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Sample records for acquired microcephaly loss

  1. Microcephaly

    MedlinePlus

    ... take only a few seconds while the measuring tape is placed around the infant's head. The provider ... be slowing down. If your provider diagnoses your child with microcephaly, you should note it in your ...

  2. Hearing Loss in Infants with Microcephaly and Evidence of Congenital Zika Virus Infection - Brazil, November 2015-May 2016.

    PubMed

    Leal, Mariana C; Muniz, Lilian F; Ferreira, Tamires S A; Santos, Cristiane M; Almeida, Luciana C; Van Der Linden, Vanessa; Ramos, Regina C F; Rodrigues, Laura C; Neto, Silvio S Caldas

    2016-01-01

    Congenital infection with Zika virus causes microcephaly and other brain abnormalities (1). Hearing loss associated with other congenital viral infections is well described; however, little is known about hearing loss in infants with congenital Zika virus infection. A retrospective assessment of a series of 70 infants aged 0-10 months with microcephaly and laboratory evidence of Zika virus infection was conducted by the Hospital Agamenon Magalhães in Brazil and partners. The infants were enrolled during November 2015-May 2016 and had screening and diagnostic hearing tests. Five (7%) infants had sensorineural hearing loss, all of whom had severe microcephaly; however, one child was tested after receiving treatment with an ototoxic antibiotic. If this child is excluded, the prevalence of sensorineural hearing loss was 5.8% (four of 69), which is similar to that seen in association with other congenital viral infections. Additional information is needed to understand the prevalence and spectrum of hearing loss in children with congenital Zika virus infection; all infants born to women with evidence of Zika virus infection during pregnancy should have their hearing tested, including infants who appear normal at birth. PMID:27585248

  3. Novel loss-of-function variants in DIAPH1 associated with syndromic microcephaly, blindness, and early onset seizures.

    PubMed

    Al-Maawali, Almundher; Barry, Brenda J; Rajab, Anna; El-Quessny, Malak; Seman, Ann; Coury, Stephanie Newton; Barkovich, A James; Yang, Edward; Walsh, Christopher A; Mochida, Ganeshwaran H; Stoler, Joan M

    2016-02-01

    Exome sequencing identified homozygous loss-of-function variants in DIAPH1 (c.2769delT; p.F923fs and c.3145C>T; p.R1049X) in four affected individuals from two unrelated consanguineous families. The affected individuals in our report were diagnosed with postnatal microcephaly, early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections. A heterozygous DIAPH1 mutation was originally reported in one family with autosomal dominant deafness. Recently, however, a homozygous nonsense DIAPH1 mutation (c.2332C4T; p.Q778X) was reported in five siblings in a single family affected by microcephaly, blindness, early onset seizures, developmental delay, and bronchiectasis. The role of DIAPH1 was supported using parametric linkage analysis, RNA and protein studies in their patients' cell lines and further studies in human neural progenitors cells and a diap1 knockout mouse. In this report, the proband was initially brought to medical attention for profound metopic synostosis. Additional concerns arose when his head circumference did not increase after surgical release at 5 months of age and he was diagnosed with microcephaly and epilepsy at 6 months of age. Clinical exome analysis identified a homozygous DIAPH1 mutation. Another homozygous DIAPH1 mutation was identified in the research exome analysis of a second family with three siblings presenting with a similar phenotype. Importantly, no hearing impairment is reported in the homozygous affected individuals or in the heterozygous carrier parents in any of the families demonstrating the autosomal recessive microcephaly phenotype. These additional families provide further evidence of the likely causal relationship between DIAPH1 mutations and a neurodevelopmental disorder. PMID:26463574

  4. A novel nonsense CDK5RAP2 mutation in a Somali child with primary microcephaly and sensorineural hearing loss.

    PubMed

    Pagnamenta, Alistair T; Murray, Jennie E; Yoon, Grace; Sadighi Akha, Elham; Harrison, Victoria; Bicknell, Louise S; Ajilogba, Kaseem; Stewart, Helen; Kini, Usha; Taylor, Jenny C; Keays, David A; Jackson, Andrew P; Knight, Samantha J L

    2012-10-01

    Primary microcephaly is a genetically heterogeneous condition characterized by reduced head circumference (-3 SDS or more) and mild-to-moderate learning disability. Here, we describe clinical and molecular investigations of a microcephalic child with sensorineural hearing loss. Although consanguinity was unreported initially, detection of 13.7 Mb of copy neutral loss of heterozygosity (cnLOH) on chromosome 9 implicated the CDK5RAP2 gene. Targeted sequencing identified a homozygous E234X mutation, only the third mutation to be described in CDK5RAP2, the first in an individual of non-Pakistani descent. Sensorineural hearing loss is not generally considered to be consistent with autosomal recessive microcephaly and therefore it seems likely that the deafness in this individual is caused by the co-occurrence of a further gene mutation, independent of CDK5RAP2. Nevertheless, further detailed clinical descriptions of rare CDK5RAP2 patients, including hearing assessments will be needed to resolve fully the phenotypic range associated with mutations in this gene. This study also highlights the utility of SNP-array testing to guide disease gene identification where an autosomal recessive condition is plausible. PMID:22887808

  5. Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans.

    PubMed

    Ercan-Sencicek, A Gulhan; Jambi, Samira; Franjic, Daniel; Nishimura, Sayoko; Li, Mingfeng; El-Fishawy, Paul; Morgan, Thomas M; Sanders, Stephan J; Bilguvar, Kaya; Suri, Mohnish; Johnson, Michele H; Gupta, Abha R; Yuksel, Zafer; Mane, Shrikant; Grigorenko, Elena; Picciotto, Marina; Alberts, Arthur S; Gunel, Murat; Šestan, Nenad; State, Matthew W

    2015-02-01

    The combination of family-based linkage analysis with high-throughput sequencing is a powerful approach to identifying rare genetic variants that contribute to genetically heterogeneous syndromes. Using parametric multipoint linkage analysis and whole exome sequencing, we have identified a gene responsible for microcephaly (MCP), severe visual impairment, intellectual disability, and short stature through the mapping of a homozygous nonsense alteration in a multiply-affected consanguineous family. This gene, DIAPH1, encodes the mammalian Diaphanous-related formin (mDia1), a member of the diaphanous-related formin family of Rho effector proteins. Upon the activation of GTP-bound Rho, mDia1 generates linear actin filaments in the maintenance of polarity during adhesion, migration, and division in immune cells and neuroepithelial cells, and in driving tangential migration of cortical interneurons in the rodent. Here, we show that patients with a homozygous nonsense DIAPH1 alteration (p.Gln778*) have MCP as well as reduced height and weight. diap1 (mDia1 knockout (KO))-deficient mice have grossly normal body and brain size. However, our histological analysis of diap1 KO mouse coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement, indicating that this mutant mouse shows both important similarities as well as differences with human pathology. We also found that mDia1 protein is expressed in human neuronal precursor cells during mitotic cell division and has a major impact in the regulation of spindle formation and cell division. PMID:24781755

  6. Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans

    PubMed Central

    Ercan-Sencicek, A Gulhan; Jambi, Samira; Franjic, Daniel; Nishimura, Sayoko; Li, Mingfeng; El-Fishawy, Paul; Morgan, Thomas M; Sanders, Stephan J; Bilguvar, Kaya; Suri, Mohnish; Johnson, Michele H; Gupta, Abha R; Yuksel, Zafer; Mane, Shrikant; Grigorenko, Elena; Picciotto, Marina; Alberts, Arthur S; Gunel, Murat; Šestan, Nenad; State, Matthew W

    2015-01-01

    The combination of family-based linkage analysis with high-throughput sequencing is a powerful approach to identifying rare genetic variants that contribute to genetically heterogeneous syndromes. Using parametric multipoint linkage analysis and whole exome sequencing, we have identified a gene responsible for microcephaly (MCP), severe visual impairment, intellectual disability, and short stature through the mapping of a homozygous nonsense alteration in a multiply-affected consanguineous family. This gene, DIAPH1, encodes the mammalian Diaphanous-related formin (mDia1), a member of the diaphanous-related formin family of Rho effector proteins. Upon the activation of GTP-bound Rho, mDia1 generates linear actin filaments in the maintenance of polarity during adhesion, migration, and division in immune cells and neuroepithelial cells, and in driving tangential migration of cortical interneurons in the rodent. Here, we show that patients with a homozygous nonsense DIAPH1 alteration (p.Gln778*) have MCP as well as reduced height and weight. diap1 (mDia1 knockout (KO))-deficient mice have grossly normal body and brain size. However, our histological analysis of diap1 KO mouse coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement, indicating that this mutant mouse shows both important similarities as well as differences with human pathology. We also found that mDia1 protein is expressed in human neuronal precursor cells during mitotic cell division and has a major impact in the regulation of spindle formation and cell division. PMID:24781755

  7. Pediatric sensorineural hearing loss, part 2: syndromic and acquired causes.

    PubMed

    Huang, B Y; Zdanski, C; Castillo, M

    2012-03-01

    This article is the second in a 2-part series reviewing neuroimaging in childhood SNHL. Previously, we discussed the clinical work-up of children with hearing impairment, the classification of inner ear malformations, and congenital nonsyndromic causes of hearing loss. Here, we review and illustrate the most common syndromic hereditary and acquired causes of childhood SNHL, with an emphasis on entities that demonstrate inner ear abnormalities on cross-sectional imaging. Syndromes discussed include BOR syndrome, CHARGE syndrome, Pendred syndrome, Waardenburg syndrome, and X-linked hearing loss with stapes gusher. We conclude the article with a review of acquired causes of childhood SNHL, including infections, trauma, and neoplasms. PMID:21596810

  8. Interstitial deletion of 6q25.2–q25.3: a novel microdeletion syndrome associated with microcephaly, developmental delay, dysmorphic features and hearing loss

    PubMed Central

    Nagamani, Sandesh Chakravarthy Sreenath; Erez, Ayelet; Eng, Christine; Ou, Zhishuo; Chinault, Craig; Workman, Laura; Coldwell, James; Stankiewicz, Pawel; Patel, Ankita; Lupski, James R; Cheung, Sau Wai

    2009-01-01

    Interstitial deletions of 6q are rare. We report a detailed clinical and molecular characterization of four patients with interstitial deletion involving 6q25. All of our patients presented with microcephaly, developmental delay, dysmorphic features and hearing loss, whereas two of them had agenesis of the corpus callosum. We determined the size, extent and genomic content of the deletions using high-density array-comparative genomic hybridization (a-CGH), and found that a common segment spanning 3.52 Mb within the 6q25.2–q25.3 region was deleted in all four cases. We hypothesize that a subset of genes in the commonly deleted region are dosage sensitive and that haploinsufficieny of these genes impairs normal development of the brain and hearing. PMID:19034313

  9. The desmosterolosis phenotype: spasticity, microcephaly and micrognathia with agenesis of corpus callosum and loss of white matter

    PubMed Central

    Zolotushko, Jenny; Flusser, Hagit; Markus, Barak; Shelef, Ilan; Langer, Yshaia; Heverin, Maura; Björkhem, Ingemar; Sivan, Sara; Birk, Ohad S

    2011-01-01

    Desmosterolosis is a rare autosomal recessive disorder of elevated levels of the cholesterol precursor desmosterol in plasma, tissue and cultured cells. With only two sporadic cases described to date with two very different phenotypes, the clinical entity arising from mutations in 24-dehydrocholesterol reductase (DHCR24) has yet to be defined. We now describe consanguineous Bedouin kindred with four surviving affected individuals, all presenting with severe failure to thrive, psychomotor retardation, microcephaly, micrognathia and spasticity with variable degree of hand contractures. Convulsions near birth, nystagmus and strabismus were found in most. Brain MRI demonstrated significant reduction in white matter and near agenesis of corpus callosum in all. Genome-wide linkage analysis and fine mapping defined a 6.75 cM disease-associated locus in chromosome 1 (maximum multipoint LOD score of six), and sequencing of candidate genes within this locus identified in the affected individuals a homozygous missense mutation in DHCR24 leading to dramatically augmented plasma desmosterol levels. We thus establish a clear consistent phenotype of desmosterolosis (MIM 602398). PMID:21559050

  10. Neural Alterations in Acquired Age-Related Hearing Loss

    PubMed Central

    Mudar, Raksha A.; Husain, Fatima T.

    2016-01-01

    Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although, we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches. PMID:27313556

  11. Microcephaly and Macrocephaly in Autism.

    ERIC Educational Resources Information Center

    Fombonne, Eric; Roge, Bernadette; Claverie, Jacques; Courty, Stephanie; Fremolle, Jeanne

    1999-01-01

    Analysis of data from 126 children with autism found macrocephaly (head circumstance microcephaly (head circumference <3rd centile) was found in 15.1%. Microcephaly was significantly associated with the presence of medical disorders. (Author/DB)

  12. Loss-of-function mutations in WDR73 are responsible for microcephaly and steroid-resistant nephrotic syndrome: Galloway-Mowat syndrome.

    PubMed

    Colin, Estelle; Huynh Cong, Evelyne; Mollet, Géraldine; Guichet, Agnès; Gribouval, Olivier; Arrondel, Christelle; Boyer, Olivia; Daniel, Laurent; Gubler, Marie-Claire; Ekinci, Zelal; Tsimaratos, Michel; Chabrol, Brigitte; Boddaert, Nathalie; Verloes, Alain; Chevrollier, Arnaud; Gueguen, Naig; Desquiret-Dumas, Valérie; Ferré, Marc; Procaccio, Vincent; Richard, Laurence; Funalot, Benoit; Moncla, Anne; Bonneau, Dominique; Antignac, Corinne

    2014-12-01

    Galloway-Mowat syndrome is a rare autosomal-recessive condition characterized by nephrotic syndrome associated with microcephaly and neurological impairment. Through a combination of autozygosity mapping and whole-exome sequencing, we identified WDR73 as a gene in which mutations cause Galloway-Mowat syndrome in two unrelated families. WDR73 encodes a WD40-repeat-containing protein of unknown function. Here, we show that WDR73 was present in the brain and kidney and was located diffusely in the cytoplasm during interphase but relocalized to spindle poles and astral microtubules during mitosis. Fibroblasts from one affected child and WDR73-depleted podocytes displayed abnormal nuclear morphology, low cell viability, and alterations of the microtubule network. These data suggest that WDR73 plays a crucial role in the maintenance of cell architecture and cell survival. Altogether, WDR73 mutations cause Galloway-Mowat syndrome in a particular subset of individuals presenting with late-onset nephrotic syndrome, postnatal microcephaly, severe intellectual disability, and homogenous brain MRI features. WDR73 is another example of a gene involved in a disease affecting both the kidney glomerulus and the CNS. PMID:25466283

  13. Zika Virus Infection and Microcephaly.

    PubMed

    Millichap, J Gordon

    2016-01-01

    A Task Force established by the Brazil Ministry of Health investigated the possible association of microcephaly with Zika virus infection during pregnancy and a registry for microcephaly cases among women suspected to have had Zika virus infection during pregnancy. PMID:27004142

  14. Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities.

    PubMed

    Narayanan, Mohan; Ramsey, Keri; Grebe, Theresa; Schrauwen, Isabelle; Szelinger, Szabolcs; Huentelman, Matthew; Craig, David; Narayanan, Vinodh

    2015-01-01

    Microcephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infection or hypoxic ischemic encephalopathy), or be a part of a genetic syndrome. There are over 1000 conditions listed in OMIM (Online Mendelian Inheritance in Man) where microcephaly is a key finding; many of these are associated with specific somatic features and non-CNS anomalies. The term primary microcephaly is used when microcephaly and delayed development are the primary features, and they are not part of another recognized syndrome. In this case report, we present the clinical features of siblings (brother and sister) with primary microcephaly and delayed development, and subtle dysmorphic features. Both children had brain MRI studies that showed periventricular and subcortical T2/FLAIR hyperintensities, without signs of white matter volume loss, and no parenchymal calcifications by CT scan. The family was enrolled in a research study for whole exome sequencing of probands and parents. Analysis of variants determined that the children were compound heterozygotes for nonsense mutations, c.277C>T (p.Arg93*) and c.397C>T (p.Arg133*), in the TRMT10A gene. Mutations in this gene have only recently been reported in children with microcephaly and early onset diabetes mellitus. Our report adds to current knowledge of TRMT10A related neurodevelopmental disorders and demonstrates imaging findings suggestive of delayed or abnormal myelination of the white matter in this disorder. Accurate diagnosis through genomic testing, as in the children described here, allows for early detection and management of medical complications, such as diabetes mellitus. PMID:26535115

  15. Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities

    PubMed Central

    Narayanan, Mohan; Ramsey, Keri; Grebe, Theresa; Schrauwen, Isabelle; Szelinger, Szabolcs; Huentelman, Matthew; Craig, David; Narayanan, Vinodh

    2015-01-01

    Microcephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infection or hypoxic ischemic encephalopathy), or be a part of a genetic syndrome. There are over 1000 conditions listed in OMIM (Online Mendelian Inheritance in Man) where microcephaly is a key finding; many of these are associated with specific somatic features and non-CNS anomalies. The term primary microcephaly is used when microcephaly and delayed development are the primary features, and they are not part of another recognized syndrome. In this case report, we present the clinical features of siblings (brother and sister) with primary microcephaly and delayed development, and subtle dysmorphic features. Both children had brain MRI studies that showed periventricular and subcortical T2/FLAIR hyperintensities, without signs of white matter volume loss, and no parenchymal calcifications by CT scan. The family was enrolled in a research study for whole exome sequencing of probands and parents. Analysis of variants determined that the children were compound heterozygotes for nonsense mutations, c.277C>T (p.Arg93*) and c.397C>T (p.Arg133*), in the TRMT10A gene. Mutations in this gene have only recently been reported in children with microcephaly and early onset diabetes mellitus. Our report adds to current knowledge of TRMT10A related neurodevelopmental disorders and demonstrates imaging findings suggestive of delayed or abnormal myelination of the white matter in this disorder. Accurate diagnosis through genomic testing, as in the children described here, allows for early detection and management of medical complications, such as diabetes mellitus. PMID:26535115

  16. Microcephaly and the Zika virus.

    PubMed

    2016-09-12

    Cases of microcephaly brought about by the Zika virus have brought professional and personal challenges for nurses in Brazil. Paediatric nurses, such as Roberta Seabra (pictured), take over as part of the multidisciplinary team once the baby is born. In this article health writer Jacqui Thornton presents some personal stories. PMID:27615590

  17. Autosomal recessive primary microcephalies (MCPH).

    PubMed

    Kaindl, Angela M

    2014-07-01

    Autosomal recessive primary microcephaly (MCPH) is a genetically heterogeneous disease characterized by a pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. Here, we summarize the genetic causes of MCPH types 1-12 known to date. PMID:24780602

  18. Eye color as a risk factor for acquired sensorineural hearing loss: a review.

    PubMed

    Mujica-Mota, Mario A; Schermbrucker, Jonah; Daniel, Sam J

    2015-02-01

    Eye color may be an indicator of inner ear melanin content and has been associated with hearing loss. There is controversy as to whether eye color has an effect on acquired causes of sensorineural hearing loss. This review was conducted to analyze the literature evaluating the relationship between eye color and causes of sensorineural hearing loss. Six databases were searched to identify eligible studies. Included articles were independently assessed for quality by two authors. Eighteen articles were eligible for review. Eye color was not found to have an effect in the non-exposed population or in presbycusis. In noise-induced sensorineural hearing loss, light-eyed patients had more significant loss following noise exposure, although the variability reported due to eye color was modest (r(2) = 0.01-0.14). Two out of three studies reported that dark eye color is associated with cisplatin ototoxicity. In one study, green-eyed patients were found to be at higher risk of radiation-induced hearing loss. Eye color does not appear to play a role in hearing loss in non-exposed individuals or presbycusis. It is possible that dark-eyed individuals, with greater inner ear melanin content, are better protected against noise-induced hearing loss. Evidence suggests that melanin can be protective against radiation-induced sensorineural hearing loss, but may predispose individuals to cisplatin ototoxicity. Future studies are required to support these conclusions. PMID:25529530

  19. Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update.

    PubMed

    Huang, Lijia; Vanstone, Megan R; Hartley, Taila; Osmond, Matthew; Barrowman, Nick; Allanson, Judith; Baker, Laura; Dabir, Tabib A; Dipple, Katrina M; Dobyns, William B; Estrella, Jane; Faghfoury, Hanna; Favaro, Francine P; Goel, Himanshu; Gregersen, Pernille A; Gripp, Karen W; Grix, Art; Guion-Almeida, Maria-Leine; Harr, Margaret H; Hudson, Cindy; Hunter, Alasdair G W; Johnson, John; Joss, Shelagh K; Kimball, Amy; Kini, Usha; Kline, Antonie D; Lauzon, Julie; Lildballe, Dorte L; López-González, Vanesa; Martinezmoles, Johanna; Meldrum, Cliff; Mirzaa, Ghayda M; Morel, Chantal F; Morton, Jenny E V; Pyle, Louise C; Quintero-Rivera, Fabiola; Richer, Julie; Scheuerle, Angela E; Schönewolf-Greulich, Bitten; Shears, Deborah J; Silver, Josh; Smith, Amanda C; Temple, I Karen; van de Kamp, Jiddeke M; van Dijk, Fleur S; Vandersteen, Anthony M; White, Sue M; Zackai, Elaine H; Zou, Ruobing; Bulman, Dennis E; Boycott, Kym M; Lines, Matthew A

    2016-02-01

    Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5-116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated ∼27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late "catch-up" growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2). PMID:26507355

  20. Study IDs 2 Zika Virus Proteins Linked to Microcephaly

    MedlinePlus

    ... Study IDs 2 Zika Virus Proteins Linked to Microcephaly Discovery might one day lead to a way ... Zika virus linked to the severe birth defect microcephaly. Babies with microcephaly have abnormally small heads and ...

  1. Zika Virus Associated with Microcephaly.

    PubMed

    Mlakar, Jernej; Korva, Misa; Tul, Nataša; Popović, Mara; Poljšak-Prijatelj, Mateja; Mraz, Jerica; Kolenc, Marko; Resman Rus, Katarina; Vesnaver Vipotnik, Tina; Fabjan Vodušek, Vesna; Vizjak, Alenka; Pižem, Jože; Petrovec, Miroslav; Avšič Županc, Tatjana

    2016-03-10

    A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain. PMID:26862926

  2. Microcephaly in Infants, Pernambuco State, Brazil, 2015.

    PubMed

    2016-06-01

    We studied the clinical characteristics for 104 infants born with microcephaly in the delivery hospitals of Pernambuco State, Brazil, during 2015. Testing is ongoing to exclude known infectious causes. However, microcephaly peaked in October and demonstrated central nervous system abnormalities with brain dysgenesis and intracranial calcifications consistent with an intrauterine infection. PMID:27071041

  3. Microcephaly in Infants, Pernambuco State, Brazil, 2015

    PubMed Central

    2016-01-01

    We studied the clinical characteristics for 104 infants born with microcephaly in the delivery hospitals of Pernambuco State, Brazil, during 2015. Testing is ongoing to exclude known infectious causes. However, microcephaly peaked in October and demonstrated central nervous system abnormalities with brain dysgenesis and intracranial calcifications consistent with an intrauterine infection. PMID:27071041

  4. Acquired color vision loss and a possible mechanism of ganglion cell death in glaucoma.

    PubMed Central

    Nork, T M

    2000-01-01

    PURPOSE: First, to study the cellular mechanisms of acquired color vision loss in retinal detachment and diabetic retinopathy. Second, to learn why, in glaucoma, the type of color vision deficit that is observed is more characteristic of a retinal injury than it is of an optic neuropathy. Third, to test a hypothesis of photoreceptor-induced, ganglion cell death in glaucoma. METHODS: Various histologic techniques were employed to distinguish the L/M-cones (long/medium wavelength-sensitive cones, or red/green sensitive cones) from the S-cones (short wavelength-sensitive cones, or blue sensitive cones) in humans and monkeys with retinal detachment, humans with diabetic retinopathy, and both humans and monkeys with glaucoma. To test if the photoreceptors were contributing to ganglion cell death, laser photocoagulation was used in a experimental model of glaucoma to focally eliminate the photoreceptors. As a control, optic nerve transection was done following retinal laser photocoagulation in one animal. RESULTS: Selective and widespread loss of the S-cones was found in retinal detachment as well as diabetic retinopathy. By contrast, in human as well as experimental glaucoma, marked swelling of the L/M-cones was the predominant histopathologic feature. Retinal laser photocoagulation followed by experimental glaucoma resulted in selective protection of ganglion cells overlying the laser spots. This was not seen with retinal laser photocoagulation by optic nerve transection. CONCLUSIONS: In retinal detachment and diabetic retinopathy, acquired tritan-like color vision loss could be caused, or contributed to, by selective loss of the S-cones. Both L- and M-cones are affected in glaucoma, which is also consistent with a tritan-like deficit. Although not a therapeutic option, protection of ganglion cells by retinal laser in experimental glaucoma is consistent with an hypothesis of anterograde, photoreceptor-induced, ganglion cell death. Images FIGURE 1 FIGURE 2 FIGURE 3

  5. Clinical significance of acquired loss of the X chromosome in bone marrow.

    PubMed

    Tang, Zhenya; Li, Yan; Wang, Sa A; Hu, Shimin; Li, Shaoying; Lu, Xinyan; Khoury, Joseph D; Medeiros, L Jeffrey; Tang, Guilin

    2016-08-01

    Acquired loss of the X chromosome (-X) as a sole abnormality is detected rarely in bone marrow (BM) and its clinical importance remains largely unknown. We studied 38 patients with isolated -X in BM. All patients were women, with a median age of 71 years. At the time of -X detection, BM was positive for myeloid neoplasm in 14 patients, lymphoma/myeloma in 10 patients, and was normal in 14 patients. -X was detected as a major clone in 15 patients (11 of them had myeloid neoplasm) and a minor clone in 23 patients. Combined morphologic and FISH analysis was performed in 16 cases, -X was detected in myeloid/erythroid cells in all 16 patients and in lymphocytes in 15 patients. With a median of 23 months follow-up, none of the patients with a negative BM or BM with involvement by lymphoid neoplasms developed a secondary myeloid neoplasm. We conclude that isolated -X is a rare finding in BM. In majority of patients, -X presents as a minor clone and is likely to be an aging effect or a benign finding; whereas when -X presents as a major clone in BM, it is often disease associated. PMID:27299973

  6. [Molecular genetics of lissencephaly and microcephaly].

    PubMed

    Mochida, Ganeshwaran Hitoshi

    2008-04-01

    Genetic malformations of the cerebral cortex are an important cause of neurological disability in children. The genes implicated in these disorders are essential for normal cerebral cortical development. Therefore, identifying these genes and studying their functions will help us further the understanding of the normal biological mechanisms of brain development. Lissencephaly and microcephaly are two groups of disorders that have been intensely studied and several causative genes within each group have been identified. Type I (classical) lissencephaly is characterized by a smooth-appearing brain with a lack or severe reduction of normal gyri. Three of its identified causative genes (LIS1, DCX and TUBA1A) are related to microtubules, which are essential for neuronal migration in the developing cerebral cortex. Microcephaly vera is a form of microcephaly with four responsible genes reported to date. Three of them (ASPM, CENPJ and CDK5RAP2) localize to the mitotic centrosome, and one (MCPH1) is implicated in cell cycle checkpoint regulation and DNA damage response. This suggests that abnormalities of neural progenitor cell division are fundamental to the pathogenesis of microcephaly vera. These genes for microcephaly vera are also suggested to have played a role in evolutionary volume expansion of the human cerebral cortex. These examples show that genetic studies of lissencephaly and microcephaly have been very fruitful in providing novel insights into various aspects of human cerebral cortical development. PMID:18421985

  7. CDC Concludes Zika Causes Microcephaly and Other Birth Defects

    MedlinePlus

    ... concluded, after careful review of existing evidence, that Zika virus is a cause of microcephaly and other severe ... have microcephaly born to mothers infected by the Zika virus is the tip of the iceberg of what ...

  8. The Design and Screening of Drugs to Prevent Acquired Sensorineural Hearing Loss

    PubMed Central

    Mukherjea, Debashree; Rybak, Leonard P.; Sheehan, Kelly E; Kaur, Tejbeer; Ramkumar, Vickram; Jajoo, Sarvesh; Sheth, Sandeep

    2011-01-01

    Introduction Sensorineural hearing loss affects a high percentage of the population. Ototoxicity is a serious and pervasive problem in patients treated with cisplatin. Strategies to ameliorate ototoxicity without compromising on antitumor activity of treatments are urgently needed. Similar problems occur with aminoglycoside antibiotic therapy for infections. Noise-induced hearing loss affects a large number of people. The use of ear protection is not always possible or effective. The prevention of hearing loss with drug therapy would have a huge impact in reducing the number of persons with hearing loss from these major causes. Areas covered This review discusses significant research findings dealing with the use of protective agents against hearing loss caused by cisplatin, aminoglycoside antibiotics and noise trauma. The efficacy in animal studies and the application of these protective agents in clinical trials that are ongoing are presented. Expert opinion The reader will gain new insights into current and projected future strategies to prevent sensorineural hearing loss from cisplatin chemotherapy, aminoglycoside antibiotic therapy and noise exposure. The future appears to offer numerous agents to prevent hearing loss caused by cisplatin, aminoglycoside antibiotics and noise. Novel delivery systems will provide ways to guide these protective agents to the desired target areas in the inner ear and will circumvent problems with therapeutic interference of anti-tumor and antibiotics agents and will minimize undesired side effects. PMID:22646075

  9. Zika and the Risk of Microcephaly.

    PubMed

    2016-08-01

    Zika and the Risk of Microcephaly Perspective, N Engl J Med 2016;375:1-4. In Figure 1 (page 2), the second-trimester and third-trimester graphs (Panels D and F) were transposed. The article is correct at NEJM.org. PMID:27518688

  10. Age-related hearing impairment and the triad of acquired hearing loss

    PubMed Central

    Yang, Chao-Hui; Schrepfer, Thomas; Schacht, Jochen

    2015-01-01

    Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species (ROS) and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI) in human and animal models and address selected aspects of the commonality (or lack thereof) of cellular responses in ARHI to drugs and noise. PMID:26283913

  11. Comparative Genomics Suggests That the Human Pathogenic Fungus Pneumocystis jirovecii Acquired Obligate Biotrophy through Gene Loss

    PubMed Central

    Cissé, Ousmane H.; Pagni, Marco; Hauser, Philippe M.

    2014-01-01

    Pneumocystis jirovecii is a fungal parasite that colonizes specifically humans and turns into an opportunistic pathogen in immunodeficient individuals. The fungus is able to reproduce extracellularly in host lungs without eliciting massive cellular death. The molecular mechanisms that govern this process are poorly understood, in part because of the lack of an in vitro culture system for Pneumocystis spp. In this study, we explored the origin and evolution of the putative biotrophy of P. jirovecii through comparative genomics and reconstruction of ancestral gene repertoires. We used the maximum parsimony method and genomes of related fungi of the Taphrinomycotina subphylum. Our results suggest that the last common ancestor of Pneumocystis spp. lost 2,324 genes in relation to the acquisition of obligate biotrophy. These losses may result from neutral drift and affect the biosyntheses of amino acids and thiamine, the assimilation of inorganic nitrogen and sulfur, and the catabolism of purines. In addition, P. jirovecii shows a reduced panel of lytic proteases and has lost the RNA interference machinery, which might contribute to its genome plasticity. Together with other characteristics, that is, a sex life cycle within the host, the absence of massive destruction of host cells, difficult culturing, and the lack of virulence factors, these gene losses constitute a unique combination of characteristics which are hallmarks of both obligate biotrophs and animal parasites. These findings suggest that Pneumocystis spp. should be considered as the first described obligate biotrophs of animals, whose evolution has been marked by gene losses. PMID:25062922

  12. The value of success: acquiring gains, avoiding losses, and simply being successful.

    PubMed

    Mowrer, Samantha M; Jahn, Andrew A; Abduljalil, Amir; Cunningham, William A

    2011-01-01

    A large network of spatially contiguous, yet anatomically distinct regions in medial frontal cortex is involved in reward processing. Although it is clear these regions play a role in critical aspects of reward-related learning and decision-making, the individual contributions of each component remains unclear. We explored dissociations in reward processing throughout several key regions in the reward system and aimed to clarify the nature of previously observed outcome-related activity in a portion of anterior medial orbitofrontal cortex (mOFC). Specifically, we tested whether activity in anterior mOFC was related to processing successful actions, such that this region would respond similarly to rewards with and without tangible benefits, or whether this region instead encoded only quantifiable outcome values (e.g., money). Participants performed a task where they encountered monetary gains and losses (and non-gains and non-losses) during fMRI scanning. Critically, in addition to the outcomes with monetary consequences, the task included trials that provided outcomes without tangible benefits (participants were simply told that they were correct or incorrect). We found that anterior mOFC responded to all successful outcomes regardless of whether they carried tangible benefits (monetary gains and non-losses) or not (controls). These results support the hypothesis that anterior mOFC processes rewards in terms of a common currency and is capable of providing reward-based signals for everything we value, whether it be primary or secondary rewards or simply a successful experience without objectively quantifiable benefits. PMID:21966494

  13. The Microcephaly-Capillary Malformation Syndrome

    PubMed Central

    Mirzaa, Ghayda M.; Paciorkowski, Alex R.; Smyser, Christopher D.; Willing, Marcia C.; Lind, Anne C.; Dobyns, William B.

    2012-01-01

    We report on three children from two families with a new pattern recognition malformation syndrome consisting of severe congenital microcephaly (MIC), intractable epilepsy including infantile spasms, and generalized capillary malformations that was first reported recently in this journal [Carter et al. (2011); Am J Med Genet A 155: 301–306]. Two of our reported patients are an affected brother and sister, suggesting this is an autosomal recessive severe congenital MIC syndrome. PMID:21815250

  14. Genetic disorders associated with postnatal microcephaly.

    PubMed

    Seltzer, Laurie E; Paciorkowski, Alex R

    2014-06-01

    Several genetic disorders are characterized by normal head size at birth, followed by deceleration in head growth resulting in postnatal microcephaly. Among these are classic disorders such as Angelman syndrome and MECP2-related disorder (formerly Rett syndrome), as well as more recently described clinical entities associated with mutations in CASK, CDKL5, CREBBP, and EP300 (Rubinstein-Taybi syndrome), FOXG1, SLC9A6 (Christianson syndrome), and TCF4 (Pitt-Hopkins syndrome). These disorders can be identified clinically by phenotyping across multiple neurodevelopmental and neurobehavioral realms, and enough data are available to recognize these postnatal microcephaly disorders as separate diagnostic entities in their own right. A second diagnostic grouping, comprised of Warburg MICRO syndrome, Cockayne syndrome, and Cerebral-oculo-facial skeletal syndrome, share similar features of somatic growth failure, ophthalmologic, and dysmorphologic features. Many postnatal microcephaly syndromes are caused by mutations in genes important in the regulation of gene expression in the developing forebrain and hindbrain, although important synaptic structural genes also play a role. This is an emerging group of disorders with a fascinating combination of brain malformations, specific epilepsies, movement disorders, and other complex neurobehavioral abnormalities. PMID:24839169

  15. De novo POGZ mutations are associated with neurodevelopmental disorders and microcephaly

    PubMed Central

    Ye, Yizhou; Cho, Megan T.; Retterer, Kyle; Alexander, Nora; Ben-Omran, Tawfeg; Al-Mureikhi, Mariam; Cristian, Ingrid; Wheeler, Patricia G.; Crain, Carrie; Zand, Dina; Weinstein, Veronique; Vernon, Hilary J.; McClellan, Rebecca; Krishnamurthy, Vidya; Vitazka, Patrik; Millan, Francisca; Chung, Wendy K.

    2015-01-01

    Seven patients with similar phenotypes of developmental delay and microcephaly were found by whole-exome sequencing to have de novo loss-of-function mutations in POGZ. POGZ is a pogo transposable element-derived protein with a zinc finger cluster. The protein is involved in normal kinetochore assembly and mitotic sister chromatid cohesion and mitotic chromosome segregation. POGZ deficiency may affect mitosis, disrupting brain development and function. PMID:27148570

  16. The impact of acquired brain damage in terms of epidemiology, economics and loss in quality of life

    PubMed Central

    2011-01-01

    Background Patients with acquired brain damage (ABD) have suffered a brain lesion that interrupts vital development in the physical, psychological and social spheres. Stroke and traumatic brain injury (TBI) are the two main causes. The objectives of this study were to estimate the incidence and prevalence of ABD in the population of the Basque Country and Navarre in 2008, to calculate the associated cost of the care required and finally to assess the loss in health-related quality of life. Methods On the one hand, a cross-sectional survey was carried out, in order to estimate the incidence of ABD and its consequences in terms of costs and loss in quality of life from the evolution of a sample of patients diagnosed with stroke and TBI. On the other hand, a discrete event simulation model was built that enabled the prevalence of ABD to be estimated. Finally, a calculation was made of the formal and informal costs of ABD in the population of the Basque Country and Navarre (2,750,000 people). Results The cross-sectional study showed that the incidences of ABD caused by stroke and TBI were 61.8 and 12.5 cases per 100,000 per year respectively, while the overall prevalence was 657 cases per 100,000 people. The SF-36 physical and mental component scores were 28.9 and 44.5 respectively. The total economic burden was calculated to be 382.14 million euro per year, distributed between 215.27 and 166.87 of formal and informal burden respectively. The average cost per individual was 21,040 € per year. Conclusions The main conclusion of this study is that ABD has a high impact in both epidemiological and economic terms as well as loss in quality of life. The overall prevalence obtained is equivalent to 0.7% of the total population. The substantial economic burden is distributed nearly evenly between formal and informal costs. Specifically, it was found that the physical dimensions of quality of life are the most severely affected. The prevalence-based approach showed adequate

  17. Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay

    PubMed Central

    Ben-Salem, Salma; Gleeson, Joseph G.; Al-Shamsi, Aisha M.; Islam, Barira; Hertecant, Jozef; Ali, Bassam R.

    2016-01-01

    Deficiency of Asparagine Synthetase (ASNSD, MIM 615574) is a very rare autosomal recessive disorder presenting with some brain abnormalities. Affected individuals have congenital microcephaly and progressive encephalopathy associated with severe intellectual disability and intractable seizures. The loss of function of the asparagine synthetase (ASNS, EC 6.3.5.4), particularly in the brain, is the major cause of this particular congenital microcephaly. In this study, we clinically evaluated an affected child from a consanguineous Emirati family presenting with congenital microcephaly and epileptic encephalopathy. In addition, whole-exome sequencing revealed a novel homozygous substitution mutation (c.1193A>C) in the ASNS gene. This mutation resulted in the substitution of highly conserved tyrosine residue by cysteine (p.Y398C). Molecular modeling analysis predicts hypomorphic and damaging effects of this mutation on the protein structure and altering its enzymatic activity. Therefore, we conclude that the loss of ASNS function is most likely the cause of this condition in the studied family. This report brings the number of reported families with this very rare disorder to five and the number of pathogenic mutations in the ASNS gene to four. This finding extends the ASNS pathogenic mutations spectrum and highlights the utility of whole-exome sequencing in elucidation the causes of rare recessive disorders that are heterogeneous and/or overlap with other conditions. PMID:25227173

  18. Cdk5rap2 exposes the centrosomal root of microcephaly syndromes.

    PubMed

    Megraw, Timothy L; Sharkey, James T; Nowakowski, Richard S

    2011-08-01

    Autosomal recessive primary microcephaly (MCPH) is characterized by small brain size as a result of deficient neuron production in the developing cerebral cortex. Although MCPH is a rare disease, the questions surrounding its etiology strike at the core of stem cell biology. The seven genes implicated in MCPH all encode centrosomal proteins and disruption of the MCPH gene Cdk5rap2 in mice revealed its role in neural progenitor proliferation and in maintaining normal centriole replication control. We discuss here the impact that centrosome regulation has upon neural progenitors in the developing brain. We integrate the impact of centriole replication defects with the functions of Cdk5rap2 and other MCPH proteins, propose mechanisms for progenitor loss in MCPH, and discuss links to two other microcephaly syndromes. PMID:21632253

  19. Many roads lead to primary autosomal recessive microcephaly.

    PubMed

    Kaindl, Angela M; Passemard, Sandrine; Kumar, Pavan; Kraemer, Nadine; Issa, Lina; Zwirner, Angelika; Gerard, Benedicte; Verloes, Alain; Mani, Shyamala; Gressens, Pierre

    2010-03-01

    Autosomal recessive primary microcephaly (MCPH), historically referred to as Microcephalia vera, is a genetically and clinically heterogeneous disease. Patients with MCPH typically exhibit congenital microcephaly as well as mental retardation, but usually no further neurological findings or malformations. Their microcephaly with grossly preserved macroscopic organization of the brain is a consequence of a reduced brain volume, which is evident particularly within the cerebral cortex and thus results to a large part from a reduction of grey matter. Some patients with MCPH further provide evidence of neuronal heterotopias, polymicrogyria or cortical dysplasia suggesting an associated neuronal migration defect. Genetic causes of MCPH subtypes 1-7 include mutations in genes encoding microcephalin, cyclin-dependent kinase 5 regulatory associated protein 2 (CDK5RAP2), abnormal spindle-like, microcephaly associated protein (ASPM), centromeric protein J (CENPJ), and SCL/TAL1-interrupting locus (STIL) as well as linkage to the two loci 19q13.1-13.2 and 15q15-q21. Here, we provide a timely overview of current knowledge on mechanisms leading to microcephaly in humans with MCPH and abnormalities in cell division/cell survival in corresponding animal models. Understanding the pathomechanisms leading to MCPH is of high importance not only for our understanding of physiologic brain development (particularly of cortex formation), but also for that of trends in mammalian evolution with a massive increase in size of the cerebral cortex in primates, of microcephalies of other etiologies including environmentally induced microcephalies, and of cancer formation. PMID:19931588

  20. Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting.

    PubMed

    Grinspoon, S; Corcoran, C; Lee, K; Burrows, B; Hubbard, J; Katznelson, L; Walsh, M; Guccione, A; Cannan, J; Heller, H; Basgoz, N; Klibanski, A

    1996-11-01

    The acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS) is a devastating complication of human immunodeficiency virus infection characterized by a disproportionate decrease in lean body mass. The pathogenesis of the AWS is unknown, but recent data suggest that endogenous secretion of the potent anabolic hormone, testosterone; is decreased in 30-50% of men with AIDS. However, it is unknown whether decreased androgen levels are associated with decreased lean body mass and/or functional decreases in muscle strength and aerobic capacity in hypogonadal men with the AWS. In addition, testosterone is known to have stimulatory effects on GH secretion, and the loss of these effects on the GH-insulin-like growth factor I (IGF-I) axis may be an additional mechanism of decreased lean body mass in this population. Twenty hypogonadal subjects (free-testosterone < 12 pg/mL) with weight loss > 10% of preillness weight or absolute weight < 90% ideal body weight (IBW) were enrolled in the study. None of the subjects were receiving Megace. Lean body mass and fat-free mass were determined by potassium-40 isotope analysis (40K) and dual-energy x-ray absorptiometry, respectively, and analyzed with respect to gonadal function by linear regression analysis. Muscle mass was determined by urinary creatinine excretion, and exercise functional capacity was assessed by a 6-min walk test, a sit-to-stand test, and a timed get-up-and-go test. Results also were compared with gonadal function by regression analysis. IGF-I and mean overnight GH levels, determined from frequent sampling (q20 min from 2000-0800 h), were compared with results obtained from age- and sex-matched normal controls. Subjects were 26-58 yr of age (39 +/- 7 yr, mean +/- SD) with a CD4 cell count of 150 +/- 186 cells/mm3. Serum levels of FSH were elevated in 30% of the subjects. Muscle mass was significantly reduced, compared with expected mass for height (23.3 +/- 5.5 vs. 29.3 +/- 1.7 kg, P = 0.0001) and was

  1. A syndrome of microcephaly, short stature, polysyndactyly, and dental anomalies caused by a homozygous KATNB1 mutation.

    PubMed

    Yigit, Gökhan; Wieczorek, Dagmar; Bögershausen, Nina; Beleggia, Filippo; Möller-Hartmann, Claudia; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Wollnik, Bernd

    2016-03-01

    Using whole-exome sequencing, we identified a homozygous acceptor splice-site mutation in intron 6 of the KATNB1 gene in a patient from a consanguineous Turkish family who presented with congenital microcephaly, lissencephaly, short stature, polysyndactyly, and dental abnormalities. cDNA analysis revealed complete loss of the natural acceptor splice-site resulting either in the usage of an alternative, exonic acceptor splice-site inducing a frame-shift and premature protein truncation or, to a minor extent, in complete skipping of exon 7. Both effects most likely lead to complete loss of KATNB1 function. Homozygous and compound heterozygous mutations in KATNB1 have very recently been described as a cause of microcephaly with brain malformations and seizures. We extend the KATNB1 associated phenotype by describing a syndrome characterized by primordial dwarfism, lissencephaly, polysyndactyly, and dental anomalies, which is caused by a homozygous truncating KATNB1 mutation. PMID:26640080

  2. Molecular genetics of human primary microcephaly: an overview

    PubMed Central

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  3. What primary microcephaly can tell us about brain growth.

    PubMed

    Cox, James; Jackson, Andrew P; Bond, Jacquelyn; Woods, Christopher G

    2006-08-01

    Autosomal recessive primary microcephaly (MCPH) is a neuro-developmental disorder that causes a great reduction in brain growth in utero. MCPH is hypothesized to be a primary disorder of neurogenic mitosis, leading to reduced neuron number. Hence, MCPH proteins are likely to be important components of cellular pathways regulating human brain size. At least six genes can cause this disorder and four of these have recently been identified: autosomal recessive primary microcephaly 1 (MCPH1), abnormal spindle-like, microcephaly associated (ASPM), cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) and centromere protein J (CENPJ). Whereas aberration of ASPM is the most common cause of MCPH, MCPH1 patients can be more readily diagnosed by the finding of increased numbers of "prophase-like cells" on routine cytogenetic investigation. Three MCPH proteins are centrosomal components but have apparently diverse roles that affect mitosis. There is accumulating evidence that evolutionary changes to the MCPH genes have contributed to the large brain size seen in primates, particularly humans. The aim of this article is to review what has been learnt about the rare condition primary microcephaly and the information this provides about normal brain growth. PMID:16829198

  4. Molecular genetics of human primary microcephaly: an overview.

    PubMed

    Faheem, Muhammad; Naseer, Muhammad Imran; Rasool, Mahmood; Chaudhary, Adeel G; Kumosani, Taha A; Ilyas, Asad Muhammad; Pushparaj, Peter; Ahmed, Farid; Algahtani, Hussain A; Al-Qahtani, Mohammad H; Saleh Jamal, Hasan

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  5. Microcephaly genes evolved adaptively throughout the evolution of eutherian mammals

    PubMed Central

    2014-01-01

    Background Genes associated with the neurodevelopmental disorder microcephaly display a strong signature of adaptive evolution in primates. Comparative data suggest a link between selection on some of these loci and the evolution of primate brain size. Whether or not either positive selection or this phenotypic association are unique to primates is unclear, but recent studies in cetaceans suggest at least two microcephaly genes evolved adaptively in other large brained mammalian clades. Results Here we analyse the evolution of seven microcephaly loci, including three recently identified loci, across 33 eutherian mammals. We find extensive evidence for positive selection having acted on the majority of these loci not just in primates but also across non-primate mammals. Furthermore, the patterns of selection in major mammalian clades are not significantly different. Using phylogenetically corrected comparative analyses, we find that the evolution of two microcephaly loci, ASPM and CDK5RAP2, are correlated with neonatal brain size in Glires and Euungulata, the two most densely sampled non-primate clades. Conclusions Together with previous results, this suggests that ASPM and CDK5RAP2 may have had a consistent role in the evolution of brain size in mammals. Nevertheless, several limitations of currently available data and gene-phenotype tests are discussed, including sparse sampling across large evolutionary distances, averaging gene-wide rates of evolution, potential phenotypic variation and evolutionary reversals. We discuss the implications of our results for studies of the genetic basis of brain evolution, and explicit tests of gene-phenotype hypotheses. PMID:24898820

  6. Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015.

    PubMed

    Schuler-Faccini, Lavinia; Ribeiro, Erlane M; Feitosa, Ian M L; Horovitz, Dafne D G; Cavalcanti, Denise P; Pessoa, André; Doriqui, Maria Juliana R; Neri, Joao Ivanildo; Neto, Joao Monteiro de Pina; Wanderley, Hector Y C; Cernach, Mirlene; El-Husny, Antonette S; Pone, Marcos V S; Serao, Cassio L C; Sanseverino, Maria Teresa V

    2016-01-01

    In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil's 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear

  7. The WHO-DAS II: psychometric properties in the measurement of functional health status in adults with acquired hearing loss.

    PubMed

    Chisolm, Theresa H; Abrams, Harvey B; McArdle, Rachel; Wilson, Richard H; Doyle, Patrick J

    2005-01-01

    The World Health Organization's (WHO) Disability Assessment Scale II (WHO-DAS II) is a generic health-status instrument firmly grounded in the WHO's International Classification of Functioning, Disability and Health (WHO-ICF). As such, it assesses functioning for six domains: communication, mobility, self-care, interpersonal, life activities, and participation. Domain scores aggregate to a total score. Because the WHO-DAS II contains questions relevant to hearing and communication, it has good face validity for use as an outcome measure for audiologic intervention. The purpose of the present study was to determine the psychometric properties of the WHO-DAS II on a sample of individuals with adult-onset hearing loss, including convergent validity, internal consistency, and test-retest stability. Convergent validity was established by examining correlations between the WHO-DAS II (domain and total scores) and the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Hearing Aid Handicap for the Elderly (HHIE), two disease-specific measures, as well as with the Short Form-36 for veterans (SF-36V), a second generic measure. Data on all four measures were collected from 380 older individuals with adult-onset hearing loss who were not hearing aid users. The results of the convergent validity analysis revealed that the WHODAS II communication domain score was moderately and significantly correlated with scores on the APHAB and the HHIE. WHO-DAS II interpersonal and participation domain scores and the total scores were also moderately and significantly correlated with HHIE scores. These findings support the validity of using the WHO-DAS II for assessing activity limitations and participation restrictions of adult-onset hearing loss. Several WHO-DAS II domain scores and the total score were also significantly and moderately-markedly correlated with scores from the SF-36V. These findings support the validity of the WHO-DAS II as a generic health-status instrument

  8. CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination

    PubMed Central

    Marjanović, Marko; Sánchez-Huertas, Carlos; Terré, Berta; Gómez, Rocío; Scheel, Jan Frederik; Pacheco, Sarai; Knobel, Philip A.; Martínez-Marchal, Ana; Aivio, Suvi; Palenzuela, Lluís; Wolfrum, Uwe; McKinnon, Peter J.; Suja, José A.; Roig, Ignasi; Costanzo, Vincenzo; Lüders, Jens; Stracker, Travis H.

