Alien Registration- Dube, Marie A. (Lewiston, Androscoggin County)

https://digitalmaine.com/alien_docs/29471/thumbnail.jp

Alien Registration- Dube, Marie A. (Lewiston, Androscoggin County)

https://digitalmaine.com/alien_docs/29471/thumbnail.jp

A novel PLP1 mutation further expands the clinical heterogeneity at the locus

Objectives: To characterize at clinical and molecular levels a family presenting with X-linked recessive Hereditary Spastic Paraplegia (HSP). Background: HSPs are a large group of genetically heterogeneous neurodegenerative disorders characterized by progressive upper motor neuron signs. Mutations in the proteolipid protein (PLP1) gene have been identified in families linked to the SPG2 locus on chromosome Xq22. However, Pelizaeus-Merzbacher disease (PMD) is also an X-linked recessive neurological disorder caused by PLP1 mutations. Methods: The SPG2 locus was investigated by linkage analysis in the family. The PLP1 gene was screened by sequencing. We present findings in a large French-Canadian family with an X-linked recessive HSP. The proband presented early with developmental delay and developed progressive spastic paraplegia. He has been wheelchair-bound since the age of three years. At the latest follow-up, he was 20 years-old and had severe spasticity predominantly affecting the lower extremities, moderate cerebellar dysfunction, and optic atrophy. Results: Linkage to SPG2 was established and a G to A mutation (MIR) in the initiation codon of the PLP1 gene was identified, likely resulting in the complete absence of proteolipid protein. Conclusions: We report a new PLP1 gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome

Including diverse and admixed populations in genetic epidemiology research

The inclusion of ancestrally diverse participants in genetic studies can lead to new discoveries and is important to ensure equitable health care benefit from research advances. Here, members of the Ethical, Legal, Social, Implications (ELSI) committee of the International Genetic Epidemiology Society (IGES) offer perspectives on methods and analysis tools for the conduct of inclusive genetic epidemiology research, with a focus on admixed and ancestrally diverse populations in support of reproducible research practices. We emphasize the importance of distinguishing socially defined population categorizations from genetic ancestry in the design, analysis, reporting, and interpretation of genetic epidemiology research findings. Finally, we discuss the current state of genomic resources used in genetic association studies, functional interpretation, and clinical and public health translation of genomic findings with respect to diverse populations

"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire

Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work

Unexpected random urinary protein:creatinine ratio results-limitations of the pyrocatechol violet-dye method.

BACKGROUND: For clinicians, it is important to rely on accurate laboratory results for patient care and optimal use of health care resources. We sought to explore our observations that urine protein:creatinine ratios (PrCr) ≥30 mg/mmol are seen not infrequently associated with normal pregnancy outcome. METHODS: Urine samples were collected prospectively from 160 pregnant women attending high-risk maternity clinics at a tertiary care facility. Urinary protein was measured using a pyrocatechol violet assay and urinary creatinine by an enzymatic method on Vitros analysers. Maternal/perinatal outcomes were abstracted from hospital records. RESULTS: 91/233 (39.1%) samples had a PrCr ≥30 mg/mmol, especially when urinary creatinine concentration was <3 mM (94.1%) vs. ≥3 mM (16.4%) (p < 0.001). When using the last sample before delivery, 47/160 (29.4%) had a PrCr ≥30 mg/mmol in diluted urine vs. only 17/160 (15.4%) in more concentrated urine (p < 0.001); PrCr positive results were also more frequent among the 32 (20.0%) women with known normal pregnancy outcome (90.9% vs. 0) (p < 0.001). Using the same analyser, 0.12 g/L urinary protein was 'detected' in deionised water. Re-analysis of data from two cohorts revealed substantially less inflation of PrCr in dilute urine using a pyrogallol red assay. CONCLUSIONS: Random urinary PrCr was overestimated in dilute urine when tested using a common pyrocatechol violet dye-based method. This effect was reduced in cohorts when pyrogallol red assays were used. False positive results can impact on diagnosis and patient care. This highlights the need for both clinical and laboratory quality improvement projects and standardization of laboratory protein measurement

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices—such as population-level screening for lung cancer—are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens

How Can the EU Beating Cancer Plan Help in Tackling Lung Cancer, Colorectal Cancer, Breast Cancer and Melanoma?

Cancer is the second leading cause of mortality in EU countries, and the needs to tackle cancer are obvious. New scientific understanding, techniques and methodologies are opening up horizons for significant improvements in diagnosis and care. However, take-up is uneven, research needs and potential outstrip currently available resources, manifestly beneficial practices—such as population-level screening for lung cancer—are still not generalised, and the quality of life of patients and survivors is only beginning to be given attention it merits. This paper, mainly based on a series of multistakeholder expert workshops organised by the European Alliance for Personalised Medicine (EAPM), looks at some of those specifics in the interest of planning a way forward. Part of this exercise also involves taking account of the specific nature of Europe and its constituent countries, where the complexities of planning a way forward are redoubled by the wide variations in national and regional approaches to cancer, local epidemiology and the wide disparities in health systems. Despite all the differences between cancers and national and regional resources and approaches to cancer care, there is a common objective in pursuing broader and more equal access to the best available care for all European citizens

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Counteraction of Tetherin Antiviral Activity by Two Closely Related SIVs Differing by the Presence of a Vpu Gene

In different primate lentiviruses, three proteins (Vpu, Env and Nef) have been shown to have anti-tetherin activities. SIVden is a primate lentivirus harbored by a Cercopithecus denti (C. denti) whose genome code for a Vpu gene. We have compared the activity of HIV-1 Vpu and of SIVden Vpu on tetherin proteins from humans, from C. denti and from Cercopithecus neglectus (C. neglectus), a monkey species that is naturally infected by SIVdeb, a virus closely related to SIVden but which does not encode a Vpu protein. Here, we demonstrate that SIVden Vpu, is active against C. denti tetherin, but not against human tetherin. Interestingly, C. neglectus tetherin was more sensitive to SIVden Vpu than to HIV-1 Vpu. We also identify residues in the tetherin transmembrane domains that are responsible for the species-specific Vpu effect. Simultaneous mutation (P40L and T45I) of human tetherin conferred sensitivity to SIVden Vpu, while abolishing its sensitivity to HIV-1 Vpu. We next analyzed the anti-tetherin activity of the Nef proteins from HIV-1, SIVden and SIVdeb. All three Nef proteins were unable to rescue virus release in the presence of human or C. denti tetherin. Conversely, SIVdeb Nef enhanced virus release in the presence of C. neglectus tetherin, suggesting that SIVdeb relies on Nef in its natural host. Finally, while HIV-1 Vpu not only removed human tetherin from the cell surface but also directed it for degradation, SIVden Vpu only induced the redistribution of both C. denti and C. neglectus tetherins, resulting in a predominantly perinuclear localization