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Legal actions determine the allocation and magnitude of climate-related financial risk exposures.
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Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.
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Facies , Glucuronidasa/genética , Enfermedades Urológicas/genética , Encéfalo/metabolismo , Niño , Preescolar , Mapeo Cromosómico , Cromosomas Humanos Par 10 , Femenino , Genes Recesivos , Glucuronidasa/química , Glucuronidasa/metabolismo , Humanos , Masculino , Modelos Moleculares , Músculos/metabolismo , Mutación , Linaje , Síndrome , Vejiga Urinaria/metabolismoRESUMEN
Climate targets that depend heavily on CO2 removal may contravene international law.
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The question of whether, how, and to what extent climate change is affecting health is central to many climate and health studies. We describe a set of formal methods, termed detection and attribution, used by climatologists to determine whether a climate trend or extreme event has changed and to estimate the extent to which climate change influenced that change. We discuss events where changing weather patterns were attributed to climate change and extend these analyses to include health impacts from heat waves in 2018 and 2019 in Europe and Japan, and we show how such impact attribution could be applied to melting ice roads in the Arctic. Documenting the causal chain from emissions of greenhouse gases to observed human health outcomes is important input into risk assessments that prioritize health system preparedness and response interventions and into financial investments and communication about potential risk to policy makers and to the public.
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Cambio Climático , Tiempo (Meteorología) , Europa (Continente) , Humanos , Japón , Salud Pública , Medición de RiesgoRESUMEN
We describe a further patient with cranio-cerebellar-cardiac or 3C syndrome. She presented with the characteristic features of Dandy-Walker malformation of the brain, congenital cardiac defect, dysmorphic facies and post-natal growth failure. She had gastro-oesophageal reflux and severe feeding difficulties which are still present at the age of four years. Despite her numerous medical problems, she is demonstrating near-normal development. Feeding difficulties appear to be a prominent feature of the 3C syndrome.
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Anomalías Múltiples/diagnóstico , Cerebelo/anomalías , Anomalías Craneofaciales/patología , Síndrome de Dandy-Walker/diagnóstico , Cardiopatías Congénitas/patología , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Preescolar , Síndrome de Dandy-Walker/patología , Diagnóstico Diferencial , Facies , Trastornos de Alimentación y de la Ingestión de Alimentos/patología , Femenino , Reflujo Gastroesofágico/diagnóstico , Humanos , Uñas Malformadas , Pakistán/etnología , SíndromeRESUMEN
A 52-year-old man presented with sudden onset symptoms of multiple cranial nerve palsies (IX, X and XII) following a 10-day history of coryzal illness. Follow-up examination established atrophy of the trapezius suggesting additional involvement of the spinal accessory nerve (XI). Further investigation including CT and MRI demonstrated dissection of the internal carotid artery. Given the involvement of cranial nerves IX to XII, and that the patient demonstrated no signs of Horner's syndrome, we suggested that this patient fits the description of Collet-Sicard syndrome. On vascular opinion the carotid dissection was expected to resolve without intervention but the patient was prescribed aspirin for thromboprophylaxis. Gradual resolution of neurological symptoms was observed at 8-week follow-up.
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Disección de la Arteria Carótida Interna/complicaciones , Enfermedades de los Nervios Craneales/etiología , Disección de la Arteria Carótida Interna/patología , Humanos , Masculino , Persona de Mediana Edad , SíndromeRESUMEN
The 3q29 microdeletion syndrome is caused by a recurrent 1.6 Mb deletion of the 3q subtelomeric region. Though sometimes visible on routine microscopy, the deletion is detected more reliably using subtelomeric fluorescence in-situ hybridization (FISH) or molecular karyotyping. The clinical features associated with a 3q29 microdeletion are variable and include developmental delay, autistic features, skeletal abnormalities and dysmorphic facial features with a relatively long face, long nose with a high bridge and broad tip, short philtrum and large ears. Orofacial clefting, cardiac defects, ocular anomalies and genitourinary malformations have been reported occasionally. We report a three generation family where four individuals were confirmed to have a 3q29 microdeletion and compare their clinical features to those of previously reported patients. This family shows that the learning difficulties associated with a 3q29 deletion may be relatively mild. The history of a severe depressive disorder commencing in adulthood in the affected grandmother also supports previous studies linking the 3q29 region to bipolar disorder and links with the observation of Digilio et al. (2009) who also reported a history of depression in an adult woman with a similar deletion.
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Trastorno Bipolar/genética , Deleción Cromosómica , Cromosomas Humanos Par 3/genética , Adolescente , Niño , Preescolar , Familia , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Linaje , Embarazo , SíndromeRESUMEN
Cystic transformation of the lungs in Proteus syndrome is considered an important manifestation of this disease. We describe a case of an 11-year-old girl with a diagnosis of Proteus syndrome with lung involvement. Low-dose multidetector computed tomography (CT) revealed extensive diffuse cystic lung disease with left lung predominance, affecting mostly the lower lung zones. The cystic lesions had various sizes and variable wall thickness. Postprocessing using CT histogram densitometric volumetry software (CT densitovolumetry), using the threshold -950 Houndsfield units (HU) for quantifying emphysema, revealed that 31% of her total lung volume was composed of areas with CT attenuation values below -950 HU.
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Enfermedades Pulmonares/diagnóstico por imagen , Síndrome de Proteo/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Niño , Femenino , Humanos , Interpretación de Imagen Radiográfica Asistida por Computador , Radiografía TorácicaRESUMEN
Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability and recurrent pneumonia. We identified an Xq28 duplication in three families where several male patients had presented with intestinal pseudo-obstruction or bladder distension. The affected boys had similar dysmorphic facial appearances. Subsequently, we ascertained seven further families where the proband presented with similar features. We demonstrated duplications of the Xq28 region in five of these additional families. In addition to MECP2, these duplications encompassed several other genes already known to be associated with diseases including SLC6A8, L1CAM and Filamin A (FLNA). The two remaining families were shown to have intragenic duplications of FLNA only. We discuss which elements of the Xq28 duplication phenotype may be associated with the various genes in the duplication. We propose that duplication of FLNA may contribute to the bowel and bladder phenotype seen in these seven families.