    2015-01-01

    CEP63 is a centrosomal protein that facilitates centriole duplication and is regulated by the DNA damage response. Mutations in CEP63 cause Seckel syndrome, a human disease characterized by microcephaly and dwarfism. Here we demonstrate that Cep63 deficient mice recapitulate Seckel syndrome pathology. The attrition of neural progenitor cells involves p53-dependent cell death and brain size is rescued by the deletion of p53. Cell death is not the result of an aberrant DNA damage response but is triggered by centrosome-based mitotic errors. In addition, Cep63 loss severely impairs meiotic recombination, leading to profound male infertility. Cep63 deficient spermatocytes display numerical and structural centrosome aberrations, chromosome entanglements and defective telomere clustering, suggesting that a reduction in centrosome-mediated chromosome movements underlies recombination failure. Our results provide novel insight into the molecular pathology of microcephaly and establish a role for the centrosome in meiotic recombination. PMID:26158450

  9. MC32 tumor cells acquire Ag-specific CTL resistance through the loss of CEA in a colon cancer model

    PubMed Central

    Lee, Sang-Yeul; Sin, Jeong-Im

    2015-01-01

    We previously reported that MC32 cells resist carcinoembryonic antigen (CEA) DNA vaccination by losing their antigen presentation to Ag-specific CTLs in the context of MHC class I antigens in a colon cancer therapeutic model. In this study, we selected 2 tumor cells, MC32-S2–2 and MC32-S4–2, which have the ability to form tumors in CEA DNA vaccine-immunized mice. Wild type MC32 cells grew significantly less in CEA-immunized mice (with Ag-specific CTL lytic activity) than in control mice (with no Ag-specific CTL lytic activity). However, MC32-S2–2 and MC32-S4–2 cells grew at a similar rate in both control and CEA-immunized mice, confirming their resistant status against CEA DNA vaccination. MC32-S2–2 and MC32-S4–2 cells were not susceptible to lysis by CEA-specific CD8+ T cells. Moreover, when MC32-S2–2 and MC32-S4–2 cells were used as stimulating agents of CEA-specific immune cells for IFN-γ production, these cells failed to stimulate the induction of Ag-specific IFN-γ, suggesting a loss of tumor cell recognition by Ag-specific immune cells. However, MC32-S2–2 and MC32-S4–2 cells expressed MHC class I antigens in a manner similar to that of wild type MC32 cells. Finally, Western blot assay confirmed that in MC32-S2–2 and MC32-S4–2 cells, CEA expression remained absent but mouse CEA was expressed. Taken together, these data show that MC32 cells may also be able to achieve resistance to CEA-specific CTLs by antigen loss in this model. PMID:25902414

  10. Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival

    PubMed Central

    Kamal, A M; Bulmer, J N; DeCruze, S B; Stringfellow, H F; Martin-Hirsch, P; Hapangama, D K

    2016-01-01

    Background: Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described. Methods: The expression pattern and prognostic value of AR in relation to oestrogen (ERα and ERβ) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n=85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR. Results: Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P<0.001) and ERα (P=0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P<0.0001), PR (P<0.0001) and ERβ (P<0.035) compared with LGEC, whilst maintaining weak to moderate ERα. Unlike PR, AR expression in metastatic lesions was significantly (P=0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P<0.0001, P<0.0001, respectively). Conclusions: Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ERα and ERβ may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC. PMID:26930451

  11. CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.

    PubMed

    Basit, Sulman; Al-Harbi, Khalid M; Alhijji, Sabri A M; Albalawi, Alia M; Alharby, Essa; Eldardear, Amr; Samman, Mohammed I

    2016-10-01

    Autosomal recessive primary microcephaly (MCPH) is a static neurodevelopmental disorder characterized by congenital small head circumference and non-progressive intellectual disability without additional severe brain malformations. MCPH is a genetically heterogeneous disorder. Sixteen genes (MCPH1-MCPH16) have been discovered so far, mutations thereof lead to autosomal recessive primary microcephaly. In a family, segregating MCPH in an autosomal recessive manner, genome-wide homozygosity mapping mapped a disease locus to 16.9-Mb region on chromosome 12q24.11-q24.32. Following this, exome sequencing in three affected individuals of the family discovered a splice site variant (c.753+3A>T) in citron kinase (CIT) gene, segregating with the disorder in the family. CIT co-localizes to the midbody ring during cytokinesis, and its loss of expression results in defects in neurogenic cytokinesis in both humans and mice. Splice site variant in CIT, identified in this study, is predicted to abolish splice donor site. cDNA sequence of an affected individual showed retention of an intron next to the splice donor site. The study, presented here, revealed the first variant in the CIT causing MCPH in the family. PMID:27519304

  12. Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly

    PubMed Central

    Lines, Matthew A.; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L.; Lynch, Danielle C.; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W.; Lohmann, Dietmar R.; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E.; Wieczorek, Dagmar; Boycott, Kym M.

    2012-01-01

    Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. PMID:22305528

  13. Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly.

    PubMed

    Li, Hongda; Bielas, Stephanie L; Zaki, Maha S; Ismail, Samira; Farfara, Dorit; Um, Kyongmi; Rosti, Rasim O; Scott, Eric C; Tu, Shu; Chi, Neil C; Gabriel, Stacey; Erson-Omay, Emine Z; Ercan-Sencicek, A Gulhan; Yasuno, Katsuhito; Çağlayan, Ahmet Okay; Kaymakçalan, Hande; Ekici, Barış; Bilguvar, Kaya; Gunel, Murat; Gleeson, Joseph G

    2016-08-01

    Cell division terminates with cytokinesis and cellular separation. Autosomal-recessive primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by a reduction in brain and head size at birth in addition to non-progressive intellectual disability. MCPH is genetically heterogeneous, and 16 loci are known to be associated with loss-of-function mutations predominantly affecting centrosomal-associated proteins, but the multiple roles of centrosomes in cellular function has left questions about etiology. Here, we identified three families affected by homozygous missense mutations in CIT, encoding citron rho-interacting kinase (CIT), which has established roles in cytokinesis. All mutations caused substitution of conserved amino acid residues in the kinase domain and impaired kinase activity. Neural progenitors that were differentiated from induced pluripotent stem cells (iPSCs) derived from individuals with these mutations exhibited abnormal cytokinesis with delayed mitosis, multipolar spindles, and increased apoptosis, rescued by CRISPR/Cas9 genome editing. Our results highlight the importance of cytokinesis in the pathology of primary microcephaly. PMID:27453578

  14. Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia.

    PubMed

    Betensky, Marisol; Babushok, Daria; Roth, Jacquelyn J; Mason, Philip J; Biegel, Jaclyn A; Busse, Tracy M; Li, Yimei; Lind, Curt; Papazoglou, Anna; Monos, Dimitri; Podsakoff, Gregory; Bessler, Monica; Olson, Timothy S

    2016-01-01

    Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune destruction of hematopoietic stem cells. Factors predicting response to immune suppression therapy (IST) or development of myelodysplastic syndrome (MDS) are beginning to be elucidated. Our recent data suggest most patients with aAA treated with IST develop clonal somatic genetic alterations in hematopoietic cells. One frequent acquired abnormality is copy-number neutral loss of heterozygosity on chromosome 6p (6p CN-LOH) involving the human leukocyte antigen (HLA) locus. We hypothesized that because 6p CN-LOH clones may arise from selective pressure to escape immune surveillance through deletion of HLA alleles, the development of 6p CN-LOH may affect response to IST. We used single nucleotide polymorphism array genotyping and targeted next-generation sequencing of HLA alleles to assess frequency of 6p CN-LOH, identity of HLA alleles lost through 6p CN-LOH, and impact of 6p CN-LOH on response to IST. 6p CN-LOH clones were present in 11.3% of patients, remained stable over time, and were not associated with development of MDS-defining cytogenetic abnormalities. Notably, no patient with 6p CN-LOH treated with IST achieved a complete response. In summary, clonal 6p CN-LOH in aAA defines a unique subgroup of patients that may provide insights into hematopoietic clonal evolution. PMID:26702937

  15. Studies using IPS cells support a possible link between ZIKA and microcephaly.

    PubMed

    Guo, Jia

    2016-01-01

    There is a suspected link between Brazilian babies born with microcephaly and Zika virus (ZIKV) infection. However, little is know about the brain cell targets and the mechanisms that Zika virus may cause microcephaly. A recent report demonstrated that Zika virus infection increases cell death and dysregulates cell-cycle, resulting in attenuated human neural progenitor cells growth. This study fills a major gap and serves as an entry point to establish a mechanistic link between Zika infection and microcephaly. PMID:27119012

  16. Blastopathies and microcephaly in a Chornobyl impacted region of Ukraine.

    PubMed

    Wertelecki, Wladimir; Yevtushok, Lyubov; Zymak-Zakutnia, Natalia; Wang, Bin; Sosyniuk, Zoriana; Lapchenko, Serhiy; Hobart, Holly H

    2014-08-01

    This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors. PMID:24666273

  17. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans

    PubMed Central

    Shamseldin, Hanan; Alazami, Anas M.; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A. Micheil; Parboosingh, Jillian S.; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P.; Alkuraya, Fowzan S.

    2015-01-01

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963∗] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. PMID:26608784

  18. Microcephaly genes and risk of late-onset Alzheimer disease.

    PubMed

    Erten-Lyons, Deniz; Wilmot, Beth; Anur, Pavana; McWeeney, Shannon; Westaway, Shawn K; Silbert, Lisa; Kramer, Patricia; Kaye, Jeffrey

    2011-01-01

    Brain development in the early stages of life has been suggested to be one of the factors that may influence an individual's risk of Alzheimer disease (AD) later in life. Four microcephaly genes, which regulate brain development in utero and have been suggested to play a role in the evolution of the human brain, were selected as candidate genes that may modulate the risk of AD. We examined the association between single nucleotide polymorphisms tagging common sequence variations in these genes and risk of AD in two case-control samples. We found that the G allele of rs2442607 in microcephalin 1 was associated with an increased risk of AD (under an additive genetic model, P=0.01; odds ratio=3.41; confidence interval, 1.77-6.57). However, this association was not replicated using another case-control sample research participants from the Alzheimer Disease Neuroimaging Initiative. We conclude that the common variations we measured in the 4 microcephaly genes do not affect the risk of AD or that their effect size is small. PMID:21297427

  19. Blastopathies and microcephaly in a Chornobyl impacted region of Ukraine

    PubMed Central

    Wertelecki, Wladimir; Yevtushok, Lyubov; Zymak-Zakutnia, Natalia; Wang, Bin; Sosyniuk, Zoriana; Lapchenko, Serhiy; Hobart, Holly H

    2014-01-01

    This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors. PMID:24666273

  20. Microcephaly-lymphedema syndrome: report of a family with short stature as additional manifestation.

    PubMed

    Strenge, S; Froster, U G

    1998-12-28

    Patients with the rare autosomal dominant microcephaly-lymphedema syndrome have apparently normal intelligence. We report on a boy with microcephaly, lymphedema, and short stature as an additional manifestation. The family history of our patient suggests autosomal dominant inheritance with reduced penetrance and variable expressivity. However, X-linked inheritance cannot be excluded. PMID:9880217

  1. Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice.

    PubMed

    Li, Cui; Xu, Dan; Ye, Qing; Hong, Shuai; Jiang, Yisheng; Liu, Xinyi; Zhang, Nana; Shi, Lei; Qin, Cheng-Feng; Xu, Zhiheng

    2016-07-01

    The link between Zika virus (ZIKV) infection and microcephaly has raised urgent global alarm. The historical African ZIKV MR766 was recently shown to infect cultured human neural precursor cells (NPCs), but unlike the contemporary ZIKV strains, it is not believed to cause microcephaly. Here we investigated whether the Asian ZIKV strain SZ01 could infect NPCs in vivo and affect brain development. We found that SZ01 replicates efficiently in embryonic mouse brain by directly targeting different neuronal linages. ZIKV infection leads to cell-cycle arrest, apoptosis, and inhibition of NPC differentiation, resulting in cortical thinning and microcephaly. Global gene expression analysis of infected brains reveals upregulation of candidate flavirus entry receptors and dysregulation of genes associated with immune response, apoptosis, and microcephaly. Our model provides evidence for a direct link between Zika virus infection and microcephaly, with potential for further exploration of the underlying mechanisms and management of ZIKV-related pathological effects during brain development. PMID:27179424

  2. Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans.

    PubMed

    Fujimori, Akira; Yaoi, Takeshi; Ogi, Hiroshi; Wang, Bing; Suetomi, Katsutoshi; Sekine, Emiko; Yu, Dong; Kato, Takamitsu; Takahashi, Sentaro; Okayasu, Ryuichi; Itoh, Kyoko; Fushiki, Shinji

    2008-05-01

    Microcephaly is a malformation associated with in utero exposed atomic bomb survivors and can be induced in mice by fetal exposure to ionizing radiation (IR). The pathogenesis of IR-induced microcephaly, however, has not been fully understood. Our analyses of high-coverage expression profiling (HiCEP) demonstrated that the abnormal spindle-like microcephaly associated gene (ASPM) was down-regulated in irradiated human diploid fibroblasts. ASPM was recently reported as the causative gene for MCPH-5, the most common type of congenital microcephaly in humans. Here, we show that the expression of the Aspm gene was significantly reduced by IR in various human and murine cells. Additionally, Aspm was found downregulated in the irradiated fetal mouse brain, particularly in the ventricular zones. A similar suppression was observed in the irradiated neurosphere cultures. This is the first report suggesting that the suppression of Aspm by IR could be the initial molecular target leading to the future microcephaly formation. PMID:18331833

  3. Association between Zika virus and microcephaly in French Polynesia, 2013–2015: a retrospective study

    PubMed Central

    Cauchemez, Simon; Besnard, Marianne; Bompard, Priscillia; Dub, Timothée; Guillemette-Artur, Prisca; Eyrolle-Guignot, Dominique; Salje, Henrik; Van Kerkhove, Maria D.; Abadie, Véronique; Garel, Catherine; Fontanet, Arnaud; Mallet, Henri-Pierre

    2016-01-01

    Background The emergence of Zika virus (ZIKV) in the Americas has coincided with an increase in the report of birth of infants with microcephaly. On 1 February 2016, the World Health Organization declared the suspected link between ZIKV and microcephaly a Public Health Emergency of International Concern. However, to date, precise quantification of this association is lacking. Methods We retrospectively analysed data from a ZIKV outbreak in French Polynesia in October 2013–April 2014, which was the largest ever documented prior to the outbreak in the Americas. Serological and surveillance data were used to estimate the probability of ZIKV infection for each week of the epidemic. We also conducted an exhaustive search of medical records to identify all microcephaly cases from September 2013–July 2015. Simple models were developed to determine the period during pregnancy when ZIKV infection may increase the risk of microcephaly and estimate the associated risk. Findings Sixty-six percent (95% CI: 62, 70) of Polynesians were infected by ZIKV. Of the eight microcephaly cases identified during the 23-month study period, seven (88%) occurred in the four-month period following the ZIKV outbreak. This pattern was best explained by a model that assumed ZIKV infection in the first trimester of pregnancy increased the risk of microcephaly. In this model, the risk of microcephaly associated with ZIKV infection was 95 (95 CI: 34, 191) per 10,000 women infected in the first trimester of pregnancy while the prevalence of microcephaly was 2 (95% CI: 0, 8) per 10,000 neonates. Models where the risk of microcephaly also increased if infection occurred in trimesters 2 and 3 were not significantly worse fitting than this model. Interpretation This study provides the first quantitative estimate of the risk of microcephaly in a foetus/neonate whose mother was infected by ZIKV. Funding Labex-IBEID, NIH-MIDAS, AXA Research fund and EU-PREDEMICS. PMID:26993883

  4. Effects of a Cognitive Behavioral Self-Help Program on Emotional Problems for People with Acquired Hearing Loss: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Garnefski, Nadia; Kraaij, Vivian

    2012-01-01

    The aim of the study was to examine whether a cognitive-behavioral self-help program was effective in improving depressed mood and anxiety in people with acquired deafness. Participants were 45 persons with acquired deafness, randomly allocated to the Cognitive-Behavioral Self-help (CBS) group or the Waiting List Control (WLC) group. Depression…

  5. Molecular and Cellular Basis of Autosomal Recessive Primary Microcephaly

    PubMed Central

    2014-01-01

    Autosomal recessive primary microcephaly (MCPH) is a rare hereditary neurodevelopmental disorder characterized by a marked reduction in brain size and intellectual disability. MCPH is genetically heterogeneous and can exhibit additional clinical features that overlap with related disorders including Seckel syndrome, Meier-Gorlin syndrome, and microcephalic osteodysplastic dwarfism. In this review, we discuss the key proteins mutated in MCPH. To date, MCPH-causing mutations have been identified in twelve different genes, many of which encode proteins that are involved in cell cycle regulation or are present at the centrosome, an organelle crucial for mitotic spindle assembly and cell division. We highlight recent findings on MCPH proteins with regard to their role in cell cycle progression, centrosome function, and early brain development. PMID:25548773

  6. Molecular and cellular basis of autosomal recessive primary microcephaly.

    PubMed

    Barbelanne, Marine; Tsang, William Y

    2014-01-01

    Autosomal recessive primary microcephaly (MCPH) is a rare hereditary neurodevelopmental disorder characterized by a marked reduction in brain size and intellectual disability. MCPH is genetically heterogeneous and can exhibit additional clinical features that overlap with related disorders including Seckel syndrome, Meier-Gorlin syndrome, and microcephalic osteodysplastic dwarfism. In this review, we discuss the key proteins mutated in MCPH. To date, MCPH-causing mutations have been identified in twelve different genes, many of which encode proteins that are involved in cell cycle regulation or are present at the centrosome, an organelle crucial for mitotic spindle assembly and cell division. We highlight recent findings on MCPH proteins with regard to their role in cell cycle progression, centrosome function, and early brain development. PMID:25548773

  7. Primary microcephaly: do all roads lead to Rome?

    PubMed

    Thornton, Gemma K; Woods, C Geoffrey

    2009-11-01

    The relatively large brain and expanded cerebral cortex of humans is unusual in the animal kingdom and is thought to have promoted our adaptability and success as a species. One approach for investigating neurogenesis is the study of autosomal recessive primary microcephaly (MCPH), in which prenatal brain growth is significantly reduced without an effect on brain structure. To date, eight MCPH loci and five genes have been identified. Unexpectedly, all MCPH proteins are ubiquitous and localise to centrosomes for at least part of the cell cycle. Here, we focus on recent functional studies of MCPH proteins that reveal the centrosome as a final integration point for many regulatory pathways affecting prenatal neurogenesis in mammals. PMID:19850369

  8. Microcephaly/lymphedema and terminal deletion of the long arm of chromosome 13

    SciTech Connect

    Fryns, J.P.

    1995-07-03

    Recently, we examined a 2-year-old boy with the association of microcephaly and significant pedal edema that extended to the distal parts of the legs. Prometaphase chromosome studies showed a small terminal deletion in the long arm of chromosome 13 of band 13q34, karyotype 46,XY,del(13)(q34{yields}qter). The present finding of a small terminal 13q34 deletion in this young boy with microcephaly/lymphedema is a first indication that the lymphedema/microcephaly association can be due to a small terminal 13q deletion. 2 refs.

  9. Asymmetric crying facies with microcephaly and mental retardation. An autosomal dominant syndrome with variable expressivity.

    PubMed

    Silengo, M C; Bell, G L; Biagioli, M; Guala, A; Bianco, R; Strandoni, P; De Sario, P N; Franceschini, P

    1986-12-01

    An infant boy with asymmetric crying facies, microcephaly, developmental retardation and failure to thrive is reported. His two siblings died in the newborn period because of complex congenital heart defects. The mother and the maternal grandmother have asymmetric crying facies, microcephaly and normal intelligence. A maternal aunt has severe physical and mental retardation, facial asymmetry, microcephaly, and cleft palate. This family allows an expansion of the spectrum of malformations associated with asymmetric crying facies and suggests autosomal dominant inheritance with variable expressivity. PMID:3815881

  10. Autosomal-Recessive Mutations in the tRNA Splicing Endonuclease Subunit TSEN15 Cause Pontocerebellar Hypoplasia and Progressive Microcephaly.

    PubMed

    Breuss, Martin W; Sultan, Tipu; James, Kiely N; Rosti, Rasim O; Scott, Eric; Musaev, Damir; Furia, Bansri; Reis, André; Sticht, Heinrich; Al-Owain, Mohammed; Alkuraya, Fowzan S; Reuter, Miriam S; Abou Jamra, Rami; Trotta, Christopher R; Gleeson, Joseph G

    2016-07-01

    The tRNA splicing endonuclease is a highly evolutionarily conserved protein complex, involved in the cleavage of intron-containing tRNAs. In human it consists of the catalytic subunits TSEN2 and TSEN34, as well as the non-catalytic TSEN54 and TSEN15. Recessive mutations in the corresponding genes of the first three are known to cause pontocerebellar hypoplasia (PCH) types 2A-C, 4, and 5. Here, we report three homozygous TSEN15 variants that cause a milder version of PCH2. The affected individuals showed progressive microcephaly, delayed developmental milestones, intellectual disability, and, in two out of four cases, epilepsy. None, however, displayed the central visual failure seen in PCH case subjects where other subunits of the TSEN are mutated, and only one was affected by the extensive motor defects that are typical in other forms of PCH2. The three amino acid substitutions impacted the protein level of TSEN15 and the stoichiometry of the interacting subunits in different ways, but all resulted in an almost complete loss of in vitro tRNA cleavage activity. Taken together, our results demonstrate that mutations in any known subunit of the TSEN complex can cause PCH and progressive microcephaly, emphasizing the importance of its function during brain development. PMID:27392077

  11. Novel Mutation in the DKC1 Gene: Neonatal Hoyeraal-Hreidarsson Syndrome As a Rare Differential Diagnosis in Pontocerebellar Hypoplasia, Primary Microcephaly, and Progressive Bone Marrow Failure.

    PubMed

    Dehmel, Maria; Brenner, Sebastian; Suttorp, Meinolf; Hahn, Gabriele; Schützle, Heike; Dinger, Jürgen; Di Donato, Nataliya; Mackenroth, Luisa; von der Hagen, Maja

    2016-06-01

    Primary microcephaly and severe developmental delay are complex but unspecific signs pointing to various genetic or acquired diseases. A concomitant finding of hematological failure may lead to the differential diagnosis of rare genetic diseases such as chromosome breakage disorders or diseases associated with telomere dysfunction. X-linked Hoyeraal-Hreidarsson syndrome (HHS) is a rare heterogenic disorder characterized by severe neurological impairment and progressive bone marrow failure. The latter represents the main cause of mortality, usually in early childhood. We report on the clinical course of an infant with HHS due to a novel mutation in the DKC1 gene and the particular finding of pontocerebellar hypoplasia. PMID:26951492

  12. Mosaic variegated aneuploidy with microcephaly: A rare cytogenetic syndrome

    SciTech Connect

    Meck, J.M.; Kozma, C.; Stratakis, C.

    1994-09-01

    The term {open_quotes}mosaic variegated aneuploidy with microcephaly{close_quotes} describes the finding of a variety of chromosomal aneuploidies within the same individual. This mutation affecting mitotic segregation has been reported previously in only 7 persons. We report here on male and female siblings with this condition. Proband 1 died at 57 days of age; proband 2 is 7 months old. Amniocentesis performed on the first sibling only revealed multiple aneuploidies (+2, +6, +X, tetrasomy 2, double trisomy X and 11, and deletion Xq); the majority of cells were normal and the abnormal cells did not constitute true mosaicism. Postnatally, blood on proband 1 had 20/50 cells (40%) with +18, single cells with +10 and +20, and 28/50 normal cells (56%). This was initially interpreted as trisomy 18 mosaicism not detected in amniocytes. Blood from proband 2 showed the following; after 48 hrs in culture, 4/50 trisomic cells (+3, +6, +18, XXY); after 72 hrs 3/50 trisomic cells (+5, +6, +18); after 96 hrs, 7/50 aneuploid cells (+2, +8, +9, +10, +18, double trisomy 11 and 18, tetrasomy 2 with +18). Skin biopsy on proband 2 revealed trisomy 2 in 5/140 cells (4%), one cell each +18 and +19, on cell tetrasomy 2, one cell XXY and +5; 131 cells (94%) were normal. Paternal skin fibroblasts had trisomy 6 in 2/100 cells and 1 cell trisomy 5; the remainder were normal. One trisomic cell (+18) in 100 was found in maternal skin fibroblasts. Trisomy 18 was the most common aneuploidy in the probands` blood. Aneuploidy for chromosomes 2 and X were more common in amniocytes and skin. No trisomies of chromosomes 1, 4, 12-17, 22 or Y were observed; acrocentrics rarely malsegregated. These findings are consistent with those of the other 7 reported patients, and constitute a distinct syndrome of multiple chromosomal aneuploidies associated with microcephaly. Although rare, cytogeneticists and clinical geneticists should be aware of this mitotic mutant.

  13. Radiological Characterization of Cerebral Phenotype in Newborn Microcephaly Cases from 2015 Outbreak in Brazil

    PubMed Central

    Ramalho Rocha, Yuri Raoni; Cavalcanti Costa, José Ricardo; Almeida Costa, Pericles; Maia, Gessica; Vasconcelos, Rafael de Medeiros; Ramos Tejo, Cynthia; Martins Batista, Rafaella; Lima Neto, Manoel; Martins de Lima, Gustavo Graco; Negromonte, Francisco; Borba, Marcelle; Bezerra Jeronimo, Selma Maria; Sequerra, Eduardo Bouth; Moreira Neto, Manuel

    2016-01-01

    Introduction: Brazil is facing, since October of 2015, an outbreak of microcephalic fetuses. This outbreak is correlated with the beginning of circulation of Zika virus (ZIKV) in the country. Although it is clear that the size of the head is diminished in these fetuses, the brain phenotype associated with these malformations is unknown. Methods: We collected computed tomography images of the microcephaly cases from the region of Natal, Rio Grande do Norte, from September 2015 to February 2016. Findings: The microcephalies derived from the current outbreak are associated with intracerebral calcifications, malformation of the ventricular system, migratory disorders in the telencephalon and, in a lower frequency, malformation of the cerebellum and brainstem. Discussion: The characteristics described herein are not usually found in other types of microcephaly. We suggest that this work can be used as a guideline to identify microcephaly cases associated to the current outbreak.

  14. Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly

    PubMed Central

    2011-01-01

    Background Autosomal recessive primary microcephaly is a disorder of neurogenic mitosis that causes reduction in brain size. It is a rare heterogeneous condition with seven causative genes reported to date. Mutations in WD repeat protein 62 are associated with autosomal recessive primary microcephaly with cortical malformations. This study was initiated to screen WDR62 mutations in four consanguineous Pakistani families with autosomal recessive primary microcephaly. Methods As part of a large study to detect the genetic basis of primary microcephaly in Pakistan, homozygosity mapping and DNA sequencing was used to explore the genetic basis of autosomal recessive primary microcephaly in four families. Results Four out of 100 families recruited in the study revealed linkage to the MCPH2 locus on chromosome 19, which harbor WDR62 gene. DNA sequencing in these MCPH2 linked families result in the identification of a novel nonsense mutation (p.Q648X) and three previously known mutations. Conclusion Our data indicate that WDR62 mutations cause about 4% of autosomal recessive primary microcephaly in Pakistan. PMID:21961505

  15. Sex-dependent association of common variants of microcephaly genes with brain structure.

    PubMed

    Rimol, Lars M; Agartz, Ingrid; Djurovic, Srdjan; Brown, Andrew A; Roddey, J Cooper; Kähler, Anna K; Mattingsdal, Morten; Athanasiu, Lavinia; Joyner, Alexander H; Schork, Nicholas J; Halgren, Eric; Sundet, Kjetil; Melle, Ingrid; Dale, Anders M; Andreassen, Ole A

    2010-01-01

    Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717-728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637-644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions. PMID:20080800

  16. PEX6 is Expressed in Photoreceptor Cilia and Mutated in Deafblindness with Enamel Dysplasia and Microcephaly.

    PubMed

    Zaki, Maha S; Heller, Raoul; Thoenes, Michaela; Nürnberg, Gudrun; Stern-Schneider, Gabi; Nürnberg, Peter; Karnati, Srikanth; Swan, Daniel; Fateen, Ekram; Nagel-Wolfrum, Kerstin; Mostafa, Mostafa I; Thiele, Holger; Wolfrum, Uwe; Baumgart-Vogt, Eveline; Bolz, Hanno J

    2016-02-01

    Deafblindness is part of several genetic disorders. We investigated a consanguineous Egyptian family with two siblings affected by congenital hearing loss and retinal degeneration, initially diagnosed as Usher syndrome type 1. At teenage, severe enamel dysplasia, developmental delay, and microcephaly became apparent. Genome-wide homozygosity mapping and whole-exome sequencing detected a homozygous missense mutation, c.1238G>T (p.Gly413Val), affecting a highly conserved residue of peroxisomal biogenesis factor 6, PEX6. Biochemical profiling of the siblings revealed abnormal and borderline plasma phytanic acid concentration, and cerebral imaging revealed white matter disease in both. We show that Pex6 localizes to the apical extensions of secretory ameloblasts and differentiated odontoblasts at early stages of dentin synthesis in mice, and to cilia of retinal photoreceptor cells. We propose PEX6, and possibly other peroxisomal genes, as candidate for the rare cooccurrence of deafblindness and enamel dysplasia. Our study for the first time links peroxisome biogenesis disorders to retinal ciliopathies. PMID:26593283

  17. Homozygous STIL Mutation Causes Holoprosencephaly and Microcephaly in Two Siblings

    PubMed Central

    Mouden, Charlotte; de Tayrac, Marie; Dubourg, Christèle; Rose, Sophie; Carré, Wilfrid; Hamdi-Rozé, Houda; Babron, Marie-Claude; Akloul, Linda; Héron-Longe, Bénédicte; Odent, Sylvie; Dupé, Valérie; Giet, Régis; David, Véronique

    2015-01-01

    Holoprosencephaly (HPE) is a frequent congenital malformation of the brain characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been identified in HPE patients that account for only 30% of HPE cases, suggesting the existence of other HPE genes. Data from homozygosity mapping and whole-exome sequencing in a consanguineous Turkish family were combined to identify a homozygous missense mutation (c.2150G>A; p.Gly717Glu) in STIL, common to the two affected children. STIL has a role in centriole formation and has previously been described in rare cases of microcephaly. Rescue experiments in U2OS cells showed that the STIL p.Gly717Glu mutation was not able to fully restore the centriole duplication failure following depletion of endogenous STIL protein indicating the deleterious role of the mutation. In situ hybridization experiments using chick embryos demonstrated that expression of Stil was in accordance with a function during early patterning of the forebrain. It is only the second time that a STIL homozygous mutation causing a recessive form of HPE was reported. This result also supports the genetic heterogeneity of HPE and increases the panel of genes to be tested for HPE diagnosis. PMID:25658757

  18. Acquired hyperpigmentations*

    PubMed Central

    Cestari, Tania Ferreira; Dantas, Lia Pinheiro; Boza, Juliana Catucci

    2014-01-01

    Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis PMID:24626644

  19. Focal cortical dysplasia, microcephaly and epilepsy in a boy with 1q21.1-q21.3 duplication.

    PubMed

    Milone, Roberta; Valetto, Angelo; Battini, Roberta; Bertini, Veronica; Valvo, Giulia; Cioni, Giovanni; Sicca, Federico

    2016-05-01

    The recent advance of new molecular technologies like array - Comparative Genomic Hybridization has fostered the detection of genomic imbalances in subjects with intellectual disability, epilepsy, and/or congenital anomalies. Though some of the rearrangements are relatively frequent, their consequences on phenotypes can be strongly variable. We report on a boy harbouring a de novo 8.3 Mb duplication of chromosome 1q21.1-q21.3 whose complex unusual phenotype deserves attention, due to the presence of focal cortical dysplasia, microcephaly, and epilepsy. Loss-of-function (LOF) effects of genes associated with human disease involved in the rearrangement have been only partially established, and have not been previously associated with brain malformations in several deletion syndromes. Less is known, instead, about the consequences of their duplication on neuronal migration and brain development process. Further advance in neuroimaging and genetic research will help in defining their actual role in neurodevelopment and cerebral cortex malformations. PMID:26975584

  20. Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data.

    PubMed

    De Carvalho, Newton Sérgio; De Carvalho, Beatriz Freitas; Fugaça, Cyllian Arias; Dóris, Bruna; Biscaia, Evellyn Silverio

    2016-01-01

    In November of 2015, the Ministry of Health of Brazil published an announcement confirming the relationship between Zika virus and the microcephaly outbreak in the Northeast, suggesting that infected pregnant women might have transmitted the virus to their fetuses. The objectives of this study were to conduct a literature review about Zika virus infection and microcephaly, evaluate national and international epidemiological data, as well as the current recommendations for the health teams. Zika virus is an arbovirus, whose main vector is the Aedes sp. The main symptoms of the infection are maculopapular rash, fever, non-purulent conjunctivitis, and arthralgia. Transmission of this pathogen occurs mainly by mosquito bite, but there are also reports via the placenta. Microcephaly is defined as a measure of occipto-frontal circumference being more than two standard deviations below the mean for age and gender. The presence of microcephaly demands evaluation of the patient, in order to diagnose the etiology. Health authorities issued protocols, reports and notes concerning the management of microcephaly caused by Zika virus, but there is still controversy about managing the cases. The Ministry of Health advises notifying any suspected or confirmed cases of children with microcephaly related to the pathogen, which is confirmed by a positive specific laboratory test for the virus. The first choice for imaging exam in children with this malformation is transfontanellar ultrasound. The most effective way to control this outbreak of microcephaly probably caused by this virus is to combat the vector. Since there is still uncertainty about the period of vulnerability of transmission via placenta, the use of repellents is crucial throughout pregnancy. More investigations studying the consequences of this viral infection on the body of newborns and in their development are required. PMID:27102780

  1. Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.

    PubMed

    Mao, Hanqian; McMahon, John J; Tsai, Yi-Hsuan; Wang, Zefeng; Silver, Debra L

    2016-09-01

    The exon junction complex (EJC) is an RNA binding complex comprised of the core components Magoh, Rbm8a, and Eif4a3. Human mutations in EJC components cause neurodevelopmental pathologies. Further, mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly. Yet despite the requirement of these genes for neurodevelopment, the pathogenic mechanisms linking EJC dysfunction to microcephaly remain poorly understood. Here we employ mouse genetics, transcriptomic and proteomic analyses to demonstrate that haploinsufficiency for each of the 3 core EJC components causes microcephaly via converging regulation of p53 signaling. Using a new conditional allele, we first show that Eif4a3 haploinsufficiency phenocopies aberrant neurogenesis and microcephaly of Magoh and Rbm8a mutant mice. Transcriptomic and proteomic analyses of embryonic brains at the onset of neurogenesis identifies common pathways altered in each of the 3 EJC mutants, including ribosome, proteasome, and p53 signaling components. We further demonstrate all 3 mutants exhibit defective splicing of RNA regulatory proteins, implying an EJC dependent RNA regulatory network that fine-tunes gene expression. Finally, we show that genetic ablation of one downstream pathway, p53, significantly rescues microcephaly of all 3 EJC mutants. This implicates p53 activation as a major node of neurodevelopmental pathogenesis following EJC impairment. Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease. PMID:27618312

  2. Zika Virus-Associated Microcephaly and Eye Lesions in the Newborn.

    PubMed

    Valentine, Gregory; Marquez, Lucila; Pammi, Mohan

    2016-09-01

    On February 1, 2016, Zika virus (ZIKV) was designated as a Public Health Emergency of International Concern by the director of the World Health Organization. Zika virus has spread to numerous countries throughout the Americas, affecting up to an estimated 1.3 million people since the first reports from Brazil in early 2015. Although ZIKV infections are self-limiting, fetal microcephaly and ophthalmic anomalies have been associated with ZIKV infection as a possible result of perinatal transmission. The causal link between maternal ZIKV infection and newborn microcephaly and eye lesions has not been proven beyond doubt and is currently debated. We discuss the possibility of causality by ZIKV using Koch's postulates and the more appropriate Bradford Hill criteria. In this review, we summarize and consolidate the current literature on newborn microcephaly and eye lesions associated with ZIKV infection and discuss current perspectives and controversies. PMID:27405738

  3. Antarctic notothenioid fish: what are the future consequences of 'losses' and 'gains' acquired during long-term evolution at cold and stable temperatures?

    PubMed

    Beers, Jody M; Jayasundara, Nishad

    2015-06-01

    Antarctic notothenioids dominate the fish fauna of the Southern Ocean. Evolution for millions of years at cold and stable temperatures has led to the acquisition of numerous biochemical traits that allow these fishes to thrive in sub-zero waters. The gain of antifreeze glycoproteins has afforded notothenioids the ability to avert freezing and survive at temperatures often hovering near the freezing point of seawater. Additionally, possession of cold-adapted proteins and membranes permits them to sustain appropriate metabolic rates at exceptionally low body temperatures. The notothenioid genome is also distinguished by the disappearance of traits in some species, losses that might prove costly in a warmer environment. Perhaps the best-illustrated example is the lack of expression of hemoglobin in white-blooded icefishes from the family Channichthyidae. Loss of key elements of the cellular stress response, notably the heat shock response, has also been observed. Along with their attainment of cold tolerance, notothenioids have developed an extreme stenothermy and many species perish at temperatures only a few degrees above their habitat temperatures. Thus, in light of today's rapidly changing climate, it is critical to evaluate how these extreme stenotherms will respond to rising ocean temperatures. It is conceivable that the remarkable cold specialization of notothenioids may ultimately leave them vulnerable to future thermal increases and threaten their fitness and survival. Within this context, our review provides a current summary of the biochemical losses and gains that are known for notothenioids and examines these cold-adapted traits with a focus on processes underlying thermal tolerance and acclimation capacity. PMID:26085661

  4. CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation

    PubMed Central

    Kramer, Jamie M.; Merkx, Gerard; Lugtenberg, Dorien; Smeets, Dominique F.; Oortveld, Merel A. W.; Blokland, Ellen A. W.; Agrawal, Jyoti; Schenck, Annette; van Bokhoven, Hans; Huys, Erik; Schoenmakers, Eric F.; van Kessel, Ad Geurts; van Nouhuys, C. Erik

    2010-01-01

    Microcephaly, mental retardation and congenital retinal folds along with other systemic features have previously been reported as a separate clinical entity. The sporadic nature of the syndrome and lack of clear inheritance patterns pointed to a genetic heterogeneity. Here, we report a genetic analysis of a female patient with microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation. Karyotyping revealed a de novo pericentric inversion in chromosome 6 with breakpoints in 6p12.1 and 6q21. Fluorescence in situ hybridization analysis narrowed down the region around the breakpoints, and the breakpoint at 6q21 was found to disrupt the CDK19 gene. CDK19 was found to be expressed in a diverse range of tissues including fetal eye and fetal brain. Quantitative PCR of the CDK19 transcript from Epstein–Barr virus-transformed lymphoblastoid cell lines of the patient revealed ~50% reduction in the transcript (p = 0.02), suggesting haploinsufficiency of the gene. cdk8, the closest orthologue of human CDK19 in Drosophila has been shown to play a major role in eye development. Conditional knock-down of Drosophila cdk8 in multiple dendrite (md) neurons resulted in 35% reduced dendritic branching and altered morphology of the dendritic arbour, which appeared to be due in part to a loss of small higher order branches. In addition, Cdk8 mutant md neurons showed diminished dendritic fields revealing an important role of the CDK19 orthologue in the developing nervous system of Drosophila. This is the first time the CDK19 gene, a component of the mediator co-activator complex, has been linked to a human disease. PMID:20563892

  5. Acquired cystic disease-associated renal cell carcinoma with gain of chromosomes 3, 7, and 16, gain of chromosome X, and loss of chromosome Y.

    PubMed

    Kuroda, Naoto; Shiotsu, Tomoyuki; Hes, Ondrej; Michal, Michal; Shuin, Taro; Lee, Gang-Hong

    2010-12-01

    Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) has been recently described. To date, there are no reports on genetic findings of G-band karyotype of ACD-associated RCC. In this article, we report the first report of G-band karyotype of ACD-associated RCC. A 66-year-old Japanese man was found to have a left renal tumor during the follow-up of hemodialysis consequent to chronic renal failure. Left nephrectomy was performed. Histological examination of three tumors in the left kidney showed the cribriform or microcystic growth pattern of neoplastic cells with eosinophilic cytoplasm, and many oxalate crystals were observed. The G-band karyotype of ACD-associated RCC showed 49, X, +X, -Y, +3, +7, +16. These chromosomal abnormalities resemble those of sporadic papillary RCC that has been previously reported. Finally, we suggest that this tumor may show a close relationship between ACD-associated RCC and papillary RCC, but a large-scale study will be needed to clarify the relationship between ACD-associated RCC and papillary RCC. PMID:21267700

  6. Diagnostic dilemmas in four infants with nephrotic syndrome, microcephaly and severe developmental delay.

    PubMed

    de Vries, B B; van'tHoff, W G; Surtees, R A; Winter, R M

    2001-04-01

    We present four cases with nephrotic syndrome, microcephaly and severe developmental delay. In the differential diagnosis the Galloway-Mowat syndrome, PEHO syndrome, ARC syndrome and the carbohydrate-deficient glycoprotein (CDG) syndrome are considered and discussed. One case may fall into the Galloway-Mowat spectrum and another case was diagnosed with the CDG syndrome. This case is the third report of a nephrotic syndrome as a part of the CDG syndrome. Two remaining cases with cerebellar and brain stem atrophy, and without major histopathological changes in the kidney were left without a definite unifying diagnosis and may well represent a different unknown condition. Although microcephaly and nephrotic syndrome with or without hiatus hernia has been equated with Galloway-Mowat syndrome in the literature, the brain and renal pathology in these reported cases has been very variable. It is likely that this group as a whole is aetiologically heterogeneous. PMID:11310991

  7. The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes

    PubMed Central

    Waters, Aoife M; Asfahani, Rowan; Carroll, Paula; Bicknell, Louise; Lescai, Francesco; Bright, Alison; Chanudet, Estelle; Brooks, Anthony; Christou-Savina, Sonja; Osman, Guled; Walsh, Patrick; Bacchelli, Chiara; Chapgier, Ariane; Vernay, Bertrand; Bader, David M; Deshpande, Charu; O’ Sullivan, Mary; Ocaka, Louise; Stanescu, Horia; Stewart, Helen S; Hildebrandt, Friedhelm; Otto, Edgar; Johnson, Colin A; Szymanska, Katarzyna; Katsanis, Nicholas; Davis, Erica; Kleta, Robert; Hubank, Mike; Doxsey, Stephen; Jackson, Andrew; Stupka, Elia; Winey, Mark; Beales, Philip L

    2015-01-01

    Background Mutations in microtubule-regulating genes are associated with disorders of neuronal migration and microcephaly. Regulation of centriole length has been shown to underlie the pathogenesis of certain ciliopathy phenotypes. Using a next-generation sequencing approach, we identified mutations in a novel centriolar disease gene in a kindred with an embryonic lethal ciliopathy phenotype and in a patient with primary microcephaly. Methods and results Whole exome sequencing data from a non-consanguineous Caucasian kindred exhibiting mid-gestation lethality and ciliopathic malformations revealed two novel non-synonymous variants in CENPF, a microtubule-regulating gene. All four affected fetuses showed segregation for two mutated alleles [IVS5-2A>C, predicted to abolish the consensus splice-acceptor site from exon 6; c.1744G>T, p.E582X]. In a second unrelated patient exhibiting microcephaly, we identified two CENPF mutations [c.1744G>T, p.E582X; c.8692 C>T, p.R2898X] by whole exome sequencing. We found that CENP-F colocalised with Ninein at the subdistal appendages of the mother centriole in mouse inner medullary collecting duct cells. Intraflagellar transport protein-88 (IFT-88) colocalised with CENP-F along the ciliary axonemes of renal epithelial cells in age-matched control human fetuses but did not in truncated cilia of mutant CENPF kidneys. Pairwise co-immunoprecipitation assays of mitotic and serum-starved HEKT293 cells confirmed that IFT88 precipitates with endogenous CENP-F. Conclusions Our data identify CENPF as a new centriolar disease gene implicated in severe human ciliopathy and microcephaly related phenotypes. CENP-F has a novel putative function in ciliogenesis and cortical neurogenesis. PMID:25564561

  8. Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages.

    PubMed

    Doobin, David J; Kemal, Shahrnaz; Dantas, Tiago J; Vallee, Richard B

    2016-01-01

    Microcephaly is a cortical malformation disorder characterized by an abnormally small brain. Recent studies have revealed severe cases of microcephaly resulting from human mutations in the NDE1 gene, which is involved in the regulation of cytoplasmic dynein. Here using in utero electroporation of NDE1 short hairpin RNA (shRNA) in embryonic rat brains, we observe cell cycle arrest of proliferating neural progenitors at three distinct stages: during apical interkinetic nuclear migration, at the G2-to-M transition and in regulation of primary cilia at the G1-to-S transition. RNAi against the NDE1 paralogue NDEL1 has no such effects. However, NDEL1 overexpression can functionally compensate for NDE1, except at the G2-to-M transition, revealing a unique NDE1 role. In contrast, NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. These results reveal that the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage. PMID:27553190

  9. Severe NDE1-mediated microcephaly results from neural progenitor cell cycle arrests at multiple specific stages

    PubMed Central

    Doobin, David J.; Kemal, Shahrnaz; Dantas, Tiago J.; Vallee, Richard B.

    2016-01-01

    Microcephaly is a cortical malformation disorder characterized by an abnormally small brain. Recent studies have revealed severe cases of microcephaly resulting from human mutations in the NDE1 gene, which is involved in the regulation of cytoplasmic dynein. Here using in utero electroporation of NDE1 short hairpin RNA (shRNA) in embryonic rat brains, we observe cell cycle arrest of proliferating neural progenitors at three distinct stages: during apical interkinetic nuclear migration, at the G2-to-M transition and in regulation of primary cilia at the G1-to-S transition. RNAi against the NDE1 paralogue NDEL1 has no such effects. However, NDEL1 overexpression can functionally compensate for NDE1, except at the G2-to-M transition, revealing a unique NDE1 role. In contrast, NDE1 and NDEL1 RNAi have comparable effects on postmitotic neuronal migration. These results reveal that the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage. PMID:27553190

  10. Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings.

    PubMed

    Woods, C Geoffrey; Bond, Jacquelyn; Enard, Wolfgang

    2005-05-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder. It is characterized by two principal features, microcephaly present at birth and nonprogressive mental retardation. The microcephaly is the consequence of a small but architecturally normal brain, and it is the cerebral cortex that shows the greatest size reduction. There are at least seven MCPH loci, and four of the genes have been identified: MCPH1, encoding Microcephalin; MCPH3, encoding CDK5RAP2; MCPH5, encoding ASPM; and MCPH6, encoding CENPJ. These findings are starting to have an impact on the clinical management of families affected with MCPH. Present data suggest that MCPH is the consequence of deficient neurogenesis within the neurogenic epithelium. Evolutionary interest in MCPH has been sparked by the suggestion that changes in the MCPH genes might also be responsible for the increase in brain size during human evolution. Indeed, evolutionary analyses of Microcephalin and ASPM reveal evidence for positive selection during human and great ape evolution. So an understanding of this rare genetic disorder may offer us significant insights into neurogenic mitosis and the evolution of the most striking differences between us and our closest living relatives: brain size and cognitive ability. PMID:15806441

  11. Zika virus and autoimmunity: From microcephaly to Guillain-Barré syndrome, and beyond.

    PubMed

    Lucchese, Guglielmo; Kanduc, Darja

    2016-08-01

    Zika virus (ZIKV) infection during pregnancy may be linked to fetal neurological complications that include brain damage and microcephaly. How the viral infection relates to fetal brain malformations is unknown. This study analyzes ZIKV polyprotein for peptide sharing with human proteins that, when altered, associate with microcephaly and brain calcifications. Results highlight a vast viral versus human peptide commonality that, in particular, involves centriolar and centrosomal components canonically cataloged as microcephaly proteins, i.e., C2CD3, CASC5, CP131, GCP4, KIF2A, STIL, and TBG. Likewise, a search for ZIKV peptide occurrences in human proteins linked to Guillain-Barré-like syndromes also show a high, unexpected level of peptide sharing. Of note, further analyses using the Immune Epitope DataBase (IEDB) resource show that many of the shared peptides are endowed with immunological potential. The data indicate that immune reactions following ZIKV infection might be a considerable source of crossreactions with brain-specific proteins and might contribute to the ZIKV-associated neuropathologic sequelae. PMID:27019049

  12. The Epidemic of Zika Virus-Related Microcephaly in Brazil: Detection, Control, Etiology, and Future Scenarios.

    PubMed

    Teixeira, Maria G; Costa, Maria da Conceição N; de Oliveira, Wanderson K; Nunes, Marilia Lavocat; Rodrigues, Laura C

    2016-04-01

    We describe the epidemic of microcephaly in Brazil, its detection and attempts to control it, the suspected causal link with Zika virus infection during pregnancy, and possible scenarios for the future. In October 2015, in Pernambuco, Brazil, an increase in the number of newborns with microcephaly was reported. Mothers of the affected newborns reported rashes during pregnancy and no exposure to other potentially teratogenic agents. Women delivering in October would have been in the first trimester of pregnancy during the peak of a Zika epidemic in March. By the end of 2015, 4180 cases of suspected microcephaly had been reported. Zika spread to other American countries and, in February 2016, the World Health Organization declared the Zika epidemic a public health emergency of international concern. This unprecedented situation underscores the urgent need to establish the evidence of congenital infection risk by gestational week and accrue knowledge. There is an urgent call for a Zika vaccine, better diagnostic tests, effective treatment, and improved mosquito-control methods. PMID:26959259

  13. Prospective study of cytotoxic T lymphocyte responses to influenza and antibodies to human T lymphotropic virus-III in homosexual men. Selective loss of an influenza-specific, human leukocyte antigen-restricted cytotoxic T lymphocyte response in human T lymphotropic virus-III positive individuals with symptoms of acquired immunodeficiency syndrome and in a patient with acquired immunodeficiency syndrome.

