Tratamiento ortopédico funcional de los maxilares y ortodóntico en paciente con síndrome del cromosoma X- frágil. Reporte de caso / Functional orthopedic jaw and orthodontic treatment in a patient with fragile-X syndrome. A case report

El síndrome X frágil (SXF) es un trastorno ligado al cromosoma X, en el brazo largo Xq27.3, que provoca diversas alteraciones como problemas de conducta, deficiencia intelectual, macroorquidia, pabellones auditivos grandes y prominentes, paladar profundo y ojival, prognatismo mandibular, maloclusión y anomalías dentarias. El objetivo de este informe fue presentar el caso clínico de una paciente de 16 años con SXF, leucodermia, que se sometió a un tratamiento ortopédico funcional de los maxilares para la corrección del apiñamiento dentario. En el examen clínico se observaron timidez, ansiedad, inestabilidad emocional, trastornos conductuales esporádicos asociados a discapacidad intelectual leve, alteraciones craneofaciales y oclusales. Luego del estudio, evaluación radiográfica panorámica y trazados cefalométricos, se decidió instalar un dispositivo ortopédico funcional de maxilar, tipo Pistas Planas Indirectas, para posterior tratamiento ortodóncico correctivo. Bien al inicio del tratamiento se observó dificultad de comprensión y colaboración por parte de la paciente y su responsable (madre) y, luego de 5 meses, aún con mejoras en las funciones estomatognáticas, se inició el tratamiento ortodóntico con dispositivo fijo, el que fue concluido luego de dos años. El éxito del tratamiento de ortopedia funcional de los maxilares y/u ortodóntico, principalmente en el SXF, se basa en el abordaje comportamental y motivación en todas las etapas del tratamiento por el profesional, así como en un ambiente familiar colaborativo.

The Fragile-X Syndrome (FXS) is a disorder linked to X chromosome, on the long arm Xq27.3, causing several changes such as behavioral problems, intellectual disability, macroorchidism, large and prominent auricles, deep and ogival palate, mandibular prognathism, increased mandibular angle, malocclusion, and dental anomalies. The objective was to present a case of a 16-year-old patient with FXS, leukoderma, submitted to orthopedic functional maxillary treatment to correct dental crowding. In general, clinical examination, behavioral changes such as shyness, anxiety, emotional lability, sporadic disturbances of behavior associated with mild mental disabilities were remarkable. After panoramic radiographic evaluation and cephalometric tracings, it was decided to install the functional orthopedic appliance of the jaws, Indirect Flat Planes type, for later corrective orthodontic treatment. At beginning of treatment, there was a difficulty in understanding and collaborating, not only from the patient's side but also from the mother's. After five months, even with the improvement in stomatognathic functions, orthodontic treatment with a fixed appliance was started, which was concluded after two years. Success of functional and / or orthodontic jaw orthopedics treatment, especially in FXS, is based on behavioral approach and motivation in all stages, by the professional as well as a collaborative family environment.

Acaricidal activity of flavonoids extract of Borago officinalis L. (Boraginaceae) against brown dog tick, Rhipicephalus sanguineus (Latreille, 1806).

Borago officinalis L. (Boraginaceae) is a plant of the Boraginaceae family, used in Algeria for food and medicinal purposes. This study reports the effect of flavonoids extracted from the aerial part of Borago officinalis L. (Boraginaceae) on the larvae and engorged adult females of the brown dog tick Rhipicephalus sanguineus (Latreille, 1806) using adults immersion test (AIT) and larval immersion test (LIT). For this purpose, the larvae and engorged female of Rhipicephalus sanguineus (Latreille, 1806) were exposed to serial dilutions of flavonoids extract (50 mg/ml, 25 mg/ml, 12.5 mg/ml and 6.25 mg/ml) using "dipping method" in vitro. The plant extract was obtained by fractionation using appropriate solvents. The extraction yield is 22% with a flavonoids concentration equal to 129.12 µg equivalent of quercetin/ml of the extract. The chromatographic analysis by high performance thin layer chromatography (HPTLC) reveals the presence of gallic acid, vanillic acid, kaempferol, dihydroxybenzoic and quercetin. The results obtained show that the flavonoids extract of Borago officunalis L. (Boraginaceae) considerably reduces the oviposition and the hatching rate of the eggs of Rhipicephalus sanguineus (Latreille, 1806) and was shown to be toxic against newly hatched larvae of Rhipicephalus sanguineus (Latreille, 1806) (P < 0.05).

Invited Article: A precise instrument to determine the Planck constant, and the future kilogram.

