle between the carbazole system and the dimethoxy-substituted nitrophenyl ring is 57.05 (10)°. The aldehyde C atom deviates by 0.164 (5) Å from its attached carbazole ring system. The molecular structure is stabilized by C—H⋯O interactions which generate two S(6) and one S(7) ring motif. In the crystal, molecules are linked by C—H⋯O hydrogen bonds, forming R
3(15) ring motifs, which are further crosslinked by R
2(19) ring motifs, resulting in (002) layers. The crystal packing also features C—H⋯π interactions.
Eleven protease mutations have been associated with reduced susceptibility to darunavir. In this study of 87 HIV-1-infected patients experiencing virological failure to second-line regimens containing protease inhibitors boosted with ritonavir (viral load >1,000 HIV RNA copies/ml), we observed a low prevalence (3%) of ≥3 darunavir resistance-associated mutations, indicating that this drug may be a good option for third-line antiretroviral therapy in southern India.
The field of DNA mismatch repair (MMR) has rapidly expanded after the discovery of the MutHLS repair system in bacteria. By the mid 1990s yeast and human homologues to bacterial MutL and MutS had been identified and their contribution to hereditary non-polyposis colorectal cancer (HNPCC; Lynch Syndrome) was under intense investigation. The human MutS homologue 6 protein (hMSH6), was first reported in 1995 as a G:T binding partner (GTBP) of hMSH2, forming the hMutSα mismatch-binding complex. Signal transduction from each DNA-bound hMutSα complex is accomplished by the hMutLα heterodimer (hMLH1 and hPMS2). Molecular mechanisms and cellular regulation of individual MMR proteins are now areas of intensive research. This review will focus on molecular mechanisms associated with mismatch binding, as well as emerging evidence that MutSα and in particular, MSH6, is a key protein in MMR-dependent DNA damage response and communication with other DNA repair pathways within the cell. MSH6 is unstable in the absence of MSH2, however it is the DNA lesion-binding partner of this heterodimer. MSH6, but not MSH2, has a conserved Phe-X-Glu motif that recognizes and binds several different DNA structural distortions, initiating different cellular responses. hMSH6 also contains the nuclear localization sequences required to shuttle hMutSα into the nucleus. For example, upon binding to O6meG:T, MSH6 triggers a DNA damage response that involves altered phosphorylation within the N-terminal disordered domain of this unique protein. While many investigations have focused on MMR as a post-replication DNA repair mechanism, MMR proteins are expressed and active in all phases of the cell cycle. There is much more to be discovered about regulatory cellular roles that require the presence of MutSα and, in particular, MSH6.
DNA mismatch repair; MSH2; MSH6; DNA damage signaling; N-terminal disordered domain
Hair dye poisoning has been rising in incidence in the recent years. Apart from the commoner manifestations of upper airway edema, rhabdomyolysis and acute renal failure, cardiac toxicity, convulsions and sudden cardiac death are relatively rare complications. We discuss a case of hair dye poisoning manifesting as oropharyngeal edema along with cardiac complication. The patient survived.
Hair dye poisoning; Paraphenylenediamine; Myocarditis
Key pathways like insulin signaling, AMP activated kinase (AMPK) activation and inflammatory signaling are involved in the complex pathological network of hepatic insulin resistance. Our aim is to investigate whether grape seed proanthocyanidins (GSP) and metformin (MET) target any of these pathways in insulin resistant rat liver. Albino Wistar rats were rendered insulin resistant by feeding a high fat-fructose diet (HFFD). Either GSP (100 mg/kg b.w), MET(50 mg/kg b.w) or both were administered to insulin resistant rats as therapeutic options. HFFD-feeding caused hyperglycemia, hyperinsulinemia, increased gluconeogenesis, decreased tyrosine phosphorylation of insulin receptor-β(IR-β) and insulin receptor substrate-1 (IRS-1) and increased serine phosphorylation of IRS-1. The association of p85α subunit of phosphotidyl inositol 3 kinase(PI3K) with IRS-1 and subsequent Akt phosphorylation were reduced while the expression of mitogen activated protein kinases (MAPK) were increased in HFFD rats. Both MET and GSP reduced hyperglycemia and hyperinsulinemia and improved glycolysis, tyrosine phosphorylation of IR-β and IRS-1, IRS-1-PI3K association and Akt activation. However, activation of tumor necrosis factor-α, interleukin-6, leptin and suppressor of cytokine signaling-3 and reduction in adiponectin caused by chronic HFFD feeding were reversed by GSP better than by MET. Activation of AMPK by GSP was much less compared to that by MET. These findings suggest that GSP might activate PI3K pathway and promote insulin action by reducing serine kinase activation and cytokine signaling and MET by targeting AMPK. The beneficial effects were enhanced during combination therapy. Thus, combination therapy with MET and GSP may be considered for the management of metabolic syndrome.
High fat-fructose diet; Grape seed proanthocyanidins; Metformin; Insulin signaling; Inflammation
Kinetic resolution of 1-phenyl-2-propyn-1-ol, an important chiral synthon, was studied through trans-esterification with acyl acetate to investigate synergism between microwave irradiation and enzyme catalysis. Lipases from different microbial origins were employed for the kinetic resolution of (R/S)-1-phenyl-2-propyn-1-ol, among which Candida antarctica lipase B, immobilized on acrylic resin (Novozym 435), was found to be the best catalyst in n-hexane as solvent. Vinyl acetate was the most effective among different acyl esters studied. The effect of various parameters was studied in a systematic manner. Definite synergism between microwave and enzyme was observed. The initial rate was improved around 1.28 times under microwave irradiation than conventional heating. Under optimum conditions, maximum conversion (48.78%) and high enantiomeric excess (93.25%) were obtained in 2 h. From modeling studies, it is concluded that the reaction follows the Ping-Pong bi-bi mechanism with dead end alcohol inhibition. Kinetic parameters were obtained by using nonlinear regression. This process is green, clean, and easily scalable as compared to the chemical process.
In the title compound, C28H24N2O7S, the carbazole system is essentially planar, with a maximum deviation of 0.0644 (19) Å for the C atom connected to the 4,5-dimethoxy-2-nitrophenyl group. The dihedral angle between the carbazole moiety and the dimethoxy-substituted nitrophenyl ring is 58.55 (7)°. The sulfonyl group forms two intramolecular C—H⋯O bonds with the adjacent carbazole system, forming two cyclic S(6) motifs. In the crystal, molecules are linked along the a axis in bands consisting of cyclic R
3(15) motifs through two further C—H⋯O hydrogen bonds.