    PubMed Central

    Shearer, G M; Salahuddin, S Z; Markham, P D; Joseph, L J; Payne, S M; Kriebel, P; Bernstein, D C; Biddison, W E; Sarngadharan, M G; Gallo, R C

    1985-01-01

    Peripheral blood leukocytes (PBL) from 18 homosexual men who did not have acquired immunodeficiency syndrome (AIDS) and from 9 heterosexual men were repetitively tested for their ability to generate HLA self-restricted cytotoxic T lymphocyte responses to influenza virus (flu-self) over a 2-yr period. The sera of the same donors were tested for antibodies to human T lymphotropic virus-III (HTLV-III). Six of the homosexual and none of the heterosexual donors consistently generated weak cytotoxic T lymphocyte responses to flu-self. Seven of the homosexual and none of the heterosexual donors were seropositive for antibodies to HTLV-III. No obvious correlation was detected between weak flu-self cytotoxic T lymphocyte responses and antibodies to HTLV-III. However, one homosexual donor generated no detectable cytotoxic T lymphocyte activity to flu-self, although he was a strong responder to HLA-alloantigens. This donor had an OKT4:OKT8 ratio of 0.4 and was seropositive for HTLV-III antigens; HTLV-III virus was identified in his PBL; and he developed AIDS during the course of this study. A second donor with lymphadenopathy and who was seropositive for HTLV-III antigens exhibited marginal cytotoxic T lymphocyte activity to flu-self which he subsequently lost. PBL from two patients, one with Kaposi's sarcoma and one with generalized lymphadenopathy, were also tested for cytotoxic T lymphocyte responses to flu-self and to alloantigens. Both donors failed to generate cytotoxic T lymphocyte to flu-self, but generated strong cytotoxic T lymphocyte responses to alloantigens. The selective loss of an HLA-restricted cytotoxic T lymphocyte response without loss of HLA alloantigenic cytotoxic T lymphocyte activity may be an important functional immunologic characteristic in the development of AIDS. PMID:2997287

  14. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases.

    PubMed

    Hagberg, B; Aicardi, J; Dias, K; Ramos, O

    1983-10-01

    Thirty-five patients, exclusively girls, from three countries had a uniform and striking progressive encephalopathy. After normal general and psychomotor development up to the age of 7 to 18 months, developmental stagnation occurred, followed by rapid deterioration of higher brain functions. Within one-and-a-half years this deterioration led to severe dementia, autism, loss of purposeful use of the hands, jerky truncal ataxia, and acquired microcephaly. The destructive stage was followed by apparent stability lasting through decades. Additional insidious neurological abnormalities supervened, mainly spastic parapareses, vasomotor disturbances of the lower limbs, and epilepsy. Prior extensive laboratory investigations have not revealed the cause. The condition is similar to a virtually overlooked syndrome described by Rett in the German literature. The exclusive involvement of females, correlated with findings in family data analyses, suggests a dominant mutation on one X chromosome that results in affected girls and nonviable male hemizygous conceptuses. PMID:6638958

  15. A novel homozygous splicing mutation of CASC5 causes primary microcephaly in a large Pakistani family.

    PubMed

    Szczepanski, Sandra; Hussain, Muhammad Sajid; Sur, Ilknur; Altmüller, Janine; Thiele, Holger; Abdullah, Uzma; Waseem, Syeda Seema; Moawia, Abubakar; Nürnberg, Gudrun; Noegel, Angelika Anna; Baig, Shahid Mahmood; Nürnberg, Peter

    2016-02-01

    Primary microcephaly is a disorder characterized by a small head and brain associated with impaired cognitive capabilities. Mutations in 13 different genes encoding centrosomal proteins and cell cycle regulators have been reported to cause the disease. CASC5, a gene encoding a protein important for kinetochore formation and proper chromosome segregation during mitosis, has been suggested to be associated with primary microcephaly-4 (MCPH4). This was based on one mutation only and circumstantial functional evidence. By combining homozygosity mapping and whole-exome sequencing in an MCPH family from Pakistan, we identified a second mutation (NM_170589.4;c.6673-19T>A) in CASC5. This mutation induced skipping of exon 25 of CASC5 resulting in a frameshift and the introduction of a premature stop codon (p.Met2225Ilefs*7). The C-terminally truncated protein lacks 118 amino acids that encompass the region responsible for the interaction with the hMIS12 complex, which is essential for proper chromosome alignment and segregation. Furthermore, we showed a down-regulation of CASC5 mRNA and reduction of the amount of CASC5 protein by quantitative RT-PCR and western blot analysis, respectively. As a further sign of functional deficits, we observed dispersed dots of CASC5 immunoreactive material outside the metaphase plate of dividing patient fibroblasts. Normally, CASC5 is a component of the kinetochore of metaphase chromosomes. A higher mitotic index in patient cells indicated a mitotic arrest in the cells carrying the mutation. We also observed lobulated and fragmented nuclei as well as micronuclei in the patient cells. Moreover, we detected an altered DNA damage response with higher levels of γH2AX and 53BP1 in mutant as compared to control fibroblasts. Our findings substantiate the proposed role of CASC5 for primary microcephaly and suggest that it also might be relevant for genome stability. PMID:26621532

  16. Adaptive evolution of four microcephaly genes and the evolution of brain size in anthropoid primates.

    PubMed

    Montgomery, Stephen H; Capellini, Isabella; Venditti, Chris; Barton, Robert A; Mundy, Nicholas I

    2011-01-01

    The anatomical basis and adaptive function of the expansion in primate brain size have long been studied; however, we are only beginning to understand the genetic basis of these evolutionary changes. Genes linked to human primary microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans. However, these studies focus narrowly on apes, and the link between microcephaly gene evolution and brain evolution is disputed. We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates. Contrary to prevailing assumptions, positive selection was not limited to or intensified along the lineage leading to humans. In fact we show that all four loci were subject to positive selection across the anthropoid primate phylogeny. We developed clearly defined hypotheses to explicitly test if selection on these loci was associated with the evolution of brain size. We found positive relationships between both CDK5RAP2 and ASPM and neonatal brain mass and somewhat weaker relationships between these genes and adult brain size. In contrast, there is no evidence linking CENPJ and MCPH1 to brain size evolution. The stronger association of ASPM and CDK5RAP2 evolution with neonatal brain size than with adult brain size is consistent with these loci having a direct effect on prenatal neuronal proliferation. These results suggest that primate brain size may have at least a partially conserved genetic basis. Our results contradict a previous study that linked adaptive evolution of ASPM to changes in relative cortex size; however, our analysis indicates that this conclusion is not robust. Our finding that the coding regions of two widely expressed loci has experienced pervasive positive selection in relation to a complex, quantitative developmental phenotype provides a notable counterexample to the commonly asserted

  17. Syndrome of absent abdominal muscles: two cases with microcephaly, polymicrogyria, and cerebellar malformations

    PubMed Central

    Heffner, Reid R.

    1970-01-01

    Two unique cases of the syndrome of absent abdominal muscles with central nervous system involvement are presented. Microcephaly, polymicrogyria, and cerebellar heterotopiae were present in both. In case 1 there was also absence of the corpus callosum and agenesis of the cerebellar vermis. In case 2 a count of anterior horn cells in the spinal cord showed a reduction of approximately 50% in the lower thoracic region. The pertinent literature is briefly discussed. The findings in the nervous system suggest that the syndrome is the result of defective embryogenesis during the first trimester. Images PMID:4250700

  18. Time Lags between Exanthematous Illness Attributed to Zika Virus, Guillain-Barré Syndrome, and Microcephaly, Salvador, Brazil

    PubMed Central

    Paploski, Igor A.D.; Prates, Ana Paula P.B.; Cardoso, Cristiane W.; Kikuti, Mariana; Silva, Monaise M. O.; Waller, Lance A.; Reis, Mitermayer G.; Kitron, Uriel

    2016-01-01

    Zika virus infection emerged as a public health emergency after increasing evidence for its association with neurologic disorders and congenital malformations. In Salvador, Brazil, outbreaks of acute exanthematous illness (AEI) attributed to Zika virus, Guillain-Barré syndrome (GBS), and microcephaly occurred in 2015. We investigated temporal correlations and time lags between these outbreaks to identify a common link between them by using epidemic curves and time series cross-correlations. Number of GBS cases peaked after a lag of 5–9 weeks from the AEI peak. Number of suspected cases of microcephaly peaked after a lag of 30–33 weeks from the AEI peak, which corresponded to time of potential infections of pregnant mothers during the first trimester. These findings support the association of GBS and microcephaly with Zika virus infection and provide evidence for a temporal relationship between timing of arboviral infection of pregnant women during the first trimester and birth outcome. PMID:27144515

  19. Time Lags between Exanthematous Illness Attributed to Zika Virus, Guillain-Barré Syndrome, and Microcephaly, Salvador, Brazil.

    PubMed

    Paploski, Igor A D; Prates, Ana Paula P B; Cardoso, Cristiane W; Kikuti, Mariana; Silva, Monaise M O; Waller, Lance A; Reis, Mitermayer G; Kitron, Uriel; Ribeiro, Guilherme S

    2016-08-01

    Zika virus infection emerged as a public health emergency after increasing evidence for its association with neurologic disorders and congenital malformations. In Salvador, Brazil, outbreaks of acute exanthematous illness (AEI) attributed to Zika virus, Guillain-Barré syndrome (GBS), and microcephaly occurred in 2015. We investigated temporal correlations and time lags between these outbreaks to identify a common link between them by using epidemic curves and time series cross-correlations. Number of GBS cases peaked after a lag of 5-9 weeks from the AEI peak. Number of suspected cases of microcephaly peaked after a lag of 30-33 weeks from the AEI peak, which corresponded to time of potential infections of pregnant mothers during the first trimester. These findings support the association of GBS and microcephaly with Zika virus infection and provide evidence for a temporal relationship between timing of arboviral infection of pregnant women during the first trimester and birth outcome. PMID:27144515

  20. TALEN-based generation of a cynomolgus monkey disease model for human microcephaly.

    PubMed

    Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

    2016-09-01

    Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

  1. 10q26.1 Microdeletion: Redefining the critical regions for microcephaly and genital anomalies.

    PubMed

    Choucair, Nancy; Abou Ghoch, Joelle; Fawaz, Ali; Mégarbané, André; Chouery, Eliane

    2015-11-01

    Distal 10q deletion syndrome is a well-characterized chromosomal disorder consisting of neurodevelopmental impairment, facial dysmorphism, cardiac malformations, genital and urinary tract defects, as well as digital anomalies. Patients with interstitial deletions involving band 10q26.1 present a phenotype similar to the ones with the distal 10q deletion syndrome, which led to the definition of a causal 600 kb smallest region of overlap (SRO). In this report, we describe a male patient with an interstitial 4.5 Mb deletion involving exclusively the 10q26.1 segment. He had growth and psychomotor retardation, microcephaly, flat feet, micropenis, and cryptorchidism. The patient's deleted region does not overlap the 10q SRO. We reviewed the clinical phenotype of patients with similar deletions and suggest the presence of two new SROs, one associated with microcephaly, growth and psychomotor retardation, and the other associated to genital anomalies. Interestingly, we narrowed those regions to segments encompassing five and two genes, respectively. FGFR2, NSMCE4A, and ATE1 were suggested as candidates for facial dysmorphism, growth cessation, and heart defects, respectively. WDR11 was linked to idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Its haploinsufficiency could play a crucial role in the genital anomalies of these patients. PMID:26114870

  2. A case report: Autosomal recessive microcephaly caused by a novel mutation in MCPH1 gene.

    PubMed

    Ghafouri-Fard, Soudeh; Fardaei, Majid; Gholami, Milad; Miryounesi, Mohammad

    2015-10-15

    Autosomal Recessive Primary Microcephaly (MCPH-MIM 251200) is distinguished by congenital decrease in occipito-frontal head circumference (OFC) of at least 2 standard deviations (SD) below population average in addition to non-progressive mental retardation, without any prominent neurological disorder. Mutations in MCPH1, which encodes the protein microcephalin have been detected in this disorder. Here we report a consanguineous Iranian family with 2 children affected with microcephaly. Despite the severe mental retardation observed in the male patient, the female patient had normal intelligent with no delay in motor milestones or speech. A novel splice-acceptor site homozygous mutation has been detected in intron 4 of MCPH1 gene (c.322-2A>T) which results in an RNA processing defect with a 15-nucleotide deletion in exon 5 of the mRNA transcript (r.322_336del15, p.R108_Q112del5). This novel mutation has resulted in different phenotypes in affected male and female patients of this family. The sex-specific variations in gene regulation during brain development may partially explain such difference in phenotypes probably in addition to other mechanisms such as modifier genes. PMID:26192461

  3. Microcephaly with Simplified Gyration, Epilepsy, and Infantile Diabetes Linked to Inappropriate Apoptosis of Neural Progenitors

    PubMed Central

    Poulton, Cathryn J.; Schot, Rachel; Kia, Sima Kheradmand; Jones, Marta; Verheijen, Frans W.; Venselaar, Hanka; de Wit, Marie-Claire Y.; de Graaff, Esther; Bertoli-Avella, Aida M.; Mancini, Grazia M.S.

    2011-01-01

    We describe a syndrome of primary microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes in two unrelated consanguineous families with at least three affected children. Linkage analysis revealed a region on chromosome 18 with a significant LOD score of 4.3. In this area, two homozygous nonconserved missense mutations in immediate early response 3 interacting protein 1 (IER3IP1) were found in patients from both families. IER3IP1 is highly expressed in the fetal brain cortex and fetal pancreas and is thought to be involved in endoplasmic reticulum stress response. We reported one of these families previously in a paper on Wolcott-Rallison syndrome (WRS). WRS is characterized by increased apoptotic cell death as part of an uncontrolled unfolded protein response. Increased apoptosis has been shown to be a cause of microcephaly in animal models. An autopsy specimen from one patient showed increased apoptosis in the cerebral cortex and pancreas beta cells, implicating premature cell death as the pathogenetic mechanism. Both patient fibroblasts and control fibroblasts treated with siRNA specific for IER3IP1 showed an increased susceptibility to apoptotic cell death under stress conditions in comparison to controls. This directly implicates IER3IP1 in the regulation of cell survival. Identification of IER3IP1 mutations sheds light on the mechanisms of brain development and on the pathogenesis of infantile epilepsy and early-onset permanent diabetes. PMID:21835305

  4. A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features.

    PubMed

    Pavone, Piero; Praticò, Andrea Domenico; Gentile, Giulia; Falsaperla, Raffaele; Iemmolo, Rosario; Guarnaccia, Maria; Cavallaro, Sebastiano; Ruggieri, Martino

    2016-05-01

    Neurocutaneous disorders represent a heterogeneous group of conditions affecting the skin (with pigmentary/vascular abnormalities, hamartomas or tumors) and the central and peripheral nervous systems. In recent years, besides the well-known neurocutaneous diseases (e.g., the different forms of neurofibromatosis, tuberous sclerosis complex, Sturge-Weber syndrome and mosaic pigmentary/hamartomatous disorders), new distinctive syndromes have been characterized, extending our knowledge on the spectrum of these conditions. The concurrent presence of pigmentary abnormalities (both of the hypo- and hyperpigmented type), and primary microcephaly has not been commonly reported. We report on a 4.5-year-old girl with primary microcephaly, who had in addition moderate to severe developmental delay, behavioral and stereotypic abnormalities and a cutaneous pattern of paired hypo- and hyperpigmented lesions variously distributed over the body, particularly on the trunk. Failure to thrive and mild facial dysmorphic features were also present. To our knowledge, this complex malformation (neurocutaneous) phenotype has not been previously reported. PMID:26979654

  5. Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.

    PubMed

    Kodani, Andrew; Yu, Timothy W; Johnson, Jeffrey R; Jayaraman, Divya; Johnson, Tasha L; Al-Gazali, Lihadh; Sztriha, Lāszló; Partlow, Jennifer N; Kim, Hanjun; Krup, Alexis L; Dammermann, Alexander; Krogan, Nevan J; Walsh, Christopher A; Reiter, Jeremy F

    2015-01-01

    Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication. PMID:26297806

  6. Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication

    PubMed Central

    Kodani, Andrew; Yu, Timothy W; Johnson, Jeffrey R; Jayaraman, Divya; Johnson, Tasha L; Al-Gazali, Lihadh; Sztriha, Lāszló; Partlow, Jennifer N; Kim, Hanjun; Krup, Alexis L; Dammermann, Alexander; Krogan, Nevan J; Walsh, Christopher A; Reiter, Jeremy F

    2015-01-01

    Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication. DOI: http://dx.doi.org/10.7554/eLife.07519.001 PMID:26297806

  7. Primary microcephaly, impaired DNA replication, and genomic instability caused by compound heterozygous ATR mutations.

    PubMed

    Mokrani-Benhelli, Houda; Gaillard, Laetitia; Biasutto, Patricia; Le Guen, Tangui; Touzot, Fabien; Vasquez, Nadia; Komatsu, Jun; Conseiller, Emmanuel; Pïcard, Capucine; Gluckman, Eliane; Francannet, Christine; Fischer, Alain; Durandy, Anne; Soulier, Jean; de Villartay, Jean-Pierre; Cavazzana-Calvo, Marina; Revy, Patrick

    2013-02-01

    Ataxia telangiectasia-mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) kinases are two key regulators of DNA-damage responses (DDR) that are mainly activated in response to DNA double-strand breaks and single-stranded DNA damages, respectively. Seckel syndrome, a rare genetic disorder characterized by a microcephaly and a markedly reduced body size, has been associated with defective ATR-dependent DNA damage signaling. However, the only human genetic ATR defect reported so far is a hypomorphic splicing mutation identified in five related individuals with Seckel syndrome. Here, we report the first case of primary microcephaly with compound heterozygous mutations in ATR: a 540 kb genomic deletion on one allele and a missense mutation leading to splice dysregulation on the other, which ultimately lead to a sharp decrease in ATR expression. DNA combing technology revealed a profound spontaneous alteration of several DNA replication parameters in patient's cells and FISH analyses highlighted the genomic instability caused by ATR deficiency. Collectively, our results emphasize the crucial role for ATR in the control of DNA replication, and reinforce the complementary and nonredundant contributions of ATM and ATR in human cells to face DNA damages and warrant genome integrity. PMID:23111928

  8. Hospital-acquired pneumonia

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000146.htm Hospital-acquired pneumonia To use the sharing features on this page, please enable JavaScript. Hospital-acquired pneumonia is an infection of the lungs ...

  9. Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy

    PubMed Central

    Bicknell, Louise S; Leitch, Andrea; Nürnberg, Gudrun; Toliat, Mohammad Reza; Murray, Jennie E; Hunt, David; Khan, Fawad; Ali, Zafar; Tinschert, Sigrid; Ding, James; Keith, Charlotte; Harley, Margaret E; Heyn, Patricia; Müller, Rolf; Hoffmann, Ingrid; Cormier-Daire, Valérie; Dollfus, Hélène; Dupuis, Lucie; Bashamboo, Anu; McElreavey, Kenneth; Kariminejad, Ariana; Mendoza-Londono, Roberto; Moore, Anthony T; Saggar, Anand; Schlechter, Catie; Weleber, Richard; Thiele, Holger; Altmüller, Janine; Höhne, Wolfgang; Hurles, Matthew E; Noegel, Angelika Anna; Baig, Shahid Mahmood; Nürnberg, Peter; Jackson, Andrew P

    2015-01-01

    Centrioles are essential for ciliogenesis. However, mutations in centriole biogenesis genes have been reported in primary microcephaly and Seckel syndrome, disorders without the hallmark clinical features of ciliopathies. Here we identify mutations in the master regulator of centriole duplication, the PLK4 kinase, and its substrate TUBGCP6 in patients with microcephalic primordial dwarfism and additional congenital anomalies including retinopathy, extending the human phenotype spectrum associated with centriole dysfunction. Furthermore, we establish that different levels of impaired PLK4 activity result in growth and cilia phenoptyes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features. PMID:25344692

  10. Mutations in CIT, encoding citron rho-interacting serine/threonine kinase, cause severe primary microcephaly in humans.

    PubMed

    Shaheen, Ranad; Hashem, Amal; Abdel-Salam, Ghada M H; Al-Fadhli, Fatima; Ewida, Nour; Alkuraya, Fowzan S

    2016-10-01

    Primary microcephaly is a clinical phenotype in which the head circumference is significantly reduced at birth due to abnormal brain development, primarily at the cortical level. Despite the marked genetic heterogeneity, most primary microcephaly-linked genes converge on mitosis regulation. Two consanguineous families segregating the phenotype of severe primary microcephaly, spasticity and failure to thrive had overlapping autozygomes in which exome sequencing identified homozygous splicing variants in CIT that segregate with the phenotype within each family. CIT encodes citron, an effector of the Rho signaling that is required for cytokinesis specifically in proliferating neuroprogenitors, as well as for postnatal brain development. In agreement with the critical role assigned to the kinase domain in effecting these biological roles, we show that both splicing variants predict variable disruption of this domain. The striking phenotypic overlap between CIT-mutated individuals and the knockout mice and rats that are specifically deficient in the kinase domain supports the proposed causal link between CIT mutation and primary microcephaly in humans. PMID:27503289

  11. New Recessive Syndrome of Microcephaly, Cerebellar Hypoplasia, and Congenital Heart Conduction Defect

    PubMed Central

    Zaki, Maha S; Salam, Ghada M H Abdel; Saleem, Sahar N; Dobyns, William B; Issa, Mahmoud Y; Sattar, Shifteh; Gleeson, Joseph G

    2011-01-01

    We identified a two-branch consanguineous family in which four affected members (three females and one male) presented with constitutive growth delay, severe psychomotor retardation, microcephaly, cerebellar hypoplasia, and second-degree heart block. They also shared distinct facial features and similar appearance of their hands and feet. Childhood-onset insulin-dependent diabetes mellitus developed in one affected child around the age of 9 years. Molecular analysis excluded mutations in potentially related genes such as PTF1A, EIF2AK3, EOMES, and WDR62. This condition appears to be unique of other known conditions, suggesting a unique clinical entity of autosomal recessive mode of inheritance. © 2011 Wiley Periodicals, Inc. PMID:22002884

  12. Microcephaly-dystonia due to mutated PLEKHG2 with impaired actin polymerization.

    PubMed

    Edvardson, Simon; Wang, Haibo; Dor, Talya; Atawneh, Osamah; Yaacov, Barak; Gartner, Jutta; Cinnamon, Yuval; Chen, Songhai; Elpeleg, Orly

    2016-01-01

    Rearrangement of the actin cytoskeleton is controlled by RhoGTPases which are activated by RhoGEFs. We identified homozygosity for Arg204Trp mutation in the Rho guanidine exchange factor (RhoGEF) PLEKHG2 gene in five patients with profound mental retardation, dystonia, postnatal microcephaly, and distinct neuroimaging pattern. The activity of the mutant PLEKHG2 was significantly decreased, both in basal state and when Gβγ- or lysophosphatidic acid (LPA)-stimulated. SDF1a-stimulated actin polymerization was significantly impaired in patient cells, and this abnormality was duplicated in control cells when PLEKHG2 expression was downregulated. These results underscore the role of PLEKHG2 in actin polymerization and delineate the clinical and radiological findings in PLEKHG2 deficiency. PMID:26573021

  13. Autosomal Recessive Primary Microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum.

    PubMed

    Mahmood, Saqib; Ahmad, Wasim; Hassan, Muhammad J

    2011-01-01

    Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder. PMID:21668957

  14. Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum

    PubMed Central

    2011-01-01

    Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder. PMID:21668957

  15. Acquired reactive perforating collagenosis.

    PubMed

    Basak, P Y; Turkmen, C

    2001-01-01

    Acquired perforating disorder has been recognized as an uncommon distinct dermatosis in which altered collagen is eliminated through the epidermis. Several disorders accompanied by itching and scratching were reported to be associated with reactive perforating collagenosis. A 67-year-old white woman diagnosed as acquired reactive perforating collagenosis with poorly controlled diabetes mellitus and congestive cardiac failure is presented. PMID:11525959

  16. Acquired Cystic Kidney Disease

    MedlinePlus

    ... a kidney transplant or blood-filtering treatments called dialysis. The cysts are more likely to develop in people who are on kidney dialysis. The chance of developing acquired cystic kidney disease ...

  17. Hospital-acquired pneumonia

    MedlinePlus

    ... tends to be more serious than other lung infections because: People in the hospital are often very sick and cannot fight off ... prevent pneumonia. Most hospitals have programs to prevent hospital-acquired infections.

  18. Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly

    PubMed Central

    Cottee, Matthew A; Muschalik, Nadine; Wong, Yao Liang; Johnson, Christopher M; Johnson, Steven; Andreeva, Antonina; Oegema, Karen; Lea, Susan M; Raff, Jordan W; van Breugel, Mark

    2013-01-01

    Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1:1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP–STIL interaction constitutes a conserved key step in centriole biogenesis. DOI: http://dx.doi.org/10.7554/eLife.01071.001 PMID:24052813

  19. Simplified gyral pattern in severe developmental microcephalies? New insights from allometric modeling for spatial and spectral analysis of gyrification.

    PubMed

    Germanaud, D; Lefèvre, J; Fischer, C; Bintner, M; Curie, A; des Portes, V; Eliez, S; Elmaleh-Bergès, M; Lamblin, D; Passemard, S; Operto, G; Schaer, M; Verloes, A; Toro, R; Mangin, J F; Hertz-Pannier, L

    2014-11-15

    The strong positive-allometric relationship between brain size, cortical extension and gyrification complexity, recently highlighted in the general population, could be modified by brain developmental disorders. Indeed, in case of brain growth insufficiency, the pathophysiological relevance of the "simplified gyral pattern" phenotype is strongly disputed since almost no genotype-phenotype correlations have been found in primary microcephalies. Using surface scaling analysis and newly-developed spectral analysis of gyrification (Spangy), we tested whether the gyral simplification in groups of severe microcephalies related to ASPM, PQBP1 or fetal-alcohol-syndrome could be fully explained by brain size reduction according to the allometric scaling law established in typically-developing control groups, or whether an additional disease effect was to be suspected. We found the surface area reductions to be fully explained by scaling effect, leading to predictable folding intensities measured by gyrification indices. As for folding pattern assessed by spectral analysis, scaling effect also accounted for the majority of the variations, but an additional negative or positive disease effect was found in the case of ASPM and PQBP1-linked microcephalies, respectively. Our results point out the necessity of taking allometric scaling into account when studying the gyrification variability in pathological conditions. They also show that the quantitative analysis of gyrification complexity through spectral analysis can enable distinguishing between even (predictable, non-specific) and uneven (unpredictable, maybe disease-specific) gyral simplifications. PMID:25107856

  20. CO-OCCURRENCE OF PRIMARY MICROCEPHALY CAUSED BY A NOVEL HOMOZYGOUS ASPM MUTATION ALONG WITH X-LINKED ICHTHYOSIS IN THE SAME PATIENT.

    PubMed

    Abdel-Hamid, M S; Ismail, M F; Darwish, H A; Effat, L K; Zaki, M S; Abdel-Salam, G M H

    2016-01-01

    Autosomal recessive primary microcephaly is a heterogeneous genetic disorder caused by genes that affect neurogenesis. This form of microcephaly has not been associated with other congenital anomalies. ASPM mutations have been identified as the major cause implicated in autosomal recessive primary microcephaly. X-linked recessive ichthyosis, is an inborn error of steroid sulfatase metabolism characterized by dark and adhesive scaly skin. Here, we examined an Egyptian boy presenting with microcephaly and simplified gyral pattern. Additionally, he had ichthyosis that goes with the X-linked type. Mutation analyses of the ASPM gene for autosomal recessive primary microcephaly and STS gene of X-linked recessive ichthyosis were conducted revealing a co-occurrence of a novel homozygous splice site mutation of ASPM gene (c.2936+1G>A) and a partial deletion of STS spanning from exon 7-10. We propose that the phenotype of our patient results from the combined effects of mutations in both ASPM and STS that account for the neurological signs and skin manifestations, respectively. The association of isolated X-linked recessive ichthyosis and autosomal recessive primary microcephaly has never been reported in the literature. Careful clinical and genetic assessment of patients with atypical clinical phenotypes is crucial for detecting such rare double mutations and thus proper genetic counseling. PMID:27192889

  1. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly.

    PubMed

    Buck, Dietke; Malivert, Laurent; de Chasseval, Régina; Barraud, Anne; Fondanèche, Marie-Claude; Sanal, Ozden; Plebani, Alessandro; Stéphan, Jean-Louis; Hufnagel, Markus; le Deist, Françoise; Fischer, Alain; Durandy, Anne; de Villartay, Jean-Pierre; Revy, Patrick

    2006-01-27

    DNA double-strand breaks (DSBs) occur at random upon genotoxic stresses and represent obligatory intermediates during physiological DNA rearrangement events such as the V(D)J recombination in the immune system. DSBs, which are among the most toxic DNA lesions, are preferentially repaired by the nonhomologous end-joining (NHEJ) pathway in higher eukaryotes. Failure to properly repair DSBs results in genetic instability, developmental delay, and various forms of immunodeficiency. Here we describe five patients with growth retardation, microcephaly, and immunodeficiency characterized by a profound T+B lymphocytopenia. An increased cellular sensitivity to ionizing radiation, a defective V(D)J recombination, and an impaired DNA-end ligation process both in vivo and in vitro are indicative of a general DNA repair defect in these patients. All five patients carry mutations in the Cernunnos gene, which was identified through cDNA functional complementation cloning. Cernunnos/XLF represents a novel DNA repair factor essential for the NHEJ pathway. PMID:16439204

  2. TGFBR2 Deletion in a 20-Month-Old Female With Developmental Delay and Microcephaly

    PubMed Central

    Campbell, Ian M.; Kolodziejska, Katarzyna E.; Quach, Michael M.; Wolf, Varina Louise; Cheung, Sau Wai; Lalani, Seema R.; Ramocki, Melissa B.; Stankiewicz, Pawel

    2013-01-01

    To date, over 70 mutations in the TGFBR2 gene have been reported in patients with Loeys–Dietz syndrome (LDS), Marfan syndrome type 2 (MFS2), or other hereditary thoracic aortic aneurysms and dissections. Whereas almost all of mutations analyzed thus far are predicted to disrupt the constitutively active C-terminal serine/threonine kinase domain of TGFBR2, mounting evidence suggests that the molecular mechanism underlying these diseases is more complex than simple haploinsufficiency. Using exon-targeted oligonucleotide array comparative genomic hybridization, we identified an ~896 kb deletion of TGFBR2 in a 20-month-old female with microcephaly and global developmental delay, but no stigmata of LDS. FISH analysis showed no evidence of this deletion in the parental peripheral blood samples; however, somatic mosaicism was detected using PCR in the paternal DNA from peripheral blood lymphocytes and lymphoblasts. Our data suggest that TGFBR2 haploinsufficiency may cause a phenotype, which is distinct from LDS. Moreover, we propose that somatic mosaicism below the detection threshold of FISH analysis in asymptomatic parents of children with genomic disorders may be more common than previously recognized. PMID:21567932

  3. Induction of Excess Centrosomes in Neural Progenitor Cells during the Development of Radiation-Induced Microcephaly

    PubMed Central

    Shimada, Mikio; Matsuzaki, Fumio; Kato, Akihiro; Kobayashi, Junya; Matsumoto, Tomohiro; Komatsu, Kenshi

    2016-01-01

    The embryonic brain is one of the tissues most vulnerable to ionizing radiation. In this study, we showed that ionizing radiation induces apoptosis in the neural progenitors of the mouse cerebral cortex, and that the surviving progenitor cells subsequently develop a considerable amount of supernumerary centrosomes. When mouse embryos at Day 13.5 were exposed to γ-rays, brains sizes were reduced markedly in a dose-dependent manner, and these size reductions persisted until birth. Immunostaining with caspase-3 antibodies showed that apoptosis occurred in 35% and 40% of neural progenitor cells at 4 h after exposure to 1 and 2 Gy, respectively, and this was accompanied by a disruption of the apical layer in which mitotic spindles were positioned in unirradiated mice. At 24 h after 1 Gy irradiation, the apoptotic cells were completely eliminated and proliferation was restored to a level similar to that of unirradiated cells, but numerous spindles were localized outside the apical layer. Similarly, abnormal cytokinesis, which included multipolar division and centrosome clustering, was observed in 19% and 24% of the surviving neural progenitor cells at 48 h after irradiation with 1 and 2 Gy, respectively. Because these cytokinesis aberrations derived from excess centrosomes result in growth delay and mitotic catastrophe-mediated cell elimination, our findings suggest that, in addition to apoptosis at an early stage of radiation exposure, radiation-induced centrosome overduplication could contribute to the depletion of neural progenitors and thereby lead to microcephaly. PMID:27367050

  4. A nonsense mutation in the DNA repair factor Hebo causes mild bone marrow failure and microcephaly.

    PubMed

    Zhang, Shu; Pondarre, Corinne; Pennarun, Gaelle; Labussiere-Wallet, Helene; Vera, Gabriella; France, Benoit; Chansel, Marie; Rouvet, Isabelle; Revy, Patrick; Lopez, Bernard; Soulier, Jean; Bertrand, Pascale; Callebaut, Isabelle; de Villartay, Jean-Pierre

    2016-05-30

    Inherited bone marrow failure syndromes are human conditions in which one or several cell lineages of the hemopoietic system are affected. They are present at birth or may develop progressively. They are sometimes accompanied by other developmental anomalies. Three main molecular causes have been recognized to result in bone marrow failure syndromes: (1) defects in the Fanconi anemia (FA)/BRCA DNA repair pathway, (2) defects in telomere maintenance, and (3) abnormal ribosome biogenesis. We analyzed a patient with mild bone marrow failure and microcephaly who did not present with the typical FA phenotype. Cells from this patient showed increased sensitivity to ionizing radiations and phleomycin, attesting to a probable DNA double strand break (dsb) repair defect. Linkage analysis and whole exome sequencing revealed a homozygous nonsense mutation in the ERCC6L2 gene. We identified a new ERCC6L2 alternative transcript encoding the DNA repair factor Hebo, which is critical for complementation of the patient's DNAdsb repair defect. Sequence analysis revealed three structured regions within Hebo: a TUDOR domain, an adenosine triphosphatase domain, and a new domain, HEBO, specifically present in Hebo direct orthologues. Hebo is ubiquitously expressed, localized in the nucleus, and rapidly recruited to DNAdsb's in an NBS1-dependent manner. PMID:27185855

  5. The microcephaly gene aspm is involved in brain development in zebrafish

    SciTech Connect

    Kim, Hyun-Taek; Lee, Mi-Sun; Choi, Jung-Hwa; Jung, Ju-Yeon; Ahn, Dae-Gwon; Yeo, Sang-Yeob; Choi, Dong-Kug; Kim, Cheol-Hee

    2011-06-17

    Highlights: {yields} We identified a zebrafish aspm/mcph5 gene that is expressed in proliferating cells in the CNS during early development. {yields} Embryos injected with the aspm MO consistently showed a reduced head and eye size but were otherwise grossly normal, closely mimicking the known phenotypes of human microcephaly patients. {yields} Knock-down of aspm causes cell cycle arrest and apoptotic cell death during early development. -- Abstract: MCPH is a neurodevelopmental disorder characterized by a global reduction in cerebral cortical volume. Homozygous mutation of the MCPH5 gene, also known as ASPM, is the most common cause of the MCPH phenotype. To elucidate the roles of ASPM during embryonic development, the zebrafish aspm was identified, which is specifically expressed in proliferating cells in the CNS. Morpholino-mediated knock-down of aspm resulted in a significant reduction in head size. Furthermore, aspm-deficient embryos exhibited a mitotic arrest during early development. These findings suggest that the reduction in brain size in MCPH might be caused by lack of aspm function in the mitotic cell cycle and demonstrate that the zebrafish can provide a model system for congenital diseases of the human nervous system.

  6. Eleven Polish patients with microcephaly, immunodeficiency, and chromosomal instability: The Nijmegan breakage syndrome

    SciTech Connect

    Chrzanowska, K.H.; Krajewska-Walasek, M.; Gutkowska, A.

    1995-07-03

    We report on 11 patients with 8 independent families (3 pairs of sibs) with a complex clinical pattern including microcephaly, peculiar {open_quotes}bird-like{close_quotes} face, growth retardation, and, in some cases, mild-to-moderate mental deficiency. Most of the patients have recurring respiratory tract infections. One girl has developed B-cell lymphoma. A detailed anthropometric study of 15 physical parameters, including 3 cephalic traits, was performed. It was possible to study the chromosomes of PHA-stimulated lymphocytes in all of the patients. We found structural aberrations with multiple rearrangements, preferentially involving chromosomes 7 and 14 in a proportion of metaphases in all individuals. Profound humoral and cellular immune defects were observed. Serum AFP levels were within normal range. Radioresistant DNA synthesis was strongly increased in all 8 patients who were hitherto studied in this respect. Our patients fulfill the criteria of the Nijmegen breakage syndrome, which belongs to the growing category of ataxia telangiectasia-related genetic disorders. In light of the increased predisposition to malignancy in this syndrome, an accurate diagnosis is important for the patient. 27 refs., 5 figs., 4 tabs.

  7. Microcephaly models in the developing zebrafish retinal neuroepithelium point to an underlying defect in metaphase progression

    PubMed Central

    Novorol, Claire; Burkhardt, Janina; Wood, Kirstin J.; Iqbal, Anila; Roque, Claudio; Coutts, Nicola; Almeida, Alexandra D.; He, Jie; Wilkinson, Christopher J.; Harris, William A.

    2013-01-01

    Autosomal recessive primary microcephaly (MCPH) is a congenital disorder characterized by significantly reduced brain size and mental retardation. Nine genes are currently known to be associated with the condition, all of which encode centrosomal or spindle pole proteins. MCPH is associated with a reduction in proliferation of neural progenitors during fetal development. The cellular mechanisms underlying the proliferation defect, however, are not fully understood. The zebrafish retinal neuroepithelium provides an ideal system to investigate this question. Mutant or morpholino-mediated knockdown of three known MCPH genes (stil, aspm and wdr62) and a fourth centrosomal gene, odf2, which is linked to several MCPH proteins, results in a marked reduction in head and eye size. Imaging studies reveal a dramatic rise in the fraction of proliferating cells in mitosis in all cases, and time-lapse microscopy points to a failure of progression through prometaphase. There was also increased apoptosis in all the MCPH models but this appears to be secondary to the mitotic defect as we frequently saw mitotically arrested cells disappear, and knocking down p53 apoptosis did not rescue the mitotic phenotype, either in whole retinas or clones. PMID:24153002

  8. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach. PMID:26186969

  9. A Case Of Bilateral Acquired Localized Lipoatrophy

    PubMed Central

    Tanrıkulu, Osman; Yesilova, Yavuz; Aksoy, Mustafa

    2016-01-01

    Lipoatrophy is characterized by inflammation and tissue loss in fatty tissue. This disease may be congenital or acquired, primary or secondary. Secondary lipoatrophy develops with infections, collagen tissue diseases, tumors and drug injections. In this report, we present the case of a 14-year-old female patient who developed lipoatrophy following intramuscular steroid injection to both buttocks. PMID:27504088

  10. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    Schwartz, Stacey Hunter

    This paper reviews the Acquired Brain Injury (ABI) Program at Coastline Community College (California). The ABI Program is a two-year, for-credit educational curriculum designed to provide structured cognitive retraining for adults who have sustained an ABI due to traumatic (such as motor vehicle accident or fall) or non-traumatic(such as…

  11. Acquired von Willebrand disease.

    PubMed

    Petrini, P

    1999-05-01

    Acquired von Willebrand disease (AvWD) is a syndrome that has clinical and laboratory features similar to hereditary vWD. In contrast to the latter it occurs in patients without a family history of previous bleeding tendency. PMID:23401904

  12. Mutations in Centrosomal Protein CEP152 in Primary Microcephaly Families Linked to MCPH4

    PubMed Central

    Guernsey, Duane L.; Jiang, Haiyan; Hussin, Julie; Arnold, Marc; Bouyakdan, Khalil; Perry, Scott; Babineau-Sturk, Tina; Beis, Jill; Dumas, Nadine; Evans, Susan C.; Ferguson, Meghan; Matsuoka, Makoto; Macgillivray, Christine; Nightingale, Mathew; Patry, Lysanne; Rideout, Andrea L.; Thomas, Aidan; Orr, Andrew; Hoffmann, Ingrid; Michaud, Jacques L.; Awadalla, Philip; Meek, David C.; Ludman, Mark; Samuels, Mark E.

    2010-01-01

    Primary microcephaly is a rare condition in which brain size is substantially diminished without other syndromic abnormalities. Seven autosomal loci have been genetically mapped, and the underlying causal genes have been identified for MCPH1, MCPH3, MCPH5, MCPH6, and MCPH7 but not for MCPH2 or MCPH4. The known genes play roles in mitosis and cell division. We ascertained three families from an Eastern Canadian subpopulation, each with one microcephalic child. Homozygosity analysis in two families using genome-wide dense SNP genotyping supported linkage to the published MCPH4 locus on chromosome 15q21.1. Sequencing of coding exons of candidate genes in the interval identified a nonconservative amino acid change in a highly conserved residue of the centrosomal protein CEP152. The affected children in these two families were both homozygous for this missense variant. The third affected child was compound heterozygous for the missense mutation plus a second, premature-termination mutation truncating a third of the protein and preventing its localization to centrosomes in transfected cells. CEP152 is the putative mammalian ortholog of Drosphila asterless, mutations in which affect mitosis in the fly. Published data from zebrafish are also consistent with a role of CEP152 in centrosome function. By RT-PCR, CEP152 is expressed in the embryonic mouse brain, similar to other MCPH genes. Like some other MCPH genes, CEP152 shows signatures of positive selection in the human lineage. CEP152 is a strong candidate for the causal gene underlying MCPH4 and may be an important gene in the evolution of human brain size. PMID:20598275

  13. Molecular and phenotypic spectrum of ASPM-related primary microcephaly: Identification of eight novel mutations.

    PubMed

    Abdel-Hamid, Mohamed S; Ismail, Manal F; Darwish, Hebatallh A; Effat, Laila K; Zaki, Maha S; Abdel-Salam, Ghada M H

    2016-08-01

    Autosomal recessive primary microcephaly (MCPH) is an abnormal proliferation of neurons during brain development that leads to a small brain size but architecturally normal in most instances. Mutations in the ASPM gene have been identified to be the most prevalent. Thirty-seven patients from 30 unrelated families with a clinical diagnosis of MCPH were enrolled in this study. Screening of ASPM gene mutations was performed by targeted linkage analysis followed by direct sequencing. Thirteen protein truncating mutations of the ASPM were identified in 15 families (50%), eight of which were novel mutations. The mutations detected were eight nonsense, four frameshift, and one splice site. Two of these mutations (p.R1327* and p.R3181*) were recurrent and shared similar haplotypes suggesting founder effect. Patients with ASPM mutations had mild to severe intellectual disability and variable degrees of simplified gyral pattern and small frontal lobe. In addition, hypoplasia of corpus callosum (18 patients), mildly small cerebellar vermis (10 patients), and relatively small pons (13 patients) were found in 85.7%, 47.6%, and 61.9%, respectively. Furthermore, one patient had porencephaly and another had a small midline cyst. Epilepsy was documented in two patients (9.5%). Non-neurologic abnormalities consisted of growth retardation (four patients), and co-incidental association of oculo-cutaneous albinism (one patient). Our study expands the mutation spectrum of ASPM. Moreover, the simplified gyral pattern and small frontal lobe together with hypoplastic corpus callosum, small cerebellum and pons enable ASPM mutated patients to be distinguished. © 2016 Wiley Periodicals, Inc. PMID:27250695

  14. Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly.

    PubMed

    Kumar, Arun; Girimaji, Satish C; Duvvari, Mahesh R; Blanton, Susan H

    2009-02-01

    Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterized by smaller-than-normal brain size and mental retardation. MCPH is genetically heterogeneous with six known loci: MCPH1-MCPH6. We report mapping of a novel locus, MCPH7, to chromosome 1p32.3-p33 between markers D1S2797 and D1S417, corresponding to a physical distance of 8.39 Mb. Heterogeneity analysis of 24 families previously excluded from linkage to the six known MCPH loci suggested linkage of five families (20.83%) to the MCPH7 locus. In addition, four families were excluded from linkage to the MCPH7 locus as well as all of the six previously known loci, whereas the remaining 15 families could not be conclusively excluded or included. The combined maximum two-point LOD score for the linked families was 5.96 at marker D1S386 at theta = 0.0. The combined multipoint LOD score was 6.97 between markers D1S2797 and D1S417. Previously, mutations in four genes, MCPH1, CDK5RAP2, ASPM, and CENPJ, that code for centrosomal proteins have been shown to cause this disorder. Three different homozygous mutations in STIL, which codes for a pericentriolar and centrosomal protein, were identified in patients from three of the five families linked to the MCPH7 locus; all are predicted to truncate the STIL protein. Further, another recently ascertained family was homozygous for the same mutation as one of the original families. There was no evidence for a common haplotype. These results suggest that the centrosome and its associated structures are important in the control of neurogenesis in the developing human brain. PMID:19215732

  15. A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome.

    PubMed

    Kumar, Ashutosh; Singh, Himanshu N; Pareek, Vikas; Raza, Khursheed; Dantham, Subrahamanyam; Kumar, Pavan; Mochan, Sankat; Faiq, Muneeb A

    2016-01-01

    Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)-microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker "retinoic acid" in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5'-AGGTCA-3') in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and embryological

  16. Pneumonia - adults (community acquired)

    MedlinePlus

    ... Fever , which may be mild or high Shaking chills Shortness of breath (may only occur when you ... or unexplained weight loss Shortness of breath, shaking chills, or persistent fevers Signs of pneumonia and a ...

  17. Acquired von Willebrand disease.

    PubMed

    Kumar, Shaji; Pruthi, Rajiv K; Nichols, William L

    2002-02-01

    Acquired von Willebrand disease (AvWD) is a relatively rare acquired bleeding disorder that usually occurs in elderly patients, in whom its recognition may be delayed. Patients usually present predominantly with mucocutaneous bleeding, with no previous history of bleeding abnormalities and no clinically meaningful family history. Various underlying diseases have been associated with AvWD, most commonly hematoproliferative disorders, including monoclonal gammopathies, lymphoproliferative disorders, and myeloproliferative disorders. The pathogenesis of AvWD remains incompletely understood but includes autoantibodies directed against the von Willebrand factor (vWF), leading to a more rapid clearance from the circulation or interference with its function, adsorption of vWF by tumor cells, and nonimmunologic mechanisms of destruction. Laboratory evaluation usually reveals a pattern of prolonged bleeding time and decreased levels of vWF antigen, ristocetin cofactor activity, and factor VIII coagulant activity consistent with a diagnosis of vWD. Acquired vWD is distinguished from the congenital form by age at presentation, absence of a personal and family history of bleeding disorders, and, often, presence of a hematoproliferative or autoimmune disorder. The severity of the bleeding varies considerably among patients. Therapeutic options include desmopressin and certain factor VIII concentrates that also contain vWF. Successful treatment of the associated illness can reverse the clinical and laboratory manifestations. Intravenous immunoglobulins have also shown some efficacy in the management of AvWD, especially cases associated with monoclonal gammopathies. Awareness of AvWD is essential for diagnosis and appropriate management. PMID:11838652

  18. [Acquired von Willebrand syndrome].

    PubMed

    Franchini, Massimo

    2006-01-01

    Acquired von Willebrand syndrome (aVWS) is a rare, but probably underestimated, bleeding disorder that mimics the congenital form of von Willebrand disease (VWD) in terms of laboratory findings and clinical presentation. However, unlike congenital VWD, it arises in individuals with no personal or family history of bleeding. AVWS occurs in association with a variety of underlying disorders, including lymphoproliferative disorders, myeloproliferative disorders and cardiovascular diseases. The main pathogenic, clinical, laboratory and therapeutic aspects of this syndrome are concisely reported in this review. PMID:16913181

  19. Acquired Monocular Disability.

    ERIC Educational Resources Information Center

    Schein, J. D.

    1988-01-01

    This paper outlines perceptual consequences of loss of binocular vision; complicating factors in monocular impairment such as age at onset and degree of residual vision; empirical evidence of the severity of monocular impairments, in terms of driving accidents and rehabilitation prospects; and the impairment's economic, psychological, and social…

  20. Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations.

    PubMed

    Jones, Gabriela E; Ostergaard, Pia; Moore, Anthony T; Connell, Fiona C; Williams, Denise; Quarrell, Oliver; Brady, Angela F; Spier, Isabel; Hazan, Filiz; Moldovan, Oana; Wieczorek, Dagmar; Mikat, Barbara; Petit, Florence; Coubes, Christine; Saul, Robert A; Brice, Glen; Gordon, Kristiana; Jeffery, Steve; Mortimer, Peter S; Vasudevan, Pradeep C; Mansour, Sahar

    2014-07-01

    Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing. PMID:24281367

  1. Inactivating Mutations in MFSD2A, Required for Omega-3 Fatty Acid Transport in Brain, Cause a Lethal Microcephaly Syndrome

    PubMed Central

    Guemez-Gamboa, Alicia; Nguyen, Long N.; Yang, Hongbo; Zaki, Maha S.; Kara, Majdi; Ben-Omran, Tawfeg; Akizu, Naiara; Rosti, Rasim Ozgur; Rosti, Basak; Scott, Eric; Schroth, Jana; Copeland, Brett; Vaux, Keith K.; Cazenave-Gassiot, Amaury; Quek, Debra Q.Y.; Wong, Bernice H.; Tan, Bryan C.; Wenk, Markus R.; Gunel, Murat; Gabriel, Stacey; Chi, Neil C.; Silver, David L.; Gleeson, Joseph G.