A precise instrument, called a watt balance, compares mechanical power measured in terms of the meter, the second, and the kilogram to electrical power measured in terms of the volt and the ohm. A direct link between mechanical action and the Planck constant is established by the practical realization of the electrical units derived from the Josephson and the quantum Hall effects. We describe in this paper the fourth-generation watt balance at the National Institute of Standards and Technology (NIST), and report our initial determination of the Planck constant obtained from data taken in late 2015 and the beginning of 2016. A comprehensive analysis of the data and the associated uncertainties led to the SI value of the Planck constant, h = 6.626 069 83(22) × 10(-34) J s. The relative standard uncertainty associated with this result is 34 × 10(-9).

Bridging classical and quantum mechanics.

Using a watt balance and a frequency comb, a mass-energy equivalence is derived. The watt balance compares mechanical power measured in terms of the meter, the second, and the kilogram to electrical power measured in terms of the volt and the ohm. A direct link between mechanical action and the Planck constant is established by the practical realization of the electrical units derived from the Josephson and the quantum Hall effects. By using frequency combs to measure velocities and acceleration of gravity, the unit of mass can be realized from a set of three defining constants: the Planck constant h, the speed of light c, and the hyperfine splitting frequency of 133Cs.

Dynamin-related protein 1 is required for normal mitochondrial bioenergetic and synaptic function in CA1 hippocampal neurons.

Disrupting particular mitochondrial fission and fusion proteins leads to the death of specific neuronal populations; however, the normal functions of mitochondrial fission in neurons are poorly understood, especially in vivo, which limits the understanding of mitochondrial changes in disease. Altered activity of the central mitochondrial fission protein dynamin-related protein 1 (Drp1) may contribute to the pathophysiology of several neurologic diseases. To study Drp1 in a neuronal population affected by Alzheimer's disease (AD), stroke, and seizure disorders, we postnatally deleted Drp1 from CA1 and other forebrain neurons in mice (CamKII-Cre, Drp1lox/lox (Drp1cKO)). Although most CA1 neurons survived for more than 1 year, their synaptic transmission was impaired, and Drp1cKO mice had impaired memory. In Drp1cKO cell bodies, we observed marked mitochondrial swelling but no change in the number of mitochondria in individual synaptic terminals. Using ATP FRET sensors, we found that cultured neurons lacking Drp1 (Drp1KO) could not maintain normal levels of mitochondrial-derived ATP when energy consumption was increased by neural activity. These deficits occurred specifically at the nerve terminal, but not the cell body, and were sufficient to impair synaptic vesicle cycling. Although Drp1KO increased the distance between axonal mitochondria, mitochondrial-derived ATP still decreased similarly in Drp1KO boutons with and without mitochondria. This indicates that mitochondrial-derived ATP is rapidly dispersed in Drp1KO axons, and that the deficits in axonal bioenergetics and function are not caused by regional energy gradients. Instead, loss of Drp1 compromises the intrinsic bioenergetic function of axonal mitochondria, thus revealing a mechanism by which disrupting mitochondrial dynamics can cause dysfunction of axons.

Thermographic characterization of masticatory muscle regions in volunteers with and without myogenous temporomandibular disorder: preliminary results.

OBJECTIVES: This study aims to conduct a non-invasive measurement of the cutaneous temperature of selected masticatory muscle regions of volunteers with and without myogenous temporomandibular disorder (TMD), using infrared thermography. METHODS: 23 females (10 myogenous TMD volunteers and 13 controls) were recruited and studied. The temperature at the surface of the facial area over the anterior temporalis and masseter muscles was assessed by medical thermography, using regional lateral views and clinical examination. RESULTS: The temperature levels measured at the masseter and anterior temporalis muscle regions in myogenous TMD volunteers (32.85 ± 0.85 and 34.37 ± 0.64 ºC, respectively) were significantly lower (p < 0.05) than those measured in controls (33.49 ± 0.92 and 34.78 ± 0.44 ºC, respectively). Medical infrared imaging indicated a mean difference of 1.4 ºC between the masseter and anterior temporalis regions. Analysis of the comparison between the absolute and normalized mean temperatures was performed using the pairwise comparison of receiver operating characteristic curves, and no statistically significant difference was observed (p > 0.05). The sensitivity and specificity of the thermographic assessment for the masseter region was of 70% and 73%, respectively and for the anterior temporalis region was of 80% and 62%, respectively. CONCLUSIONS: This method of evaluating masticatory muscle regions of this preliminary study seems to indicate that it can be used as an aid in complimentary diagnosing of TMDs.

Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.

Thermographic and clinical correlation of myofascial trigger points in the masticatory muscles.