    2015-01-01

    Docosahexanoic acid (DHA) is the most abundant omega-3 fatty acid in brain, and although considered essential, deficiency has not been linked to disease1,2. Despite the large mass of DHA in phospholipids, the brain does not synthesize it. DHA is imported across the blood-brain barrier (BBB) through the Major Facilitator Superfamily Domain 2a (Mfsd2a)3. Mfsd2a transports DHA as well as other fatty acids in the form of lysophosphatidylcholine (LPC). We identify two families displaying MFSD2A mutations in conserved residues. Patients exhibited a lethal microcephaly syndrome linked to inadequate uptake of LPC lipids. The MFSD2A mutations impaired transport activity in a cell-based assay. Moreover, when expressed in mfsd2aa zebrafish morphants, mutants failed to rescue microcephaly, BBB breakdown and lethality. Our results establish a link between transport of DHA and LPCs by MFSD2A and human brain growth and function, presenting the first evidence of monogenic disease related to transport of DHA in humans. PMID:26005868

  2. A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin disorder

    PubMed Central

    KOUFARIS, COSTAS; ALEXANDROU, ANGELOS; TANTELES, GEORGE A.; ANASTASIADOU, VIOLETTA; SISMANI, CAROLINA

    2016-01-01

    Approximately 10–15% of intellectual disability (ID) cases are caused by genetic aberrations affecting chromosome X, a condition termed X-linked ID (XLID). Examination by whole-exome sequencing of two male siblings with microcephaly and suspected XLID with an unknown genetic basis revealed that they were both hemizygous for a predicted pathogenic variant (p.Ala897Val) causing a non-synonymous substitution of an evolutionary conserved amino acid within the host cell factor C1 (HCFC1) gene. Subsequent analysis determined that this was a rare variant not identified in 100 control individuals or in online databases of control individuals. Recent studies have reported mutations affecting HCFC1 in patients with ID and dysmorphic features that are associated with defective cobalamin metabolism. Biochemical investigations did not find evidence of an association between the variant identified in the present study and cobalamin metabolic disorder. This study offers further support for mutations of HCFC1 being implicated in XLID and microcephaly, but that these are not necessarily associated with cobalamin disorder. PMID:26893841

  3. Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly

    PubMed Central

    Paciorkowski, Alex R.; McDaniel, Sharon S.; Jansen, Laura A.; Tully, Hannah; Tuttle, Emily; Ghoneim, Dalia H.; Tupal, Srinivasan; Gunter, Sonya A.; Vasta, Valeria; Zhang, Qing; Tran, Thao; Liu, Yi B.; Ozelius, Laurie J.; Brashear, Allison; Sweadner, Kathleen J.; Dobyns, William B.; Hahn, Si Houn

    2014-01-01

    Objective Mutations of ATP1A3 have been associated with Rapid Onset Dystonia-Parkinsonism and more recently with Alternating Hemiplegia of Childhood. Here we report one child with catastrophic early life epilepsy and shortened survival, and another with epilepsy, episodic prolonged apnea, postnatal microcephaly, and severe developmental disability. Novel heterozygous mutations (p.Gly358Val and p.Ile363Asn) were identified in ATP1A3 in these children. Methods Subjects underwent next-generation sequencing under a research protocol. Clinical data were collected retrospectively. The biochemical effects of the mutations on ATP1A3 protein function were investigated. Post-mortem neuropathologic specimens from control and affected subjects were studied. Results The mutations localized to the P domain of the Na,K-ATPase α3 protein, and resulted in significant reduction of Na,K-ATPase activity in vitro. We demonstrate in both control human brain tissue and that from the subject with the p.Gly358Val mutation that ATP1A3 immunofluorescence is prominently associated with interneurons in the cortex, which may provide some insight into the pathogenesis of the disease. Significance The findings indicate these mutations cause severe phenotypes of ATP1A3-related disorder spectrum that include catastrophic early life epilepsy, episodic apnea, and postnatal microcephaly. PMID:25656163

  4. What next-generation sequencing (NGS) technology has enabled us to learn about primary autosomal recessive microcephaly (MCPH).

    PubMed

    Morris-Rosendahl, Deborah J; Kaindl, Angela M

    2015-10-01

    The impact that next-generation sequencing technology (NGS) is having on many aspects of molecular and cell biology, is becoming increasingly apparent. One of the most noticeable outcomes of the new technology in human genetics, has been the accelerated rate of identification of disease-causing genes. Especially for rare, heterogeneous disorders, such as autosomal recessive primary microcephaly (MCPH), the handful of genes previously known to harbour disease-causing mutations, has grown at an unprecedented rate within a few years. Knowledge of new genes mutated in MCPH over the last four years has contributed to our understanding of the disorder at both the clinical and cellular levels. The functions of proteins such as WDR62, CASC5, PHC1, CDK6, CENP-E, CENP-F, CEP63, ZNF335, PLK4 and TUBGPC, have been added to the complex network of critical cellular processes known to be involved in brain growth and size. In addition to the importance of mitotic spindle assembly and structure, centrosome and centriole function and DNA repair and damage response, new mechanisms involving kinetochore-associated proteins and chromatin remodelling complexes have been elucidated. Two of the major contributions to our clinical knowledge are the realisation that primary microcephaly caused by mutations in genes at the MCPH loci is seldom an isolated clinical feature and is often accompanied either by additional cortical malformations or primordial dwarfism. Gene-phenotype correlations are being revisited, with a new dimension of locus heterogeneity and phenotypic variability being revealed. PMID:26050940

  5. AIDS: acquired immunodeficiency syndrome *

    PubMed Central

    Gilmore, N.J.; Beaulieu, R.; Steben, M.; Laverdière, M.

    1992-01-01

    Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi's sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of the utmost importance. PMID:1544049

  6. Community-acquired pneumonia.

    PubMed

    Polverino, E; Torres Marti, A

    2011-02-01

    Despite the remarkable advances in antibiotic therapies, diagnostic tools, prevention campaigns and intensive care, community-acquired pneumonia (CAP) is still among the primary causes of death worldwide, and there have been no significant changes in mortality in the last decades. The clinical and economic burden of CAP makes it a major public health problem, particularly for children and the elderly. This issue provides a clinical overview of CAP, focusing on epidemiology, economic burden, diagnosis, risk stratification, treatment, clinical management, and prevention. Particular attention is given to some aspects related to the clinical management of CAP, such as the microbial etiology and the available tools to achieve it, the usefulness of new and old biomarkers, and antimicrobial and other non-antibiotic adjunctive therapies. Possible scenarios in which pneumonia does not respond to treatment are also analyzed to improve clinical outcomes of CAP. PMID:21242952

  7. Acquired Porphyria Cutanea Tarda

    PubMed Central

    Koval, Andrew; Danby, C. W. E.; Petermann, H.

    1965-01-01

    Currently, the porphyrias are classified in four main groups: congenital porphyria, acute intermittent porphyria, porphyria cutanea tarda hereditaria, and porphyria cutanea tarda symptomatica. The acquired form of porphyria (porphyria cutanea tarda symptomatica) occurs in older males and is nearly always associated with chronic alcoholism and hepatic cirrhosis. The main clinical changes are dermatological, with excessive skin fragility and photosensitivity resulting in erosions and bullae. Biochemically, high levels of uroporphyrin are found in the urine and stools. Treatment to date has been symptomatic and usually unsuccessful. A case of porphyria cutanea tarda symptomatica is presented showing dramatic improvement of both the skin lesions and porphyrin levels in urine and blood following repeated phlebotomy. Possible mechanisms of action of phlebotomy on porphyria cutanea tarda symptomatica are discussed. ImagesFig. 1Fig. 2 PMID:14341652

  8. [ICU acquired neuromyopathy].

    PubMed

    Gueret, G; Guillouet, M; Vermeersch, V; Guillard, E; Talarmin, H; Nguyen, B-V; Rannou, F; Giroux-Metges, M-A; Pennec, J-P; Ozier, Y

    2013-09-01

    ICU acquired neuromyopathy (IANM) is the most frequent neurological pathology observed in ICU. Nerve and muscle defects are merged with neuromuscular junction abnormalities. Its physiopathology is complex. The aim is probably the redistribution of nutriments and metabolism towards defense against sepsis. The main risk factors are sepsis, its severity and its duration of evolution. IANM is usually diagnosed in view of difficulties in weaning from mechanical ventilation, but electrophysiology may allow an earlier diagnosis. There is no curative therapy, but early treatment of sepsis, glycemic control as well as early physiotherapy may decrease its incidence. The outcomes of IANM are an increase in morbi-mortality and possibly long-lasting neuromuscular abnormalities as far as tetraplegia. PMID:23958176

  9. Acute Acquired Concomitant Esotropia

    PubMed Central

    Chen, Jingchang; Deng, Daming; Sun, Yuan; Shen, Tao; Cao, Guobin; Yan, Jianhua; Chen, Qiwen; Ye, Xuelian

    2015-01-01

    Abstract Acute acquired concomitant esotropia (AACE) is a rare, distinct subtype of esotropia. The purpose of this retrospective study was to describe the clinical characteristics and discuss the classification and etiology of AACE. Charts from 47 patients with AACE referred to our institute between October 2010 and November 2014 were reviewed. All participants underwent a complete medical history, ophthalmologic and orthoptic examinations, and brain and orbital imaging. Mean age at onset was 26.6 ± 12.2 years. Of the 18 cases with deviations ≤ 20 PD, 16 presented with diplopia at distance and fusion at near vision at the onset of deviation; differences between distance and near deviations were < 8 PD; all cases except one were treated with prism and diplopia resolved. Of the 29 cases with deviations > 20 PD, 5 were mild hypermetropic with age at onset between 5 and 19 years, 16 were myopic, and 8 were emmetropic with age at onset > 12 years; 24 were surgically treated and 5 cases remained under observation; all 24 cases achieved normal retinal correspondence or fusion or stereopsis on postoperative day 1 in synoptophore; in 23 cases diplopia or visual confusion resolved postoperatively. Of the 47 cases, brain and orbital imaging in 2 cases revealed a tumor in the cerebellopontine angle and 1 case involved spinocerebellar ataxia as revealed by genetic testing. AACE in this study was characterized by a sudden onset of concomitant nonaccommodative esotropia with diplopia or visual confusion at 5 years of age or older and the potential for normal binocular vision. We suggest that AACE can be divided into 2 subgroups consisting of patients with relatively small versus large angle deviations. Coexisting or underlying neurological diseases were infrequent in AACE. PMID:26705210

  10. Dosage Changes of a Segment at 17p13.1 Lead to Intellectual Disability and Microcephaly as a Result of Complex Genetic Interaction of Multiple Genes

    PubMed Central

    Carvalho, Claudia M.B.; Vasanth, Shivakumar; Shinawi, Marwan; Russell, Chad; Ramocki, Melissa B.; Brown, Chester W.; Graakjaer, Jesper; Skytte, Anne-Bine; Vianna-Morgante, Angela M.; Krepischi, Ana C.V.; Patel, Gayle S.; Immken, LaDonna; Aleck, Kyrieckos; Lim, Cynthia; Cheung, Sau Wai; Rosenberg, Carla; Katsanis, Nicholas; Lupski, James R.

    2014-01-01

    The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO. PMID:25439725

  11. Hearing Loss

    MedlinePlus

    ... version of this page please turn Javascript on. Hearing Loss What is Hearing Loss? Hearing loss is a common problem caused by ... sec Click to watch this video Types of Hearing Loss Hearing loss comes in many forms. It can ...

  12. [Musical pseudo-hallucination in acquired hearing loss].

    PubMed

    Klostermann, W; Vieregge, P; Kömpf, D

    1992-07-01

    Auditory hallucinations take various forms including the perception of tinnitus, voices, and, rarely, music. While formed hallucinations are usually ascribed to psychiatric illness, we describe a syndrome of musical hallucinations in mentally sane patients, who are hard of hearing or deaf. 26 cases from the literature are supplemented by 6 own observations, including the first description of two cases in a single family. The different modes of emergence, the spectrum of clinical features and their course are outlined. Differential diagnostic, pathogenetic and therapeutic aspects are discussed. PMID:1500041

  13. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... confer control of X and therefore will file as an acquiring person. Because A held the plant prior to the... within two persons, “A” and “B.” Under this section, if V is to acquire corporation X, both “A” and “B... person. Examples: 1. Assume that person “Q” will acquire voting securities of corporation X held by...

  14. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... confer control of X and therefore will file as an acquiring person. Because A held the plant prior to the... within two persons, “A” and “B.” Under this section, if V is to acquire corporation X, both “A” and “B... person. Examples: 1. Assume that person “Q” will acquire voting securities of corporation X held by...

  15. A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE) Consensus Sequence Repeats in the Viral Genome

    PubMed Central

    Kumar, Ashutosh; Singh, Himanshu N.; Pareek, Vikas; Raza, Khursheed; Dantham, Subrahamanyam; Kumar, Pavan; Mochan, Sankat; Faiq, Muneeb A.

    2016-01-01

    Owing to the reports of microcephaly as a consistent outcome in the fetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV)—microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favor of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1) sequence homology between ZIKV genome and the response element of an early neural tube developmental marker “retinoic acid” in human DNA and (2) comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE) consensus sequence (5′–AGGTCA–3′) in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly) and other viruses available in National Institute of Health genetic sequence database (GenBank) for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause fetal brain defects (for which maternal-fetal transmission during developing stage may be required). The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although, bioinformatic evidence and

  16. The Bowen-Conradi syndrome -- a highly lethal autosomal recessive syndrome of microcephaly, micrognathia, low birth weight, and joint deformities.

    PubMed

    Hunter, A G; Woerner, S J; Montalvo-Hicks, L D; Fowlow, S B; Haslam, R H; Metcalf, P J; Lowry, R B

    1979-01-01

    This paper describes six Hutterite children from five families who appear to have been affected by the same syndrome that was described in two brothers by Bowen and Conradi [1]. Our additional cases confirm that the major features of the syndrome include porportionate intrauterine growth retardation, microcephaly, micrognathia, a prominent nose, rocker-bottom feet, joint limitation, and failure to thrive, with death within the first year of life. Bowen-Conradi syndrome is an autosomal recessive trait and pedigree records show that all six families now known are related to each other through two couples born in the late 1700s but that there are additional earlier possible sources of the responsible gene. The differential diagnosis of this syndrome is discussed. PMID:484596

  17. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.

    PubMed

    Ji, Jianling; Lee, Hane; Argiropoulos, Bob; Dorrani, Naghmeh; Mann, John; Martinez-Agosto, Julian A; Gomez-Ospina, Natalia; Gallant, Natalie; Bernstein, Jonathan A; Hudgins, Louanne; Slattery, Leah; Isidor, Bertrand; Le Caignec, Cédric; David, Albert; Obersztyn, Ewa; Wiśniowiecka-Kowalnik, Barbara; Fox, Michelle; Deignan, Joshua L; Vilain, Eric; Hendricks, Emily; Horton Harr, Margaret; Noon, Sarah E; Jackson, Jessi R; Wilkens, Alisha; Mirzaa, Ghayda; Salamon, Noriko; Abramson, Jeff; Zackai, Elaine H; Krantz, Ian; Innes, A Micheil; Nelson, Stanley F; Grody, Wayne W; Quintero-Rivera, Fabiola

    2015-11-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs. PMID:25944381

  18. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... acquired person is the pre-acquisition ultimate parent entity of the entity. (ii) The value of an... directors of B. A is deemed to be acquiring all of the assets of B as a result. (g) Transfers of patent... transfer of patent rights covered by this paragraph constitutes an asset acquisition; and (3) Patent...

  19. Current treatment options of acquired flatfoot.

    PubMed

    Lesić, Aleksandar R; Atkinson, Henry Dushan E; Zagorac, Slavisa G; Bumbasirević, Marko

    2013-01-01

    Symptomatic acquired flatfoot is an important orthopaedic problem, due to progressive loss of whole foot function and the increasing problem of patient disability. It is a complex entity, involving the tibialis posterior tendon, ankle joint, hindfoot and midfoot. In most cases the posterior tibial tendon (PTT) is the root cause of acquired flat foot, but there are other contributors and many different factors have an influence. The clinical picture varies depending on the stage of the deformity, as well as the treatment approach. Initially soft tissue procedures, synoviectomy and augmentation of the PTT are advised. In stage 2, lateral column lengthening and calcaneal osteotomy, with soft tissue - tendon transfers (TA, FHL, FDL) are recommended. In stage 3 subtalar, double or triplearthodesis is preferable, while in stage 4 pantalar fusion is indicated. This article elaborates on the etiology, the clinical picture, diagnosis and treatment modalities. PMID:24669559

  20. Children Acquire Emotion Categories Gradually

    ERIC Educational Resources Information Center

    Widen, Sherri C.; Russell, James A.

    2008-01-01

    Some accounts imply that basic-level emotion categories are acquired early and quickly, whereas others imply that they are acquired later and more gradually. Our study examined this question for fear, happiness, sadness, and anger in the context of children's categorization of emotional facial expressions. Children (N=168, 2-5 years) first labeled…

  1. The alkylglycerol monooxygenase (AGMO) gene previously involved in autism also causes a novel syndromic form of primary microcephaly in a consanguineous Saudi family.

    PubMed

    Alrayes, Nuha; Mohamoud, Hussein Sheikh Ali; Ahmed, Saleem; Almramhi, Mona Mohammad; Shuaib, Taghreed Mohammad; Wang, Jun; Al-Aama, Jumana Yousuf; Everett, Kate; Nasir, Jamal; Jelani, Musharraf

    2016-04-15

    Autosomal recessive primary microcephaly (MCPH) refers to a genetically heterogeneous group of neurodevelopmental disorders in which patients exhibit a marked decrease in occipitofrontal head circumference at birth and a variable degree of intellectual disability. To date, 18 genes have been reported for MCPH worldwide. We enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. Whole exome sequencing (WES) with 100× coverage was performed on two affected siblings after defining common regions of homozygosity through genome-wide single nucleotide polymorphism (SNP) microarray genotyping. WES data analysis, confirmed by subsequent Sanger sequence validation, identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase (AGMO) gene on chromosome 7p21.2. Population screening of 178 ethnically matched control chromosomes and consultation of the Exome Aggregation Consortium database, containing 60,706 individuals' exomes worldwide, confirmed that this mutation was not present outside the family. To the best of our knowledge, this is the first evidence of an AGMO mutation underlying primary microcephaly and intellectual disability in humans. Our findings further expand the genetic heterogeneity of MCPH in familial cases. PMID:27000257

  2. The first case of CDK5RAP2-related primary microcephaly in a non-consanguineous patient identified by next generation sequencing.

    PubMed

    Tan, Christopher A; Topper, Scott; Ward Melver, Catherine; Stein, Jennifer; Reeder, Amanda; Arndt, Kelly; Das, Soma

    2014-04-01

    Primary autosomal recessive microcephaly (MCPH) is a genetically heterogeneous condition characterized by congenital microcephaly and intellectual disability. To date, 10 MCPH loci have been identified and due to the genetic heterogeneity of this condition, molecular testing for MCPH can be complicated. Our methods involved employing a next generation sequencing panel of MCPH-related genes allowing for the evaluation of multiple disease loci simultaneously. Next generation sequencing analysis of a 6 year old female with primary microcephaly identified novel compound heterozygous mutations (c.524_528del and c.4005-1G>A) in the CDK5RAP2 gene. A review of the published literature to date reveals that only three mutations have been previously reported in the CDK5RAP2 gene in the homozygous state in three Northern Pakistani and one Somali consanguineous MCPH families. Our patient represents the first non-consanguineous Caucasian individual to have been identified with CDK5RAP2-related MCPH. As only a handful of patients have been reported in the literature with CDK5RAP2-related MCPH, we anticipate the identification of individuals with CDK5RAP2 mutations from all ethnic backgrounds will continue. Our patient contributes to the ethnic and genotypic spectrum of CDK5RAP2-related MCPH and supports the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations. Our results also highlight the utility of multi-gene sequencing panels to elucidate the etiology of genetically heterogeneous conditions. PMID:23726037

  3. Mutations in TUBGCP4 Alter Microtubule Organization via the γ-Tubulin Ring Complex in Autosomal-Recessive Microcephaly with Chorioretinopathy

    PubMed Central

    Scheidecker, Sophie; Etard, Christelle; Haren, Laurence; Stoetzel, Corinne; Hull, Sarah; Arno, Gavin; Plagnol, Vincent; Drunat, Séverine; Passemard, Sandrine; Toutain, Annick; Obringer, Cathy; Koob, Mériam; Geoffroy, Véronique; Marion, Vincent; Strähle, Uwe; Ostergaard, Pia; Verloes, Alain; Merdes, Andreas; Moore, Anthony T.; Dollfus, Hélène

    2015-01-01

    We have identified TUBGCP4 variants in individuals with autosomal-recessive microcephaly and chorioretinopathy. Whole-exome sequencing performed on one family with two affected siblings and independently on another family with one affected child revealed compound-heterozygous mutations in TUBGCP4. Subsequent Sanger sequencing was performed on a panel of individuals from 12 French families affected by microcephaly and ophthalmic manifestations, and one other individual was identified with compound-heterozygous mutations in TUBGCP4. One synonymous variant was common to all three families and was shown to induce exon skipping; the other mutations were frameshift mutations and a deletion. TUBGCP4 encodes γ-tubulin complex protein 4, a component belonging to the γ-tubulin ring complex (γ-TuRC) and known to regulate the nucleation and organization of microtubules. Functional analysis of individual fibroblasts disclosed reduced levels of the γ-TuRC, altered nucleation and organization of microtubules, abnormal nuclear shape, and aneuploidy. Moreover, zebrafish treated with morpholinos against tubgcp4 were found to have reduced head volume and eye developmental anomalies with chorioretinal dysplasia. In summary, the identification of TUBGCP4 mutations in individuals with microcephaly and a spectrum of anomalies in eye development, particularly photoreceptor anomalies, provides evidence of an important role for the γ-TuRC in brain and eye development. PMID:25817018

  4. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities.

    PubMed

    Brunetti-Pierri, Nicola; Berg, Jonathan S; Scaglia, Fernando; Belmont, John; Bacino, Carlos A; Sahoo, Trilochan; Lalani, Seema R; Graham, Brett; Lee, Brendan; Shinawi, Marwan; Shen, Joseph; Kang, Sung-Hae L; Pursley, Amber; Lotze, Timothy; Kennedy, Gail; Lansky-Shafer, Susan; Weaver, Christine; Roeder, Elizabeth R; Grebe, Theresa A; Arnold, Georgianne L; Hutchison, Terry; Reimschisel, Tyler; Amato, Stephen; Geragthy, Michael T; Innis, Jeffrey W; Obersztyn, Ewa; Nowakowska, Beata; Rosengren, Sally S; Bader, Patricia I; Grange, Dorothy K; Naqvi, Sayed; Garnica, Adolfo D; Bernes, Saunder M; Fong, Chin-To; Summers, Anne; Walters, W David; Lupski, James R; Stankiewicz, Pawel; Cheung, Sau Wai; Patel, Ankita

    2008-12-01

    Chromosome region 1q21.1 contains extensive and complex low-copy repeats, and copy number variants (CNVs) in this region have recently been reported in association with congenital heart defects, developmental delay, schizophrenia and related psychoses. We describe 21 probands with the 1q21.1 microdeletion and 15 probands with the 1q21.1 microduplication. These CNVs were inherited in most of the cases in which parental studies were available. Consistent and statistically significant features of microcephaly and macrocephaly were found in individuals with microdeletion and microduplication, respectively. Notably, a paralog of the HYDIN gene located on 16q22.2 and implicated in autosomal recessive hydrocephalus was inserted into the 1q21.1 region during the evolution of Homo sapiens; we found this locus to be deleted or duplicated in the individuals we studied, making it a probable candidate for the head size abnormalities observed. We propose that recurrent reciprocal microdeletions and microduplications within 1q21.1 represent previously unknown genomic disorders characterized by abnormal head size along with a spectrum of developmental delay, neuropsychiatric abnormalities, dysmorphic features and congenital anomalies. These phenotypes are subject to incomplete penetrance and variable expressivity. PMID:19029900

  5. A missense mutation in PPP1R15B causes a syndrome including diabetes, short stature and microcephaly

    PubMed Central

    Igoillo-Esteve, Mariana; Daures, Mathilde; Romero, Sophie; Philippi, Anne; Senée, Valérie; Lopes, Miguel; Cunha, Daniel A.; Harding, Heather P.; Derbois, Céline; Bendelac, Nathalie; Hattersley, Andrew T.; Eizirik, Décio L.; Ron, David

    2015-01-01

    Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation, CReP), encoding the regulatory subunit of an eIF2α-specific phosphatase, in two siblings affected by a novel syndrome of diabetes of youth, with short stature, intellectual disability and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation, and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multi-system abnormalities. PMID:26159176

  6. Microcephaly protein Asp focuses the minus ends of spindle microtubules at the pole and within the spindle

    PubMed Central

    Ito, Ami

    2015-01-01

    Depletion of Drosophila melanogaster Asp, an orthologue of microcephaly protein ASPM, causes spindle pole unfocusing during mitosis. However, it remains unclear how Asp contributes to pole focusing, a process that also requires the kinesin-14 motor Ncd. We show that Asp localizes to the minus ends of spindle microtubule (MT) bundles and focuses them to make the pole independent of Ncd. We identified a critical domain in Asp exhibiting MT cross-linking activity in vitro. Asp was also localized to, and focuses the minus ends of, intraspindle MTs that were nucleated in an augmin-dependent manner and translocated toward the poles by spindle MT flux. Ncd, in contrast, functioned as a global spindle coalescence factor not limited to MT ends. We propose a revised molecular model for spindle pole focusing in which Asp at the minus ends cross-links MTs at the pole and within the spindle. Additionally, this study provides new insight into the dynamics of intraspindle MTs by using Asp as a minus end marker. PMID:26644514

  7. CDK5RAP2 expression during murine and human brain development correlates with pathology in primary autosomal recessive microcephaly.

    PubMed

    Issa, Lina; Kraemer, Nadine; Rickert, Christian H; Sifringer, Marco; Ninnemann, Olaf; Stoltenburg-Didinger, Gisela; Kaindl, Angela M

    2013-09-01

    Homozygous mutations in the cyclin-dependent kinase-5 regulatory subunit-associated protein 2 gene CDK5RAP2 cause primary autosomal recessive microcephaly (MCPH). MCPH is characterized by a pronounced reduction of brain volume, particularly of the cerebral cortex, and mental retardation. Though it is a rare developmental disorder, MCPH has moved into the spotlight of neuroscience because of its proposed central role in stem-cell biology and brain development. Investigation of the neural basis of genetically defined MCPH has been limited to animal studies and neuroimaging of affected patients as no neuropathological studies have been published. In the present study, we depict the spatiotemporal expression of CDK5RAP2 in the developing brain of mouse and human. We found intriguing concordance between regions of high CDK5RAP2 expression in the mouse and sites of pathology suggested by neuroimaging studies in humans and mouse. Our findings in human tissue confirm those in mouse tissues, underlining the function of CDK5RAP2 in cell proliferation and arguing for a conserved role of this protein in the development of the mammalian cerebral cortex. PMID:22806269

  8. How many entities exist for the spectrum of disorders associated with brachydactyly, syndactyly, short stature, microcephaly, and intellectual disability?

    PubMed

    Ravel, Aimé; Chouery, Eliane; Stora, Samantha; Jalkh, Nadine; Villard, Laurent; Temtamy, Samia; Mégarbané, André

    2011-04-01

    We describe a French young man with digital anomalies consisting of brachydactyly, F1-5 bilateral camptodactyly, interdigital webbing, F5 bilateral radial clinodactyly, and partial syndactyly of some fingers and toes. He had psychomotor retardation, short stature, umbilical hernia, a secundum atrial septal defect, seizures, hearing impairment, and dysmorphic features consisting of microcephaly, a prominent metopic ridge, upslanting palpebral fissures, synophrys, enophthalmia, large ears, a bulbous nose, a high palate, a smooth and short philtrum, a low hanging columella, a thin upper vermillion, an everted lower lip, prognathism, pectum excavatum, and supernumerary nipples. Osteotendinous reflexes were brisk. Mild nystagmus, myopia, and astigmatia were also noted. Total body X-rays showed short terminal phalanges of the hands, short middle phalanges of the index and little fingers, clinodactyly of the little fingers, short and fused proximal 4th and 5th metacarpals of the right hand, a short 5th metacarpal of the left hand, a fused left lunate-triquetrum, fused capitate-hamates, a prominent mandibula, and partial sacral agenesis. A thin posterior corpus callosum was apparent by MRI. Differential diagnoses for mainly the Rubinstein-Taybi syndrome, the Tsukahara syndrome, the Filippi syndrome, the Feingold syndrome, and the Tonoki syndrome are discussed, and the possibility that we might be reporting a novel entity is raised. © 2011 Wiley-Liss, Inc. PMID:21416592

  9. Microcephaly protein Asp focuses the minus ends of spindle microtubules at the pole and within the spindle.

    PubMed

    Ito, Ami; Goshima, Gohta

    2015-12-01

    Depletion of Drosophila melanogaster Asp, an orthologue of microcephaly protein ASPM, causes spindle pole unfocusing during mitosis. However, it remains unclear how Asp contributes to pole focusing, a process that also requires the kinesin-14 motor Ncd. We show that Asp localizes to the minus ends of spindle microtubule (MT) bundles and focuses them to make the pole independent of Ncd. We identified a critical domain in Asp exhibiting MT cross-linking activity in vitro. Asp was also localized to, and focuses the minus ends of, intraspindle MTs that were nucleated in an augmin-dependent manner and translocated toward the poles by spindle MT flux. Ncd, in contrast, functioned as a global spindle coalescence factor not limited to MT ends. We propose a revised molecular model for spindle pole focusing in which Asp at the minus ends cross-links MTs at the pole and within the spindle. Additionally, this study provides new insight into the dynamics of intraspindle MTs by using Asp as a minus end marker. PMID:26644514

  10. Acquired Equivalence Changes Stimulus Representations

    ERIC Educational Resources Information Center

    Meeter, M.; Shohamy, D.; Myers, C. E.

    2009-01-01

    Acquired equivalence is a paradigm in which generalization is increased between two superficially dissimilar stimuli (or antecedents) that have previously been associated with similar outcomes (or consequents). Several possible mechanisms have been proposed, including changes in stimulus representations, either in the form of added associations or…

  11. Comparison of Presentation, Course, and Outcome of Congenital and Acquired Cytomegalovirus Infection in Twins

    PubMed Central

    Samedi, Veronica Mugarab; Skappak, Christopher; Jantzie, Lindsay; Trevenen, Cynthia; Kamaluddeen, Majeeda; Ekwalanga, Pauline; Al Awad, Essa Hamdan

    2015-01-01

    Background Cytomegalovirus (CMV) is one of the most common causes of serious viral intrauterine infections. It is universally distributed among the human population with an average incidence of 0.15 to 2%. Indeed, at least half of the women in the reproductive age have evidence of prior CMV infection. Epidemiology and Pathogenicity However, it is not a usual practice to screen asymptomatic pregnant woman or neonates for CMV. Even if a mother developed a primary CMV infection during pregnancy, up to 90% of the newborns with congenital CMV will be asymptomatic at the time of birth. Only 5 to 7% of the infected babies will be acutely symptomatic, and the typical clinical presentation includes intrauterine growth restriction, microcephaly, various cutaneous manifestations (including petechiae and purpura), hematological abnormalities (particularly resistant thrombocytopenia), hepatosplenomegaly, chorioretinitis, hepatitis, etc. In contrast, acquired CMV infection is extremely unlikely to cause any serious sequelae for the infant. Cases  We present a case of congenital and acquired CMV infection in twins with a focus of dissimilarity in presentation, clinical course, and outcome. PMID:26929859

  12. Haploinsufficiency of MBD5 associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures

    PubMed Central

    Williams, Stephen R; Mullegama, Sureni V; Rosenfeld, Jill A; Dagli, Aditi I; Hatchwell, Eli; Allen, William P; Williams, Charles A; Elsea, Sarah H

    2010-01-01

    Microdeletion of chromosome 2q23.1 results in a novel syndrome previously reported in five individuals. Many of the del(2)(q23.1) cases were thought to have other syndromes such as Angelman, Prader–Willi, or Smith–Magenis because of certain overlapping clinical features. We report two new cases of the 2q23.1 microdeletion syndrome, describe the syndrome phenotype, define the minimal critical region, and analyze the expression of critical region genes toward identification of the causative gene(s) for the disorder. Individuals with del(2)(q23.1) have severe developmental and cognitive delays, minimal speech, seizures, microcephaly, mild craniofacial dysmorphism, behavioral disorders, and short stature. The deletions encompassing 2q23.1 range from >4 Mb to <200 kb, as identified by oligonucleotide and BAC whole-genome array comparative hybridization. The minimal critical region includes a single gene, MBD5, deleted in all cases, whereas all but one case also include deletion of EPC2. Quantitative real-time PCR of patient lymphoblasts/lymphocytes showed an ∼50% reduced expression of MBD5 and EPC2 compared with controls. With similar phenotypes among the 2q23.1 deletion patients, the idea of one or more common genes causing the pathological defect seen in these patients becomes evident. As all five previous cases and the two cases in this report share one common gene, MBD5, we strongly suspect that haploinsufficiency of MBD5 causes most of the features observed in this syndrome. PMID:19904302

  13. Human temporal bone findings in acquired hypothyroidism.

    PubMed

    Hald, J; Milroy, C M; Jensen, K D; Parving, A

    1991-11-01

    Histological studies of the auditory organ in patients with acquired hypothyroidism are scarce. Thus the aim of the present study was to examine the temporal bones and the brain in subjects with hypothyroidism. Four temporal bones and two brains from clinically and biochemically hypothyroid subjects were removed and evaluated by light microscopy determine to the morphological changes and deposition of neutral and acid glycosaminoglycans. An audiogram from one of the patients showed a sensorineural hearing loss, which could be ascribed to occupational noise exposure. The study revealed histological changes compatible with age and infectious disease. No accumulation of neutral or acid glycosaminoglycans could be demonstrated in the temporal bones, or in the brains. PMID:1761939

  14. Mass loss

    NASA Technical Reports Server (NTRS)

    Goldberg, Leo

    1987-01-01

    Observational evidence for mass loss from cool stars is reviewed. Spectra line profiles are used for the derivation of mass-loss rates with the aid of the equation of continuity. This equation implies steady mass loss with spherical symmetry. Data from binary stars, Mira variables, and red giants in globular clusters are examined. Silicate emission is discussed as a useful indicator of mass loss in the middle infrared spectra. The use of thermal millimeter-wave radiation, Very Large Array (VLA) measurement of radio emission, and OH/IR masers are discussed as a tool for mass loss measurement. Evidence for nonsteady mass loss is also reviewed.

  15. Hair Loss

    MedlinePlus

    ... may cause hair loss in women. If your hair loss has occurred gradually with advancing age, FOLLICULAR DEGENERATION may be the cause. Post-pregnancy hormone changes usually reverse themselves without any treatment. While follicular degeneration cannot ...

  16. Acquired causes of intestinal malabsorption.

    PubMed

    van der Heide, F

    2016-04-01

    This review focuses on the acquired causes, diagnosis, and treatment of intestinal malabsorption. Intestinal absorption is a complex process that depends on many variables, including the digestion of nutrients within the intestinal lumen, the absorptive surface of the small intestine, the membrane transport systems, and the epithelial absorptive enzymes. Acquired causes of malabsorption are classified by focussing on the three phases of digestion and absorption: 1) luminal/digestive phase, 2) mucosal/absorptive phase, and 3) transport phase. Most acquired diseases affect the luminal/digestive phase. These include short bowel syndrome, extensive small bowel inflammation, motility disorders, and deficiencies of digestive enzymes or bile salts. Diagnosis depends on symptoms, physical examination, and blood and stool tests. There is no gold standard for the diagnosis of malabsorption. Further testing should be based on the specific clinical context and the suspected underlying disease. Therapy is directed at nutritional support by enteral or parenteral feeding and screening for and supplementation of deficiencies in vitamins and minerals. Early enteral feeding is important for intestinal adaptation in short bowel syndrome. Medicinal treatment options for diarrhoea in malabsorption include loperamide, codeine, cholestyramine, or antibiotics. PMID:27086886

  17. Mucocutaneous manifestations of acquired hypoparathyroidism: An observational study.

    PubMed

    Sarkar, Somenath; Mondal, Modhuchanda; Das, Kapildev; Shrimal, Arpit

    2012-09-01

    Hypoparathyroidism is a disorder of calcium and phosphorus metabolism due to decreased secretion of parathyroid hormone. Hypoparathyroidism can be hereditary and acquired. Acquired hypoparathyroidism usually occurs following neck surgery (thyroid surgery or parathyroid surgery). Along with systemic manifestations, hypoparathyroidism produces some skin manifestations. Lack of study regarding mucocutaneous manifestations of acquired hypoparathyroidism prompted us to undertake this study. To evaluate the mucocutaneous manifestations of acquired hypoparathyroidism. An observational study done in a tertiary care hospital of Kolkata by comprehensive history taking, through clinical examination and relevant laboratory investigations. Twenty-one patients were included in the study. The commonest form of acquired hypoparathyroidism was neck surgery (thyroidectomy and parathyroidectomy operation). Mucocutaneous manifestations were present in 76.19% of patients. The most frequent mucocutaneous manifestation was found in the hairs like the loss of axillary hair (61.9%), loss of pubic hair (52.38%), coarsening of body hair (47.62%), and alopecia areata (9.52%). The nail changes noted were brittle and ridged nail, followed by onycholysis, onychosezia, and onychomedesis. The most common skin features were xerotic skin in 11 patients (52.38%), followed by pellagra-like skin pigmentation, pustular psoriasis and acne form eruption, bullous impetigo, etc. Mucosa was normal in all the cases excepting the one which showed oral candidiasis. PMID:23087872

  18. 26 CFR 1.381(c)(3)-1 - Capital loss carryovers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... capital losses. If the distributor, transferor, or acquiring corporation sustains a net capital loss in a... acquiring corporation in each of the taxable years to which the net capital loss giving rise to such... which bears the same ratio to the acquiring corporation's capital gain net income (net capital gain...

  19. Microcephaly Information Page

    MedlinePlus

    ... German measles), varicella (chicken pox) virus, or possibly Zika virus; was exposed to certain toxic chemicals; or had ... viral-induced brain injury, such as with the Zika virus, there is often widespread tissue and cell death ...

  20. Perioperatively acquired disorders of coagulation

    PubMed Central

    Grottke, Oliver; Fries, Dietmar; Nascimento, Bartolomeu

    2015-01-01

    Purpose of review To provide an overview of acquired coagulopathies that can occur in various perioperative clinical settings. Also described are coagulation disturbances linked to antithrombotic medications and currently available strategies to reverse their antithrombotic effects in situations of severe hemorrhage. Recent findings Recent studies highlight the link between low fibrinogen and decreased fibrin polymerization in the development of acquired coagulopathy. Particularly, fibrin(ogen) deficits are observable after cardiopulmonary bypass in cardiac surgery, on arrival at the emergency room in trauma patients, and with ongoing bleeding after child birth. Regarding antithrombotic therapy, although new oral anticoagulants offer the possibility of efficacy and relative safety compared with vitamin K antagonists, reversal of their anticoagulant effect with nonspecific agents, including prothrombin complex concentrate, has provided conflicting results. Specific antidotes, currently being developed, are not yet licensed for clinical use, but initial results are promising. Summary Targeted hemostatic therapy aims to correct coagulopathies in specific clinical settings, and reduce the need for allogeneic transfusions, thus preventing massive transfusion and its deleterious outcomes. Although there are specific guidelines for reversing anticoagulation in patients treated with antiplatelet agents or warfarin, there is currently little evidence to advocate comprehensive recommendations to treat drug-induced coagulopathy associated with new oral anticoagulants. PMID:25734869

  1. Foodborne listeriosis acquired in hospitals.

    PubMed

    Silk, Benjamin J; McCoy, Morgan H; Iwamoto, Martha; Griffin, Patricia M

    2014-08-15

    Listeriosis is characterized by bacteremia or meningitis. We searched for listeriosis case series and outbreak investigations published in English by 2013, and assessed the strength of evidence for foodborne acquisition among patients who ate hospital food. We identified 30 reports from 13 countries. Among the case series, the median proportion of cases considered to be hospital-acquired was 25% (range, 9%-67%). The median number of outbreak-related illnesses considered to be hospital-acquired was 4.0 (range, 2-16). All patients were immunosuppressed in 18 of 24 (75%) reports with available data. Eight outbreak reports with strong evidence for foodborne acquisition in a hospital implicated sandwiches (3 reports), butter, precut celery, Camembert cheese, sausage, and tuna salad (1 report each). Foodborne acquisition of listeriosis among hospitalized patients is well documented internationally. The number of listeriosis cases could be reduced substantially by establishing hospital policies for safe food preparation for immunocompromised patients and by not serving them higher-risk foods. PMID:24846635

  2. A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.

    PubMed

    Khan, Muzammil A; Rupp, Verena M; Orpinell, Meritxell; Hussain, Muhammad S; Altmüller, Janine; Steinmetz, Michel O; Enzinger, Christian; Thiele, Holger; Höhne, Wolfgang; Nürnberg, Gudrun; Baig, Shahid M; Ansar, Muhammad; Nürnberg, Peter; Vincent, John B; Speicher, Michael R; Gönczy, Pierre; Windpassinger, Christian

    2014-11-15

    Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly. PMID:24951542

  3. De Novo Nonsense Mutations in KAT6A, a Lysine Acetyl-Transferase Gene, Cause a Syndrome Including Microcephaly and Global Developmental Delay

    PubMed Central

    Arboleda, Valerie A.; Lee, Hane; Dorrani, Naghmeh; Zadeh, Neda; Willis, Mary; Macmurdo, Colleen Forsyth; Manning, Melanie A.; Kwan, Andrea; Hudgins, Louanne; Barthelemy, Florian; Miceli, M. Carrie; Quintero-Rivera, Fabiola; Kantarci, Sibel; Strom, Samuel P.; Deignan, Joshua L.; Grody, Wayne W.; Vilain, Eric; Nelson, Stanley F.

    2015-01-01

    Chromatin remodeling through histone acetyltransferase (HAT) and histone deactylase (HDAC) enzymes affects fundamental cellular processes including the cell-cycle, cell differentiation, metabolism, and apoptosis. Nonsense mutations in genes that are involved in histone acetylation and deacetylation result in multiple congenital anomalies with most individuals displaying significant developmental delay, microcephaly and dysmorphism. Here, we report a syndrome caused by de novo heterozygous nonsense mutations in KAT6A (a.k.a., MOZ, MYST3) identified by clinical exome sequencing (CES) in four independent families. The same de novo nonsense mutation (c.3385C>T [p.Arg1129∗]) was observed in three individuals, and the fourth individual had a nearby de novo nonsense mutation (c.3070C>T [p.Arg1024∗]). Neither of these variants was present in 1,815 in-house exomes or in public databases. Common features among all four probands include primary microcephaly, global developmental delay including profound speech delay, and craniofacial dysmorphism, as well as more varied features such as feeding difficulties, cardiac defects, and ocular anomalies. We further demonstrate that KAT6A mutations result in dysregulation of H3K9 and H3K18 acetylation and altered P53 signaling. Through histone and non-histone acetylation, KAT6A affects multiple cellular processes and illustrates the complex role of acetylation in regulating development and disease. PMID:25728775

  4. De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay.

    PubMed

    Arboleda, Valerie A; Lee, Hane; Dorrani, Naghmeh; Zadeh, Neda; Willis, Mary; Macmurdo, Colleen Forsyth; Manning, Melanie A; Kwan, Andrea; Hudgins, Louanne; Barthelemy, Florian; Miceli, M Carrie; Quintero-Rivera, Fabiola; Kantarci, Sibel; Strom, Samuel P; Deignan, Joshua L; Grody, Wayne W; Vilain, Eric; Nelson, Stanley F

    2015-03-01

    Chromatin remodeling through histone acetyltransferase (HAT) and histone deactylase (HDAC) enzymes affects fundamental cellular processes including the cell-cycle, cell differentiation, metabolism, and apoptosis. Nonsense mutations in genes that are involved in histone acetylation and deacetylation result in multiple congenital anomalies with most individuals displaying significant developmental delay, microcephaly and dysmorphism. Here, we report a syndrome caused by de novo heterozygous nonsense mutations in KAT6A (a.k.a., MOZ, MYST3) identified by clinical exome sequencing (CES) in four independent families. The same de novo nonsense mutation (c.3385C>T [p.Arg1129∗]) was observed in three individuals, and the fourth individual had a nearby de novo nonsense mutation (c.3070C>T [p.Arg1024∗]). Neither of these variants was present in 1,815 in-house exomes or in public databases. Common features among all four probands include primary microcephaly, global developmental delay including profound speech delay, and craniofacial dysmorphism, as well as more varied features such as feeding difficulties, cardiac defects, and ocular anomalies. We further demonstrate that KAT6A mutations result in dysregulation of H3K9 and H3K18 acetylation and altered P53 signaling. Through histone and non-histone acetylation, KAT6A affects multiple cellular processes and illustrates the complex role of acetylation in regulating development and disease. PMID:25728775

  5. Generalized acquired cutis laxa type 1: a case report and brief review of literature.

    PubMed

    Kumar, Piyush; Savant, Sushil S; Das, Anupam

    2016-01-01

    Cutis laxa, clinically characterized by loose and pendulous skin related to loss of elastic tissue, is a rare heterogeneous condition. It is classified into congenital and acquired types. We report a case of generalized acquired cutis laxa type 1 in a young man following pruritic urticarial plaques. We have done a brief review of literature. PMID:27136630

  6. 12 CFR 955.6 - Risk-based capital requirement for acquired member assets.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Risk-based capital requirement for acquired... ASSETS AND OFF-BALANCE SHEET ITEMS ACQUIRED MEMBER ASSETS § 955.6 Risk-based capital requirement for... losses as support for the credit risk of all AMA estimated by the Bank to represent a credit risk that...

  7. 12 CFR 955.6 - Risk-based capital requirement for acquired member assets.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Risk-based capital requirement for acquired... ASSETS AND OFF-BALANCE SHEET ITEMS ACQUIRED MEMBER ASSETS § 955.6 Risk-based capital requirement for... losses as support for the credit risk of all AMA estimated by the Bank to represent a credit risk that...

  8. 12 CFR 955.6 - Risk-based capital requirement for acquired member assets.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Risk-based capital requirement for acquired... ASSETS AND OFF-BALANCE SHEET ITEMS ACQUIRED MEMBER ASSETS § 955.6 Risk-based capital requirement for... losses as support for the credit risk of all AMA estimated by the Bank to represent a credit risk that...

  9. 12 CFR 955.6 - Risk-based capital requirement for acquired member assets.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Risk-based capital requirement for acquired... ASSETS AND OFF-BALANCE SHEET ITEMS ACQUIRED MEMBER ASSETS § 955.6 Risk-based capital requirement for... losses as support for the credit risk of all AMA estimated by the Bank to represent a credit risk that...

  10. Acquired immunodeficiency syndrome: neuroradiologic findings.

    PubMed

    Kelly, W M; Brant-Zawadzki, M

    1983-11-01

    Central nervous system complications depicted by CT in ten patients with acquired immunodeficiency syndrome are described. Three patients had multifocal intra-axial enhancing lesions representing atypical brain abscesses (two with toxoplasmosis, one with candidiasis). A fourth patient with multifocal "ring" lesions whose biopsy was interpreted as suggestive of toxoplasmosis responded poorly to treatment. Following his death three months later of Pneumocystis carinii pneumonia, autopsy revealed primary intracerebral immunoblastic lymphoma. One patient had Kaposi sarcoma involving the right frontal lobe (seen as an enhancing mass on the CT scan). CT findings in the remaining five patients revealed mild to moderate enlargement of cerebrospinal fluid spaces (including ventricles and basal cisternae) as a result of cryptococcal meningitis in three patients and "aseptic" meningitis in two. The two patients in whom early biopsy confirmed toxoplasmosis responded well to anti-infective therapy, resulting in dramatic clinical recoveries. PMID:6622693

  11. Bejel: acquirable only in childhood?

    PubMed

    Rothschild, Bruce M; Rothschild, Christine; Naples, Virginia; Billard, Michel; Panero, Barbara

    2006-10-01

    Bejel clearly has a long history in the Middle East and the Sudan, but was it transmitted to Europe? As the major manifestation of bejel is presence of periosteal reaction in 20-40% of afflicted populations, absence of significant population frequency of periosteal reaction in Europe would exclude that diagnosis. Examination of skeletal populations from continental Europe revealed no significant periosteal reaction at the time of and immediately subsequent to the Crusades. Thus, there is no evidence for bejel in Europe, in spite of clear contact (the mechanism of bejel transmission in children) between warring groups, at least during the Crusades. This supports the hypothesis that bejel is a childhood-acquired disease and apparently cannot be contracted in adulthood. PMID:17049474

  12. Lymphoma in acquired generalized lipodystrophy.

    PubMed

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip

    2016-01-01

    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression. PMID:25864863

  13. Unexpected postpartum hemorrhage due to an acquired factor VIII inhibitor.

    PubMed

    Paidas, Michael J; Hossain, Nazli

    2014-09-01

    Unexplained postpartum hemorrhage (PPH) refractory to standard hemostatic measures should trigger a heightened clinical suspicion of an acquired bleeding disorder. When hemostatic medical interventions and surgical procedures fail to control the bleeding, then significant postoperative blood loss, debilitating morbidity, loss of fertility, and death may occur. In the setting of an autoantibody inhibitor to factor VIII (FVIII), control of life-threatening PPH and avoidance of subsequent bleeding episodes depends on a timely and accurate diagnosis, prompt hemostatic treatment and eradication of FVIII inhibitors, and appropriate long-term patient care and management. Acquired postpartum hemophilia due to a FVIII inhibitor is a rare cause of PPH; however, delayed treatment can lead to increased maternal morbidity and mortality. Acquired FVIII inhibitors also pose an emerging bleeding threat to the neonate as a result of possible transplacental transfer of FVIII autoantibodies to the fetus during the last trimester of pregnancy. The purpose of this review is to increase awareness among hematologists and obstetricians/gynecologists regarding the occurrence of FVIII neutralizing autoantibodies as a cause of PPH, and emphasize the importance of collaboration between obstetrician/gynecologists and hematology specialists to optimize the diagnostic evaluation, treatment, and long-term management of women who experience PPH due to an acquired FVIII inhibitor. PMID:24338123

  14. Office-based management of adult-acquired flatfoot deformity.

    PubMed

    Miniaci-Coxhead, Sara Lyn; Flemister, Adolph Samuel

    2014-03-01

    Adult-acquired flatfoot deformity is associated with dysfunction of the posterior tibial tendon, leading to loss of the medial arch. Patients tend to present with medial pain and swelling, but later in the disease process can also present with lateral-sided pain. The mainstay of nonoperative treatment is nonsteroidal anti-inflammatory drugs, weight loss, and orthotic insoles or brace use. The goals of therapy are to provide relief of symptoms and prevent progression of the deformity. If nonoperative management fails, a variety of surgical procedures are available; however, these require a lengthy recovery, and therefore patients should be advised accordingly. PMID:24559875

  15. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  16. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  17. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  18. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  19. Seeing the eyes in acquired prosopagnosia.

    PubMed

    Pancaroglu, Raika; Hills, Charlotte S; Sekunova, Alla; Viswanathan, Jayalakshmi; Duchaine, Brad; Barton, Jason J S

    2016-08-01

    Case reports have suggested that perception of the eye region may be impaired more than that of other facial regions in acquired prosopagnosia. However, it is unclear how frequently this occurs, whether such impairments are specific to a certain anatomic subtype of prosopagnosia, and whether these impairments are related to changes in the scanning of faces. We studied a large cohort of 11 subjects with this rare disorder, who had a variety of occipitotemporal or anterior temporal lesions, both unilateral and bilateral. Lesions were characterized by functional and structural imaging. Subjects performed a perceptual discrimination test in which they had to discriminate changes in feature position, shape, or external contour. Test conditions were manipulated to stress focused or divided attention across the whole face. In a second experiment we recorded eye movements while subjects performed a face memory task. We found that greater impairment for eye processing was more typical of subjects with occipitotemporal lesions than those with anterior temporal lesions. This eye selectivity was evident for both eye position and shape, with no evidence of an upper/lower difference for external contour. A greater impairment for eye processing was more apparent under attentionally more demanding conditions. Despite these perceptual deficits, most subjects showed a normal tendency to scan the eyes more than the mouth. We conclude that occipitotemporal lesions are associated with a partially selective processing loss for eye information and that this deficit may be linked to loss of the right fusiform face area, which has been shown to have activity patterns that emphasize the eye region. PMID:27288649

  20. Memory loss

    MedlinePlus

    ... usually include asking questions of family members and friends. For this reason, they should come to the appointment. Medical history questions may include: Type of memory loss, such as short-term or long-term ...

  1. Hair loss

    MedlinePlus

    ... that is applied to the scalp to stimulate hair growth. Other medicines, such as hormones, may be prescribed to decrease hair loss and promote hair growth. Drugs such as finasteride and dutasteride can be ...

  2. Hair Loss

    MedlinePlus

    ... Common baldness" usually means male-pattern baldness, or permanent-pattern baldness. It is also called androgenetic alopecia. ... will grow back normally. However, scarring can cause permanent hair loss. Hot oil hair treatments or chemicals ...

  3. Hair Loss

    MedlinePlus

    ... are stress, a low protein diet, a family history, or poor nutrition. Treatment for hair loss depends on the cause. In some cases, treating the underlying cause will correct the problem. Other treatments include medicines and hair restoration.

  4. Hearing Loss

    MedlinePlus

    ... Devices Can Help? Hearing aids. Hearing aids are electronic, battery-run devices that make sounds louder. There ... to turn up the volume. Cochlear implants. These electronic devices are for people with severe hearing loss. ...

  5. Acquired prosopagnosia: structural basis and processing impairments.

    PubMed

    Davies-Thompson, Jodie; Pancaroglu, Raika; Barton, Jason

    2014-01-01

    Cognitive models propose a hierarchy of parallel processing stages in face perception, and functional neuroimaging shows a network of regions involved in face processing. Reflecting this, acquired prosopagnosia is not a single entity but a family of disorders with different anatomic lesions and different functional deficits. One classic distinction is between an apperceptive variant, in which there is impaired perception of facial structure, and an associative/amnestic variant, in which perception is relatively intact, with subsequent problems matching perception to facial memories, because of either disconnection or loss of those memories. These disorders also have to be distinguished from people-specific amnesia, a multimodal impairment, and prosop-anomia, in which familiarity with faces is preserved but access to names is disrupted. These different disorders can be conceived as specific deficits at different processing stages in cognitive models, and suggests that these functional stages may have distinct neuroanatomic substrates. It remains to be seen whether a similar anatomic and functional variability is present in developmental prosopagnosia. PMID:24389150

  6. Acquired immune deficiency syndrome (AIDS).

    PubMed

    1987-02-01

    The International Planned Parenthood Medical Advisory Panel has developed recommendations to assist family planning associations in playing a more active role in the prevention and control of acquired immunodeficiency syndrome (AIDS). Of primary importance is an effective program of information and education aimed at communicating the following facts: AIDS is a fatal disease for which there is no cure; AIDS is spread by sexual intercourse, contaminated blood, and contaminated needles; an infected woman can transmit AIDS to her fetus during pregnancy; a monogamous sexual relationship is the surest way to avoid AIDS infection; condom use is good protection; an infected person can look and feel well, yet still be able to transmit the AIDS virus; and AIDS is not spread by ordinary contact with an infected person. Family planning associations should include information on AIDS in all existing IEC projects, as well as develop new materials. Among the target audiences for IEC activities are family planning workers, family planning clients, and the general public including youth, teachers, parents, employers, and national leaders. Special attention should be given to high-risk groups such as homosexual and bisexual men, hemophiliacs, male and female prostitutes, clients of sexually transmitted disease clinics, people with many sexual partners, illegal users of intravenous drugs, and the sexual partners of those in any of these groups. Wide promotion of condom use is a priority activity for family planning organizations. PMID:12340977

  7. Infections Acquired in the Garden.

    PubMed

    Cunha, Cheston B; Cunha, Burke A

    2015-10-01

    Gardening is a wonderful pastime, and the garden is a very peaceful place to enjoy one's vacation. However, the garden may be a treacherous place for very young or compromised hosts when one takes into account the infectious potential residing in the soil, as well as the insect vectors on plants and animals. Even normal hosts may acquire a variety of infections from the soil, animals, or animal-related insect bites. The location of the garden, its natural animal and insect inhabitants, and the characteristics of the soil play a part in determining its infectious potential. The most important factor making the garden an infectious and dangerous place is the number and interaction of animals, whether they are pets or wild, that temporarily use the garden for part of their daily activities. The clinician should always ask about garden exposure, which will help in eliminating the diagnostic possibilities for the patient. The diagnostic approach is to use epidemiological principles in concert with clinical clues, which together should suggest a reasonable list of diagnostic possibilities. Organ involvement and specific laboratory tests help further narrow the differential diagnosis and determine the specific tests necessary to make a definitive diagnosis. PMID:26542044

  8. Associative Learning Through Acquired Salience

    PubMed Central

    Treviño, Mario

    2016-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction. PMID:26793078

  9. Associative Learning Through Acquired Salience.

    PubMed

    Treviño, Mario

    2015-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction. PMID:26793078

  10. Postnatal microcephaly and pain insensitivity due to a de novo heterozygous DNM1L mutation causing impaired mitochondrial fission and function.

    PubMed

    Sheffer, Ruth; Douiev, Liza; Edvardson, Simon; Shaag, Avraham; Tamimi, Khaled; Soiferman, Devorah; Meiner, Vardiella; Saada, Ann

    2016-06-01

    An emerging class of mitochondrial disorders is caused by mutations in nuclear genes affecting mitochondrial dynamics and function. One of these is the DNM1L gene encoding the dynamin-related protein 1 (DRP1), which is pivotal in the mitochondrial fission process. Here, we describe a patient with a novel dominant-negative, de novo DNM1L mutation, which expands the clinical spectrum. The patient reported here exhibits a chronic neurological disorder, characterized by postnatal microcephaly, developmental delay, and pain insensitivity. Muscle biopsy disclosed decreased respiratory chain complex IV activity. Exome sequencing showed a de novo heterozygous c.1084G>A (p.G362S) mutation. Subsequent studies of patient skin fibroblasts showed markedly impaired mitochondrial fission and a partial respiratory chain defect while peroxisomal morphology remained intact. Human foreskin fibroblasts over-expressing the mutant DNM1L gene displayed aberrant mitochondrial morphology. © 2016 Wiley Periodicals, Inc. PMID:26992161

  11. Novel splice-site mutation in WDR62 revealed by whole-exome sequencing in a Sudanese family with primary microcephaly.

    PubMed

    Bastaki, Fatma; Mohamed, Madiha; Nair, Pratibha; Saif, Fatima; Tawfiq, Nafisa; Aithala, Gururaj; El-Halik, Majdi; Al-Ali, Mahmoud; Hamzeh, Abdul Rezzak

    2016-05-01

    The WDR62 gene encodes a scaffold protein of the c-Jun N-terminal kinase (JNK) pathway. It plays a critical role in laying out various cellular layers in the cerebral cortex during embryogenesis, and hence the dramatic clinical features resulting from WDR62 mutations. These mutations are associated with autosomal recessive primary microcephaly 2, with or without cortical malformations (MCPH2). Using whole exome sequencing we uncovered a novel WDR62 variant; c.390G > A, from two Sudanese siblings whose parents are first cousins. The patients suffered MCPH2 with incomplete lissencephaly and developmental delay. The mutation affects the last nucleotide of exon4, and probably leads to aberrant splicing, which may result in a truncated protein lacking all functional domains. PMID:26577670

  12. Clinicopathological associations of acquired erythroblastopenia

    PubMed Central

    Gunes, Gursel; Malkan, Umit Yavuz; Yasar, Hatime Arzu; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Demiroglu, Haluk; Sayinalp, Nilgun; Aksu, Salih; Etgul, Sezgin; Aslan, Tuncay; Goker, Hakan; Ozcebe, Osman Ilhami; Buyukasik, Yahya

    2015-01-01

    Introduction: Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. Background: Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. Material and method: Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. Results: Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). Discussion: As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. Conclusion: To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated. PMID:26885236

  13. Surface Sampler Arm Acquiring Sample

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Operation of the surface sampler in obtaining Martian soil for Viking 2's molecular analysis experiment last Saturday (September 25) was closely monitored by one of the Lander cameras because of the precision required in trenching the small area--8 by 9 inches-surrounded by rocks. Dubbed 'Bonneville Salt Flats,' the exposure of thin crust appeared unique in contrast with surrounding materials and became a prime target for organic analysis in spite of potential hazards. Large rock in foreground is 8 inches high. At left, the sampler scoop has touched the surface, missing the rock at upper left by a comfortable 6 inches, and the backhoe has penetrated the surface about one-half inch. The scoop was then pulled back to sample the desired point and (second photo) the backhoe furrowed the surface pulling a piece of thin crust toward the spacecraft. The initial touchdown and retraction sequence was used to avoid a collision between a rock in the shadow of the arm and a plate joining the arm and scoop. The rock was cleared by 2 to 3 inches. The third picture was taken 8 minutes after the scoop touched the surface and shows that the collector head has acquired a quantity of soil. With surface sampler withdrawn (right), the foot-long trench is seen between the rocks. The trench is three inches wide and about 1 1/2 to 2 inches deep. The scoop reached to within 3 inches of the rock at far end of trench. Penetration appears to have left a cavernous opening roofed by the crust and only about one inch of undisturbed crust separates the deformed surface and the rock.

  14. X-linked congenital ptosis and associated intellectual disability, short stature, microcephaly, cleft palate, digital and genital abnormalities define novel Xq25q26 duplication syndrome.

    PubMed

    Møller, R S; Jensen, L R; Maas, S M; Filmus, J; Capurro, M; Hansen, C; Marcelis, C L M; Ravn, K; Andrieux, J; Mathieu, M; Kirchhoff, M; Rødningen, O K; de Leeuw, N; Yntema, H G; Froyen, G; Vandewalle, J; Ballon, K; Klopocki, E; Joss, S; Tolmie, J; Knegt, A C; Lund, A M; Hjalgrim, H; Kuss, A W; Tommerup, N; Ullmann, R; de Brouwer, A P M; Strømme, P; Kjaergaard, S; Tümer, Z; Kleefstra, T

    2014-05-01

    Submicroscopic duplications along the long arm of the X-chromosome with known phenotypic consequences are relatively rare events. The clinical features resulting from such duplications are various, though they often include intellectual disability, microcephaly, short stature, hypotonia, hypogonadism and feeding difficulties. Female carriers are often phenotypically normal or show a similar but milder phenotype, as in most cases the X-chromosome harbouring the duplication is subject to inactivation. Xq28, which includes MECP2 is the major locus for submicroscopic X-chromosome duplications, whereas duplications in Xq25 and Xq26 have been reported in only a few cases. Using genome-wide array platforms we identified overlapping interstitial Xq25q26 duplications ranging from 0.2 to 4.76 Mb in eight unrelated families with in total five affected males and seven affected females. All affected males shared a common phenotype with intrauterine- and postnatal growth retardation and feeding difficulties in childhood. Three had microcephaly and two out of five suffered from epilepsy. In addition, three males had a distinct facial appearance with congenital bilateral ptosis and large protruding ears and two of them showed a cleft palate. The affected females had various clinical symptoms similar to that of the males with congenital bilateral ptosis in three families as most remarkable feature. Comparison of the gene content of the individual duplications with the respective phenotypes suggested three critical regions with candidate genes (AIFM1, RAB33A, GPC3 and IGSF1) for the common phenotypes, including candidate loci for congenital bilateral ptosis, small head circumference, short stature, genital and digital defects. PMID:24326587

  15. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND... Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired....

  16. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which...

  17. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which...

  18. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which...

  19. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND... Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired....

  20. Hair Loss

    MedlinePlus

    ... psychosocial impact of hair loss have found patients’ self-esteem, body image and self-confidence to be negatively ... 1-2 Known psychosocial complications include depression, low self-esteem, altered self-image, and less frequent and enjoyable ...

  1. Acquired tracheoesophageal fistula in infancy and childhood.

    PubMed

    Szold, A; Udassin, R; Seror, D; Mogle, P; Godfrey, S

    1991-06-01

    Acquired tracheoesophageal fistula (TEF) is a rare entity in the pediatric age group. We report two pediatric patients with acquired TEF caused by shells of pistachio nuts. In both patients the primary operation did not resolve the problem and a second intervention for recurrent fistula was needed. The special nature of acquired TEF, particularly the one described herein, requires delayed surgical intervention and meticulous separation of the respiratory and alimentary tracts by an intercostal muscle flap. PMID:1941455

  2. Acquired stuttering due to recurrent anaplastic astrocytoma

    PubMed Central

    Peters, Katherine B; Turner, Scott

    2013-01-01

    Acquired (neurogenic) stuttering is a rare phenomenon seen after cerebral infarction or brain injury. Aetiology of this symptom is unclear, but recent evidence supports that it is a disturbance in the left hemispheric neural network involving the interplay between the cortex and basal ganglia. We present the case of a patient who develops acquired stuttering after a recurrence of a right temporoparietal anaplastic astrocytoma (WHO grade III). We also review other cases of acquired stuttering and known anatomical correlates. PMID:24252834

  3. 26 CFR 1.381(c)(3)-1 - Capital loss carryovers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... expropriation capital losses. If the distributor, transferor, or acquiring corporation sustains a net capital... acquiring corporation in each of the taxable years to which the net capital loss giving rise to such... which bears the same ratio to the acquiring corporation's capital gain net income (net capital gain...

  4. 26 CFR 1.381(c)(3)-1 - Capital loss carryovers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... expropriation capital losses. If the distributor, transferor, or acquiring corporation sustains a net capital... acquiring corporation in each of the taxable years to which the net capital loss giving rise to such... which bears the same ratio to the acquiring corporation's capital gain net income (net capital gain...

  5. 26 CFR 1.381(c)(3)-1 - Capital loss carryovers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... expropriation capital losses. If the distributor, transferor, or acquiring corporation sustains a net capital... acquiring corporation in each of the taxable years to which the net capital loss giving rise to such... which bears the same ratio to the acquiring corporation's capital gain net income (net capital gain...

  6. Hair loss in children.

    PubMed

    Alves, Rubina; Grimalt, Ramon

    2015-01-01

    Hair diseases represent frequent complaints in dermatology clinics, and they can be caused by a number of conditions reflected by specific diagnoses. Hair loss is not uncommon in the pediatric group, but its patterns in this group are different from those seen in adults. Additionally, in children, these disorders can have psychological effects that can interfere with growth and development. Hair is easily accessible for examination, and dermatologists are in the enviable situation of being able to study many disorders using simple diagnostic techniques. To fully understand hair loss during childhood, a basic comprehension of normal hair growth is necessary. Knowledge of the normal range and variation observed in the hair of children further enhances its assessment. This chapter has been written in an attempt to facilitate the diagnostic process during daily practice by helping to distinguish between acquired and congenital hair diseases. It can sometimes be difficult to differentiate between abnormality and normality in neonatal hair aspects. Management of hair disorders can be quite a daunting task for the attending physician and mandates a holistic approach to the patient. Some hair disturbances have no effective treatment, and for others, no single treatment is 100% successful. If no effective treatment for a hair loss disease exists, a cosmetic approach is important. PMID:26370644

  7. Pregnancy loss.

    PubMed

    Robinson, Gail Erlick

    2014-01-01

    Women who lose desired pregnancies by miscarriage, stillbirth, or genetic termination are at risk of suffering from grief, anxiety, guilt and self-blame that may even present in subsequent pregnancies. It is important to find effective means of helping women deal with these losses. The approach to stillbirth has shifted from immediately removing the child from the mother to encouraging the parents to view and hold the baby. This approach has been questioned as possibly causing persistent anxiety and post-traumatic stress disorder. Women who miscarry are currently encouraged to find ways to memorialise the lost fetus. Couples who decide to terminate a pregnancy after discovering a defect may deal not only with sadness but also guilt. Immediate crisis intervention and follow-up care should be available, recognising that individual women may experience different reactions and their specific post-loss needs must be assessed. PMID:24047642

  8. Beam loss

    NASA Astrophysics Data System (ADS)

    VanGinneken, A.; Edwards, D.; Harrison, M.

    1989-04-01

    This paper presents results from simulations of beam losses during the operation of a superconducting accelerator. The calculations use a combination of hadron/electromagnetic cascade plus elastic scattering codes with accelerator tracking routines. These calculations have been used in conjunction with the design of the Fermilab Tevatron. First accelerator geometry is described. The rest of the paper discusses a detailed attempt to simulate a fast extraction cycle, essentially in chronological order. Beginning with an unperturbed beam, the simulation generates proton phase-space distributions incident on the electrostatic septum. These interact either elastically or inelastically with the septum wires, and the products of these interactions are traced through the machine. Where these leave the accelerator, energy deposition levels in the magnets are calculated together with the projected response of the beam-loss monitors in this region. Finally, results of the calculation are compared with experimental data. (AIP)

  9. Loss-of-Function CNKSR2 Mutation Is a Likely Cause of Non-Syndromic X-Linked Intellectual Disability

    PubMed Central

    Houge, G.; Rasmussen, I.H.; Hovland, R.

    2012-01-01

    In a non-dysmorphic 5-year-old boy with developmental delay, well-controlled epilepsy, and microcephaly, a 234-kb deletion of Xp22.12 was detected by copy number analysis. The maternally inherited deletion removed the initial 15 of the 21 exons of the connector enhancer of KSR-2 gene called CNKSR2 or CNK2. Our finding suggests that loss of CNKSR2 is a novel cause of non-syndromic X-linked mental retardation, an assumption supported by high gene expression in the brain, localization to the post-synaptic density, and a role in RAS/MAPK-dependent signal transduction. PMID:22511892

  10. Loss-of-Function CNKSR2 Mutation Is a Likely Cause of Non-Syndromic X-Linked Intellectual Disability.

    PubMed

    Houge, G; Rasmussen, I H; Hovland, R

    2012-01-01

    In a non-dysmorphic 5-year-old boy with developmental delay, well-controlled epilepsy, and microcephaly, a 234-kb deletion of Xp22.12 was detected by copy number analysis. The maternally inherited deletion removed the initial 15 of the 21 exons of the connector enhancer of KSR-2 gene called CNKSR2 or CNK2. Our finding suggests that loss of CNKSR2 is a novel cause of non-syndromic X-linked mental retardation, an assumption supported by high gene expression in the brain, localization to the post-synaptic density, and a role in RAS/MAPK-dependent signal transduction. PMID:22511892

  11. Acquired Surface Dyslexia: The Evidence from Hebrew.

    ERIC Educational Resources Information Center

    Birnboim, Smadar

    1995-01-01

    Investigates the symptoms of acquired surface dyslexia in Hebrew. Four acquired surface dyslexic adults were compared with eight normal second graders in terms of reading strategy. Homophones and homographs were a major source of difficulty for native Hebrew surface dyslexic readers; the normal second graders used a non-lexical strategy. (45…

  12. Acquiring and Managing Electronic Journals. ERIC Digest.

    ERIC Educational Resources Information Center

    Curtis, Donnelyn; Yue, Paoshan

    Electronic journals are both a blessing and a curse for libraries. To be meaningful in the current information environment--to meet users' ever-increasing demands--libraries must acquire as many appropriate full text resources as possible, as quickly as possible, and make them easy to use. This Digest provides tips for acquiring and providing…

  13. Acquired Zinc Deficiency in an Adult Female

    PubMed Central

    Saritha, Mohanan; Gupta, Divya; Chandrashekar, Laxmisha; Thappa, Devinder M; Rajesh, Nachiappa G

    2012-01-01

    Acrodermatitis enteropathica is an autosomal recessive inherited disorder of zinc absorption. Acquired cases are reported occasionally in patients with eating disorders or Crohn's disease. We report a 24-year-old housewife with acquired isolated severe zinc deficiency with no other comorbidities to highlight the rare occurrence of isolated nutritional zinc deficiency in an otherwise normal patient. PMID:23248371

  14. Acquired hemophilia masked by warfarin therapy.

    PubMed

    Kantor, R; Mayan, H; Puritz, L; Varon, D; Farfel, Z

    2000-03-01

    People without hemophilia but with autoantibodies specifically directed against the procoagulant activity of factor VIII are known to have acquired hemophilia. The bleeding diathesis in these patients is often severe and life-threatening. The definite laboratory diagnosis of this disorder includes demonstration of low factor VIII levels in plasma with a high titer of factor VIII inhibitors, but the initial suspicion for its presence should rise in view of a prolonged partial thromboblastin time (PTT) and a normal prothrombin time associated with an acquired bleeding disorder. Oral anticoagulant treatment is known to prolong PTT as well, and the merger of these 2 situations may cause delayed diagnosis of acquired hemophilia with devastating consequences. We describe here the first reported case of acquired hemophilia diagnosed in a patient treated with warfarin. In such patients prolonged PTT may be ascribed to warfarin therapy rather than to acquired hemophilia, thus causing a dangerous delay in diagnosis. PMID:10746834

  15. Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

    PubMed Central

    van der Linden, Vanessa; Brainer-Lima, Alessandra Mertens; Coeli, Regina Ramos; Rocha, Maria Angela; Sobral da Silva, Paula; Durce Costa Gomes de Carvalho, Maria; van der Linden, Ana; Cesario de Holanda, Arthur; Valenca, Marcelo Moraes

    2016-01-01

    Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Design Retrospective study with a case series. Setting Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. Participants 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Results Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus—the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Conclusion Severe cerebral damage was

  16. Potential disadvantages of using socially acquired information.

    PubMed Central

    Giraldeau, Luc-Alain; Valone, Thomas J; Templeton, Jennifer J

    2002-01-01

    The acquisition and use of socially acquired information is commonly assumed to be profitable. We challenge this assumption by exploring hypothetical scenarios where the use of such information either provides no benefit or can actually be costly. First, we show that the level of incompatibility between the acquisition of personal and socially acquired information will directly affect the extent to which the use of socially acquired information can be profitable. When these two sources of information cannot be acquired simultaneously, there may be no benefit to socially acquired information. Second, we assume that a solitary individual's behavioural decisions will be based on cues revealed by its own interactions with the environment. However, in many cases, for social animals the only socially acquired information available to individuals is the behavioural actions of others that expose their decisions, rather than the cues on which these decisions were based. We argue that in such a situation the use of socially acquired information can lead to informational cascades that sometimes result in sub-optimal behaviour. From this theory of informational cascades, we predict that when erroneous cascades are costly, individuals should pay attention only to socially generated cues and not behavioural decisions. We suggest three scenarios that might be examples of informational cascades in nature. PMID:12495513

  17. Acquired antithrombin III deficiency: laboratory diagnosis, incidence, clinical implications, and treatment with antithrombin III concentrate.

    PubMed

    Büller, H R; ten Cate, J W

    1989-09-11

    Antithrombin III (ATIII) is the predominant naturally occurring inhibitor of serine proteases generated during blood coagulation [Rosenberg RD: Annu Rev Med 1978; 29: 367-378]. Since 1965, several assays have been developed that allow rapid and precise determination of ATIII in plasma. As a consequence, the existence of acquired ATIII deficiency in many pathologic conditions has been described. Acquired ATIII deficiency is based on decreased synthesis, increased loss or increased consumption, or induced by drugs. An inherited ATIII deficiency is associated with a lifelong tendency to venous thromboembolism. In contrast, the clinical significance of acquired ATIII deficiency has been less well defined. A precise estimate of the risk of thromboembolism in the acquired ATIII deficiency state cannot easily be provided, owing to the lack of studies in consecutive patients. In 1978, a purified human ATIII concentrate became available for clinical investigation. Despite numerous small studies, the value of ATIII replacement therapy in patients with acquired deficiency remains to be demonstrated. PMID:2679070

  18. 26 CFR 1.1502-21 - Net operating losses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... the P group's return in Year 2. The $600 amount of the CNOL attributable to T is a net operating loss... forms T, and T sustains a $100 net operating loss that is carried forward. P acquires all the stock of T..., Individual A forms P, and P sustains a $40 net operating loss that is carried forward. P has no income...

  19. 26 CFR 1.1502-21 - Net operating losses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the P group's return in Year 2. The $600 amount of the CNOL attributable to T is a net operating loss... forms T, and T sustains a $100 net operating loss that is carried forward. P acquires all the stock of T..., Individual A forms P, and P sustains a $40 net operating loss that is carried forward. P has no income...

  20. 26 CFR 1.1502-21 - Net operating losses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the P group's return in Year 2. The $600 amount of the CNOL attributable to T is a net operating loss... forms T, and T sustains a $100 net operating loss that is carried forward. P acquires all the stock of T..., Individual A forms P, and P sustains a $40 net operating loss that is carried forward. P has no income...

  1. PIAS4 is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome.

    PubMed

    Nevado, Julián; Rosenfeld, Jill A; Mena, Rocío; Palomares-Bralo, María; Vallespín, Elena; Ángeles Mori, María; Tenorio, Jair A; Gripp, Karen W; Denenberg, Elizabeth; Del Campo, Miguel; Plaja, Alberto; Martín-Arenas, Rubén; Santos-Simarro, Fernando; Armengol, Lluis; Gowans, Gordon; Orera, María; Sanchez-Hombre, M Carmen; Corbacho-Fernández, Esther; Fernández-Jaén, Alberto; Haldeman-Englert, Chad; Saitta, Sulagna; Dubbs, Holly; Bénédicte, Duban B; Li, Xia; Devaney, Lani; Dinulos, Mary Beth; Vallee, Stephanie; Crespo, M Carmen; Fernández, Blanca; Fernández-Montaño, Victoria E; Rueda-Arenas, Inmaculada; de Torres, María Luisa; Ellison, Jay W; Raskin, Salmo; Venegas-Vega, Carlos A; Fernández-Ramírez, Fernando; Delicado, Alicia; García-Miñaúr, Sixto; Lapunzina, Pablo

    2015-12-01

    Array comparative genomic hybridization (aCGH) is a powerful genetic tool that has enabled the identification of novel imbalances in individuals with intellectual disability (ID), autistic disorders and congenital malformations. Here we report a 'genotype first' approach using aCGH on 13 unrelated patients with 19p13.3 submicroscopic rearrangement (11 deletions and 2 duplications) and review cases in the literature and in public databases. Shared phenotypic features suggest that these patients represent an interstitial microdeletion/microduplication syndrome at 19p13.3. Common features consist of abnormal head circumference in most patients (macrocephaly with the deletions and microcephaly with the duplications), ID with developmental delay (DD), hypotonia, speech delay and common dysmorphic features. The phenotype is associated with at least a ~0.113 Mb critical region harboring three strong candidate genes probably associated with DD, ID, speech delay and other dysmorphic features: MAP2K2, ZBTB7A and PIAS4, an E3 ubiquitin ligase involved in the ubiquitin signaling pathways, which we hypothesize for the first time to be associated with head size in humans. PMID:25853300

  2. De novo PIK3R1 gain-of-function with recurrent sinopulmonary infections, long-lasting chronic CMV-lymphadenitis and microcephaly.

    PubMed

    Kuhlen, Michaela; Hönscheid, Andrea; Loizou, Loizos; Nabhani, Schafiq; Fischer, Ute; Stepensky, Polina; Schaper, Jörg; Klapper, Wolfram; Siepermann, Meinolf; Schuster, Friedhelm; Meisel, Roland; Borkhardt, Arndt

    2016-01-01

    PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1) gain-of-function has recently been described in patients with recurrent sinopulmonary infections, chronic CMV-/EBV-infections, lymphoproliferation, and hypogammaglobulinemia. Here we report a 15-year-old boy with treatment refractory CMV lymphadenitis, severe combined immunodeficiency, microcephaly and a severe developmental defect of Th17 cells. To avoid poor outcome, hematopoietic stem cell transplantation (HSCT) was performed. Subsequently, whole exome sequencing revealed a de novo heterozygous G-to-C mutation (chr5: 5:67,589,663: G>C) at the splice donor site of the PIK3R1 gene. Our data suggest that PIK3R1 gain-of-function leads to developmental defects in helper and regulatory T-cell subsets, the latter expanding the immunological features of PIK3R1 gain-of-function. T-cell subsets play a critical role in the regulation of immune response against infectious agents and of autoimmunity and thus may be particularly accountable for the clinical phenotype of affected patients. PMID:26529633

  3. Microcephaly in a 14-month male with minimal developmental delay (speech) and mild dysmorphology with unusual mosaicism involving a ring chromosome 5

    SciTech Connect

    Grady, V.; Lieber, E.; Yu, M.T.

    1994-09-01

    This male at birth weighed 5 lbs, 14 oz and was full term. His mother was G3 P2012. His height and weight follow the 3rd percentile; however, his head circumference is below the 3rd percentile. His hearing is age-appropriate; however, his speech is poor to absent. His hearing is intact. He had 2-5 cafe-au-lait spots (0.5 to 1.0 cm) on his trunk and extremities. His face showed mild dysmorphology (non-specific). His tone and central nervous system are intact. Because of the microcephaly, a chromosome study was performed. A skin fibroblast culture was performed because of his appropriate milestones. One cell in the peripheral blood and one cell in the skin biopsy demonstrated two normal chromosome 5s. FISH studies using chromosome 5 painting probe confirmed the observations of routine cytogenetic studies. The marker chromosome was identified as part of chromosome 5. At 14 months, the patient does not have the appearance associated with the Cri-du-chat syndrome. Additional studies with probes for the specific region associated with this syndrome are planned.

  4. Thrombophilia and early pregnancy loss.

    PubMed

    McNamee, Kelly; Dawood, Feroza; Farquharson, Roy G

    2012-02-01

    Early pregnancy loss is the most common pregnancy complication. About 15% of pregnancies result in pregnancy loss and 1% of women experience recurrent miscarriage (more than three consecutive miscarriages). The influence of thrombophilia in pregnancy is a popular research topic in recurrent miscarriage. Both acquired and inherited thrombophilia are associated with a risk of pregnancy failure. Antiphospholipid syndrome is the only thrombophilia known to have a direct adverse effect on pregnancy. Historically, clinical research studying thrombophilia treatment in recurrent miscarriage has been of limited value owing to small participant numbers, poor study design and heterogeneity. The debate on the efficacy of aspirin and heparin has advanced with recently published randomised-controlled trials. Multi-centre collaboration is required to ascertain the effect of thrombophilia on early pregnancy loss and to establish an evidence-based treatment protocol. PMID:22079389

  5. Rapid weight loss

    MedlinePlus

    ... loss-rapid weight loss; Overweight-rapid weight loss; Obesity-rapid weight loss; Diet-rapid weight loss ... for people who have health problems because of obesity. For these people, losing a lot of weight ...

  6. Memory loss.

    PubMed

    Flicker, Leon A; Ford, Andrew H; Beer, Christopher D; Almeida, Osvaldo P

    2012-02-01

    Most older people with memory loss do not have dementia. Those with mild cognitive impairment are at increased risk of progressing to dementia, but no tests have been shown to enhance the accuracy of assessing this risk. Although no intervention has been convincingly shown to prevent dementia, data from cohort studies and randomised controlled trials are compelling in indicating that physical activity and treatment of hypertension decrease the risk of dementia. There is no evidence that pharmaceutical treatment will benefit people with mild cognitive impairment. In people with Alzheimer's disease, treatment with a cholinesterase inhibitor or memantine (an N-methyl- D-aspartate receptor antagonist) may provide symptomatic relief and enhance quality of life, but does not appear to alter progression of the illness. Non-pharmacological strategies are recommended as first-line treatments for behavioural and psychological symptoms of dementia, which are common in Alzheimer's disease. Atypical antipsychotics have modest benefit in reducing agitation and psychotic symptoms but increase the risk of cardiovascular events. The role of antidepressants in managing depressive symptoms in patients with mild cognitive impairment is uncertain and may increase the risk of delirium and falls. PMID:22304604

  7. Unpleasant odors increase aversion to monetary losses.

    PubMed

    Stancak, Andrej; Xie, Yuxin; Fallon, Nicholas; Bulsing, Patricia; Giesbrecht, Timo; Thomas, Anna; Pantelous, Athanasios A

    2015-04-01

    Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger. PMID:25711689

  8. Incidence, Outcomes, and Risk Factors of Community-Acquired and Hospital-Acquired Acute Kidney Injury

    PubMed Central

    Hsu, Chien-Ning; Lee, Chien-Te; Su, Chien-Hao; Wang, Yu-Ching Lily; Chen, Hsiao-Ling; Chuang, Jiin-Haur; Tain, You-Lin

    2016-01-01

    Abstract The disease burden and outcomes of community-acquired (CA-) and hospital-acquired acute kidney injury (HA-AKI) are not well understood. The aim of the study was to investigate the incidence, outcomes, and risk factors of AKI in a large Taiwanese adult cohort. This retrospective cohort study examined 734,340 hospital admissions from a group of hospitals within an organization in Taiwan between January 1, 2010 and December 31, 2014. Patients with AKI at discharge were classified as either CA- or HA-AKI based on the RIFLE (risk, injury, failure, loss of function, end stage of kidney disease) classification criteria. Outcomes were in-hospital mortality, dialysis, recovery of renal function, and length of stay. Risks of developing AKI were determined using multivariate logistic regression based on demographic and baseline clinical characteristics and nephrotoxin use before admission. AKI occurred in 1.68% to 2% hospital discharges among adults without and with preexisting chronic kidney disease (CKD), respectively. The incidence of CA-AKI was 17.25 and HA-AKI was 8.14 per 1000 admissions. The annual rate of CA-AKI increased from 12.43 to 19.96 per 1000 people, but the change in HA-AKI was insignificant. Comparing to CA-AKI, those with HA-AKI had higher levels of in-hospital mortality (26.07% vs 51.58%), mean length of stay (21.25 ± 22.35 vs 35.84 ± 34.62 days), and dialysis during hospitalization (1.45% vs 2.06%). Preexisting systemic diseases, including CKD were associated with increased risks of CA-AKI, and nephrotoxic polypharmacy increased risk of both CA- and HA-AKI. Patients with HA-AKI had more severe outcomes than patients with CA-AKI, and demonstrated different spectrum of risk factors. Although patients with CA-AKI with better outcomes, the incidence increased over time. It is also clear that optimal preventive and management strategies of HA- and CA-AKI are urgently needed to limit the risks in susceptible individuals. PMID:27175701

  9. Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

    Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge

  10. Acquired cutis laxa associated with cutaneous mastocytosis.

    PubMed

    Hoang, Minh Van; Dang, Phuoc Van; Bui, Duc Van; Mejbel, Haider; Mani, Divya Thomas; Smoller, Bruce Robert; Phung, Thuy Linh

    2015-07-01

    Cutis laxa is characterized by dramatic wrinkling of skin that is lacking in elasticity due to inherent defects in dermal elastic fibers. Cutis laxa can be caused by genetic and metabolic disorders. It can also be acquired, possibly resulting from inflammatory processes with destruction of elastic fibers. This report describes a 26-year old woman who developed acquired cutis laxa and cutaneous mastocytosis leading to premature aging. She represents a unique co-occurrence of these two separate disease entities. To our knowledge, there has been only one published case report of acquired cutis laxa occurring in association with urticaria pigmentosa in a 4-year old girl. Our case would be a second case that exhibits the coexistence of these two disorders in an adult female. PMID:26436968

  11. Magnetic resonance imaging of acquired cardiac disease.

    PubMed Central

    Carrol, C L; Higgins, C B; Caputo, G R

    1996-01-01

    Over the last 15 years, advances in magnetic resonance imaging techniques have increased the accuracy and applicability of cardiovascular magnetic resonance imaging. These advances have improved the utility of magnetic resonance imaging in evaluating cardiac morphology, blood flow, and myocardial contractility, all significant diagnostic features in the evaluation of the patient with acquired heart disease. Utilization of cardiovascular magnetic resonance imaging has been limited, primarily due to clinical reliance upon nuclear scintigraphy and echocardiography. Recent developments in fast and ultrafast imaging should continue to enhance the significance of magnetic resonance imaging in this field. Widespread use of magnetic resonance imaging in the evaluation of the cardiovascular system will ultimately depend upon its maturation into a comprehensive, noninvasive imaging technique for the varying manifestations of acquired heart disease, including cardiomyopathy, ischemic heart disease, and acquired valvular disease. Images PMID:8792545

  12. Primary Microcephaly Gene MCPH1 Shows Signatures of Tumor Suppressors and Is Regulated by miR-27a in Oral Squamous Cell Carcinoma

    PubMed Central

    Venkatesh, Thejaswini; Nagashri, Mathighatta Nagaraj; Swamy, Shivananda S.; Mohiyuddin, S. M. Azeem; Gopinath, Kodaganur S.; Kumar, Arun

    2013-01-01

    Mutations in the MCPH1 (microcephalin 1) gene, located at chromosome 8p23.1, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. MCPH1 has also been shown to be downregulated in breast, prostate and ovarian cancers, and mutated in 1/10 breast and 5/41 endometrial tumors, suggesting that it could also function as a tumor suppressor (TS) gene. To test the possibility of MCPH1 as a TS gene, we first performed LOH study in a panel of 81 matched normal oral tissues and oral squamous cell carcinoma (OSCC) samples, and observed that 14/71 (19.72%) informative samples showed LOH, a hallmark of TS genes. Three protein truncating mutations were identified in 1/15 OSCC samples and 2/5 cancer cell lines. MCPH1 was downregulated at both the transcript and protein levels in 21/41 (51.22%) and 19/25 (76%) OSCC samples respectively. A low level of MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. We further observed that overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, cell invasion and tumor size in nude mice, indicating its tumor suppressive function. Using bioinformatic approaches and luciferase assay, we showed that the 3′-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27a which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in OSCC. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is regulated by miR-27a. PMID:23472065

  13. Homozygous mutation in the eukaryotic translation initiation factor 2alpha phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature and intellectual disability

    PubMed Central

    Kernohan, Kristin D.; Tétreault, Martine; Liwak-Muir, Urszula; Geraghty, Michael T.; Qin, Wen; Venkateswaran, Sunita; Davila, Jorge; Holcik, Martin; Majewski, Jacek; Richer, Julie; Boycott, Kym M.

    2015-01-01

    Protein translation is an essential cellular process initiated by the association of a methionyl–tRNA with the translation initiation factor eIF2. The Met-tRNA/eIF2 complex then associates with the small ribosomal subunit, other translation factors and mRNA, which together comprise the translational initiation complex. This process is regulated by the phosphorylation status of the α subunit of eIF2 (eIF2α); phosphorylated eIF2α attenuates protein translation. Here, we report a consanguineous family with severe microcephaly, short stature, hypoplastic brainstem and cord, delayed myelination and intellectual disability in two siblings. Whole-exome sequencing identified a homozygous missense mutation, c.1972G>A; p.Arg658Cys, in protein phosphatase 1, regulatory subunit 15b (PPP1R15B), a protein which functions with the PPP1C phosphatase to maintain dephosphorylated eIF2α in unstressed cells. The p.R658C PPP1R15B mutation is located within the PPP1C binding site. We show that patient cells have greatly diminished levels of PPP1R15B–PPP1C interaction, which results in increased eIF2α phosphorylation and resistance to cellular stress. Finally, we find that patient cells have elevated levels of PPP1R15B mRNA and protein, suggesting activation of a compensatory program aimed at restoring cellular homeostasis which is ineffective due to PPP1R15B alteration. PPP1R15B now joins the expanding list of translation-associated proteins which when mutated cause rare genetic diseases. PMID:26307080

  14. A case report of a patient with microcephaly, facial dysmorphism, chromosomal radiosensitivity and telomere length alterations closely resembling "Nijmegen breakage syndrome" phenotype.

    PubMed

    Berardinelli, F; di Masi, A; Salvatore, M; Banerjee, S; Myung, K; De Villartay, J P; Revy, P; Plebani, A; Soresina, A; Taruscio, D; Tanzarella, C; Antoccia, A

    2007-01-01

    Genetic heterogeneity in Nijmegen breakage syndrome (NBS) is highlighted by patients showing clinical and cellular features of NBS but with no mutations in NBS1 and normal levels of nibrin. NBS is an autosomal recessive disorder, whose clinical cellular signs include growth and developmental defects, dysmorphic facies, immunodeficiency, cancer predisposition, chromosomal instability and radiosensitivity. NBS is caused by mutations in the NBS1 gene, whose product is part of the MRE11/RAD50/NBS1 complex involved in the DNA double-strand break (DSB) response pathway. Since the identification of the NBS1 gene, patients with NBS clinical signs, particularly severe congenital microcephaly, are screened for mutations in the NBS1 gene. Further analyses include X-ray-induced chromosome aberrations, telomere analysis, kinetics of DSBs repair, levels of a panel of proteins involved in the maintenance of genetic stability, radiation-induced phosphorylation of various substrates and cell cycle analysis. We describe a patient with a NBS clinical phenotype, chromosomal sensitivity to X-rays but without mutations in the whole NBS1 or in the Cernunnos gene. Enhanced response to irradiation was mediated neither by DSBs rejoining defects nor by the NBS/AT-dependent DNA-damage response pathway. Notably, we found that primary fibroblasts from this patient displayed telomere length alterations. Cross-talk between pathways controlling response to DSBs and those involved in maintaining telomeres has been shown in the present patient. Dissecting the cellular phenotype of radiosensitive NBS-like patients represents a useful tool for the research of new genes involved in the cellular response to DSBs. PMID:17395558

  15. Acquired aphasia without deafness in childhood--the Landau-Kleffner syndrome.

    PubMed

    Hughes, A P; Appleton, R E; Hodgson, J

    1993-07-01

    A young boy presented with loss of speech and behaviour disturbance and was thought to be deaf. He was subsequently found to have the Landau-Kleffner syndrome (LKS), or acquired aphasia with epilepsy. Children with this disorder commonly present to an audiology or ENT clinic. Early recognition is important to initiate supportive, speech and educational care. PMID:15125283

  16. Vision Loss, Sudden

    MedlinePlus

    ... of age-related macular degeneration. Spotlight on Aging: Vision Loss in Older People Most commonly, vision loss ... Some Causes and Features of Sudden Loss of Vision Cause Common Features* Tests Sudden loss of vision ...

  17. Ultrasound of Inherited vs. Acquired Demyelinating Polyneuropathies

    PubMed Central

    Zaidman, Craig M.; Harms, Matthew B.; Pestronk, Alan

    2013-01-01

    Introduction We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound. Methods We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited (Charcot-Marie Tooth-1 (CMT-1) (n=35)) and acquired (Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (n=55), Guillaine-Barre Syndrome (GBS) (n=21) and Multifocal Motor Neuropathy (MMN) (n=17)) demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none- no enlargement; mild-nerves enlarged but never more than twice normal; regional- nerves normal at at least one region and enlarged more than twice normal at atleast one region; diffuse- nerves enlarged at all four regions with atleast one region more than twice normal size. Results Nerve enlargement was commonly diffuse (89%) and generally more than twice normal size in CMT-1, but not (p<0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement (CIDP (64%), GBS (95%), and MMN (100%)). In CIDP, subjects treated within three months of disease onset had less nerve enlargement than those treated later. Discussion Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement. PMID:24101129

  18. Acquiring a Second Language for School.

    ERIC Educational Resources Information Center

    Collier, Virginia P.

    1995-01-01

    This report offers a conceptual model for use with language minority children who are entering a new school when they must acquire the language of the majority student population. The model has four development components or processes: sociocultural, linguistic, academic, and cognitive. These four components are described in detail. Research is…

  19. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  20. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  1. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  2. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  3. Eye Movement Correlates of Acquired Central Dyslexia

    ERIC Educational Resources Information Center

    Schattka, Kerstin I.; Radach, Ralph; Huber, Walter

    2010-01-01

    Based on recent progress in theory and measurement techniques, the analysis of eye movements has become one of the major methodological tools in experimental reading research. Our work uses this approach to advance the understanding of impaired information processing in acquired central dyslexia of stroke patients with aphasia. Up to now there has…

  4. How Did Light Acquire a Velocity?

    ERIC Educational Resources Information Center

    Lauginie, Pierre

    2013-01-01

    We discuss how light acquired a velocity through history, from the ancient Greeks to the early modern era. Combining abstract debates, models of light, practical needs, planned research and chance, this history illustrates several key points that should be brought out in science education.

  5. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  6. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN IN... possession of raisins by a handler at his packing or processing plant or at any other established receiving station operated by him: Provided, That a handler shall not be deemed to acquire any raisins...

  7. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acquire. 926.10 Section 926.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE DATA COLLECTION, REPORTING AND...

  8. Acquiring Financial Management Software: A Prototyping Approach.

    ERIC Educational Resources Information Center

    Wilson, John H.

    1990-01-01

    When the Smithsonian Institution recently acquired a new financial management system, the concept of prototyping was used throughout the process, but in a broader sense than in software development. It was used to refine requirements, establish software management techniques, test a logistical system, and implement and apply the package. (MSE)

  9. Neural Correlates of Acquired Color Category Effects

    ERIC Educational Resources Information Center

    Clifford, Alexandra; Franklin, Anna; Holmes, Amanda; Drivonikou, Vicky G.; Ozgen, Emre; Davies, Ian R. L.

    2012-01-01

    Category training can induce category effects, whereby color discrimination of stimuli spanning a newly learned category boundary is enhanced relative to equivalently spaced stimuli from within the newly learned category (e.g., categorical perception). However, the underlying mechanisms of these acquired category effects are not fully understood.…

  10. Acquired structural defects of the hair.

    PubMed

    Chetty, G N; Kamalam, A; Thambiah, A S

    1981-03-01

    Acquired hair shaft abnormalities resembling genetic trichorrhexis nodosa were seen in two patients. Selenium shampoo and bacterial infection with trichomycosis axillaris may have been the contributing factors. There is a possibility that strongyloides larvae caused trichonodosis in one patient. PMID:7216593

  11. Community-acquired Acinetobacter meningitis in adults.

    PubMed

    Chang, W N; Lu, C H; Huang, C R; Chuang, Y C

    2000-01-01

    Community-acquired Acinetobacter meningitis in adults is an extremely rare infection of the central nervous system (CNS). Here we report one adult case of this rare CNS infection and review the clinical data of another seven cases reported in the English language literature. In total, eight patients (six men and two women) aged between 19 and 63 years were studied. The causative pathogen in our patient was Acinetobacter baumannii; in the other reported cases they were most likely Acinetobacter Iwoffii, Acinetobacter johnsonii, Acinetobacter junii, a genomic species 3 or 6. No underlying disease was found in seven of the eight cases and six of the eight patients acquired the infections before the age of 30 years. Fever and consciousness disturbance were the most common clinical manifestations. Waterhouse-Friderichsen syndrome (WFS) was found in two cases. Unlike the Acinetobacter strains found in nosocomial infections, the strain of Acinetobacter meningitis in the community-acquired case did not show multiple antibiotic resistance. Most adult patients with community-acquired Acinetobacter meningitis can be saved by timely therapy with appropriate antibiotics before deterioration of the systemic condition and impairment of consciousness. PMID:11139162

  12. Interviewing Children with Acquired Brain Injury (ABI)

    ERIC Educational Resources Information Center

    Boylan, Anne-Marie; Linden, Mark; Alderdice, Fiona

    2009-01-01

    Research into the lives of children with acquired brain injury (ABI) often neglects to incorporate children as participants, preferring to obtain the opinions of the adult carer (e.g. McKinlay et al., 2002). There has been a concerted attempt to move away from this position by those working in children's research with current etiquette…

  13. Support Network Responses to Acquired Brain Injury

    ERIC Educational Resources Information Center

    Chleboun, Steffany; Hux, Karen

    2011-01-01

    Acquired brain injury (ABI) affects social relationships; however, the ways social and support networks change and evolve as a result of brain injury is not well understood. This study explored ways in which survivors of ABI and members of their support networks perceive relationship changes as recovery extends into the long-term stage. Two…

  14. Severe sensory hearing loss in del(6q)-syndrome.

    PubMed

    Schuster, Maria; Lohscheller, Jörg; Kummer, Peter; Eysholdt, Ulrich; Rosanowski, Frank

    2003-11-01

    6q-syndrome is a rare disorder characterised by a combination of anatomic anomalies, and mental and motor retardation due to a monosomy or trisomy 6q. So far only 12 suspected cases of monosomies 6q have been reported. Hearing loss does not seem to be characteristic for this syndrome. We present the case of a girl with partial monosomy 6q. A bilateral severe sensory hearing loss was confirmed by subjective and objective audiometry at the age of 12 years. The girl was successfully equipped with hearing aids. Other features of the syndrome, i.e. mental retardation, microcephaly, asymmetric face, broad nasal bridge, hypertelorism, epicanthus, strabism, high arched palate, ventricular septum defect and seizures were seen. Additionally, a tetraplegy and diaphragmal hernia had been diagnosed. The girl was equipped with a gastrostomy tube because of nutritional disorders. In the literature, the possibility of hearing disorders in monosomy 6q is rarely mentioned, although limited verbal speech skills have been reported. A syndromic character of hearing disorders in 6q-syndrome cannot be excluded. We advise detailed and early audiological testing of children with monosomy 6q. PMID:14597381

  15. [Community-acquired Pseudomonas stutzeri meningitis in an immunocompetent patient].