OBJECTIVES: The aim of the study was to identify and correlate myofascial trigger points (MTPs) in the masticatory muscles, using thermography and algometry. METHODS: 26 female volunteers were recruited. The surface facial area over the masseter and anterior temporalis muscles was divided into 15 subareas on each side (n=780). This investigation consisted of three steps. The first step involved thermographic facial examination, using lateral views. The second step involved the pressure pain threshold (PPT), marking the MTP pattern areas for referred pain (n=131) and local pain (n=282) with a coloured pencil, and a photograph of the lateral face with the head in the same position as the infrared imaging. The last step was the fusion of these two images, using dedicated software (Reporter® 8.5-SP3 Professional Edition and QuickReport® 1.2, FLIR Systems, Wilsonville, OR); and the calculation of the temperature of each point. RESULTS: PPT levels measured at the points of referred pain in MTPs (1.28±0.45 kgf) were significantly lower than the points of local pain in MTPs (1.73±0.59 kgf; p<0.05). Infrared imaging indicated differences between referred and local pain in MTPs of 0.5 °C (p<0.05). Analysis of the correlation between the PPT and infrared imaging was done using the Spearman non-parametric method, in which the correlations were positive and moderate (0.4≤r<0.7). The sensitivity and specificity in MTPs were 62.5% and 71.3%, respectively, for referred pain, and 43.6% and 60.6%, respectively, for local pain. CONCLUSION: Infrared imaging measurements can provide a useful, non-invasive and non-ionizing examination for diagnosis of MTPs in masticatory muscles.

[MRI-based measurement of muscle damage after minimally invasive hip arthroplasty]. / MRT-basierte Messung des Muskelschadens nach minimal-invasiver Hüftprothesenimplantation.

Muscle trauma in minimally invasive hip arthroplasty using a direct anterior approach was assessed by magnetic resonance imaging (MRI) in 25 patients preoperatively, as well as 6 months after total hip replacement. The MRI evaluation included the measurement of changes in muscle cross-sectional area (CSA = atrophy) and fatty infiltration of the muscles. Using MRI, preoperatively existing and operatively caused muscle tissue damage could be detected by assessing changes in muscle CSA and fatty infiltration. Even preoperatively, a muscular atrophy and fatty infiltration could be demonstrated in the diseased hip. Using the minimally invasive direct anterior approach, a postoperative significantly reduced CSA and significantly increased fatty degeneration was detected for the M. tensor fasciae latae and the M. glutaeus minimus. No increased damage of the M. glutaeus medius could be detected.

Molecular network pathways and functional analysis of tumor signatures associated with development of resistance to viral gene therapy.

Replication-competent attenuated herpes simplex viruses have proven effective in killing many cancer cell lines. However, determinants of resistance to oncolytic therapy are mostly unknown. We developed viral therapy-resistant cells and examined changes in gene-expression pattern compared with therapy-sensitive parental cells. Colon cancer cell line HT29 and hepatoma cell line PLC5 were exposed to increasing concentrations of virus G207. Therapy-resistant cells were isolated and grown in vitro. Tumorigenicity was confirmed by ability of cell lines to form tumors in mice. Human Genome U133A complementary DNA microarray chips were used to determine gene-expression patterns, which were analyzed in the context of molecular network interactions, pathways and gene ontology. In parental cell lines, 90-100% of cells were killed by day 7 at 1.0 multiplicity of infection. In resistant cell lines, cytotoxicity assay confirmed 200- to 400-fold resistance. Microarray analysis confirmed changes in gene expressions associated with resistance: cell surface proteins affecting viral attachment and entry, cellular proteins affecting nucleotide pools and proteins altering apoptotic pathways. These changes would decrease viral infection and replication. Our study identifies gene-expression signatures associated with resistance to oncolytic viral therapy. These data provide potential targets to overcome resistance, and suggest that molecular assays may be useful in selecting patients for trial with this novel treatment.

The use of adrenaline autoinjectors by children and teenagers.

BACKGROUND: Although adrenaline is recommended as first line treatment for anaphylaxis, it is often not utilized. There has been a debate about when adrenaline autoinjectors should be prescribed and how many should be dispensed. OBJECTIVES: To see how many adrenaline autoinjectors were used during anaphylactic reactions and to determine why they were not used in situations where they were clinically indicated. METHODS: Patients were recruited prospectively at 14 paediatric allergy clinics throughout UK. Participants completed a questionnaire covering demographic data, atopic status and details of allergic reactions in the previous year and reasons for using more than one device. RESULTS: A total of 969 patients were recruited of whom 466 (48.1%, 95% CI: 37.9-58.2) had had at least one reaction in the previous year; 245 (25.3%, 95% CI: 16.2-34.4) of these reactions were anaphylaxis. An adrenaline autoinjector was used by 41 (16.7%, 95% CI: 11.7-21.3) participants experiencing anaphylaxis. Thirteen participants received more than one dose of adrenaline, for nine of these a health professional gave at least one. The commonest reasons for using more than one were severe breathing difficulties (40%), lack of improvement with first dose (20%) and miss-firing (13.3%). The commonest reasons for not using adrenaline in anaphylaxis were 'thought adrenaline unnecessary' (54.4%) and 'unsure adrenaline necessary' (19.1%). Many with wheeze did not use their autoinjector. CONCLUSIONS AND CLINICAL RELEVANCE: Adrenaline is used by only a minority of patients experiencing anaphylaxis in the community. Thirteen of the 41 patients with anaphylaxis who used their autoinjector needed another dose of adrenaline. Further research is needed to consider how to best encourage the usage of adrenaline when clinically indicated in anaphylaxis.

Vietnamese community screening for hepatitis B virus and hepatitis C virus.

Asian Americans represent an important cohort at high risk for viral hepatitis. To determine the prevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection and HBV vaccination in a Vietnamese community, a total of 322 Vietnamese subjects from a local doctor's office and annual Vietnamese Health Fair were included in this study. Demographic and clinical data were collected. 2.2% of the screened cohort tested positive for anti-HCV and 9.3% tested positive for HBsAg. Unlike HBV-positive subjects, HCV-positive subjects had significantly higher liver enzymes (P = 0.0045 and P = 0.0332, respectively). The HBV-positive group was more likely to report jaundice (P = 0.0138) and a family history of HBV (P = 0.0115) compared to HBV-negative subjects. Forty-eight patients (15.5%) reported a family history of liver disease (HBV, HCV, HCC, cirrhosis, other). Of this 48, 68.8% reported no personal history of HBV vaccination and 77.1% reported no family history of vaccination for HBV. Among the 183 subjects without a family history of liver disease, 156 (85.2%) reported no personal history of vaccination and 168 (91.8%) reported no family history of vaccination. HBV vaccination rates in those reporting a family history of liver disease were significantly higher (P =0.020). There was a high prevalence of HBV infection in this community screening. Nevertheless, the rate for HBV vaccination was low. The low prevalence of abnormal liver enzymes in HBV-positive subjects emphasizes the need for screening to be triggered by risk factors and not by abnormal liver enzymes.

ONCOLYTIC HERPES SIMPLEX VIRUS 1 (HSV-1) VECTORS: INCREASING TREATMENT EFFICACY AND RANGE THROUGH STRATEGIC VIRUS DESIGN.

Viruses have long been considered potential anticancer treatments. Wild-type viruses have been tested as anticancer agents in clinical trials since the 1960s. The possibility of viral oncolysis as an alternate cancer therapy was transformed by the emergence of modern genetic engineering. The herpes simplex virus (HSV) family offers particular advantages for use as a viral oncolytic. The engineered vectors that make up oncolytic HSVs (oHSVs) have demonstrated remarkable safety in clinical trials, with some evidence of efficacy. The past decade has seen a focus on increasing the efficacy of oncolytic vectors by adding exogenous transgenes to enhance tumor destruction. The current paper describes the various strategies for engineering HSV for increased cancer tissue specificity and efficacy. Presented are the rationale, preclinical data and clinical data where available. This is meant to illustrate a basic framework for the development of a novel therapy meant to exploit the viral life cycle for the killing of cancer.

[Anatomic bases of the infrahyoid flap: vascular pedicles and innervation]. / Bases anatomiques du lambeau infra-hyoïdien : vascularisation et innervation.

UNLABELLED: The infrahyoid flap is used in head and neck reconstruction, especially in oral defect. This study is designed to determine vascular pedicles and innervation of the infrahyoid muscles and flap. MATERIALS AND METHOD: The neck regions of 12 injected cadavers were investigated bilaterally. RESULTS: The arterial pedicles of the infrahyoid muscles are the superior and inferior thyroid arteries. The arterial pedicles of the flap are the superior thyroid artery. The venous pedicles of the muscles and flap are the superior thyroid, lingual and facial veins. The infrahyoid flap is innervated by the ansa cervicalis. CONCLUSION: The infrahyoid flap seems to be an excellent flap for oral, oropharynx and superior facial part reconstruction. It can be harvested easily in the same operation area.

The immunologic aspects of poxvirus oncolytic therapy.