    PubMed

    Sünbül, Mustafa; Zivalioğlu, Muammer; Taşdelen Fişgin, Nuriye

    2009-01-01

    Pseudomonas stutzeri which is an aerobic, non-fermentative gram-negative bacillus frequently found in soil, water and hospital environment, rarely leads to serious community-acquired infections. In this report a case of community-acquired meningitis due to P. stutzeri was presented. A 73-years-old male patient was admitted to the emergency department with the complaints of nausea, vomiting, headache, dizziness, difficulties in walking and speaking and loss of consciousness. There was no history of an underlying disease or immunosuppression. Physical examination revealed nuchal rigidity, however, Kernig and Brudzinski signs were negative. The cerebrospinal fluid (CSF) analysis revealed 0.4 mg/dl glucose (simultaneous blood glucose 145 mg/dl), and 618 mg/dl protein and 640 leucocyte/mm3 (90% PMNL). No bacteria were detected in Gram stained and Ehrlich-Ziehl-Neelsen stained CSF smears. Upon the diagnosis of acute bacterial meningitis, treatment with ceftriaxone and ampicillin was initiated, however, the patient died after 16 hours of hospitalization. CSF culture yielded the growth of gram-negative oxidase-positive bacteria and the isolate was identified as P. stutzeri by Vitek-2 Compact system (bioMerieux, France). The isolate was found to be sensitive to piperacillin/tazobactam, amikacin, gentamycin, ceftazidime, cefepime, ciprofloxacin, imipenem and meropenem. Since the patient was lost due to acute respiratory and cardiac failure, it was not possible to change the therapy to agent specific therapy. In conclusion, it should always be kept in mind that uncommon agents could lead to community-acquired meningitis in elderly patients and empirical treatment protocols might fail in such cases resulting in high morbidity and mortality. PMID:19334394

  16. Association of acquired von Willebrand syndrome with AL amyloidosis.

    PubMed

    Kos, Cynthia A; Ward, Jennifer E; Malek, Karim; Sanchorawala, Vaishali; Wright, Daniel G; O'Hara, Carl; Connors, Lawreen; Skinner, Martha; Seldin, David C

    2007-05-01

    Acquired loss of functional von Willebrand factor (VWF) has been termed the acquired von Willebrand syndrome (AVWS). AVWS is a rare adult-onset bleeding diathesis that is clinically similar to congenital von Willebrand disease (VWD), and occurs with a variety of autoimmune, lymphoproliferative, or myeloproliferative disorders. We have identified four patients with AVWS in association with immunoglobulin light chain (AL) amyloidosis. These patients, lacking any pre-existing or family history of abnormal bleeding, developed cutaneous, mucosal, or gastrointestinal bleeding in the course of their disease without deficiency of clotting factor X or other factors; the activated partial thromboplastin time (aPTT) was prolonged in three out of the four cases. Despite normal VWF antigen levels, VWF ristocetin cofactor activity (VWF:RCo) was low. Electrophoresis patterns of high molecular weight (HMW) VWF multimers were abnormal in two of the four cases. Two of the patients were treated with high-dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) and achieved hematologic remission. In these two patients, the bleeding diathesis improved and the coagulation parameters normalized, confirming a causal relationship between the plasma cell dyscrasia and the AVWS. AVWS should be considered in AL amyloidosis patients with hemorrhagic diatheses and normal clotting factor levels. PMID:17205535

  17. Clinical predictors of functioning in persons with acquired immunodeficiency syndrome.

    PubMed

    Wilson, I B; Cleary, P D

    1996-06-01

    To help clinicians better assess and treat functional disabilities in persons with acquired immunodeficiency syndrome (AIDS), the authors estimate empirical relations among biologic and physiologic variables, symptoms, and physical functioning in persons with AIDS. The sample of 305 persons with AIDS for this cross-sectional analysis came from three sites in Boston, Massachusetts: a hospital-based group practice, a human immunodeficiency virus clinic at a city hospital, and a staff-model health maintenance organization. Physical functioning, 10 AIDS-specific symptoms, and mental health were assessed by interview. Clinical diagnoses, comorbidities, health habits such as smoking, laboratory results, and selected medication use were assessed by chart review. Significant predictors of physical functioning P < 0.01, R2 = .58) in a multivariable regression model included energy/fatigue, neurologic symptoms, fever symptoms, a lower hemoglobin level, and current non-pneumonia bacterial infection. Ninety-six percent of the explained variance in physical functioning was accounted for by three symptom complexes: energy/fatigue, neurologic symptoms, and fever symptoms. Significant predictors of energy/fatigue in multivariable models included poorer mental health, lower white blood cell count, longer time since diagnosis, and weight loss (P < 0.01, R2 =.36). Significant predictors of neurologic symptoms included poorer mental health, weight loss, and no zidovudine use (P < 0.001, R2 = .30). Predictors of fever symptoms included poorer mental health, no zidovudine use, weight loss, and history of asthma or chronic obstructive pulmonary disease (P < 0.05, R2 = .25). In conclusion, symptom reports were strong predictors of physical functioning. Poorer mental health and weight loss were correlated consistently with worse symptoms, and not using zidovudine was correlated with worse neurologic and fever symptoms. These variables, and the others the authors identified, may represent

  18. Acquired Cystic Fibrosis Transmembrane Conductance Regulator Deficiency.

    PubMed

    Cho, Do-Yeon; Woodworth, Bradford A

    2016-01-01

    In the genetic airway disease cystic fibrosis (CF), deficiency or dysfunction of the cystic fibrosis membrane conductance regulator (CFTR) alters anion transport in respiratory epithelium and consequently disrupts mucociliary clearance. An enriched understanding of the role of CFTR in the maintenance of normal epithelial function has revealed that mild and variable CFTR mutations play a causative role in a number of diseases not classically associated with CF. Furthermore, recent evidence indicates that acquired defects in wild-type CFTR protein processing, endocytic recycling and function can contribute to the pathogenesis of airway diseases, such as chronic obstructive pulmonary disease. In this chapter, we discuss emerging findings implicating acquired CFTR dysfunction in the pathogenesis of chronic rhinosinusitis and propose a new and leading edge approach to future CRS therapy using CFTR potentiators. PMID:27466849

  19. Earth Knowledge Acquired by Middle School Students

    NASA Technical Reports Server (NTRS)

    Ride, Sally

    2008-01-01

    Earth Knowledge Acquired by Middle School Students (EarthKAM), an education activity, allows middle school students to program a digital camera on board the International Space Station to photograph a variety of geographical targets for study in the classroom. Photos are made available on the web for viewing and study by participating schools around the world. Educators use the images for projects involving Earth Science, geography, physics, and social science.

  20. Intrinsic and acquired resistance mechanisms in enterococcus

    PubMed Central

    Hollenbeck, Brian L.; Rice, Louis B.

    2012-01-01

    Enterococci have the potential for resistance to virtually all clinically useful antibiotics. Their emergence as important nosocomial pathogens has coincided with increased expression of antimicrobial resistance by members of the genus. The mechanisms underlying antibiotic resistance in enterococci may be intrinsic to the species or acquired through mutation of intrinsic genes or horizontal exchange of genetic material encoding resistance determinants. This paper reviews the antibiotic resistance mechanisms in Enterococcus faecium and Enterococcus faecalis and discusses treatment options. PMID:23076243

  1. [Pharmacogenetics of community-acquired pneumonia].

    PubMed

    Suleĭmanov, S Sh; Molchanova, O V; Kirpichnikova, N V; Sukhotina, N V; Gorbach, A A

    2010-01-01

    The rate of acetylation of xenobiotics affects the course and prognosis of infectious diseases. The efficacy of antibiotic therapy of community-acquired pneumonia in RA-patients is lower than that in LA-ones. In order to ensure the best antimicrobial effect on the onset of the disease it is required to use regimens with the maximum permissible dose of antibacterial drugs in the regions where the rapid type prevails. PMID:21400754

  2. Domestically acquired fascioliasis in northern California.

    PubMed

    Weisenberg, Scott A; Perlada, David E

    2013-09-01

    Two cases of domestically acquired fascioliasis are reported. Patient One was a 63-year-old male who developed a febrile illness 2 months after eating watercress in Marin County. Patient Two was a 38-year-old male who had eaten watercress with Patient One, and also developed a febrile illness. Both patients had eosinophilia and liver lesions on imaging. Diagnosis was made by serology and treatment was with triclabendazole. PMID:23836562

  3. Domestically Acquired Fascioliasis in Northern California

    PubMed Central

    Weisenberg, Scott A.; Perlada, David E.

    2013-01-01

    Two cases of domestically acquired fascioliasis are reported. Patient One was a 63-year-old male who developed a febrile illness 2 months after eating watercress in Marin County. Patient Two was a 38-year-old male who had eaten watercress with Patient One, and also developed a febrile illness. Both patients had eosinophilia and liver lesions on imaging. Diagnosis was made by serology and treatment was with triclabendazole. PMID:23836562

  4. Acquired protein energy malnutrition in glutaric acidemia.

    PubMed

    Ma, Liqiao; Savory, Stephanie; Agim, Nnenna G

    2013-01-01

    We report a case of acquired protein energy malnutrition with associated zinc deficiency in an 18-month-old boy with type 1 glutaric acidemia. Physical examination findings included generalized nonpitting edema, widespread desquamative plaques, and sparse hair with a reddish tinge. Laboratory abnormalities included low levels of zinc, albumin, alkaline phosphatase, and iron. A review of skin manifestations of nutritional deficiencies, specifically kwashiorkor, is presented, as well as the relatively new entity called acrodermatitis dysmetabolica. PMID:23330977

  5. Acquired Antibiotic Resistance Genes: An Overview

    PubMed Central

    van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

  6. System Acquires Data On Reactivities Of Foams

    NASA Technical Reports Server (NTRS)

    Walls, Joe T.

    1994-01-01

    Data-acquisition and -plotting system, called DAPS(TM), developed enabling accurate and objective determination of physical properties related to reactivities of polyurethane and polyisocyanurate foams. Automated, computer-controlled test apparatus that acquires data on rates of rise, rise profiles, exothermic temperatures, and internal pressures of foams prepared from both manual and machine-mixed batches. Data used to determine minute differences between reaction kinetics and exothermic profiles of foam formulations, properties of end products which are statistically undifferentiated.

  7. Acquired resistance to immunotherapy and future challenges.

    PubMed

    Restifo, Nicholas P; Smyth, Mark J; Snyder, Alexandra

    2016-02-01

    Advances in immunotherapy have resulted in remarkable clinical responses in some patients. However, one of the biggest challenges in cancer therapeutics is the development of resistant disease and disease progression on or after therapy. Given that many patients have now received various types of immunotherapy, we asked three scientists to give their views on the current evidence for whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy. PMID:26822578

  8. RHIC BEAM LOSS MONITOR SYSTEM INITIAL OPERATION.

    SciTech Connect

    WITKOVER,R.L.; MICHNOFF,R.J.; GELLER,J.M.

    1999-03-29

    The RHIC Beam Loss Monitor (BLM) System is designed to prevent beam loss quenching of the superconducting magnets, and acquire loss data. Four hundred ion chambers are located around the rings to detect losses. The required 8-decade range in signal current is compressed using an RC pre- integrator ahead of a low current amplifier. A beam abort may be triggered if fast or slow losses exceed programmable threshold levels. A micro-controller based VME module sets references and gains and reads trip status for up to 64 channels. Results obtained with the detectors in the RHIC Sextant Test and the prototype electronics in the AGS-to-RHIC (AtR) transfer line are presented along with the present status of the system.

  9. Ankle Deformity Secondary to Acquired Fibular Segmental Defect in Children

    PubMed Central

    Kang, Soo Hwan; Song, Seok Whan; Chung, Jin Wha; Kim, Yoon Chung; Suhl, Kyung Hwan

    2010-01-01

    Background The authors report the long-term effect of acquired pseudoarthrosis of the fibula on ankle development in children during skeletal growth, and the results of a long-term follow-up of Langenskiold's supramalleolar synostosis to correct an ankle deformity induced by an acquired fibular segmental defect in children. Methods Since 1980, 19 children with acquired pseudoarthrosis of the fibula were treated and followed up for an average of 11 years. Pseudoarthrosis was the result of a fibulectomy for tumor surgery, osteomyelitis of the fibula and traumatic segmental loss of the fibula in 10, 6, and 3 cases, respectively. Initially, a Langenskiold's operation (in 4 cases) and fusion of the lateral malleolus to the distal tibial epiphysis (in 1 case) were performed, whereas only skeletal growth was monitored in the other 14 cases. After a mean follow-up of 11 years, the valgus deformity and external tibial torsion of the ankle joint associated with proximal migration of the lateral malleolus needed to be treated with a supramallolar osteotomy in 12 cases (63%). These ankle deformities were evaluated using the serial radiographs and limb length scintigraphs. Results In all cases, early closure of the lateral part of the distal tibial physis, upward migration of the lateral malleolus, unstable valgus deformity and external tibial torsion of the ankle joint developed during a mean follow-up of 11 years (range, 5 to 21 years). The mean valgus deformity and external tibial torsion of the ankle at the final follow-up were 15.2° (range, 5° to 35°) and 10° (range, 5° to 12°), respectively. In 12 cases (12/19, 63%), a supramalleolar corrective osteotomy was performed but three children had a recurrence requiring an additional supramalleolar corrective osteotomy 2-4 times. Conclusions A valgus deformity and external tibial torsion are inevitable after acquired pseudoarthrosis of the fibula in children. Both Langenskiöld supramalleolar synostosis to prevent these

  10. Hearing Loss in Adults.

    ERIC Educational Resources Information Center

    House, John W.

    1997-01-01

    This article discusses hearing loss in adults. It begins with an explanation of the anatomy of the ear and then explains the three types of hearing loss: conductive hearing loss, sensorineural hearing loss, and mixed conductive-sensorineural hearing loss. Tinnitus, hearing aids, and cochlear implants are also addressed. (CR)

  11. Living with Hearing Loss

    MedlinePlus

    ... Issues Special Section: Focus on Communication Living with Hearing Loss Past Issues / Fall 2008 Table of Contents For ... Fast Facts There are two main types of hearing loss. Permanent hearing loss (called sensorineural) usually involves damage ...

  12. Early Pregnancy Loss

    MedlinePlus

    ... is called early pregnancy loss , miscarriage , or spontaneous abortion . How common is early pregnancy loss? Early pregnancy ... testes that can fertilize a female egg. Spontaneous Abortion: The medical term for early pregnancy loss. Trimester: ...

  13. Living with vision loss

    MedlinePlus

    Diabetes - vision loss; Retinopathy - vision loss; Low vision; Blindness - vision loss ... Low vision is a visual disability. Wearing regular glasses or contacts does not help. People with low vision have ...

  14. Acquired prosopagnosia without word recognition deficits.

    PubMed

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  15. Identification of a syndrome comprising microcephaly and intellectual disability but not white matter disease associated with a homozygous c.676C>T p.R226W DEAF1 mutation.

    PubMed

    Gund, Christian; Powis, Zöe; Alcaraz, Wendy; Desai, Sonal; Baranano, Kristin

    2016-05-01

    We evaluated a 13-year-old East Pakistani male affected with microcephaly, apparent intellectual disability, hypotonia, and brisk reflexes without spasticity. His parents were first cousins. The patient also had a brother who was similarly affected and died at 10 years due to an accident. Previous SNP array testing showed a 1.63 Mb duplication at 16p13.11 of uncertain significance along with regions of homozygosity. Exome sequencing identified a known pathogenic homozygous alteration in DEAF1, c.676C>T (p.R226W), in this patient. The alteration had been reported in two individuals from a consanguineous Saudi Arabian family. Both individuals had microcephaly, intellectual disability, hypotonia, feeding difficulties, and poor growth. The patient reported here did not have evidence of white matter disease, as had been reported with prior patients. We conclude that this DEAF1 gene alteration caused this patient's symptoms and that white matter disease should not be considered a obligate feature of this syndrome. PMID:26834045

  16. Clinicopathological correlation of acquired hypopigmentary disorders.

    PubMed

    Patel, Anisha B; Kubba, Raj; Kubba, Asha

    2013-01-01

    Acquired hypopigmentary disorders comprise a significant group of disorders that affect Indians and Asians. The pigment disturbance in darker skin individuals can be very distressing to the patient and the family. These disorders cover a wide array of pathologies including infections, autoimmune processes, lymphoproliferative disorders, and sclerosing diseases. Histological diagnosis is particularly important because treatments for these diseases are varied and specific. This review will focus on histopathological diagnosis based on clinicopathological correlation for commonly encountered disorders such as leprosy, vitiligo, lichen sclerosus, pityriasis alba (PA), and pityriasis versicolor (PV). Atypical or uncommon clinical presentation of classic diseases such as hypopigmented mycosis fungoides (HMF) and hypopigmented sarcoidosis are also included. PMID:23619442

  17. [Acquired immunodeficiency syndrome in pediatric patients].

    PubMed

    Molina Moguel, J L; Ruiz Illezcas, R; Forsbach Sánchez, S; Carreño Alvarez, S; Picco Díaz, I

    1990-12-01

    The object of this study was to determine how many of the patients treated at the Pediatric Odontology Clinic, a branch of the Maxillo-Facial Surgery Service at the Veinte de Noviembre Regional Hospital, ISSSTE, are VIH-positive of show serious manifestations of Acquired Immuno-Deficiency Syndrome (AIDS). For such purpose, 100 pediatric patients suffering from different systemic or local diseases were evaluated, the most common being hematological alterations. Results evidenced the presence of VIH in the blood of five of the pediatric subjects, all suffering from Hemophilia. PMID:2132469

  18. Acquired scalp alopecia. Part II: A review.

    PubMed

    Sullivan, J R; Kossard, S

    1999-05-01

    The neutrophil-associated and infiltrative scarring alopecias are reviewed including folliculitis decalvans, tufted folliculitis, dissecting cellulitis of the scalp, acne keloidalis and follicular degeneration syndrome. The management of acquired scalp alopecia is also reviewed including newer, promising therapies. More specific agents targeting components of the androgen system will make the treatment of androgenetic alopecia more rewarding. Similarly new immunomodulatory therapies show great promise for the lymphocyte-associated alopecias and include a new generation of macrolide immunosuppressives (tacrolimus, SDZ ASM 981, and SDZ 281-240), some of which appear to have good transcutaneous absorption. PMID:10333615

  19. Origins of species: acquired genomes and individuality

    NASA Technical Reports Server (NTRS)

    Margulis, L.

    1993-01-01

    Entire genomes with their accompanying protein synthetic systems are transferred throughout the biosphere primarily as bacteria and protists which become symbionts as they irreversibly integrate into pre-existing organisms to form more complex individuals. Individualization is stabilized by simultaneous transmission of once-separate heterologous genetic systems. The origin of new species is hypothesized to correlate with the acquisition, integration and subsequent inheritance of such acquired microbial genomes. These processes were recognized by Mereschkovsky ("Symbiogenesis" in Russian, 1909) and by Wallin ("Symbionticism", see p. 181, this issue).

  20. Acquired haemophilia masked by warfarin therapy.

    PubMed

    Vadikolia, C M; Riddell, A; Brooks, S; Yee, T T; Brown, S; Lee, C

    2007-02-01

    Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII. PMID:17224010

  1. Acquired Congenital Malalignment of the Great Toenails

    PubMed Central

    Decker, Ashley; Scher, Richard K.; Avarbock, Andrew

    2016-01-01

    Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years. PMID:27171597

  2. Acquired von Willebrand syndrome: an update.

    PubMed

    Franchini, Massimo; Lippi, Giuseppe

    2007-05-01

    Acquired von Willebrand syndrome (aVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease (VWD). However, unlike congenital VWD, it arises in individuals with no personal or family history of bleeding. aVWS occurs in association with a variety of underlying disorders, most frequently in lymphoproliferative disorders, myeloproliferative disorders, and cardiovascular diseases. Through an analysis of the more recent literature data, the pathophysiology and the clinical, laboratory, and therapeutic aspects of this syndrome are concisely reported in this review. PMID:17133419

  3. Acquired Congenital Malalignment of the Great Toenails.

    PubMed

    Decker, Ashley; Scher, Richard K; Avarbock, Andrew

    2016-02-01

    Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years. PMID:27171597

  4. Asian elephants acquire inaccessible food by blowing.

    PubMed

    Mizuno, Kaori; Irie, Naoko; Hiraiwa-Hasegawa, Mariko; Kutsukake, Nobuyuki

    2016-01-01

    Many animals acquire otherwise inaccessible food with the aid of sticks and occasionally water. As an exception, some reports suggest that elephants manipulate breathing through their trunks to acquire inaccessible food. Here, we report on two female Asian elephants (Elephas maximus) in Kamine Zoo, Japan, who regularly blew to drive food within their reach. We experimentally investigated this behaviour by placing foods in inaccessible places. The elephants blew the food until it came within accessible range. Once the food was within range, the elephants were increasingly less likely to blow as the distance to the food became shorter. One subject manipulated her blowing duration based on food distance: longer when the food was distant. These results suggest that the elephants used their breath to achieve goals: that is, they used it not only to retrieve the food but also to fine-tune the food position for easy grasping. We also observed individual differences in the elephants' aptitude for this technique, which altered the efficiency of food acquisition. Thus, we added a new example of spontaneous behaviour for achieving a goal in animals. The use of breath to drive food is probably unique to elephants, with their dexterous trunks and familiarity with manipulating the act of blowing, which is commonly employed for self-comfort and acoustic communication. PMID:26541597

  5. Tetracycline resistance genes acquired at birth.

    PubMed

    Alicea-Serrano, Angela M; Contreras, Mónica; Magris, Magda; Hidalgo, Glida; Dominguez-Bello, Maria G

    2013-06-01

    Newborns acquire their first microbiota at birth. Maternal vaginal or skin bacteria colonize newborns delivered vaginally or by C-section, respectively (Dominguez-Bello et al. 2010 #884). We aimed to determine differences in the presence of four tetracycline (tet) resistance genes, in the microbes of ten newborns and in the mouth and vagina of their mothers, at the time of birth. DNA was amplified by PCR with primers specific for [tet(M), tet(O), tet(Q), and tet(W)]. Maternal vaginas harbored all four tet resistance genes, but most commonly tet(M) and tet(O) (63 and 38 %, respectively). Genes coding for tet resistance differed by birth mode, with 50 % of vaginally delivered babies had tet(M) and tet(O) and 16 and 13 % of infants born by C-section had tet(O) and tet(W), respectively. Newborns acquire antibiotic resistance genes at birth, and the resistance gene profile varies by mode of delivery. PMID:23483141

  6. Surgery-associated acquired hemophilia A.

    PubMed

    Theodossiades, G; Tsevrenis, V; Nomikou, E; Dadiotis, L; Kontopoulou-Griva, I

    2001-11-01

    We present two patients who acquired factor VIII antibodies in the immediate postoperative period. One patient was receiving warfarin that was temporarily discontinued but reintroduced after the procedure. Preoperatively, none gave a history of bleeding, even with past surgeries, and both had normal coagulation tests. Within days of surgery, hemorrhage with prolonged activated partial thromboplastin time, low factor VIII levels, and demonstrable factor VIII antibodies were observed. For the patient who was receiving warfarin the severe bleeding was attributed, at the beginning, only to the high international normalized ratio (INR), which resulted in a fatal delay in diagnosis and appropriate treatment. We would like to raise awareness of surgery as a precipitating cause of acquired hemophilia, which is something to be considered with unusual postoperative bleeding. This syndrome is remarkable for its abrupt onset within days of surgery, severe bleeding but potential successful outcome with combined hemostatic control with recombinant activated FVII (rFVIIa) and elimination of the antibody by immunosuppression. PMID:11757731

  7. Therapeutic approaches to acquired von Willebrand syndrome.

    PubMed

    Federici, A B

    2000-02-01

    Acquired von Willebrand syndrome (AVWS) is a rare acquired bleeding disorder similar to the congenital von Willebrand disease (VWD) in terms of laboratory findings. Diagnosis of AVWS can be very difficult, with treatment normally taking an empirical form. Although more than 200 cases have been reported since 1968, no retrospective or prospective studies are available on AVWS. Recently, an International Registry on AVWS, gathering data directly from worldwide Departments of Haematology-Oncology and Haemophilia Centres, has been organised by a group working on behalf of the Subcommittee on VWF in the Scientific Standardisation Committee (SSC) of International Society on Thrombosis and Haemostasis (ISTH). Information about an additional 211 AVWS patients is now available, with more detailed data on demography, type of haemorrhage, diagnostic tests for AVWS and management of bleeding episodes. The additional 211 AVWS cases are associated with lymphoproliferative (47%) or myeloproliferative (19%) disorders, cardiovascular diseases, neoplasia (7%) and other miscellaneous diseases (14%). Bleeding episodes of AVWS patients were managed by different compounds including desmopressin (22%), FVIII/VWF concentrates (26%) and high-dose immunoglobulin (10%), plasmapheresis (2%), steroids (5%) and immunosuppressive drugs (20%). Based on complied data, we can conclude that none of the therapeutic approaches proposed are 100% effective in all AVWS cases. Therefore, treatment must be customized for each patient according to the underlying disorder, as well as to the type and the severity of bleeding episode and must be targeted to each specific case. PMID:11060681

  8. Toward immunogenetic studies of amphibian chytridiomycosis: Linking innate and acquired immunity

    USGS Publications Warehouse

    Richmond, J.Q.; Savage, Anna E.; Zamudio, Kelly R.; Rosenblum, E.B.

    2009-01-01

    Recent declines in amphibian diversity and abundance have contributed significantly to the global loss of biodiversity. The fungal disease chytridiomycosis is widely considered to be a primary cause of these declines, yet the critical question of why amphibian species differ in susceptibility remains unanswered. Considerable evidence links environmental conditions and interspecific variability of the innate immune system to differential infection responses, but other sources of individual, population, or species-typical variation may also be important. In this article we review the preliminary evidence supporting a role for acquired immune defenses against chytridiomycosis, and advocate for targeted investigation of genes controlling acquired responses, as well as those that functionally bridge the innate and acquired immune systems. Immunogenetic data promise to answer key questions about chytridiomycosis susceptibility and host-pathogen coevolution, and will draw much needed attention to the importance of considering evolutionary processes in amphibian conservation management and practice. ?? 2009 by American Institute of Biological Sciences.

  9. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition.

    PubMed

    Rathert, Philipp; Roth, Mareike; Neumann, Tobias; Muerdter, Felix; Roe, Jae-Seok; Muhar, Matthias; Deswal, Sumit; Cerny-Reiterer, Sabine; Peter, Barbara; Jude, Julian; Hoffmann, Thomas; Boryń, Łukasz M; Axelsson, Elin; Schweifer, Norbert; Tontsch-Grunt, Ulrike; Dow, Lukas E; Gianni, Davide; Pearson, Mark; Valent, Peter; Stark, Alexander; Kraut, Norbert; Vakoc, Christopher R; Zuber, Johannes

    2015-09-24

    Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukaemia (AML), bromodomain and extra terminal protein (BET) inhibitors are being explored as a promising therapeutic avenue in numerous cancers. While clinical trials have reported single-agent activity in advanced haematological malignancies, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukaemia, here we perform a chromatin-focused RNAi screen in a sensitive MLL-AF9;Nras(G12D)-driven AML mouse model, and investigate dynamic transcriptional profiles in sensitive and resistant mouse and human leukaemias. Our screen shows that suppression of the PRC2 complex, contrary to effects in other contexts, promotes BET inhibitor resistance in AML. PRC2 suppression does not directly affect the regulation of Brd4-dependent transcripts, but facilitates the remodelling of regulatory pathways that restore the transcription of key targets such as Myc. Similarly, while BET inhibition triggers acute MYC repression in human leukaemias regardless of their sensitivity, resistant leukaemias are uniformly characterized by their ability to rapidly restore MYC transcription. This process involves the activation and recruitment of WNT signalling components, which compensate for the loss of BRD4 and drive resistance in various cancer models. Dynamic chromatin immunoprecipitation sequencing and self-transcribing active regulatory region sequencing of enhancer profiles reveal that BET-resistant states are characterized by remodelled regulatory landscapes, involving the activation of a focal MYC enhancer that recruits WNT machinery in response to BET inhibition. Together, our results identify and validate WNT signalling as a driver and candidate biomarker of primary and acquired BET resistance in leukaemia, and implicate the rewiring of transcriptional programs as an important mechanism promoting

  10. Transcriptional plasticity promotes primary and acquired resistance to BET inhibition

    PubMed Central

    Neumann, Tobias; Muerdter, Felix; Roe, Jae-Seok; Muhar, Matthias; Deswal, Sumit; Cerny-Reiterer, Sabine; Peter, Barbara; Jude, Julian; Hoffmann, Thomas; Boryń, Łukasz M.; Axelsson, Elin; Schweifer, Norbert; Tontsch-Grunt, Ulrike; Dow, Lukas E.; Gianni, Davide; Pearson, Mark; Valent, Peter; Stark, Alexander; Kraut, Norbert; Vakoc, Christopher R.; Zuber, Johannes

    2016-01-01

    Summary Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukemia (AML)1,2, BET inhibitors are being explored as promising therapeutic avenue in numerous cancers3–5. While clinical trials have reported single-agent activity in advanced hematologic malignancies6, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukemia, we performed a chromatin-focused RNAi screen in a sensitive MLL/AF9; NrasG12D -driven AML model, and investigated dynamic transcriptional profiles in sensitive and resistant murine and human leukemias. Our screen reveals that suppression of the PRC2 complex, contrary to effects in other contexts, promotes BET inhibitor resistance in AML. PRC2 suppression does not directly affect the regulation of Brd4-dependent transcripts, but facilitates the remodeling of regulatory pathways that restore the transcription of key targets such as Myc. Similarly, while BET inhibition triggers acute MYC repression in human leukemias regardless of their sensitivity, resistant leukemias are uniformly characterized by their ability to rapidly restore MYC transcription. This process involves the activation and recruitment of WNT signaling components, which compensate for the loss of BRD4 and drive resistance in various cancer models. Dynamic ChIP- and STARR-seq enhancer profiles reveal that BET-resistant states are characterized by remodeled regulatory landscapes, involving the activation of a focal MYC enhancer that recruits WNT machinery in response to BET inhibition. Together, our results identify and validate WNT signaling as a driver and candidate biomarker of primary and acquired BET resistance in leukemia, and implicate the rewiring of transcriptional programs as an important mechanism promoting resistance to BET inhibitors and, potentially, other chromatin-targeted therapies. PMID:26367798

  11. Intravenous zinc therapy for acquired zinc deficiency secondary to gastric bypass surgery: a case report.

    PubMed

    Vick, Garrett; Mahmoudizad, Rod; Fiala, Katherine

    2015-01-01

    Zinc deficiency may result from either a congenitally inherited defect of zinc absorption or is acquired secondarily from a variety of factors affecting dietary zinc intake, absorption, or loss. We report a case of acquired zinc deficiency secondary to gastric bypass surgery that resulted in vulvar cutaneous manifestations of delayed onset, with failure to clear after oral supplementation with zinc. The patient experienced improvement of symptoms only after administration of intravenous zinc supplementation. Upon review of the current literature, it is thought that the patient's original suboptimal response to oral supplementation and improvement after receiving intravenous zinc were related to the intentional surgical alteration and bypass of the absorptive capacity of the duodenum and jejunum. With the current prevalence of obesity and availability of surgical weight loss therapies, it is important to be mindful of the resulting nutritional deficiencies, their clinical manifestations, and factors affecting the efficacy of therapeutic approaches as seen in this case. PMID:25754007

  12. Treatment of the acquired von Willebrand syndrome.

    PubMed

    Budde, Ulrich; Scheppenheim, Sonja; Dittmer, Rita

    2015-12-01

    Acquired von Willebrand syndrome (aVWS) accounts for 22% of patients with abnormal von Willebrand factor. Most patients with known pathophysiological mechanisms suffer from cardiovascular, myeloproliferative and lymphoproliferative disorders. Less frequent associations are of autoimmune origin, due to hyperfibrinolysis, adsorption to tumor cells, reduced synthesis and prolonged circulation. The mechanisms leading to aVWS is hitherto not known in patients with liver and kidney diseases, drug use, glycogen storage disease, virus infections and at least 18 other disease entities. Diagnosis is complicated by the battery of tests needed, and their inherent rather low sensitivity and specificity for aVWS. Thus, even in acute bleeding situations it may take days until a firm diagnosis is settled and specific therapies can be initiated. The main aim is to shed more light onto this, compared with inherited von Willebrand disease, rare disease which affects at least 2-3% of the older population. PMID:26577336

  13. Processed pseudogenes acquired somatically during cancer development.

    PubMed

    Cooke, Susanna L; Shlien, Adam; Marshall, John; Pipinikas, Christodoulos P; Martincorena, Inigo; Tubio, Jose M C; Li, Yilong; Menzies, Andrew; Mudie, Laura; Ramakrishna, Manasa; Yates, Lucy; Davies, Helen; Bolli, Niccolo; Bignell, Graham R; Tarpey, Patrick S; Behjati, Sam; Nik-Zainal, Serena; Papaemmanuil, Elli; Teixeira, Vitor H; Raine, Keiran; O'Meara, Sarah; Dodoran, Maryam S; Teague, Jon W; Butler, Adam P; Iacobuzio-Donahue, Christine; Santarius, Thomas; Grundy, Richard G; Malkin, David; Greaves, Mel; Munshi, Nikhil; Flanagan, Adrienne M; Bowtell, David; Martin, Sancha; Larsimont, Denis; Reis-Filho, Jorge S; Boussioutas, Alex; Taylor, Jack A; Hayes, Neil D; Janes, Sam M; Futreal, P Andrew; Stratton, Michael R; McDermott, Ultan; Campbell, Peter J

    2014-01-01

    Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context. PMID:24714652

  14. ACECARD. Acquire CoOmmodities Easily Card

    SciTech Connect

    Soler, E.E.

    1996-09-01

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for help with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.

  15. Acquire CoOmmodities Easily Card

    1998-05-29

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for helpmore » with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.« less

  16. Acquired Localized Hypertrichosis Induced by Rivastigmine

    PubMed Central

    Imbernón-Moya, Adrian; Podlipnik, Sebastian; Burgos, Fernando; Vargas-Laguna, Elena; Aguilar-Martínez, Antonio; Fernández-Cogolludo, Eva; Gallego-Valdes, Miguel Angel

    2016-01-01

    Hypertrichosis is the excessive hair growth in any area of the skin surface. Acquired localized hypertrichosis may be secondary to multiple causes and there is a secondary form due to several drugs, which is usually reversible with discontinuation of the causative agent. Rivastigmine is a reversible and competitive inhibitor of acetylcholinesterase and butyrylcholinesterase used for symptomatic treatment of Alzheimer dementia and Parkinson's disease. It has an adequate safety profile and cutaneous side effects are unusual. Irritant contact dermatitis, allergic dermatitis, baboon syndrome, and cutaneous rash due to rivastigmine have been reported. We report on a Caucasian 80-year-old male with personal history of Alzheimer's disease. The patient started therapy with oral rivastigmine one month prior to clinical presentation of localized hypertrichosis on both forearms. Norgalanthamine has been shown to promote hair growth activity via the proliferation of dermal papilla. Acetylcholinesterase inhibitors can induce hair growth. PMID:27073702

  17. How to divest acquired physician practices.

    PubMed

    O'Hare, P K

    1999-02-01

    When an integrated delivery system (IDS) determines it must divest itself of a previously acquired physician practice, it must manage the transaction with care. The IDS most likely will want to maintain a positive ongoing relationship with the physician practice, while avoiding concessions to the practice that could be construed as violations of state and Federal laws. Before proceeding, the IDS should evaluate the reasons for divesting the practice, assess legal issues involved in terminating contracts with the practice, decide how to deal with the practice's assets and office facilities, consider whether covenants not to compete should be enforced, ensure continued access to essential medical records, consider whether to incorporate a "non-disparagement" clause in the termination agreement, and determine what mutual general releases may be necessary. PMID:10345614

  18. The acquired immunodeficiency syndrome in gay men.

    PubMed

    Jaffe, H W; Hardy, A M; Morgan, W M; Darrow, W W

    1985-11-01

    The acquired immunodeficiency syndrome (AIDS) is a major health problem for gay men in the United States. About three fourths of all reported cases have occurred in this population, and the number is projected to double in the next year. In Manhattan and San Francisco, AIDS is now the leading cause of premature mortality in men aged 25 to 44 years who have never married. In a sample of a cohort of gay men enrolled in a San Francisco clinic, 2.7% of the men had the syndrome and 26% had related conditions in 1984. Antibody to human T-lymphotropic virus, type III/lymphadenopathy-associated virus was found in sera from 67% of the men, including 58% of asymptomatic men. Behavioral factors associated with an increased risk of AIDS include large numbers of sexual partners, receptive anal intercourse, and "fisting." The adoption of safer lifestyles is currently the basis of attempts to control the syndrome in gay men. PMID:2996396

  19. [Merits of acquiring ISO15189 accreditation].

    PubMed

    Kitagawa, Masami

    2010-01-01

    In Japan, an ISO15189 accreditation system was started in 2005. To date, 47 hospitals have been accredited. In this session, I will present the merits of acquiring accreditation regarding ISO15189 based on our experience. Our hospital has 263 beds. The Clinical Examination Section consists of 12 staff (including 5 part-time workers): 7 in change of sample examination and 5 in charge of physiological examination. The annual number of samples is approximately 150,000. Samples collected on health checkups account for 90%. To improve the quality and service, assessment by third persons has been positively utilized in our hospital. Accreditation regarding ISO9001, ISO14001, ISO27001, privacy mark, hospital function assessment, the functional assessment of "ningen-dock"/health checkup hospitals, labor/hygiene service function assessment, and ISO15189 has been acquired. Patients may not recognize ISO. So, it must be utilized, considering that the acquisition of accreditation is not a goal but a starting point. Furthermore, cost-performance should be improved to achieve utilization-related merits. It is important to not only acquire accreditation but also help clinical staff and patients become aware of some changes/merits. Patients may consult a hospital for the following reasons: confidence in the hospital, and the staffs kind/polite attitudes. Long-term management strategies should be established without pursuing only short-term profits. I will introduce several merits of acquiring accreditation regarding ISO15189. Initially, incidental conditions for bids and appeal points include accreditation regarding ISO15189. Our corporation has participated in some competitive bids regarding health checkup business. In some companies, the bid conditions included ISO acquisition. In our hospital, clinical trials have been positively carried out. For participation in trials, hospitals must pass an institutional examination. However, ISO acquisition facilitates the preparation of

  20. Acquired immunodeficiency syndrome: Ga-67 citrate imaging

    SciTech Connect

    Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

    1987-02-01

    All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

  1. Acquiring ownership and the attribution of responsibility.

    PubMed

    Palamar, Max; Le, Doan T; Friedman, Ori

    2012-08-01

    How is ownership established over non-owned things? We suggest that people may view ownership as a kind of credit given to agents responsible for making possession of a non-owned object possible. On this view, judgments about the establishment of ownership depend on attributions of responsibility. We report three experiments showing that people's judgments about the establishment of ownership are influenced by an agent's intent and control in bringing about an outcome, factors that also affect attributions of responsibility. These findings demonstrate that people do not just consider who was first to possess an object in judging who owns it, and are broadly consistent with the view that ownership is acquired through labor. The findings also suggest that rather than exclusively being the product of social conventions, judgments about the establishment of ownership over non-owned things also depend on the psychological processes underlying the attribution of responsibility. PMID:22591710

  2. Covalent targeting of acquired cysteines in cancer.

    PubMed

    Visscher, Marieke; Arkin, Michelle R; Dansen, Tobias B

    2016-02-01

    The thiolate side chain of cysteine has a unique functionality that drug hunters and chemical biologists have begun to exploit. For example, targeting cysteine residues in the ATP-binding pockets of kinases with thiol-reactive molecules has afforded increased selectivity and potency to drugs like imbrutinib, which inhibits the oncogene BTK, and CO-1686 and AZD9291 that target oncogenic mutant EGFR. Recently, disulfide libraries and targeted GDP-mimetics have been used to selectively label the G12C oncogenic mutation in KRAS. We reasoned that other oncogenes contain mutations to cysteine, and thus screened the Catalog of Somatic Mutations in Cancer for frequently acquired cysteines. Here, we describe the most common mutations and discuss how these mutations could be potential targets for cysteine-directed personalized therapeutics. PMID:26629855

  3. Processed pseudogenes acquired somatically during cancer development

    PubMed Central

    Cooke, Susanna L.; Shlien, Adam; Marshall, John; Pipinikas, Christodoulos P.; Martincorena, Inigo; Tubio, Jose M.C.; Li, Yilong; Menzies, Andrew; Mudie, Laura; Ramakrishna, Manasa; Yates, Lucy; Davies, Helen; Bolli, Niccolo; Bignell, Graham R.; Tarpey, Patrick S.; Behjati, Sam; Nik-Zainal, Serena; Papaemmanuil, Elli; Teixeira, Vitor H.; Raine, Keiran; O’Meara, Sarah; Dodoran, Maryam S.; Teague, Jon W.; Butler, Adam P.; Iacobuzio-Donahue, Christine; Santarius, Thomas; Grundy, Richard G.; Malkin, David; Greaves, Mel; Munshi, Nikhil; Flanagan, Adrienne M.; Bowtell, David; Martin, Sancha; Larsimont, Denis; Reis-Filho, Jorge S.; Boussioutas, Alex; Taylor, Jack A.; Hayes, Neil D.; Janes, Sam M.; Futreal, P. Andrew; Stratton, Michael R.; McDermott, Ultan; Campbell, Peter J.; Provenzano, Elena; van de Vijver, Marc; Richardson, Andrea L.; Purdie, Colin; Pinder, Sarah; Mac Grogan, Gaetan; Vincent-Salomon, Anne; Larsimont, Denis; Grabau, Dorthe; Sauer, Torill; Garred, Øystein; Ehinger, Anna; Van den Eynden, Gert G.; van Deurzen, C.H.M; Salgado, Roberto; Brock, Jane E.; Lakhani, Sunil R.; Giri, Dilip D.; Arnould, Laurent; Jacquemier, Jocelyne; Treilleux, Isabelle; Caldas, Carlos; Chin, Suet-Feung; Fatima, Aquila; Thompson, Alastair M.; Stenhouse, Alasdair; Foekens, John; Martens, John; Sieuwerts, Anieta; Brinkman, Arjen; Stunnenberg, Henk; Span, Paul N.; Sweep, Fred; Desmedt, Christine; Sotiriou, Christos; Thomas, Gilles; Broeks, Annegein; Langerod, Anita; Aparicio, Samuel; Simpson, Peter T.; van ’t Veer, Laura; Erla Eyfjörd, Jórunn; Hilmarsdottir, Holmfridur; Jonasson, Jon G.; Børresen-Dale, Anne-Lise; Lee, Ming Ta Michael; Wong, Bernice Huimin; Tan, Benita Kiat Tee; Hooijer, Gerrit K.J.

    2014-01-01

    Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5′ truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context. PMID:24714652

  4. Acquire CoOmmodities Easily Card

    SciTech Connect

    Soler, E. E.

    1998-05-29

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for help with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.

  5. Acquired methaemoglobinaemia related to phenazopyridine ingestion.

    PubMed

    Shahani, Lokesh; Sattovia, Stacy

    2012-01-01

    Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of haeme are oxidised to the ferric state. This results in increased affinity to the bound oxygen and decreasing its availability to tissues. Most cases of methaemoglobinaemia are acquired, resulting from an increased methaemoglobin formation by various exogenous agents. The authors report an elderly patient presenting to the emergency department with a 1-month history of shortness of breath. Around the same time she had started using over-the-counter (OTC) phenazopyridine tablets for urinary symptoms. The patient was hypoxic and cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The presence of abnormal haemoglobin was suspected and confirmed by elevated levels of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the methaemoglobinaemia, which the patient was not aware of. This case highlights the importance of always inquiring the OTC drug use especially in geriatric population. PMID:22987905

  6. Acquired methaemoglobinaemia related to phenazopyridine ingestion

    PubMed Central

    Shahani, Lokesh; Sattovia, Stacy

    2012-01-01

    Methaemoglobin is an altered state of haemoglobin in which the ferrous ions of haeme are oxidised to the ferric state. This results in increased affinity to the bound oxygen and decreasing its availability to tissues. Most cases of methaemoglobinaemia are acquired, resulting from an increased methaemoglobin formation by various exogenous agents. The authors report an elderly patient presenting to the emergency department with a 1-month history of shortness of breath. Around the same time she had started using over-the-counter (OTC) phenazopyridine tablets for urinary symptoms. The patient was hypoxic and cyanotic; however, lacked evidence of hypoxaemia on the arterial blood gas. The presence of abnormal haemoglobin was suspected and confirmed by elevated levels of methaemoglobin. Phenazopyridine was proposed to be the likely aetiology of the methaemoglobinaemia, which the patient was not aware of. This case highlights the importance of always inquiring the OTC drug use especially in geriatric population. PMID:22987905

  7. Signal regulators of systemic acquired resistance

    PubMed Central

    Gao, Qing-Ming; Zhu, Shifeng; Kachroo, Pradeep; Kachroo, Aardra

    2015-01-01

    Salicylic acid (SA) is an important phytohormone that plays a vital role in a number of physiological responses, including plant defense. The last two decades have witnessed a number of breakthroughs related to biosynthesis, transport, perception and signaling mediated by SA. These findings demonstrate that SA plays a crictical role in both local and systemic defense responses. Systemic acquired resistance (SAR) is one such SA-dependent response. SAR is a long distance signaling mechanism that provides broad spectrum and long-lasting resistance to secondary infections throughout the plant. This unique feature makes SAR a highly desirable trait in crop production. This review summarizes the recent advances in the role of SA in SAR and discusses its relationship to other SAR inducers. PMID:25918514

  8. Acquiring case adaptation knowledge: A hybrid approach

    SciTech Connect

    Leake, D.B.; Kinley, A.; Wilson, D.

    1996-12-31

    The ability of case-based reasoning (CBR) systems to apply cases to novel situations depends on their case adaptation knowledge. However, endowing CBR systems with adequate adaptation knowledge has proven to be a very difficult task. This paper describes a hybrid method for performing case adaptation, using a combination of rule-based and case-based reasoning. It shows how this approach provides a framework for acquiring flexible adaptation knowledge from experiences with autonomous adaptation and suggests its potential as a basis for acquisition of adaptation knowledge from interactive user guidance. It also presents initial experimental results examining the benefits of the approach and comparing the relative contributions of case learning and adaptation learning to reasoning performance.

  9. Identification of acquired antimicrobial resistance genes

    PubMed Central

    Zankari, Ea; Hasman, Henrik; Cosentino, Salvatore; Vestergaard, Martin; Rasmussen, Simon; Lund, Ole; Aarestrup, Frank M.; Larsen, Mette Voldby

    2012-01-01

    Objectives Identification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic laboratories and is anticipated to substitute traditional methods for resistance gene identification. Thus, the current challenge is to extract the relevant information from the large amount of generated data. Methods We developed a web-based method, ResFinder that uses BLAST for identification of acquired antimicrobial resistance genes in whole-genome data. As input, the method can use both pre-assembled, complete or partial genomes, and short sequence reads from four different sequencing platforms. The method was evaluated on 1862 GenBank files containing 1411 different resistance genes, as well as on 23 de-novo-sequenced isolates. Results When testing the 1862 GenBank files, the method identified the resistance genes with an ID = 100% (100% identity) to the genes in ResFinder. Agreement between in silico predictions and phenotypic testing was found when the method was further tested on 23 isolates of five different bacterial species, with available phenotypes. Furthermore, ResFinder was evaluated on WGS chromosomes and plasmids of 30 isolates. Seven of these isolates were annotated to have antimicrobial resistance, and in all cases, annotations were compatible with the ResFinder results. Conclusions A web server providing a convenient way of identifying acquired antimicrobial resistance genes in completely sequenced isolates was created. ResFinder can be accessed at www.genomicepidemiology.org. ResFinder will continuously be updated as new resistance genes are identified. PMID:22782487

  10. Guidelines for prevention of hospital acquired infections

    PubMed Central

    Mehta, Yatin; Gupta, Abhinav; Todi, Subhash; Myatra, SN; Samaddar, D. P.; Patil, Vijaya; Bhattacharya, Pradip Kumar; Ramasubban, Suresh

    2014-01-01

    These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. PMID:24701065

  11. Infantile and acquired nystagmus in childhood.

    PubMed

    Ehrt, Oliver

    2012-11-01

    Nystagmus is an involuntary, periodic eye movement caused by a slow drift of fixation which is followed by a fast refixation saccade (jerk nystagmus) or a slow movement back to fixation (pendular nystagmus). In childhood most cases are benign forms of nystagmus: idiopathic infantile, ocular or latent nystagmus. They arise at the age of 3 months, without oscillopsia and show the absence of the physiologic opto-kinetic nystagmus. A full ophthalmologic evaluation is all that is needed in most cases: albinism, macular or optic nerve hypoplasia and congenital retinal dystrophies are the most common forms of ocular nystagmus. Idiopathic infantile nystagmus can be hereditary, the most common and best analyzed form being a mutation of the FRMD7 gene on chromosome Xq26.2. The mutation shows a mild genotype-phenotype correlation. In all female carriers the opto-kinetic nystagmus is absent and half had mild nystagmus. Latent nystagmus is part of the infantile esotropia syndrome and shows the unique feature of change of direction when the fixing eye changes: it is always beating to the side of the fixing eye. There is no cure for infantile nystagmus but therapeutic options include magnifying visual aids or eye muscle surgery at the age of 6-8 y in patients with head turn. Less than 20% of childhood nystagmus are acquired and need further neurological and imaging work-up. Alarming signs and symptoms are: onset after the age of 4 months, oscillopsia, dissociated (asymmetric) nystagmus, preserved opto-kinetic nystagmus, afferent pupillary defect, papilloedema and neurological symptoms like vertigo and nausea. The most common cause is due to pathology of the anterior optic pathway (e.g. optic nerve gliomas). It shows the same clinical feature of dissociated nystagmus as spasmus nutans but has a higher frequency as in INO. Other forms of acquired nystagmus are due to brainstem, cerebellar or metabolic diseases. PMID:22459007

  12. TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction

    PubMed Central

    Si, Yu; Chen, Yu Bin; Chen, Sui Jun; Zheng, Yi Qing; Liu, Xiang; Liu, Yi; Jiang, Huai Li; Xu, Guo; Li, Zhuo Hao; Huang, Qiu Hong; Xiong, Hao; Zhang, Zhi Gang

    2015-01-01

    Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1β. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction, and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1β expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis. PMID:26639190

  13. Hair loss in women.

    PubMed

    Harfmann, Katya L; Bechtel, Mark A

    2015-03-01

    Hair loss is a common cause of morbidity for many women. As a key member of the woman's health care team, the obstetrician/gynecologist may be the first person to evaluate the complaint of hair loss. Common types of nonscarring hair loss, including female pattern hair loss and telogen effluvium, may be diagnosed and managed by the obstetrician/gynecologist. A systematic approach to diagnosis and management of these common forms of hair loss is presented. PMID:25517757

  14. When words fail us: insights into language processing from developmental and acquired disorders.

    PubMed

    Bishop, Dorothy V M; Nation, Kate; Patterson, Karalyn

    2014-01-01

    Acquired disorders of language represent loss of previously acquired skills, usually with relatively specific impairments. In children with developmental disorders of language, we may also see selective impairment in some skills; but in this case, the acquisition of language or literacy is affected from the outset. Because systems for processing spoken and written language change as they develop, we should beware of drawing too close a parallel between developmental and acquired disorders. Nevertheless, comparisons between the two may yield new insights. A key feature of connectionist models simulating acquired disorders is the interaction of components of language processing with each other and with other cognitive domains. This kind of model might help make sense of patterns of comorbidity in developmental disorders. Meanwhile, the study of developmental disorders emphasizes learning and change in underlying representations, allowing us to study how heterogeneity in cognitive profile may relate not just to neurobiology but also to experience. Children with persistent language difficulties pose challenges both to our efforts at intervention and to theories of learning of written and spoken language. Future attention to learning in individuals with developmental and acquired disorders could be of both theoretical and applied value. PMID:24324244

  15. When words fail us: insights into language processing from developmental and acquired disorders

    PubMed Central

    Bishop, Dorothy V. M.; Nation, Kate; Patterson, Karalyn

    2014-01-01

    Acquired disorders of language represent loss of previously acquired skills, usually with relatively specific impairments. In children with developmental disorders of language, we may also see selective impairment in some skills; but in this case, the acquisition of language or literacy is affected from the outset. Because systems for processing spoken and written language change as they develop, we should beware of drawing too close a parallel between developmental and acquired disorders. Nevertheless, comparisons between the two may yield new insights. A key feature of connectionist models simulating acquired disorders is the interaction of components of language processing with each other and with other cognitive domains. This kind of model might help make sense of patterns of comorbidity in developmental disorders. Meanwhile, the study of developmental disorders emphasizes learning and change in underlying representations, allowing us to study how heterogeneity in cognitive profile may relate not just to neurobiology but also to experience. Children with persistent language difficulties pose challenges both to our efforts at intervention and to theories of learning of written and spoken language. Future attention to learning in individuals with developmental and acquired disorders could be of both theoretical and applied value. PMID:24324244

  16. Precision Grip in Congenital and Acquired Hemiparesis: Similarities in Impairments and Implications for Neurorehabilitation

    PubMed Central

    Bleyenheuft, Yannick; Gordon, Andrew M.

    2014-01-01

    Background: Patients with congenital and acquired hemiparesis incur long-term functional deficits, among which the loss of prehension that may impact their functional independence. Identifying, understanding, and comparing the underlying mechanisms of prehension impairments represent an opportunity to better adapt neurorehabilitation. Objective: The present review aims to provide a better understanding of precision grip deficits in congenital and acquired hemiparesis and to determine whether the severity and type of fine motor control impairments depend on whether or not the lesions are congenital or acquired in adulthood. Methods: Using combinations of the following key words: fingertip force, grip force, precision grip, cerebral palsy, stroke, PubMed, and Scopus databases were used to search studies from 1984 to 2013. Results: Individuals with both congenital and acquired hemiparesis were able to some extent to use anticipatory motor control in precision grip tasks, even if this control was impaired in the paretic hand. In both congenital and acquired hemiparesis, the ability to plan efficient anticipatory motor control when the less-affected hand is used provides a possibility to remediate impairments in anticipatory motor control of the paretic hand. Conclusion: Surprisingly, we observed very few differences between the results of studies in children with congenital hemiplegia and stroke patients. We suggest that the underlying specific strategies of neurorehabilitation developed for each one could benefit the other. PMID:25071502

  17. An implementation on the social cost of hospital acquired infections.

    PubMed

    Kurutkan, Mehmet Nurullah; Kara, Oğuz; Eraslan, İsmail Hakki

    2015-01-01

    Hospital Acquired Infections (HAIs) are defined as infections developing in relation to health services at inpatient treatment facilities in general. Although health services improve, HAIs continue to be seen both in underdeveloped and developed countries. HAIs result in a range of negative externalities. Negative externalities include factors such as an increase in morbidity and mortality, extension of the hospitalization duration, impaired quality of life, loss of working power and performance. HAIs pose a big burden regarding population and community health care. This study aims to calculate the financial burden of HAIs by evaluating it within the scope of negative externality. The communal costs of HAIs patients were calculated by using a genuine approach with reference to samples obtained from the Duzce University Research and Application Hospital. This approach includes 4 stages and the results of each stage is sorted according to the data of 2013 as follows: (i) HAIs expenditure undertaken by the Social Security Institution is 5,832,167 TL, (ii) the monetary value of the work power loss of the HAIs patients who are at a working age is 126,154 TL, (iii) the relative cost of HAIs patients compared to a group of normal patients is 21,507 TL and (iv) HAIs patients' communal cost is 6,013,101 TL. Based on the received results, the annual communal cost of the estimated HAIs patients in Turkey is predicted to be 3,640,442,057 TL. In addition to these findings, HAIs patients experience 14 times longer in-patient stay at the hospitals as compared to normal patients, and their treatment expenditures are 23 times higher than the normal patients. In the conclusion part of the study, regarding the preventability (internalization) of HAIs, which was evaluated as part of negative externality, alternative applicable political suggestions are presented for the use of policymakers. PMID:26064367

  18. An implementation on the social cost of hospital acquired infections

    PubMed Central

    Kurutkan, Mehmet Nurullah; Kara, Oğuz; Eraslan, İsmail Hakki

    2015-01-01

    Hospital Acquired Infections (HAIs) are defined as infections developing in relation to health services at inpatient treatment facilities in general. Although health services improve, HAIs continue to be seen both in underdeveloped and developed countries. HAIs result in a range of negative externalities. Negative externalities include factors such as an increase in morbidity and mortality, extension of the hospitalization duration, impaired quality of life, loss of working power and performance. HAIs pose a big burden regarding population and community health care. This study aims to calculate the financial burden of HAIs by evaluating it within the scope of negative externality. The communal costs of HAIs patients were calculated by using a genuine approach with reference to samples obtained from the Duzce University Research and Application Hospital. This approach includes 4 stages and the results of each stage is sorted according to the data of 2013 as follows: (i) HAIs expenditure undertaken by the Social Security Institution is 5,832,167 TL, (ii) the monetary value of the work power loss of the HAIs patients who are at a working age is 126,154 TL, (iii) the relative cost of HAIs patients compared to a group of normal patients is 21,507 TL and (iv) HAIs patients’ communal cost is 6,013,101 TL. Based on the received results, the annual communal cost of the estimated HAIs patients in Turkey is predicted to be 3,640,442,057 TL. In addition to these findings, HAIs patients experience 14 times longer in-patient stay at the hospitals as compared to normal patients, and their treatment expenditures are 23 times higher than the normal patients. In the conclusion part of the study, regarding the preventability (internalization) of HAIs, which was evaluated as part of negative externality, alternative applicable political suggestions are presented for the use of policymakers. PMID:26064367

  19. 7 CFR 1779.90 - Disposition of acquired property.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Disposition of acquired property. 1779.90 Section..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.90 Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the...

  20. 7 CFR 1779.90 - Disposition of acquired property.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Disposition of acquired property. 1779.90 Section..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.90 Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the...

  1. 7 CFR 1779.90 - Disposition of acquired property.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Disposition of acquired property. 1779.90 Section 1779..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.90 Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the...

  2. Preschoolers Acquire General Knowledge by Sharing in Pretense

    ERIC Educational Resources Information Center

    Sutherland, Shelbie L.; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar…

  3. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  4. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  5. 7 CFR 770.8 - Use of acquired land.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Use of acquired land. 770.8 Section 770.8 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.8 Use of acquired land. (a) General. Subject to § 770.5(d) land acquired with loan funds, or other property serving as the security for a...

  6. 7 CFR 1779.90 - Disposition of acquired property.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Disposition of acquired property. 1779.90 Section..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.90 Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the...

  7. 7 CFR 1779.90 - Disposition of acquired property.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Disposition of acquired property. 1779.90 Section..., DEPARTMENT OF AGRICULTURE (CONTINUED) WATER AND WASTE DISPOSAL PROGRAMS GUARANTEED LOANS § 1779.90 Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the...

  8. 43 CFR 4110.1-1 - Acquired lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Acquired lands. 4110.1-1 Section 4110.1-1... and Preference § 4110.1-1 Acquired lands. Where lands have been acquired by the Bureau of Land... of acquisition by the Bureau of Land Management, and are not subject to the requirements of § 4110.1....

  9. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  10. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  11. Musical hallucinations associated with acquired deafness.

    PubMed

    Hammeke, T A; McQuillen, M P; Cohen, B A

    1983-06-01

    Two patients with auditory hallucinations beginning after a long history of progressive bilateral hearing loss were studied. The hallucinations included both unformed (tinnitus and irregular sounds of varying pitch and timbre) and formed (instrumental music, singing and voices) components, and were repetitive. They were affected by ambient noise levels; their content and speed were influenced by attentional and intentional factors. There was no evidence of global dementia, nor of epileptogenic or psychiatric disturbance. A combination of peripheral and associated central "disinhibition" may be responsible for the occurrence of such hallucinations. PMID:6875592

  12. Clinical significance of acquired somatic mutations in aplastic anaemia.

    PubMed

    Marsh, J C W; Mufti, G J

    2016-08-01

    Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients. PMID:27084249

  13. Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

    PubMed

    Huang, Yan-Mei; Hong, Xue-Zhi; Xu, Jia-Hua; Luo, Jiang-Xi; Mo, Han-You; Zhao, Hai-Lu

    2016-06-01

    Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis. PMID:26676359

  14. Acquired von Willebrand syndrome associated with left ventricular assist device.

    PubMed

    Nascimbene, Angelo; Neelamegham, Sriram; Frazier, O H; Moake, Joel L; Dong, Jing-Fei

    2016-06-23

    Left ventricular assist devices (LVAD) provide cardiac support for patients with end-stage heart disease as either bridge or destination therapy, and have significantly improved the survival of these patients. Whereas earlier models were designed to mimic the human heart by producing a pulsatile flow in parallel with the patient's heart, newer devices, which are smaller and more durable, provide continuous blood flow along an axial path using an internal rotor in the blood. However, device-related hemostatic complications remain common and have negatively affected patients' recovery and quality of life. In most patients, the von Willebrand factor (VWF) rapidly loses large multimers and binds poorly to platelets and subendothelial collagen upon LVAD implantation, leading to the term acquired von Willebrand syndrome (AVWS). These changes in VWF structure and adhesive activity recover quickly upon LVAD explantation and are not observed in patients with heart transplant. The VWF defects are believed to be caused by excessive cleavage of large VWF multimers by the metalloprotease ADAMTS-13 in an LVAD-driven circulation. However, evidence that this mechanism could be the primary cause for the loss of large VWF multimers and LVAD-associated bleeding remains circumstantial. This review discusses changes in VWF reactivity found in patients on LVAD support. It specifically focuses on impacts of LVAD-related mechanical stress on VWF structural stability and adhesive reactivity in exploring multiple causes of AVWS and LVAD-associated hemostatic complications. PMID:27143258

  15. Breast Cancer as an Acquired Thrombophilic State

    PubMed Central

    2012-01-01

    Cancer is an acquired thrombophilic condition manifested by increased incidence of venous and arterial thromboembolic complications. Despite progress that has been achieved in treatments over the recent years, thromboembolism remains a major complication in patients with breast cancer; it is accompanied by significant morbidity and mortality. Approximately, 1% of breast cancer patients develop venous thromboembolism within 2 years with the highest incidence occurring in the 6 months post diagnosis. Metastatic disease and their comorbidities are the strongest predictors of the development of thrombotic event. The diagnosis of venous thromboembolism is associated with a higher risk of death within 2 years of diagnosis. Thromboembolic events in cancer patients range from abnormal laboratory coagulation tests without specific symptoms to massive thomboembolism and disseminated intravascular coagulation. The underlying pathophysiology is complex and includes the prothrombotic properties of cancer cells, which can be enhanced by anticancer treatment modalities, such as surgery, hormonal agents, and chemotherapy. Primary thromboprophylaxis in cancer patients should be individualized according to risk. For secondary prevention, several clinical studies have shown that low molecular weight heparin has improved patients' compliance, cancer outcomes and overall survival. This review summarizes the available data on the pathogenesis and clinical approach of hemostatic changes in breast cancer. PMID:22807931

  16. Community-acquired Pneumonia and its Complications.

    PubMed

    Qin, Qiang; Shen, Kun-ling

    2015-08-01

    Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide in developing and developed countries, and its incidence is highest among children less than 5-y-old. Over the last five years, several international and local guidelines have been updated with new evidence concerning the epidemiology, etiology, pathogenesis, treatment and prevention of pediatric CAP, but there are still several major problems that need to be standardised. The aim of this review is to consider the available data concerning the termination, epidemiology, microbiology and pathogenesis, clinical features, diagnosis and differential diagnosis, treatment, and complications of pediatric CAP. There still are many unanswered questions concerning the management of CAP, including its definition, the difficulty to identify its etiological agents, the emergence of drug, and the lack of introduction of vaccines against respiratory pathogens in developing countries. More research is required in various areas (including therapy of atypical agents), and further efforts are needed to increase vaccination in order to reduce the incidence of the disease. PMID:25976616

  17. Natural and acquired macrolide resistance in mycobacteria.

    PubMed

    Doucet-Populaire, F; Buriánková, K; Weiser, J; Pernodet, J-L

    2002-12-01

    The genus Mycobacterium contains two of the most important human pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, the etiologic agents of tuberculosis and leprosy, respectively. Other mycobacteria are mostly saprophytic organisms, living in soil and water, but some of them can cause opportunistic infections. The increasing incidence of tuberculosis as well as infections with non-tuberculous mycobacteria (NTM) in AIDS patients has renewed interest in molecular mechanisms of drug resistance in these pathogens. Mycobacteria show a high degree of intrinsic resistance to most common antibiotics. For instance, species from the M. tuberculosis complex (MTC) are intrinsically resistant to macrolides. Nevertheless, some semi-synthetic macrolides as the erythromycin derivatives clarithromycin, azithromycin and most recently the ketolides, are active against NTM, particularly Mycobacterium avium, and some of them are widely used for infection treatment. However, shortly after the introduction of these new drugs, resistant strains appeared due to mutations in the macrolide target, the ribosome. The mycobacterial cell wall with its specific composition and structure is considered to be a major factor in promoting the natural resistance of mycobacteria to various antibiotics. However, to explain the difference in macrolide sensitivity between the MTC and NTM, the synergistic contribution of a specific resistance mechanism might be required, in addition to possible differences in cell wall permeability. This mini-review summarizes the current knowledge on the natural and acquired macrolide resistance in mycobacteria, gives an overview of potential mechanisms implicated in the intrinsic resistance and brings recent data concerning a macrolide resistance determinant in the MTC. PMID:12570741

  18. Acquired Hemophilia A Successfully Treated with Rituximab

    PubMed Central

    D’Arena, Giovanni; Grandone, Elvira; Di Minno, Matteo Nicola Dario; Musto, Pellegrino; Di Minno, Giovanni

    2015-01-01

    Acquired hemophilia A (AHA) is a rare bleeding disorder due to the development of specific autoantibodies against factor VIII. The anti-CD20 monoclonal antibody Rituximab has been proven to be effective in obtaining a long-term suppression of inhibitors of AHA, besides other immunosuppressive standard treatments. Here we describe a case of idiopathic AHA in a 60-year old man successfully treated with rituximab. He showed a complete clinical response with a normalization of clotting parameters after 5 weekly courses of rituximab given at a dose of 375 mg/sqm., but after stopping rituximab, an initial worsening of coagulation parameters induced the addition of 3 further courses. At present, the patient is in complete clinical and hematological remission after 200 days. This case confirms that Rituximab may be a safe and useful tool to treat AHA and, a prolonged administration can overcome the initial resistance. However, the precise position of this drug in the therapeutic strategy (first or second-line, alone or in combination with other drugs) remains to be established and warrants further investigation. PMID:25745551

  19. Community-acquired pneumonia among smokers.

    PubMed

    Almirall, Jordi; Blanquer, José; Bello, Salvador

    2014-06-01

    Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities. PMID:24387877

  20. The acquired immunodeficiency syndrome: an ultrastructural study.

    PubMed

    Sidhu, G S; Stahl, R E; el-Sadr, W; Cassai, N D; Forrester, E M; Zolla-Pazner, S

    1985-04-01

    Blood and a variety of tissues from 97 patients with the acquired immunodeficiency syndrome (AIDS) and 25 with the AIDS prodrome were studied ultrastructurally. Tubuloreticular structures (TRS) were found in 85 per cent of the patients with AIDS and in 92 per cent of those with the prodrome. Test tube and ring-shaped forms (TRF), found in 41 per cent of the patients with AIDS and in 8 per cent of those with the prodrome, increased with disease progression. Among the patients with AIDS, as the number of sites examined per case increased, the incidence of TRS and TRF tended to approach 100 per cent, suggesting that they are present in all patients with AIDS. Other changes seen frequently were immunologic capping of blood lymphocytes, intramitochondrial iron in blood reticulocytes and marrow normoblasts, megakaryocytic immaturity and platelet phagocytosis, collections of membranous rings in hepatocytic cytoplasm, suggestive of non-A, non-B hepatitis, and proliferations and engorgement of hepatic Ito cells with lipid. The data suggest that TRS and TRF can be used as diagnostic and prognostic markers. PMID:3872253

  1. Gastrointestinal Manifestations of the Acquired Immunodeficiency Syndrome

    PubMed Central

    Rodgers, Vance D.; Kagnoff, Martin F.

    1987-01-01

    In addition to abnormalities in systemic immune function, patients with the acquired immunodeficiency syndrome (AIDS) and the pre-AIDS syndromes have significant abnormalities in the distribution of T-cell subsets in the intestinal tract. Such immune deficits predispose such patients to opportunistic infections and tumors, many of which involve the gastrointestinal tract. For example, Candida albicans often causes stomatitis and esophagitis. Intestinal infections with parasites (Cryptosporidium, Isospora belli, Microsporidia) or bacteria (Mycobacterium avium-intracellulare) are associated with severe diarrhea and malabsorption, whereas viruses like cytomegalovirus and herpes simplex virus cause mucosal ulcerations. Clinically debilitating chronic diarrhea develops in many AIDS patients for which no clear cause can be identified. Enteric pathogens like Salmonella and Campylobacter can be associated with bacteremias. Kaposi's sarcoma and lymphoma involving the intestinal tract are now well-recognized complications of AIDS. Although AIDS is not associated with a pathognomonic liver lesion, opportunistic infections and Kaposi's sarcoma or lymphoma may involve the liver. ImagesFigure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:3825111

  2. Acquiring synaesthesia: insights from training studies

    PubMed Central

    Rothen, Nicolas; Meier, Beat

    2014-01-01

    Synaesthesia denotes a condition of remarkable individual differences in experience characterized by specific additional experiences in response to normal sensory input. Synaesthesia seems to (i) run in families which suggests a genetic component, (ii) is associated with marked structural and functional neural differences, and (iii) is usually reported to exist from early childhood. Hence, synaesthesia is generally regarded as a congenital phenomenon. However, most synaesthetic experiences are triggered by cultural artifacts (e.g., letters, musical sounds). Evidence exists to suggest that synaesthetic experiences are triggered by the conceptual representation of their inducer stimuli. Cases were identified for which the specific synaesthetic associations are related to prior experiences and large scale studies show that grapheme-color associations in synaesthesia are not completely random. Hence, a learning component is inherently involved in the development of specific synaesthetic associations. Researchers have hypothesized that associative learning is the critical mechanism. Recently, it has become of scientific and public interest if synaesthetic experiences may be acquired by means of associative training procedures and whether the gains of these trainings are associated with similar cognitive benefits as genuine synaesthetic experiences. In order to shed light on these issues and inform synaesthesia researchers and the general interested public alike, we provide a comprehensive literature review on developmental aspects of synaesthesia and specific training procedures in non-synaesthetes. Under the light of a clear working definition of synaesthesia, we come to the conclusion that synaesthesia can potentially be learned by the appropriate training. PMID:24624072

  3. Urgent operation for acquired ventricular septal defect.

    PubMed Central

    Thomas, C S; Alford, W C; Burrus, G R; Glassford, D M; Stoney, W S

    1982-01-01

    Recent experience suggests that ventricular septal defect (VSD) secondary to myocardial infarction constitutes an indication for urgent operation. Acquired VSD at St. Thomas Hospital, Nashville, was reviewed to substantiate the obsolescence of protracted medical therapy designed to allow a late, technically less demanding, repair. Twenty-two acute VSDs (less than four weeks following onset of murmur) have been treated since 1970. Five patients died during medical therapy. Two patients survived for more than four weeks without operation. One never manifested significant cardiac decompensation. The other was operated on at 33 days, after progressive deterioration. No technical advantage from the delay was apparent, although survival was achieved. Ten of 15 patients (67%) operated on during the first four weeks survived. Fourteen had reached a level of marked instability prior to operation. Of the five deaths, four were technical and were the product of an initial lack of recognition of the necessity for patch replacement of the interventricular septum. The prosthetic patch is now considered essential to minimize suture-line stress in necrotic muscle. Potentially, only one of 15 patients operated on early using current methods would have expired. This experience supports an aggressive surgical approach to any unstable patient with postinfarction VSD. Early repair requires specific techniques. Results of early operation using these techniques are dramatically superior to past efforts designed to delay definitive repair. PMID:7082062

  4. Turbo code carrier synchronization losses (Radio Losses)

    NASA Technical Reports Server (NTRS)

    Shanibayati, Shervin; Kinman, Peter; Tadjpour, Layla

    2001-01-01

    In this paper the radio loss results for (8920,1/3), (8920,1/6), (1783,1/3) and (1784,1/6) codes are presented. These radio losses were calculated through simulations for a range of data rates. These simulations included both suppressed carrier modulation and residual carrier modulation cases. The radio losses were calculated for a frame error rate of 3 x 10^-4 for (8920,1/3) and (8920,1/6) codes and 3 frame error rate of 6 x 10^-5 for (1764,1/3) and (1784,1/6) codes. The simulations for the residual carrier case were run for loop signal to noise ratios of 13dB, 15dB and 17dB with a loop bandwidth of 10Hz. The simulations for the suppressed carrier case were run for a loop of signal to noise ratio of 17dB. The results of these simulations indicate that the radio losses for turbo codes are low enough to warrant their use in deep space links (maximum of 1dB loss at 17dB loop signal to noise ratio for residual carrier and 1.3dB loss at 17dB loop signal to noise ratio for suppressed carrier at high data rates). Furthermore, these results indicate that by normalizing the radio losses for frame size, loop bandwidth and the loop signal to noise ratio, a single curve could be used for calculating the radio loss for any given data rate at any given loop signal to noise ratio.

  5. Weight-loss medications

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000346.htm Weight-loss medicines To use the sharing features on this page, please enable JavaScript. Several weight-loss medicines are available. Ask your health care provider ...

  6. Weight Loss & Acute Porphyria

    MedlinePlus

    ... Sale You are here Home Diet and Nutrition Weight loss & acute Porphyria Being overweight is a particular problem ... one of these diseases before they enter a weight-loss program. Also, they should not participate in a ...

  7. Living with hearing loss

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000360.htm Living with hearing loss To use the sharing features on this page, please enable JavaScript. If you are living with hearing loss, you know that it takes extra effort to ...

  8. Hearing Loss: Screening Newborns

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table of ... of newborns in the U.S. are screened for hearing loss before they leave the hospital. Research improves the ...

  9. Loss and Recovery

    NASA Technical Reports Server (NTRS)

    Schwer, Ken

    2002-01-01

    The author recounts his experiences of the loss of the QuickTOMS (Total Ozone Mapping Spectrometer) spacecraft, for which he was project manager. He draws from the launch failure lessons on leadership, coping with loss and maintaining morale.

  10. Photovoltaic array loss mechanisms

    NASA Technical Reports Server (NTRS)

    Gonzalez, Charles

    1986-01-01

    Loss mechanisms which come into play when solar cell modules are mounted in arrays are identified. Losses can occur either from a reduction in the array electrical performance or with nonoptimal extraction of power from the array. Electrical performance degradation is caused by electrical mismatch, transmission losses from cell surface soiling and steep angle of reflectance, and electrical losses from field wiring resistance and the voltage drop across blocking diodes. The second type of loss, concerned with the operating points of the array, can involve nonoptimal load impedance and limiting the operating envelope of the array to specific ranges of voltage and current. Each of the loss mechanisms are discussed and average energy losses expected from soiling, steep reflectance angles and circuit losses are calculated.

  11. Genetics of Hearing Loss

    MedlinePlus

    ... in Latin America Information For... Media Policy Makers Genetics of Hearing Loss Language: English Español (Spanish) Recommend ... of hearing loss in babies is due to genetic causes. There are also a number of things ...

  12. Genes and Hearing Loss

    MedlinePlus

    ... Meeting Calendar Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  13. Proven Weight Loss Methods

    MedlinePlus

    Fact Sheet Proven Weight Loss Methods What can weight loss do for you? Losing weight can improve your health in a number of ways. It can lower ... at www.hormone.org/Spanish . Proven Weight Loss Methods Fact Sheet www.hormone.org

  14. Hearing loss in space

    NASA Technical Reports Server (NTRS)

    Buckey, J. C. Jr; Musiek, F. E.; Kline-Schoder, R.; Clark, J. C.; Hart, S.; Havelka, J.

    2001-01-01

    BACKGROUND: Temporary and, in some cases, permanent hearing loss has been documented after long-duration spaceflights. METHODS: We examined all existing published data on hearing loss after space missions to characterize the losses. RESULTS: Data from Russian missions suggest that the hearing loss, when it occurs, affects mainly mid to high frequencies and that using hearing protection often might prevent the loss. Several significant questions remain about hearing loss in space. While the hearing loss has been presumed to be noise-induced, no clear link has been established between noise exposure and hearing loss during spaceflight. In one documented case of temporary hearing loss from the Shuttle-Mir program, the pattern of loss was atypical for a noise-induced loss. Continuous noise levels that have been measured on the Mir and previous space stations, while above engineering standards, are not at levels usually associated with hearing loss in ground-based studies (which have usually been limited to 8-10 h exposure periods). Attempts to measure hearing in space using threshold-based audiograms have been unsuccessful in both the American and Russian programs due to noise interference with the measurements. CONCLUSIONS: The existing data highlight the need for reliable monitoring of both hearing and noise in long-duration spaceflight.

  15. Impact of lactobacilli on orally acquired listeriosis

    PubMed Central

    Archambaud, Cristel; Nahori, Marie-Anne; Soubigou, Guillaume; Bécavin, Christophe; Laval, Laure; Lechat, Pierre; Smokvina, Tamara; Langella, Philippe; Lecuit, Marc; Cossart, Pascale

    2012-01-01

    Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. Here, we report a unique comprehensive analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired listeriosis in a gnotobiotic humanized mouse model. We first assessed the effect of treatment with each Lactobacillus on L. monocytogenes counts in host tissues and showed that each decreases L. monocytogenes systemic dissemination in orally inoculated mice. A whole genome intestinal transcriptomic analysis revealed that each Lactobacillus changes expression of a specific subset of genes during infection, with IFN-stimulated genes (ISGs) being the most affected by both lactobacilli. We also examined microRNA (miR) expression and showed that three miRs (miR-192, miR-200b, and miR-215) are repressed during L. monocytogenes infection. Treatment with each Lactobacillus increased miR-192 expression, whereas only L. casei association increased miR-200b and miR-215 expression. Finally, we showed that treatment with each Lactobacillus significantly reshaped the L. monocytogenes transcriptome and up-regulated transcription of L. monocytogenes genes encoding enzymes allowing utilization of intestinal carbon and nitrogen sources in particular genes involved in propanediol and ethanolamine catabolism and cobalamin biosynthesis. Altogether, these data reveal that the modulation of L. monocytogenes infection by treatment with lactobacilli correlates with a decrease in host gene expression, in particular ISGs, miR regulation, and a dramatic reshaping of L. monocytogenes transcriptome. PMID:23012479

  16. How to acquire customers on the Web.

    PubMed

    Hoffman, D L; Novak, T P

    2000-01-01

    Most retailers on the Web spend more to acquire customers than they will ever get back in revenue from them. Many think that sky-high spending on marketing is necessary to stake out their share of Internet space. But is it really? How do retailers know how much to pay? Consider CDnow, which has developed a multifaceted customer-acquisition strategy that reflects a clear understanding of the economics of an on-line business. At the heart of its strategy is affiliate marketing, a concept the company pioneered. Under its BuyWeb program, anyone can put a link to CDnow on his or her Web site, and if a customer uses that link to arrive at CDnow and make a purchase, the referring site owner gets a percentage of the sale. CDnow pays no money if no sale is made, which makes the marketing program completely efficient. But CDnow didn't stop there. Being a Web store, it had complete data on the number of visitors to its site and what they bought, which it used to work out the lifetime value of an average customer. CDnow used that figure to determine how much to wager on the expensive and risky world of traditional advertising to reach a wider audience that wasn't already on-line. CDnow's experience, still a work in progress, contradicts John Wanamaker's oft-quoted lament: "I know half the money I spend on advertising is wasted, but I can never find out which half." As the CDnow example demonstrates, there is a way to find out which half really works. PMID:11183979

  17. Impact of lactobacilli on orally acquired listeriosis.

    PubMed

    Archambaud, Cristel; Nahori, Marie-Anne; Soubigou, Guillaume; Bécavin, Christophe; Laval, Laure; Lechat, Pierre; Smokvina, Tamara; Langella, Philippe; Lecuit, Marc; Cossart, Pascale

    2012-10-01

    Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. Here, we report a unique comprehensive analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired listeriosis in a gnotobiotic humanized mouse model. We first assessed the effect of treatment with each Lactobacillus on L. monocytogenes counts in host tissues and showed that each decreases L. monocytogenes systemic dissemination in orally inoculated mice. A whole genome intestinal transcriptomic analysis revealed that each Lactobacillus changes expression of a specific subset of genes during infection, with IFN-stimulated genes (ISGs) being the most affected by both lactobacilli. We also examined microRNA (miR) expression and showed that three miRs (miR-192, miR-200b, and miR-215) are repressed during L. monocytogenes infection. Treatment with each Lactobacillus increased miR-192 expression, whereas only L. casei association increased miR-200b and miR-215 expression. Finally, we showed that treatment with each Lactobacillus significantly reshaped the L. monocytogenes transcriptome and up-regulated transcription of L. monocytogenes genes encoding enzymes allowing utilization of intestinal carbon and nitrogen sources in particular genes involved in propanediol and ethanolamine catabolism and cobalamin biosynthesis. Altogether, these data reveal that the modulation of L. monocytogenes infection by treatment with lactobacilli correlates with a decrease in host gene expression, in particular ISGs, miR regulation, and a dramatic reshaping of L. monocytogenes transcriptome. PMID:23012479

  18. Evolution by gene loss.

    PubMed

    Albalat, Ricard; Cañestro, Cristian

    2016-07-01

    The recent increase in genomic data is revealing an unexpected perspective of gene loss as a pervasive source of genetic variation that can cause adaptive phenotypic diversity. This novel perspective of gene loss is raising new fundamental questions. How relevant has gene loss been in the divergence of phyla? How do genes change from being essential to dispensable and finally to being lost? Is gene loss mostly neutral, or can it be an effective way of adaptation? These questions are addressed, and insights are discussed from genomic studies of gene loss in populations and their relevance in evolutionary biology and biomedicine. PMID:27087500

  19. Male acquired hypogonadotropic hypogonadism: diagnosis and treatment.

    PubMed

    Salenave, Sylvie; Trabado, Sévérine; Maione, Luigi; Brailly-Tabard, Sylvie; Young, Jacques

    2012-04-01

    Acquired hypogonadotropic hypogonadism (AHH), contrary to congenital hypogonadotropic hypogonadism (CHH) is characterized by postnatal onset of disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. AHH thus prevents the establishment of gonadotropin secretion at puberty, or its post-pubertal maintenance. Thus, postnatal AHH may prevent the onset of puberty or appear during pubertal development, but it usually emerges after the normal age of puberty. Although pituitary tumors, particularly prolactinoma, are the most common cause, sellar tumors or cyst of the hypothalamus or infundibulum, infiltrative, vascular, iron overload and other disorders may also cause AHH. Pituitary surgery and head trauma or cranial/pituitary radiation therapy are also usual causes of AHH. The clinical manifestations of AHH depend on age of onset, the degree of gonadotropin deficiency, the rapidity of its onset and the association to other pituitary function deficiencies or excess. Men with AHH have less stamina, decreased libido, erectile dysfunction and strength, and a worsened sense of well being leading to degraded quality of life. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial, body hair and muscle mass, fine facial wrinkles, gynecomastia, and hypotrophic testes are observed in long-standing and complete AHH. Spermatogenesis is impaired and the volume of ejaculate is decreased only when gonadotropins and testosterone levels are very low. Men with AHH may have normal or low serum LH and FSH concentrations, but normal gonadotropin values are inappropriate when associated with low serum testosterone. In the majority of AHH patients, serum inhibin B is "normal". The decrease of this sertolian hormone indicates a long-standing and severe gonadotropin deficiency. Symptoms, usually associated with significant testosterone deficiency in men with AHH, improve with

  20. Acquired facial lipoatrophy: pathogenesis and therapeutic options

    PubMed Central

    Olszewska, Barbara; Lemańska, Małgorzata; Purzycka-Bohdan, Dorota; Nowicki, Roman

    2015-01-01

    Facial lipoatrophy refers to the loss of subcutaneous fat tissue presenting by flattening or indentation of convex contour of the face. Facial lipoatrophy is a feature of the normal ageing process. It may be also a manifestation of chronic diseases, most frequently it affects HIV-infected individuals treated with highly active antiretroviral therapy (HAART) and may constitute a complication of connective tissue diseases, like lupus erythematosus profundus or morphea. Early recognition and treatment of the active stage of connective tissue diseases is of essential significance in prevention of subsequent scarring and atrophy lesions. In HIV-positive patients undergoing HAART therapy, the attempt to modify thetreatment scheme so it has a less lipemic effect seems to be justified. Esthetic correction of facial lipoatrophy in chronic diseases is a great challenge. Improvement of appearance is very important for affected individuals, because it diminishes their stigmatization and psychosocial dysfunction. Facial volumetric correction includes surgical and dermatological procedures such as adipose transfer and injectable dermal fillers. PMID:26015783

  1. Incidence, Outcomes, and Risk Factors of Community-Acquired and Hospital-Acquired Acute Kidney Injury: A Retrospective Cohort Study.

    PubMed

    Hsu, Chien-Ning; Lee, Chien-Te; Su, Chien-Hao; Wang, Yu-Ching Lily; Chen, Hsiao-Ling; Chuang, Jiin-Haur; Tain, You-Lin

    2016-05-01

    The disease burden and outcomes of community-acquired (CA-) and hospital-acquired acute kidney injury (HA-AKI) are not well understood. The aim of the study was to investigate the incidence, outcomes, and risk factors of AKI in a large Taiwanese adult cohort.This retrospective cohort study examined 734,340 hospital admissions from a group of hospitals within an organization in Taiwan between January 1, 2010 and December 31, 2014. Patients with AKI at discharge were classified as either CA- or HA-AKI based on the RIFLE (risk, injury, failure, loss of function, end stage of kidney disease) classification criteria. Outcomes were in-hospital mortality, dialysis, recovery of renal function, and length of stay. Risks of developing AKI were determined using multivariate logistic regression based on demographic and baseline clinical characteristics and nephrotoxin use before admission.AKI occurred in 1.68% to 2% hospital discharges among adults without and with preexisting chronic kidney disease (CKD), respectively. The incidence of CA-AKI was 17.25 and HA-AKI was 8.14 per 1000 admissions. The annual rate of CA-AKI increased from 12.43 to 19.96 per 1000 people, but the change in HA-AKI was insignificant. Comparing to CA-AKI, those with HA-AKI had higher levels of in-hospital mortality (26.07% vs 51.58%), mean length of stay (21.25 ± 22.35 vs 35.84 ± 34.62 days), and dialysis during hospitalization (1.45% vs 2.06%). Preexisting systemic diseases, including CKD were associated with increased risks of CA-AKI, and nephrotoxic polypharmacy increased risk of both CA- and HA-AKI.Patients with HA-AKI had more severe outcomes than patients with CA-AKI, and demonstrated different spectrum of risk factors. Although patients with CA-AKI with better outcomes, the incidence increased over time. It is also clear that optimal preventive and management strategies of HA- and CA-AKI are urgently needed to limit the risks in susceptible individuals. PMID:27175701

  2. Acquired pulmonary arteriovenous malformation secondary to hydatid cyst operation.

    PubMed

    Gezer, S; Turut, H; Oz, G; Demirag, F; Tastepe, I

    2007-10-01

    Pulmonary arteriovenous malformations are abnormal communications between pulmonary arteries and pulmonary veins. The majority of the cases are congenital in origin, and acquired pulmonary arteriovenous malformations are very rare. We present a case here, which - to the best of our knowledge - is the first acquired pulmonary arteriovenous malformation secondary to a hydatid cyst operation in the literature, and we discuss the etiology, clinical presentation, diagnostic modalities and treatment of acquired pulmonary arteriovenous malformations. PMID:17902072

  3. Overexpression of Specific CD44 Isoforms Is Associated with Aggressive Cell Features in Acquired Endocrine Resistance

    PubMed Central

    Bellerby, Rebecca; Smith, Chris; Kyme, Sue; Gee, Julia; Günthert, Ursula; Green, Andy; Rakha, Emad; Barrett-Lee, Peter; Hiscox, Stephen

    2016-01-01

    While endocrine therapy is the mainstay of ER+ breast cancer, the clinical effectiveness of these agents is limited by the phenomenon of acquired resistance that is associated with disease relapse and poor prognosis. Our previous studies revealed that acquired resistance is accompanied by a gain in cellular invasion and migration and also that CD44 family proteins are overexpressed in the resistant phenotype. Given the association of CD44 with tumor progression, we hypothesized that its overexpression may act to promote the aggressive behavior of endocrine-resistant breast cancers. Here, we have investigated further the role of two specific CD44 isoforms, CD44v3 and CD44v6, in the endocrine-resistant phenotype. Our data revealed that overexpression of CD44v6, but not CD44v3, in endocrine-sensitive MCF-7 cells resulted in a gain in EGFR signaling, enhanced their endogenous invasive capacity, and attenuated their response to endocrine treatment. Suppression of CD44v6 in endocrine-resistant cell models was associated with a reduction in their invasive capacity. Our data suggest that upregulation of CD44v6 in acquired resistant breast cancer may contribute to a gain in the aggressive phenotype of these cells and loss of endocrine response through transactivation of the EGFR pathway. Future therapeutic targeting of CD44v6 may prove to be an effective strategy alongside EGFR-targeted agents in delaying/preventing acquired resistance in breast cancer. PMID:27379207

  4. Functional Visual Loss

    PubMed Central

    Bruce, Beau B; Newman, Nancy J

    2010-01-01

    Synopsis Neurologists frequently evaluate patients complaining of vision loss, especially when the patient has been examined by an ophthalmologist who has found no ocular disease. A significant proportion of patients presenting to the neurologist with visual complaints will have non-organic or functional visual loss. While there are examination techniques which can aid in the detection and diagnosis of functional visual loss, the frequency with which functional visual loss occurs concomitantly with organic disease warrants substantial caution on the part of the clinician. Furthermore, purely functional visual loss is never a diagnosis of exclusion, and must be supported by positive findings on examination that demonstrate normal visual function. The relationship of true psychological disease and functional visual loss is unclear and most patients respond well to simple reassurance. PMID:20638000

  5. Drugs and hair loss.

    PubMed

    Patel, Mansi; Harrison, Shannon; Sinclair, Rodney

    2013-01-01

    Hair loss is a common complaint, both in men and women, and use of prescription medications is widespread. When there is a temporal association between the onset of hair loss and commencement of a medication, the medication is commonly thought to have caused the hair loss. However, hair loss and in particular telogen effluvium may occur in response to a number of triggers including fever, hemorrhage, severe illness, stress, and childbirth, and a thorough exclusion of these potential confounders is necessary before the hair loss can be blamed on the medication. Certain medications are known to cause hair loss by a variety of mechanisms including anagen arrest, telogen effluvium, or accentuation of androgenetic alopecia by androgens. PMID:23159177

  6. Acquired mitochondrial impairment as a cause of optic nerve disease.

    PubMed Central

    Sadun, A

    1998-01-01

    Cuban patients, as well as from Leber's patients, for study. Finally, we developed an animal model to match the low serum folic acid and high serum formate levels found in the CEON patients, by administering to rats low doses of methanol after several months of a folic acid-deficient diet. Optic nerves and other tissues obtained from these rats were analyzed and compared with those from the Cuban patients. RESULTS: Patients from the Cuban epidemic of optic neuropathy with clinical evidence of a selective loss of the papillomacular bundle did much better once their nutritional status was corrected and exposure to toxins ceased. Patients with CEON often demonstrated low levels of folic acid and high levels of formate in their blood. Histopathologic studies demonstrated losses of the longest fibers (in the sural nerve) and those of smallest caliber (papillomacular bundle) in the optic nerve, with intra-axonal accumulations just anterior to the lamina cribrosa. Our animal model duplicated the serologic changes (low folic acid, high formate) as well as these histopathologic changes. Furthermore, ultrastructural examination of rat tissues demonstrated mitochondrial changes that further matched those seen on ultrastructural examination of tissues from patients with Leber's. CONCLUSION: Mitochondria can be impaired either genetically (as in Leber's) or through acquired insults (such as nutritional or toxic factors). Either may challenge energy production in all cells of the body. While this challenge may be met through certain compensatory mechanisms (such as in the size, shape, or number of the mitochondria), there exists in neurons a threshold which, once passed, leads to catastrophic changes. This threshold may be that point at which mitochondrial derangement leads to such ATP depletion that axonal transport is compromised, and decreased mitochondrial transport results in even further ATP depletion. Neurons are singularly dependent on the axonal transport of mitochondria

  7. Clonal hematopoiesis in acquired aplastic anemia.

    PubMed

    Ogawa, Seishi

    2016-07-21

    Clonal hematopoiesis (CH) in aplastic anemia (AA) has been closely linked to the evolution of late clonal disorders, including paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), which are common complications after successful immunosuppressive therapy (IST). With the advent of high-throughput sequencing of recent years, the molecular aspect of CH in AA has been clarified by comprehensive detection of somatic mutations that drive clonal evolution. Genetic abnormalities are found in ∼50% of patients with AA and, except for PIGA mutations and copy-neutral loss-of-heterozygosity, or uniparental disomy (UPD) in 6p (6pUPD), are most frequently represented by mutations involving genes commonly mutated in myeloid malignancies, including DNMT3A, ASXL1, and BCOR/BCORL1 Mutations exhibit distinct chronological profiles and clinical impacts. BCOR/BCORL1 and PIGA mutations tend to disappear or show stable clone size and predict a better response to IST and a significantly better clinical outcome compared with mutations in DNMT3A, ASXL1, and other genes, which are likely to increase their clone size, are associated with a faster progression to MDS/AML, and predict an unfavorable survival. High frequency of 6pUPD and overrepresentation of PIGA and BCOR/BCORL1 mutations are unique to AA, suggesting the role of autoimmunity in clonal selection. By contrast, DNMT3A and ASXL1 mutations, also commonly seen in CH in the general population, indicate a close link to CH in the aged bone marrow, in terms of the mechanism for selection. Detection and close monitoring of somatic mutations/evolution may help with prediction and diagnosis of clonal evolution of MDS/AML and better management of patients with AA. PMID:27121470

  8. Nuclear EGFR Contributes to Acquired Resistance to Cetuximab

    PubMed Central

    Li, Chunrong; Iida, Mari; Dunn, Emily F.; Ghia, Amol J.; Wheeler, Deric L.

    2010-01-01

    Epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase involved in the etiology of several human cancers. Cetuximab is an EGFR blocking-antibody that has been approved for the treatment of patients with cancers of the head and neck (HNSCC) and metastatic colorectal cancer (mCRC). Previous reports have shown that EGFR translocation to the nucleus is associated with cell proliferation. Here we investigated mechanisms of acquired resistance to cetuximab using a model derived from the non-small cell lung cancer line H226. We demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin (AR), heparin-binding EGF (HB-EGF) and β-cellulin. Overexpression of these ligands is associated with the nuclear translocation of the EGFR and this process was mediated by the Src family kinases (SFK). Treatment of cetuximab-resistant cells with the SFK inhibitor, dasatinib, resulted in loss of nuclear EGFR, increased membrane expression of the EGFR and re-sensitization to cetuximab. In addition, expression of a nuclear localization sequence tagged EGFR in cetuximab-sensitive cells increased resistance to cetuximab both in vitro and in mouse xenografts. Collectively, these data suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetuximab therapy and provides a rationale for investigating nuclear EGFR as a biomarker for cetuximab response. Further, these data suggest a rationale for the design of clinical trials that examine the value of treating patients with cetuximab-resistant tumors with inhibitors of SFKs in combination with cetuximab. PMID:19684613

  9. Nuclear EGFR contributes to acquired resistance to cetuximab.

    PubMed

    Li, C; Iida, M; Dunn, E F; Ghia, A J; Wheeler, D L

    2009-10-29

    Epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase involved in the etiology of several human cancers. Cetuximab is an EGFR-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma and metastatic colorectal cancer. Previous reports have shown that EGFR translocation to the nucleus is associated with cell proliferation. Here we investigated mechanisms of acquired resistance to cetuximab using a model derived from the non-small cell lung cancer line H226. We demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin, heparin-binding EGF and beta-cellulin. Overexpression of these ligands is associated with the nuclear translocation of the EGFR and this process was mediated by the Src family kinases (SFK). Treatment of cetuximab-resistant cells with the SFK inhibitor, dasatinib, resulted in loss of nuclear EGFR, increased membrane expression of the EGFR and resensitization to cetuximab. In addition, expression of a nuclear localization sequence-tagged EGFR in cetuximab-sensitive cells increased resistance to cetuximab both in vitro and in mouse xenografts. Collectively, these data suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetuximab therapy and provides a rationale for investigating nuclear EGFR as a biomarker for cetuximab response. Further, these data suggest a rationale for the design of clinical trials that examine the value of treating patients with cetuximab-resistant tumors with inhibitors of SFKs in combination with cetuximab. PMID:19684613

  10. Energy losses in switches

    SciTech Connect

    Martin, T.H.; Seamen, J.F.; Jobe, D.O.

    1993-07-01

    The authors experiments show energy losses between 2 and 10 times that of the resistive time predictions. The experiments used hydrogen, helium, air, nitrogen, SF{sub 6} polyethylene, and water for the switching dielectric. Previously underestimated switch losses have caused over predicting the accelerator outputs. Accurate estimation of these losses is now necessary for new high-efficiency pulsed power devices where the switching losses constitute the major portion of the total energy loss. They found that the switch energy losses scale as (V{sub peak}I{sub peak}){sup 1.1846}. When using this scaling, the energy losses in any of the tested dielectrics are almost the same. This relationship is valid for several orders of magnitude and suggested a theoretical basis for these results. Currents up to .65 MA, with voltages to 3 MV were applied to various gaps during these experiments. The authors data and the developed theory indicates that the switch power loss continues for a much longer time than the resistive time, with peak power loss generally occurring at peak current in a ranging discharge instead of the early current time. All of the experiments were circuit code modeled after developing a new switch loss version based on the theory. The circuit code predicts switch energy loss and peak currents as a function of time. During analysis of the data they noticed slight constant offsets between the theory and data that depended on the dielectric. They modified the plasma conductivity for each tested dielectric to lessen this offset.

  11. Spirituality, Loss and Recovery in Children with Disabilities

    ERIC Educational Resources Information Center

    Erickson, David V.

    2008-01-01

    This article focuses on loss, recovery and spiritual dimensions of trauma in spinal cord injury (SCI) during adolescence. From a clinical perspective, while there are physical characteristics in common with congenital childhood disabilities such as spina bifida, life adjustment issues associated with acquired disabilities can be quite different,…

  12. Alcohol use among students with and without hearing loss.

    PubMed

    Pinquart, Martin; Pfeiffer, Jens P

    2015-01-01

    We compared alcohol use among adolescents with and without hearing loss. Adolescents with hearing loss reported consuming less alcohol, less binge drinking, fewer episodes of drunkenness, and a higher age at first drunkenness than their hearing peers. Alcohol use did not vary between students who were deaf or hard of hearing or between students with congenital versus acquired hearing loss. Although higher age, male gender, and larger friend networks predicted higher alcohol consumption among adolescents with and without hearing loss, worse grades at school were associated only with alcohol use among hearing students. Lower alcohol use among students with hearing loss when compared with hearing peers was, in part, explained by their lower level of peer-group integration. Although alcohol use is a less serious problem among students with hearing loss, a minority with risky consumption would benefit from interventions aimed at reducing alcohol use. PMID:25318927

  13. Hearing Loss and Cytomegalovirus.

    ERIC Educational Resources Information Center

    Strauss, Melvin

    1997-01-01

    Cytomegalovirus is the most common cause of congenital virally induced hearing loss. Maternal infection is most often asymptomatic as is the infection in the newborn. Hearing loss occurs in both clinically apparent infection and in the asymptomatic infection. Current methods of detection, treatment, and prevention and research efforts are…

  14. Hereditary Hearing Loss.

    ERIC Educational Resources Information Center

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  15. Anthocyanins and weight loss

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review evaluated the available scientific literature relative to anthocyanins and weight loss and/or obesity with mention of other effects of anthocyanins on pathologies that are closely related to obesity. Although there is considerable popular press concerning anthocyanins and weight loss, th...

  16. CEBAF beam loss accounting

    SciTech Connect

    Ursic, R.; Mahoney, K.; Hovater, C.; Hutton, A.; Sinclair, C.

    1995-12-31

    This paper describes the design and implementation of a beam loss accounting system for the CEBAF electron accelerator. This system samples the beam curent throughout the beam path and measures the beam current accurately. Personnel Safety and Machine Protection systems use this system to turn off the beam when hazardous beam losses occur.

  17. Understanding Rural Population Loss.

    ERIC Educational Resources Information Center

    McGranahan, David A.; Beale, Calvin L.

    2002-01-01

    A quarter of nonmetro counties lost population in the 1990s, but population loss was not related to poverty rate or low educational levels, perhaps because low-skill workers can no longer expect better wages in urban areas. Population loss was related to low population density and remoteness (which decrease access to services), lack of natural…

  18. Help! It's Hair Loss!

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Help! It's Hair Loss! KidsHealth > For Kids > Help! It's Hair Loss! Print A A A Text Size ... part above the skin, is dead. (That's why it doesn't hurt to get a haircut!) This ...

  19. Understanding Grief & Loss.

    ERIC Educational Resources Information Center

    Parker, Judith

    1995-01-01

    Although death is the one certainty in life, death or the grieving process is rarely discussed. Grief includes physical, emotional, spiritual, and psychological reactions to loss, and is not limited to feelings about death. Grief can be the response to loss of home or country, separation or displacement, and changes resulting from new life stages.…

  20. Weight Loss Surgery

    MedlinePlus

    Weight loss surgery helps people with extreme obesity to lose weight. It may be an option if you cannot lose weight through diet and exercise or have serious health problems caused by obesity. There are different types of weight loss surgery. They often limit the ...

  1. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional...

  2. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional...

  3. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional...

  4. 10 CFR 626.6 - Acquiring oil by direct purchase.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Acquiring oil by direct purchase. 626.6 Section 626.6 Energy DEPARTMENT OF ENERGY (CONTINUED) SALES REGULATION PROCEDURES FOR ACQUISITION OF PETROLEUM FOR THE STRATEGIC PETROLEUM RESERVE § 626.6 Acquiring oil by direct purchase. (a) General. For the direct purchase of crude oil, DOE shall, through...

  5. 27 CFR 6.45 - Assistance in acquiring license.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Assistance in acquiring license. 6.45 Section 6.45 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Furnishing Things of Value § 6.45 Assistance in acquiring license....