The concept of using replicating oncolytic viruses in cancer therapy dates to the beginning of the twentieth century. However, in the last few years, an increasing number of pre-clinical and clinical trials have been carried out with promising preliminarily results. Novel, indeed, is the suggestion that viral oncolytic therapy might not operate exclusively through an oncolysis-mediated process but additionally requires the "assistance" of the host's immune system. Originally, the host's immune response was believed to play a predominant obstructive role against viral replication, hence limiting the anti-tumor efficacy of viral vectors. Recent data, however, suggest that the immune response may also play a key role in promoting tumor destruction in association with the oncolytic process. In fact, immune effector pathways activated during oncolytic virus-induced tumor rejection seem to follow a similar pattern to those observed when the broader phenomenon of immune-mediated tissue-specific rejection occurs in other immune-related pathologies. We recently formulated the "Immunologic Constant of Rejection" hypothesis, emphasizing commonalties in transcriptional patterns observed when tissue-destruction occurs: whether with a favorable outcome, such as in tumor rejection and pathogen clearance; or a destructive one, such as in allograft rejection or autoimmunity. Here, we propose that a similar mechanism induces clearance of virally infected tumors and that such a mechanism is primarily dependent on innate immune functions.

Screening for hepatitis B, C and non-alcoholic fatty liver disease: a survey of community-based physicians.

BACKGROUND: Screening guidelines for hepatitis B (HBV) and hepatitis C viruses (HCV) as well as a position statement for non-alcoholic fatty liver disease (NAFLD) have been put forth by different sources, but awareness of these guidelines and their impact on the physician practices have not been assessed. AIM: To assess the attitudes of primary care physicians (PCPs), gastroenterologists (GEs) and hepatologists (HEPs) regarding screening for HBV, HCV and NAFLD. DESIGN: A survey questionnaire was sent to community-based PCPs and GEs to assess issues related to HBV, HCV and NAFLD. The same questionnaire was sent to hepatologists (HEPs). The questionnaire contained 10 items related to demographic and practice patterns of these physicians, 35 items related to HBV, 35 items related to HCV and 29 items related to NAFLD. RESULTS: A total of 214 physicians (103 PCPs, 59 GEs and 52 HEPs) completed the survey. A majority of PCPs, GEs and HEPs agreed on most screening issues for these causes of liver disease. Nevertheless, within group comparison of physicians (guideline aware versus guideline unaware) showed significant differences in accurate response between those who were aware of guidelines and those who were not aware. CONCLUSIONS: A large percentage of PCPs and GEs were unaware of official guidelines for viral hepatitis B and hepatitis C. Those aware of guidelines were more likely to screen appropriately and avoid unnecessary testing. More needs to be done to assess awareness and the impact implementation of guidelines in hepatology.

The NGDO Co-ordination Group for Onchocerciasis Control.

Since the beginning of the donation of Mectizan by Merck & Co., Inc., non-governmental development organizations (NGDO) have been actively involved in the mass distribution of this drug to control onchocerciasis. In 2006, the network of NGDO involved in onchocerciasis control assisted in the treatment of over 62 million people. The current strategy that is used for distribution in Africa, community-directed treatment with ivermectin (CDTI), is very well suited for integration with other health activities. NGDO have been the pioneers in integrating comprehensive eye care, insecticide-treated nets for malaria, the control of multiple 'neglected' tropical diseases, and vitamin-A supplementation. These expanded activities bring with them new challenges, which need to be addressed by all partners and where the NGDO will play an active role.

Health care at the end of the road: opportunities from 20 years of partnership in onchocerciasis control.

The unprecedented decision of Merck & Co., Inc., to donate ivermectin through the Mectizan(R) Donation Program, has catalysed an exemplary partnership, to distribute the drug to the communities at risk of onchocerciasis, and empower them to take charge of the drug distribution themselves. Integration with other activities has always been part of the plan, but has been accelerated in recent years because of the need to strengthen primary health care, and to meet the challenges of integrating the rapid impact of Neglected Tropical Disease programmes. Activities that have been integrated include provision of vitamin A capsules, elimination of lymphatic filariasis, the distribution of insecticide-treated nets, and comprehensive eye health. Although these integrated activities show promising results for all programmes involved, challenges still remain. The risk of overburdening communities with multiple activities, and the problem of remuneration at the community level, are the major concerns, as is the need for effective coordination. The expanded onchocerciasis control partnership is a model of translating the eighth Millennium Development Goal (MDG), namely 'develop a global partnership for development', into action and also addresses other key MDGs. In 2006, the partnership provided more than 62 million treatments for onchocerciasis control, and offers a firm foundation from which to deliver other needed health interventions while safeguarding the achievements of onchocerciasis control thus far.