  6. 27 CFR 6.45 - Assistance in acquiring license.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Assistance in acquiring license. 6.45 Section 6.45 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL âTIED-HOUSEâ Unlawful Inducements Furnishing Things of Value § 6.45 Assistance in acquiring license....

  7. 27 CFR 6.45 - Assistance in acquiring license.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Assistance in acquiring license. 6.45 Section 6.45 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL âTIED-HOUSEâ Unlawful Inducements Furnishing Things of Value § 6.45 Assistance in acquiring license....

  8. Free Reading: A Powerful Tool for Acquiring a Second Language

    ERIC Educational Resources Information Center

    Priya, J.; Ponniah, R. Joseph

    2013-01-01

    The paper claims that free reading is a crucial ingredient in acquiring a second or foreign language. It contributes to the development of all measures of language competence which include grammar, vocabulary, spelling, syntax, fluency and style. The review supports the claim that readers acquire language subconsciously when they receive…

  9. 34 CFR 7.4 - Option to acquire foreign rights.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Option to acquire foreign rights. 7.4 Section 7.4 Education Office of the Secretary, Department of Education EMPLOYEE INVENTIONS § 7.4 Option to acquire foreign rights. In any case where it is determined that all domestic rights should be assigned to...

  10. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household...

  11. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household...

  12. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 2 2014-04-01 2014-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household...

  13. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002-6 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5(d) of...

  14. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002-6 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section...

  15. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002-6 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section...

  16. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002-6 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section...

  17. 26 CFR 1.9002-6 - Acquiring corporation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002-6 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section...

  18. 45 CFR 7.4 - Option to acquire foreign rights.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Option to acquire foreign rights. 7.4 Section 7.4 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION EMPLOYEE INVENTIONS § 7.4 Option to acquire foreign rights. In any case where it is determined that all domestic rights should...

  19. 34 CFR 7.4 - Option to acquire foreign rights.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 1 2014-07-01 2014-07-01 false Option to acquire foreign rights. 7.4 Section 7.4 Education Office of the Secretary, Department of Education EMPLOYEE INVENTIONS § 7.4 Option to acquire foreign rights. In any case where it is determined that all domestic rights should be assigned to...

  20. Acquiring Knowledge of Derived Nominals and Derived Adjectives in Context

    ERIC Educational Resources Information Center

    Marinellie, Sally A.; Kneile, Lynn A.

    2012-01-01

    Purpose: This research investigated children's ability to acquire semantic and syntactic knowledge of derived nominals and derived adjectives in the context of short passages. The study also investigated the relation of morphological awareness and the ability to acquire knowledge of derived words in context. Method: A total of 106 children in…

  1. 43 CFR 3471.4 - Future interest, acquired lands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Future interest, acquired lands. 3471.4... Coal Management Provisions and Limitations § 3471.4 Future interest, acquired lands. An application to lease lands in which the United States has a future interest filed more than 2 years prior to the...

  2. 43 CFR 3471.4 - Future interest, acquired lands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Future interest, acquired lands. 3471.4... Coal Management Provisions and Limitations § 3471.4 Future interest, acquired lands. An application to lease lands in which the United States has a future interest filed more than 2 years prior to the...

  3. 43 CFR 3471.4 - Future interest, acquired lands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Future interest, acquired lands. 3471.4... Coal Management Provisions and Limitations § 3471.4 Future interest, acquired lands. An application to lease lands in which the United States has a future interest filed more than 2 years prior to the...

  4. 43 CFR 3471.4 - Future interest, acquired lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Future interest, acquired lands. 3471.4... Coal Management Provisions and Limitations § 3471.4 Future interest, acquired lands. An application to lease lands in which the United States has a future interest filed more than 2 years prior to the...

  5. 45 CFR 7.4 - Option to acquire foreign rights.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Option to acquire foreign rights. 7.4 Section 7.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION EMPLOYEE INVENTIONS § 7.4 Option to acquire foreign rights. In any case where it is determined that all domestic rights should be assigned to the Government, it...

  6. 45 CFR 7.4 - Option to acquire foreign rights.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Option to acquire foreign rights. 7.4 Section 7.4 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION EMPLOYEE INVENTIONS § 7.4 Option to acquire foreign rights. In any case where it is determined that all domestic rights should be assigned to the Government, it...

  7. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... States the cigarette limit is 1,000, not more than 200 of which shall have been acquired elsewhere than... beneficiary countries. (e) Exemption not applicable. The exemption does not apply to articles intended for sale or acquired on commission, i.e., for the account of another person, with or without...

  8. 19 CFR 148.33 - Articles acquired abroad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... States the cigarette limit is 1,000, not more than 200 of which shall have been acquired elsewhere than... beneficiary countries. (e) Exemption not applicable. The exemption does not apply to articles intended for sale or acquired on commission, i.e., for the account of another person, with or without...

  9. 33 CFR 211.27 - Method of acquiring Federal jurisdiction.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Method of acquiring Federal jurisdiction. 211.27 Section 211.27 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY... PROJECTS Federal Jurisdiction over Real Estate § 211.27 Method of acquiring Federal...

  10. 26 CFR 1.471-9 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.471-9 Inventories of acquiring corporations....

  11. 26 CFR 1.472-7 - Inventories of acquiring corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.472-7 Inventories of acquiring corporations....

  12. [Inner Ear Hearing Loss].

    PubMed

    Hesse, G

    2016-06-01

    Hearing loss is one of the most dominant handicaps in modern societies, which additionally very often is not realized or not admitted. About one quarter of the general population suffers from inner ear hearing loss and is therefore restricted in communicational skills. Demographic factors like increasing age play an important role as well as environmental influences and an increasing sound and noise exposure especially in leisure activities. Thus borders between a "classical" presbyacusis - if it ever existed - and envirionmentally induced hearing loss disappear. Today restrictions in hearing ability develop earlier in age but at the same time they are detected and diagnosed earlier. This paper can eventually enlighten the wide field of inner ear hearing loss only fragmentarily; therefore mainly new research, findings and developments are reviewed. The first part discusses new aspects of diagnostics of inner ear hearing loss and different etiologies. PMID:27259171

  13. Acute loss of consciousness.

    PubMed

    Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo

    2015-01-01

    Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness. PMID:25702218

  14. Intrinsic Functional Connectivity Patterns Predict Consciousness Level and Recovery Outcome in Acquired Brain Injury

    PubMed Central

    Wu, Xuehai; Zou, Qihong; Hu, Jin; Tang, Weijun; Mao, Ying; Gao, Liang; Zhu, Jianhong; Jin, Yi; Wu, Xin; Lu, Lu; Zhang, Yaojun; Zhang, Yao; Dai, Zhengjia; Gao, Jia-Hong; Weng, Xuchu; Northoff, Georg; Giacino, Joseph T.; He, Yong

    2015-01-01

    For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI. SIGNIFICANCE STATEMENT Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the

  15. Impaired acquired resistance of mice to Klebsiella pneumoniae infection induced by acute NO/sub 2/ exposure

    SciTech Connect

    Bouley, G.; Azoulay-Dupuis, E.; Gaudebout, C.

    1985-12-01

    The natural resistance of nonimmunized C57B1/6 mice to an intraperitoneal Klebsiella pneumoniae challenge was not significantly affected by prior continuous exposure to 20 ppm NO/sub 2/ for 4 days. In contrast, the acquired resistance of mice immunized just before and infected just after NO/sub 2/ exposure was seriously impaired. This could not be explained by the loss of appetite (about 30%) observed in NO/sub 2/ treated mice, for neither the natural nor acquired resistance of control air exposure mice given approximately 70% ad libitum food and water were significantly modified.

  16. Hearing Loss and Older Adults

    MedlinePlus

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Hearing Loss and Older Adults On this page: What is ... about hearing loss and older adults? What is hearing loss? Hearing loss is a sudden or gradual decrease ...

  17. Primary cardiac lymphoma in a patient with acquired immune deficiency syndrome

    SciTech Connect

    Constantino, A.; West, T.E.; Gupta, M.; Loghmanee, F.

    1987-12-01

    A 34-year-old male prisoner with a history of intravenous drug abuse presented with fever, lymphadenopathy, weight loss, and recent onset of congestive heart failure. Serologic testing was positive for antibodies to human immune deficiency virus. There was intense myocardial uptake of gallium. Autopsy showed a primary immunoblastic lymphoma involving only the myocardium. While primary cardiac lymphoma is an extremely rare condition, the incidence may be higher in patients with acquired immune deficiency syndrome (AIDS) and should be suspected in cases with atypical cardiomyopathy.

  18. Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

    PubMed

    Gilbert, Frédéric; Focquaert, Farah

    2015-01-01

    This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment. PMID:25725545

  19. Iron losses in sweat

    SciTech Connect

    Brune, M.; Magnusson, B.; Persson, H.; Hallberg, L.

    1986-03-01

    The losses of iron in whole body cell-free sweat were determined in eleven healthy men. A new experimental design was used with a very careful cleaning procedure of the skin and repeated consecutive sampling periods of sweat in a sauna. The purpose was to achieve a steady state of sweat iron losses with minimal influence from iron originating from desquamated cells and iron contaminating the skin. A steady state was reached in the third sauna period (second sweat sampling period). Iron loss was directly related to the volume of sweat lost and amounted to 22.5 micrograms iron/l sweat. The findings indicate that iron is a physiological constituent of sweat and derived not only from contamination. Present results imply that variations in the amount of sweat lost will have only a marginal effect on the variation in total body iron losses.

  20. Medications for Memory Loss

    MedlinePlus

    ... memory loss, confusion, and problems with thinking and reasoning) of Alzheimer's disease. As Alzheimer’s progresses, brain cells ... the latest Alzheimer's medications available today, and the clinical trials that may bring us closer to new ...

  1. Blindness and vision loss

    MedlinePlus

    ... eye ( chemical burns or sports injuries) Diabetes Glaucoma Macular degeneration The type of partial vision loss may differ, ... tunnel vision and missing areas of vision With macular degeneration, the side vision is normal but the central ...

  2. Living with vision loss

    MedlinePlus

    ... EH, Katz PR, Malone ML, eds. Practice of Geriatrics . 4th ed. Philadelphia, PA: Elsevier Saunders; 2007:chap ... Shega JW. Vision loss. In: Wachtel TJ, ed. Geriatric Clinical Advisor: Instant diagnosis and treatment . Philadelphia, PA: ...

  3. Living with Hearing Loss

    MedlinePlus

    ... Current Issue Past Issues Special Section: Focus on Communication Living with Hearing Loss Past Issues / Fall 2008 ... the United States suffer some form of disordered communication. The National Institute on Deafness and Other Communication ...

  4. Prizes for weight loss.

    PubMed Central

    Englberger, L.

    1999-01-01

    A programme of weight loss competitions and associated activities in Tonga, intended to combat obesity and the noncommunicable diseases linked to it, has popular support and the potential to effect significant improvements in health. PMID:10063662

  5. Occupational hearing loss

    MedlinePlus

    Over time, repeated exposure to loud noise and music can cause hearing loss. Sounds above 80 decibels ( ... Airline ground maintenance Construction Farming Jobs involving loud music or machinery In the U.S., laws regulate the ...

  6. Weight Loss Surgery

    MedlinePlus

    ... loss surgery (especially gastric bypass). Doctors call this "dumping syndrome." It can cause nausea, weakness, sweating, cramping, ... high-sugar or high-fat foods can make dumping worse. Patients need to be careful about what ...

  7. Weight loss - unintentional

    MedlinePlus

    ... of laxatives Other causes such as: Eating disorders, anorexia nervosa that have not been diagnosed yet Diabetes that ... do not know the reason. You have other symptoms along with the weight loss.

  8. Muscle function loss

    MedlinePlus

    ... nervous system that cause muscle function loss include: Amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) Bell's palsy Botulism ... of recent progress. Curr Opin Rheum Read More Amyotrophic lateral sclerosis Botulism Broken bone Guillain-Barré syndrome Muscle cramps ...

  9. Hearing loss - infants

    MedlinePlus

    ... to sounds through play. These tests, known as visual response audiometry and play audiometry, can better determine ... the cause of hearing loss. Treatment may include: Speech therapy Learning sign language Cochlear implant (for those ...

  10. Sudden Sensorineural Hearing Loss

    PubMed Central

    Kuhn, Maggie; Heman-Ackah, Selena E.; Shaikh, Jamil A.

    2011-01-01

    Sudden sensorineural hearing loss (SSNHL) is commonly encountered in audiologic and otolaryngologic practice. SSNHL is most commonly defined as sensorineural hearing loss of 30dB or greater over at least three contiguous audiometric frequencies occurring within a 72-hr period. Although the differential for SSNHL is vast, for the majority of patients an etiologic factor is not identified. Treatment for SSNHL of known etiology is directed toward that agent, with poor hearing outcomes characteristic for discoverable etiologies that cause inner ear hair cell loss. Steroid therapy is the current mainstay of treatment of idiopathic SSNHL in the United States. The prognosis for hearing recovery for idiopathic SSNHL is dependent on a number of factors including the severity of hearing loss, age, presence of vertigo, and shape of the audiogram. PMID:21606048

  11. Hearing loss and music

    MedlinePlus

    ... iPod or MP3 Player The small ear bud style headphones (inserted into the ears) do not block ... Hearing Loss. National Institute on Deafness and Other Communication Disorders. NIH Pub. No. 14-4233. Updated: March ...

  12. Bone Loss in IBD

    MedlinePlus

    ... DENSITY? Although bone seems as hard as a rock, it’s actually living tissue. Throughout your life, old ... available Bone Loss (.pdf) File: 290 KB 733 Third Avenue, Suite 510, New York, NY 10017 | 800- ...

  13. Understanding Grief and Loss

    MedlinePlus

    ... Other common behaviors include restlessness and excessive activity. Religion and spirituality Grief and loss may also cause ... The grieving person’s age and gender The life history of the person who is grieving, including previous ...

  14. Coping with Memory Loss

    MedlinePlus

    ... either using computerized axial tomography (CAT) scans or magnetic resonance imaging (MRI) – can help to identify strokes and tumors, which can sometimes cause memory loss. “The goal is to rule out factors ...

  15. Nutrition, the gastrointestinal tract and the acquired immune deficiency syndrome. Facts and perspectives.

    PubMed

    Singer, P; Rothkopf, M M; Kvetan, V; Gaare, J; Mello, L; Askanazi, J

    1989-12-01

    Diarrhoea and malnutrition are common findings in patients with the Acquired Immune Deficiency Syndrome (AIDS). In this disease, enteropathy leads to fat and D-xylose malabsorption and chronic non-specific inflammation of the small bowel. Moreover, gastrointestinal infection can induce severe diarrhoea. Depletion in real body cell mass, body fat content, and weight loss have been observed. Nutritional therapy is mandatory when weight loss is 10% or greater. Enteral feeding is not easily achieved. Parenteral feeding including fat as a nonprotein calorie source improves general condition. The use of intravenous fat emulsions has been hypothesized to have several beneficial effects. Fluidisation of human immunodeficiency virus membranes by lipid emulsions through cholesterol extraction could decrease the infectivity of the virus. Long term intravenous nutrition may be more than a treatment for malabsorption and depletion; it may possibly have direct pharmacological effects. PMID:16837303

  16. Heat Loss Imagery

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Infrared scanning devices are being used to produce images that show, by color or black-and-white shading differences, which buildings and homes are losing heat to the outdoors, and how much. Heat loss surveys done by Texas Instruments, Daedalus Enterprises, Inc. and other companies have growing acceptance of their services among industrial firms, utilities, local governments, and state and federal agencies interested in promoting heat loss awareness and inspiring corrective actions.

  17. Allopurinol in the treatment of acquired reactive perforating collagenosis*

    PubMed Central

    Tilz, Hemma; Becker, Jürgen Christian; Legat, Franz; Schettini, Antonio Pedro Mendes; Inzinger, Martin; Massone, Cesare

    2013-01-01

    Acquired reactive perforating collagenosis is a perforating dermatosis usually associated with different systemic diseases, mainly diabetes mellitus and/or chronic renal insufficiency. Different therapies have been tried but treatment is not standardized yet and remains a challenge. In the last few years, allopurinol has been reported as a good therapeutic option for acquired reactive perforating collagenosis. We describe the case of a 73-year-old man affected by acquired reactive perforating collagenosis associated with diabetes type 1 and chronic renal failure with secondary hyperparathyroidism. The patient was successfully treated with allopurinol 100mg once/day p.o.. PMID:23539010

  18. [Antibiotic therapy of severe community-acquired pneumonia].

    PubMed

    Molchanova, O V; Suleĭmanov, S Sh; Ostrovskiĭ, A B

    2009-01-01

    Combined antibiotic therapy, including the use of intravenous cefotaxime (a beta-lactam) and azithromycin (a macrolide) was shown advantageous from both clinical and economic viewpoints in the treatment of severe community-acquired pneumonia. PMID:19711847

  19. Acquired localised hypertrichosis in a Chinese child after cast immobilisation.

    PubMed

    Yuen, M W; Lai, Loretta K P; Chan, P F; Chao, David V K

    2015-08-01

    Hypertrichosis refers to excessive hair growth that is independent of any androgen effect. Hypertrichosis could be congenital or acquired, localised or generalised. The phenomenon of acquired localised hypertrichosis following cast application for a fracture is well known to orthopaedic surgeons, but is rarely encountered by primary care physicians. We describe a 28-month-old Chinese boy who had fracture of right leg as a result of an injury. He had a cast applied by an orthopaedic surgeon as treatment. On removal of the cast 6 weeks later, he was noticed to have significant hair growth on his right leg compared with the left leg. The patient was reassessed 3 months after removal of the cast. The hypertrichosis resolved completely with time. This patient was one of the youngest among the reported cases of acquired localised hypertrichosis after cast application. We illustrate the significance of management of post-cast-acquired localised hypertrichosis in the primary care setting. PMID:26238136

  20. Infection Control and Prevention: A Review of Hospital-Acquired Infections and the Economic Implications

    PubMed Central

    Reed, Deoine; Kemmerly, Sandra A.

    2009-01-01

    The Centers for Disease Control and Prevention estimates that 2 million patients suffer from hospital-acquired infections every year and nearly 100,000 of them die. Most of these medical errors are preventable. Hospital-acquired infections result in up to $4.5 billion in additional healthcare expenses annually. The U.S. government has responded to this financial loss by focusing on healthcare quality report cards and by taking strong action to curb healthcare spending. The Medicare Program has proposed changes to the Hospital Inpatient Prospective Payment System and Fiscal Year Rates: Proposed Rule CMS 1488-P-Healthcare-associated infection. Payment will be linked to performance. Under the new rule, payment will be withheld from hospitals for care associated with treating certain catheter-associated urinary tract infections, vascular catheter-associated infections, and mediastinitis after coronary artery bypass graft surgery. Infection-prevention strategies are essential. In the healthcare setting, the infection control department is categorized as non-revenue-producing. Funds dedicated to resources such as staff, educational programs, and prevention measures are vastly limited. Hospital leaders will need to balance the upfront cost needed to prevent hospital-related infections with the non-reimbursed expense accrued secondary to potentially preventable infections. The purpose of this paper is to present case studies and cost analysis of hospital-acquired infections and present strategies that reduce infections and cost. PMID:21603406

  1. EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer.

    PubMed

    Amato, Katherine R; Wang, Shan; Tan, Li; Hastings, Andrew K; Song, Wenqiang; Lovly, Christine M; Meador, Catherine B; Ye, Fei; Lu, Pengcheng; Balko, Justin M; Colvin, Daniel C; Cates, Justin M; Pao, William; Gray, Nathanael S; Chen, Jin

    2016-01-15

    Despite the success of treating EGFR-mutant lung cancer patients with EGFR tyrosine kinase inhibitors (TKI), all patients eventually acquire resistance to these therapies. Although various resistance mechanisms have been described, there are currently no FDA-approved therapies that target alternative mechanisms to treat lung tumors with acquired resistance to first-line EGFR TKI agents. Here we found that EPHA2 is overexpressed in EGFR TKI-resistant tumor cells. Loss of EPHA2 reduced the viability of erlotinib-resistant tumor cells harboring EGFR(T790M) mutations in vitro and inhibited tumor growth and progression in an inducible EGFR(L858R+T790M)-mutant lung cancer model in vivo. Targeting EPHA2 in erlotinib-resistant cells decreased S6K1-mediated phosphorylation of cell death agonist BAD, resulting in reduced tumor cell proliferation and increased apoptosis. Furthermore, pharmacologic inhibition of EPHA2 by the small-molecule inhibitor ALW-II-41-27 decreased both survival and proliferation of erlotinib-resistant tumor cells and inhibited tumor growth in vivo. ALW-II-41-27 was also effective in decreasing viability of cells with acquired resistance to the third-generation EGFR TKI AZD9291. Collectively, these data define a role for EPHA2 in the maintenance of cell survival of TKI-resistant, EGFR-mutant lung cancer and indicate that EPHA2 may serve as a useful therapeutic target in TKI-resistant tumors. PMID:26744526

  2. [Differential diagnosis of pulmonary tuberculosis and community-acquired pneumonia].

    PubMed

    Deĭkina, O N; Mishin, V Iu; Demikhova, O V

    2007-01-01

    The purpose of this investigation was to enhance the efficiency of differential diagnosis of pneumonia and pulmonary tuberculosis. A hundred and fifty-nine adult patients were examined. These included 78 patients with pulmonary tuberculosis and 81 with community-acquired p neumonia. The clinical features of infiltrative pulmonary tuberculosis (n = 48) and mild community-acquired pneumonia (n = 51) were compared. The course of caseous pneumonia (n = 30) was compared with that of moderate and severe community-acquired pneumonia (n = 30). Significant differences in the manifestations of the intoxication and bronchopulmonary syndrome were not found in patients with community-acquired pneumonia and infiltrative pulmonary tuberculosis. Physical studies showed that in patients with community-acquired pneumonia, moist rale (54.9%) and crepitation (11.8%) were prevalent, but in those with infiltrative tuberculosis rale was absent in 60.4% of cases and the pattern of respiration was unchanged in 79.2%. Chest X-ray studies indicated that in patients with community-acquired pneumonia, lower lobar inflammatory changes were predominant in 62.8% of cases whereas in those with infiltrative pulmonary tuberculosis the process was mainly bilateral (43.8%) with the presence of destructive changes (83.3%) and bronchogenic dissemination (66.7%). In patients with caseous pneumonia, the intoxication syndrome was more significant than in those with severe community-acquired pneumonia. Chest X-ray studies demonstrated that in patients with caseous pneumonia, specific changes were bilateral with the involvement of 2 lobes or more, with destruction and bronchogenic dissemination while in those with community-acquired pneumonia, the pulmonary processes were predominantly bilateral (76.6%) at the lower lobar site (36.7%). PMID:17338353

  3. Using Repeated Reading and Explicit Instruction to Teach Vocabulary to Preschoolers with Hearing Loss

    ERIC Educational Resources Information Center

    Bobzien, Jonna L.; Richels, Corrin; Schwartz, Kathryn; Raver, Sharon A.; Hester, Peggy; Morin, Lisa

    2015-01-01

    Children with hearing loss often experience communication and language delays that result in difficulties acquiring novel vocabulary and literacy skills. This research examined the effectiveness of using repeated storybook reading paired with explicit teacher instruction to teach novel vocabulary to young children with hearing loss who were…

  4. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as a resident until...

  5. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as...

  6. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 9 2012-04-01 2012-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as...

  7. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 9 2011-04-01 2011-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as...

  8. 26 CFR 1.871-5 - Loss of residence by an alien.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 9 2014-04-01 2014-04-01 false Loss of residence by an alien. 1.871-5 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Nonresident Aliens and Foreign Corporations § 1.871-5 Loss of residence by an alien. An alien who has acquired residence in the United States retains his status as...

  9. Intensive care unit-acquired weakness in the burn population.

    PubMed

    Cubitt, Jonathan J; Davies, Menna; Lye, George; Evans, Janine; Combellack, Tom; Dickson, William; Nguyen, Dai Q

    2016-05-01

    Intensive care unit-acquired weakness is an evolving problem in the burn population. As patients are surviving injuries that previously would have been fatal, the focus of treatment is shifting from survival to long-term outcome. The rehabilitation of burn patients can be challenging; however, a certain subgroup of patients have worse outcomes than others. These patients may suffer from intensive care unit-acquired weakness, and their treatment, physiotherapy and expectations need to be adjusted accordingly. This study investigates the condition of intensive care unit-acquired weakness in our burn centre. We conducted a retrospective analysis of all the admissions to our burn centre between 2008 and 2012 and identified 22 patients who suffered from intensive care unit-acquired weakness. These patients were significantly younger with significantly larger burns than those without intensive care unit-acquired weakness. The known risk factors for intensive care unit-acquired weakness are commonplace in the burn population. The recovery of these patients is significantly affected by their weakness. PMID:26975787

  10. Losses in Ferroelectric Materials

    PubMed Central

    Liu, Gang; Zhang, Shujun; Jiang, Wenhua; Cao, Wenwu

    2015-01-01

    Ferroelectric materials are the best dielectric and piezoelectric materials known today. Since the discovery of barium titanate in the 1940s, lead zirconate titanate ceramics in the 1950s and relaxor-PT single crystals (such as lead magnesium niobate-lead titanate and lead zinc niobate-lead titanate) in the 1980s and 1990s, perovskite ferroelectric materials have been the dominating piezoelectric materials for electromechanical devices, and are widely used in sensors, actuators and ultrasonic transducers. Energy losses (or energy dissipation) in ferroelectrics are one of the most critical issues for high power devices, such as therapeutic ultrasonic transducers, large displacement actuators, SONAR projectors, and high frequency medical imaging transducers. The losses of ferroelectric materials have three distinct types, i.e., elastic, piezoelectric and dielectric losses. People have been investigating the mechanisms of these losses and are trying hard to control and minimize them so as to reduce performance degradation in electromechanical devices. There are impressive progresses made in the past several decades on this topic, but some confusions still exist. Therefore, a systematic review to define related concepts and clear up confusions is urgently in need. With this objective in mind, we provide here a comprehensive review on the energy losses in ferroelectrics, including related mechanisms, characterization techniques and collections of published data on many ferroelectric materials to provide a useful resource for interested scientists and engineers to design electromechanical devices and to gain a global perspective on the complex physical phenomena involved. More importantly, based on the analysis of available information, we proposed a general theoretical model to describe the inherent relationships among elastic, dielectric, piezoelectric and mechanical losses. For multi-domain ferroelectric single crystals and ceramics, intrinsic and extrinsic energy

  11. Fluid-loss control

    SciTech Connect

    Crowe, C.W.; Trittipo, B.L. ); Hutchinson, B.H. )

    1989-08-01

    Acid fluid loss is extremely difficult to control and is generally considered to be the major factor limiting the effectiveness of acid fracturing treatments. Chemical erosion of fracture faces and the development of wormholes are largely responsible for the reduced efficiency of acid fracturing fluids. The creation of acid wormholes increases the effective area from which leakoff occurs, thus reducing the acid hydraulic efficiency. Once wormholes form, most acid fluid loss originates from these wormholes rather than penetrating uniformly into the fracture face. Methods of acid fluid-loss control are discussed and evaluated with an improved fluid-loss test procedure. This procedure uses limestone cores of sufficient length to contain wormhole growth. Studies demonstrate that if wormhole growth can be controlled, acid fluid loss approaches that of nonreactive fluids. An improved acid fracturing fluid having unique rheological characteristics is described. This acid has a low initial viscosity but temporarily becomes extremely viscous during leakoff. This high leakoff viscosity blocks wormhole development and prevents acid entry into natural fractures. After the treatment, spent-acid viscosity declines rapidly to ensure easier cleanup.

  12. Economic losses due to catastrophes

    NASA Astrophysics Data System (ADS)

    Wendel, JoAnna

    2014-04-01

    Worldwide economic loss due to catastrophic events added up to US140 billion in 2013, with insured losses adding up to 45 billion, according to a report by the insurance provider Swiss Re. Though these numbers are down from 196 billion in economic losses and 81 billion in insurance losses in 2012, Swiss Re reports an upward trend in losses.

  13. Sleep Loss and Inflammation

    PubMed Central

    Simpson, Norah S.; Meier-Ewert, Hans K.; Haack, Monika

    2012-01-01

    Controlled, experimental studies on the effects of acute sleep loss in humans have shown that mediators of inflammation are altered by sleep loss. Elevations in these mediators have been found to occur in healthy, rigorously screened individuals undergoing experimental vigils of more than 24 hours, and have also been seen in response to various durations of sleep restricted to between 25 and 50% of a normal 8 hour sleep amount. While these altered profiles represent small changes, such sub-clinical shifts in basal inflammatory cytokines are known to be associated with the future development of metabolic syndrome disease in healthy, asymptomatic individuals. Although the mechanism of this altered inflammatory status in humans undergoing experimental sleep loss is unknown, it is likely that autonomic activation and metabolic changes play key roles. PMID:21112025

  14. Perioperative visual loss.

    PubMed

    Kla, Koffi M; Lee, Lorri A

    2016-03-01

    Perioperative visual loss is an infrequent, devastating complication associated with spine surgery, most commonly from ischemic optic neuropathy. Current research and expert opinion indicate that it is associated with procedures that create elevated venous pressure in the head for prolonged periods of time. The largest case-control study on ischemic optic neuropathy associated with spine surgery found six independent and significant risk factors including male sex, obesity, Wilson frame use, longer operative times, greater blood loss, and a lower colloid to crystalloid ratio in the non-blood fluid administration. The American Society of Anesthesiologists developed a practice advisory for the prevention of this complication. In this setting, it is advisable to avoid significant physiologic and hemodynamic perturbations as much as possible, given the uncertainty of the pathophysiology. Because prevention of this complication cannot be guaranteed, consent for perioperative visual loss should be strongly considered in patients at high risk for this complication. PMID:27036604

  15. Congenital sensorineural hearing loss

    SciTech Connect

    Mafee, M.F.; Selis, J.E.; Yannias, D.A.; Valvassori, G.E.; Pruzansky, S.; Applebaum, E.L.; Capek, V.

    1984-02-01

    The ears of 47 selected patients with congenital sensorineural hearing loss were examined with complex-motion tomography. The patients were divided into 3 general categories: those with a recognized syndrome, those with sensorineural hearing loss unrelated to any known syndrome, and those with microtia. A great variety of inner ear anomalies was detected, but rarely were these characteristic of a particular clinical entity. The most common finding was the Mondini malformation or one of its variants. Isolated dysplasia of the internal auditory canal or the vestibular aqueduct may be responsible for sensorineural hearing loss in some patients. Patients with microtia may also have severe inner ear abnormalities despite the fact that the outer and inner ears develop embryologically from completely separate systems.

  16. Female pattern hair loss.

    PubMed

    Ioannides, Dimitrios; Lazaridou, Elizabeth

    2015-01-01

    Female pattern hair loss, or female pattern androgenetic alopecia, is a nonscarring alopecia with a multi-factorial etiology that mostly affects postmenopausal women and is characterized by a reduction in hair density over the crown and frontal scalp. The clinical picture is characterized by a diffuse rarefaction of scalp hair over the mid-frontal scalp and a more-or-less intact frontal hairline without any signs of inflammation or scarring. Although the disease poses only a cosmetic concern, it is chronic and may have a significant negative psychological impact on the affected person. The aim of treating female pattern hair loss is to reduce hair loss and, to a certain extent, succeed in promoting hair regrowth. Various treatment methods are available, but it remains unclear which are the most effective. Early initiation of treatment and the combination of various modalities seem to be more efficacious than monotherapy. PMID:26370643

  17. Weight Loss Nutritional Supplements

    NASA Astrophysics Data System (ADS)

    Eckerson, Joan M.

    Obesity has reached what may be considered epidemic proportions in the United States, not only for adults but for children. Because of the medical implications and health care costs associated with obesity, as well as the negative social and psychological impacts, many individuals turn to nonprescription nutritional weight loss supplements hoping for a quick fix, and the weight loss industry has responded by offering a variety of products that generates billions of dollars each year in sales. Most nutritional weight loss supplements are purported to work by increasing energy expenditure, modulating carbohydrate or fat metabolism, increasing satiety, inducing diuresis, or blocking fat absorption. To review the literally hundreds of nutritional weight loss supplements available on the market today is well beyond the scope of this chapter. Therefore, several of the most commonly used supplements were selected for critical review, and practical recommendations are provided based on the findings of well controlled, randomized clinical trials that examined their efficacy. In most cases, the nutritional supplements reviewed either elicited no meaningful effect or resulted in changes in body weight and composition that are similar to what occurs through a restricted diet and exercise program. Although there is some evidence to suggest that herbal forms of ephedrine, such as ma huang, combined with caffeine or caffeine and aspirin (i.e., ECA stack) is effective for inducing moderate weight loss in overweight adults, because of the recent ban on ephedra manufacturers must now use ephedra-free ingredients, such as bitter orange, which do not appear to be as effective. The dietary fiber, glucomannan, also appears to hold some promise as a possible treatment for weight loss, but other related forms of dietary fiber, including guar gum and psyllium, are ineffective.

  18. Avoiding personal data loss.

    PubMed

    Bergeron, B P

    1999-01-01

    The potential personal, financial, emotional, and professional costs associated with the loss of data stored in personal computing devices are difficult to appreciate a priori. Because of the potentially devastating consequences of significant data loss, it behooves all clinicians to take personal responsibility in securing their data, whether or not this responsibility is nominally assumed by Information Systems (IS) professionals. There are a variety of straightforward, easily implemented approaches that can be used to help secure personal data, including investigating IS department policies, following proper backing-up procedures, observing reasonable security precautions, keeping digital media current, and establishing a process for executing these approaches. PMID:10725050

  19. Volumetric Muscle Loss.

    PubMed

    Pollot, Beth E; Corona, Benjamin T

    2016-01-01

    Volumetric muscle loss (VML) injury is prevalent in severe extremity trauma and is an emerging focus area among orthopedic and regenerative medicine fields. VML injuries are the result of an abrupt, frank loss of tissue and therefore of different etiology from other standard rodent injury models to include eccentric contraction, ischemia reperfusion, crush, and freeze injury. The current focus of many VML-related research efforts is to regenerate the lost muscle tissue and thereby improve muscle strength. Herein, we describe a VML model in the anterior compartment of the hindlimb that is permissible to repeated neuromuscular strength assessments and is validated in mouse, rat, and pig. PMID:27492162

  20. Oligoarray comparative genomic hybridization of renal cell tumors that developed in patients with acquired cystic renal disease.

    PubMed

    Kuntz, Eva; Yusenko, Maria V; Nagy, Anetta; Kovacs, Gyula

    2010-09-01

    Renal cell carcinoma occurs at higher frequency in acquired cystic renal disease than in the general population. We have analyzed 4 tumors obtained from the kidneys of 2 patients with acquired cystic renal disease, including 2 conventional renal cell carcinomas and 2 acquired cystic renal disease-associated tumors, for genetic alterations. DNA changes were established by applying the 44K Agilent Oligonucleotide Array-Based CGH (Agilent Technologies, Waldbronn, Germany), and mutation of VHL gene was detected by direct sequencing of the tumor genome. DNA losses and mutation of the VHL gene, which are characteristic for conventional renal cell carcinomas, were seen in 2 of the tumors. The acquired cystic renal disease-associated eosinophilic-vacuolated cell tumor showed gain of chromosomes 3 and 16. No DNA alterations occurred in the papillary clear cell tumor. We suggest that not only the morphology but also the genetics of renal cell tumors associated with acquired cystic renal disease may differ from those occurring in the general population. PMID:20646738

  1. Deafness and Hearing Loss.

    ERIC Educational Resources Information Center

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This brief overview provides information on the definition, incidence, and characteristics of children with hearing impairments and deafness. The federal definitions of hearing impairment and deafness are provided. The different types of hearing loss are noted, including: (1) conductive (caused by diseases or obstructions in the outer or middle…

  2. Autism and Hearing Loss.

    ERIC Educational Resources Information Center

    Rosenhall, Ulf; Nordin, Viviann; Sandstrom, Mikael; Ahlsen, Gunilla; Gillberg, Christopher

    1999-01-01

    Children and adolescents (N=199) with autistic disorder were audiologically evaluated. Mild to moderate hearing loss was diagnosed in 7.9 percent, with deafness diagnosed in 3.5 percent of all cases, which represented a prevalence considerably above that in the general population and comparable to the prevalence found in populations with mental…

  3. Pedagogical Reflections on Loss

    ERIC Educational Resources Information Center

    Stearns, Clio

    2013-01-01

    This article examines the idea of loss in relation to elementary education. The goal is to show the importance of teachers attending to their students' individual experience and, in particular, to the ways schools can make children feel lost or found. The article relies primarily on classroom narratives, focusing heavily on stories about one…

  4. Summer Reading Loss

    ERIC Educational Resources Information Center

    Mraz, Maryann; Rasinski, Timothy V.

    2007-01-01

    Summer reading loss is a documented reality for many students. It is often of greatest concern for those who are already at risk, who typically have limited access to reading materials at home and whose parents or caregivers may be reluctant or unsure of how to help. By raising parents' awareness of the importance of supporting their children's…

  5. Cascadia's Staggering Losses

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Vogt, B.

    2001-05-01

    Recent worldwide earthquakes have resulted in staggering losses. The Northridge, California; Kobe, Japan; Loma Prieta, California; Izmit, Turkey; Chi-Chi, Taiwan; and Bhuj, India earthquakes, which range from magnitudes 6.7 to 7.7, have all occurred near populated areas. These earthquakes have resulted in estimated losses between \\3 and \\300 billion, with tens to tens of thousands of fatalities. Subduction zones are capable of producing the largest earthquakes. The 1939 M7.8 Chilean, the 1960 M9.5 Chilean, the 1964 M9.2 Alaskan, the 1970 M7.8 Peruvian, the 1985 M7.9 Mexico City and the 2001 M7.7 Bhuj earthquakes are damaging subduction zone quakes. The Cascadia fault zone poses a tremendous hazard in the Pacific Northwest due to the ground shaking and tsunami inundation hazards combined with the population. To address the Cascadia subduction zone threat, the Oregon Department of Geology and Mineral Industries conducted a preliminary statewide loss study. The 1998 Oregon study incorporated a M8.5 quake, the influence of near surface soil effects and default building, social and economic data available in FEMA's HAZUS97 software. Direct financial losses are projected at over \\$12 billion. Casualties are estimated at about 13,000. Over 5,000 of the casualties are estimated to result in fatalities from hazards relating to tsunamis and unreinforced masonry buildings.

  6. Loss and damage

    NASA Astrophysics Data System (ADS)

    Huq, Saleemul; Roberts, Erin; Fenton, Adrian

    2013-11-01

    Loss and damage is a relative newcomer to the climate change agenda. It has the potential to reinvigorate existing mitigation and adaptation efforts, but this will ultimately require leadership from developed countries and enhanced understanding of several key issues, such as limits to adaptation.

  7. Diminished acquired equivalence yet good discrimination performance in older participants

    PubMed Central

    Robinson, Jasper; Owens, Emma

    2013-01-01

    We asked younger and older human participants to perform computer-based configural discriminations that were designed to detect acquired equivalence. Both groups solved the discriminations but only the younger participants demonstrated acquired equivalence. The discriminations involved learning the preferences [“like” (+) or “dislike” (−)] for sports [e.g., tennis (t) and hockey (h)] of four fictitious people [e.g., Alice (A), Beth (B), Charlotte (C), and Dorothy (D)]. In one experiment, the discrimination had the form: At+, Bt−, Ct+, Dt−, Ah−, Bh+, Ch−, Dh+. Notice that, e.g., Alice and Charlotte are “equivalent” in liking tennis but disliking hockey. Acquired equivalence was assessed in ancillary components of the discrimination (e.g., by looking at the subsequent rate of “whole” versus “partial” reversal learning). Acquired equivalence is anticipated by a network whose hidden units are shared when inputs (e.g., A and C) signal the same outcome (e.g., +) when accompanied by the same input (t). One interpretation of these results is that there are age-related differences in the mechanisms of configural acquired equivalence. PMID:24130542

  8. Hearing Loss in Children: Types of Hearing Loss

    MedlinePlus

    ... the ear to the brain so that our brain pathways are part of our hearing. There are four types of hearing loss: Conductive Hearing Loss Hearing loss caused by something that stops sounds from getting through the outer or middle ear. This type of hearing loss can often ...

  9. A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice

    PubMed Central

    Tuzovic, Lea; Yu, Lan; Zeng, Wenqi; Li, Xiang; Lu, Hong; Lu, Hsiao-Mei; Gonzalez, Kelly DF; Chung, Wendy K

    2013-01-01

    We used whole exome sequence analysis to investigate a possible genetic etiology for a patient with the phenotype of intrauterine growth restriction, microcephaly, developmental delay, failure to thrive, congenital bilateral hip dysplasia, cerebral and cerebellar atrophy, hydrocephalus, and congenital diaphragmatic hernia (CDH). Whole exome sequencing identified a novel de novo c.2722G > T (p.E908X) mutation in the Myosin Heavy Chain 10 gene (MYH10) which encodes for non-muscle heavy chain II B (NMHC IIB). Mutations in MYH10 have not been previously described in association with human disease. The E908X mutation is located in the coiled-coil region of the protein and is expected to delete the tail domain and disrupt filament assembly. Nonmuscle myosin IIs (NM IIs) are a group of ubiquitously expressed proteins, and NM II B is specifically enriched in neuronal tissue and is thought to be important in neuronal migration. It is also expressed in cardiac myocytes along with NM IIC. Homozygous NMHC II B-/B- mouse knockouts die by embryonic day (E)14.5 with severe cardiac defects (membranous ventricular septal defect and cardiac outflow tract abnormalities) and neurodevelopmental disorders (progressive hydrocephalus and neuronal migrational abnormalities). A heterozygous MYH10 loss of function mutation produces a severe neurologic phenotype and CDH but no apparent cardiac phenotype and suggests that MYH10 may represent a novel gene for brain malformations and/or CDH. PMID:25003005

  10. Evolution of acquired resistance to anti-cancer therapy

    PubMed Central

    Foo, Jasmine; Michor, Franziska

    2014-01-01

    Acquired drug resistance is a major limitation for the successful treatment of cancer. Resistance can emerge due to a variety of reasons including host environmental factors as well as genetic or epigenetic alterations in the cancer cells. Evolutionary theory has contributed to the understanding of the dynamics of resistance mutations in a cancer cell population, the risk of resistance pre-existing before the initiation of therapy, the composition of drug cocktails necessary to prevent the emergence of resistance, and optimum drug administration schedules for patient populations at risk of evolving acquired resistance. Here we review recent advances towards elucidating the evolutionary dynamics of acquired drug resistance and outline how evolutionary thinking can contribute to outstanding questions in the field. PMID:24681298

  11. Free Auricular Composite Graft for Acquired Nasal Stenosis

    PubMed Central

    Riley, Charles A.; Lawlor, Claire M.; Gray, Mingyang Liu; Graham, H. Devon

    2016-01-01

    Background: Acquired nasal stenosis poses a reconstructive challenge for the facial plastic surgeon. Many surgical options are available, ranging from primary closure to skin grafts to free flap reconstruction for complex defects. The free auricular composite graft is a single-stage procedure that can be used to repair nasal vestibular stenosis causing nasal obstruction. Case Report: We present the case of a patient with acquired nasal stenosis as a result of prolonged nasal tampon placement secondary to severe epistaxis and subsequent nasal vestibular infection. Repair via auricular composite graft was successful, and we provide a thorough explanation of graft design and operative technique. Conclusion: Free auricular composite grafts can produce desirable functional and aesthetic outcomes and should be considered in patients presenting with acquired nasal stenosis. PMID:27303225

  12. ACQUIRE: A data acquisition system for CAMAC on SUN workstations

    SciTech Connect

    Kouzes, R.T. ); Lowry, M.M. )

    1994-02-01

    The data acquisition software package ACQUIRE has been used for many years by the Princeton University Cyclotron Laboratory for nuclear physics research applications. This code has been ported to the SUN Sparc workstation and is fully functional, including block data transfers using an in crate Event Handler. A SCSI interface to CAMAC is utilized, and the device handling software has been developed in such a way that little modification was needed in the ACQUIRE code for the SUN implementation. The Higz X windows graphics package from CERN is used for data display. ACQUIRE will be used for test and development of CAMAC based systems within the Molecular Science Research Center at Pacific Northwest Laboratory.

  13. Staphylococci in community-acquired infections: Increased resistance to penicillin.

    PubMed

    Hughes, G B; Chidi, C C; Macon, W L

    1976-04-01

    One hundred patients with community-acquired staphylococcal infections of the skin and soft tissues were treated in the Emergency Ward of Cleveland Metropolitan General Hospital from June to October of 1974. Each staphylococcal infection was considered community-acquired if, within two weeks prior to being treated for the first time, the patient had not received antibiotics, had not been hospitalized, and had not been in contact with other recently hospitalized persons. Of 100 community-acquired staphylococcal infections, 85 were resistant to penicillin. Almost no resistance to other tested antibiotics was observed. Unless indicated otherwise by bacteriologic testing, penicillin is a poor drug of choice in those skin and soft tissue infections suspected of harboring staphylococci. PMID:1267491

  14. Acquired night blindness due to bad eating patterns.

    PubMed

    Parafita-Fernández, A; Escalona-Fermín, M M; Sampil, M; Moraña, N; Viso, E; Fernández-Vila, P C

    2015-06-01

    We report a case of acquired night blindness in a developed country (Spain) without risk factors for nutritional deficiency disease or family history of hereditary retinal disease. A 76-year-old woman presented with acquired night blindness of 6-month progression. After a thorough inquiry about eating patterns she becomes suspicious of vitamin A low dietary intake, which is analytically confirmed and successfully treated. Despite being very uncommon in our environment and even more in patients without digestive problems, in a patient reporting acquired night blindness vitamin A deficiency should not be discarded until eating patterns have been investigated. It might be especially relevant in certain socioeconomic situations and eating disorders such as bulimia or anorexia nervosa. PMID:25804276

  15. Imaging of acquired coronary diseases: From children to adults.

    PubMed

    Dehaene, A; Jacquier, A; Falque, C; Gorincour, G; Gaubert, J Y

    2016-05-01

    Acquired coronary diseases include aneurysms, fistulae, dissections, and stenosis. Aneurysms may occur secondarily to Kawasaki disease, a childhood vasculitis, the prognosis of which depends on the coronary involvement, or they may be degenerative, infectious, inflammatory, or traumatic in origin. Fistulae develop between the coronary arterial system and a pulmonary or bronchial artery, or cardiac cavity. Dissections may occur spontaneously or may be post-traumatic. These coronary abnormalities may be found incidentally or may present as complications, infarction or rupture. The goals of this article are to understand acquired childhood and adult coronary diseases and their usual means of presentation, the ways of investigating them, and the principles of their treatment. PMID:27130480

  16. [Features of morbidity community-acquired pneumonia among young recruits].

    PubMed

    Serdukov, D U; Gordienko, A V; Kozlov, M S; Mikhailov, A A; Davydov, P A

    2015-10-01

    Were examined 3338 military personnel of the combined training center. 183 of them diagnosed community-acquired pneumonia, in 3155 focal and infiltrative changes in lung tissue were not identified. The analisys of prevalence been made among young recruits of the acute respiratory illness before arriving in part and at the assembly point, foci of chronic infection, smoking, low body weight. 511 military personnel arrived at the training center in the disease state with symptoms of acute respiratory illness. Examined the relationship these risk factor to the development of community-acquired pneumonia in this category of servicemen. PMID:26827502

  17. Acquired coagulation factor XIII deficiency: a case report.

    PubMed

    Jia, Yongqing; Hu, Huixian; Wei, Bin

    2016-06-01

    The main objective of the study is to summarize the clinical characteristics of acquired factor XIII (FXIII) deficiency caused by a spontaneous FXIII inhibitor. Here we report a new case of acquired FXIII deficiency caused by FXIII inhibitor and review the medical literature regarding the characteristics and treatment of this disorder. FXIII deficiency caused by FXIII inhibitors is rare and of uncertain pathogenesis. Experience with therapeutic measures is limited to data from case reports. Immunosuppressive drugs may reduce autoantibodies or inhibit the cell clone generating the antibodies and may have been of benefit in our patient. The impact of such therapy on patient prognosis is incompletely known. PMID:26588447

  18. Acquired hemophilia A in a patient with systemic lupus erythematosus.

    PubMed

    Ishikawa, T; Tsukamoto, N; Suto, M; Uchiumi, H; Mitsuhashi, H; Yokohama, A; Maesawa, A; Nojima, Y; Naruse, T

    2001-06-01

    A patient with systemic lupus erythematosus (SLE) developed acquired hemophilia A. The patient, a 24-year-old Japanese woman, was referred to our hospital because of uncontrollable bleeding following a tooth extraction. Laboratory examination revealed prolonged APTT (116 seconds), reduced factor VIII activity (2.8 %) and the presence of factor VIII inhibitor at a titer of 46.5 Bethesda units/ml. Transfusion of prothrombin complex concentrate and activated prothrombin complex concentrate followed by administration of prednisolone and cyclophosphamide successfully arrested bleeding and reduced the factor VIII inhibitor level. Acquired hemophilia A is a rare but lethal condition. Rapid diagnosis and introduction of adequate therapies are critical. PMID:11446683

  19. Geophysical weight loss diet

    NASA Astrophysics Data System (ADS)

    Schatten, Kenneth

    1984-04-01

    Having for numerous reasons acquired a three digit kilogram mass, the author is experienced at the painful struggles that the gourmand must suffer to reduce weight, particularly if he/she enjoys reasonably large amounts of good food. To the avant-garde geophysicist, utilizing the following approach could be pleasurable, rewarding, and may even enable the accomplishment of what Ghengis Khan, Alexander the Great, Napolean, and Hitler could not!The basic approach is the full utilization of Newton's formula for the attraction of two massive bodies: F=GM1M2/r2, where G, is the gravitational constant; r, the distance between the two bodies; and M1 and M2, the masses of the two bodies. Although one usually chooses M1 to be the earth's mass ME and M2 to be the mass of a small object, this unnecessarily restricts the realm of phenomena. The less restrictive assumption is M1 + M2 = ME.

  20. Adolescent pregnancy and loss.

    PubMed

    Bright, P D

    1987-01-01

    Adolescents have a perinatal and infant mortality rate two times as high as that found in the adult population, and yet few have investigated the characteristics of adolescent grief over pregnancy loss. The mourning response of adolescents appears to differ from that of older females: adult signs of depression are either nonexistent or fleeting. Adolescents who are having difficulties moving away from dependence on their mothers may become pregnant in order to demonstrate a semblance of adulthood and also to circumvent the depression common to this phase of development. When reproductive loss occurs, two outcomes often are seen: mother-daughter conflict concerning independence accelerates, which, in turn, provides the impetus for re-impregnation soon afterward. Since pregnancy interferes with mourning, the adolescent may not be able to bond with subsequent children, thus continuing the mother-child conflict into another generation. PMID:3649521