scholarly journals Differences in Peripheral Neuropathy in  Xeroderma Pigmentosum Complementation Groups A and D

2021 ◽  
Author(s):  
Tanya Lehky ◽  
Paul E. Sackstein ◽  
Deborah Tamura ◽  
Martha Quezado ◽  
Tianxia Wu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Peripheral Neuropathy ◽  
Brain Imaging ◽  
Excision Repair ◽  
Genetic Disorder ◽  
Sensory Neuropathy ◽  
Institutional Review Boards ◽  
Clinical Indicators ◽  
Institutional Review ◽  
Complementation Groups

Abstract BACKGROUNDXeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder with defective DNA nucleotide excision repair and associated with a high frequency of skin cancer. Approximately 25% of patients develop progressive neurological degeneration. Complementation groups XP-A and XP-D are most frequently associated with neurological disorders. METHODSThis is a retrospective review of patients with XP who were evaluated at NIH from 1986 to 2015 and had nerve conduction studies (NCS). Audiological, brain imaging, neuropsychological assessments were also performed on most of the patients. Limited neuropathology of XP-A and XP-D patients were compared. RESULTSThe 33 patients had NCS: XP-A (9 patients), XP-C (7 patients), XP-D (10 patients), XP-E (1 patient), XP-V (4 patients), and XP-unknown (2 patients). Peripheral neuropathy was documented only in two complementation groups: 78% (7/9) of XP-A patients had a sensorimotor neuropathy while 50% (5/10) of XP-D patients had a sensory neuropathy only. The severity of the neuropathy correlated with hearing loss. CONCLUSIONSDespite similar brain imaging and audiological findings patients, XP-A and XP-D complementation groups differ in the type of neuropathy, sensorimotor versus sensory alone. A few cases suggest that sensorineural hearing loss and absent deep tendon reflexes may precede abnormal NCS in XP and therefore serve as valuable clinical indicators of XP patients that will later develop peripheral neuropathy. TRIAL REGISTRATION: Patients were evaluated under clinical protocols, NCT00001813 and NCT00046189, approved by the NIH Institutional Review Boards.

scholarly journals Differences in peripheral neuropathy in xeroderma pigmentosum complementation groups A and D as evaluated by nerve conduction studies

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tanya J. Lehky ◽  
Paul Sackstein ◽  
Deborah Tamura ◽  
Martha Quezado ◽  
Tianxia Wu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Peripheral Neuropathy ◽  
Sensorineural Hearing Loss ◽  
Brain Imaging ◽  
Nerve Conduction ◽  
Xeroderma Pigmentosum ◽  
Nerve Conduction Studies ◽  
Sensorineural Hearing ◽  
Rapid Progression ◽  
Complementation Groups

Abstract Background Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder with defective DNA nucleotide excision repair and associated with a high frequency of skin cancer. Approximately 25% of patients develop progressive neurological degeneration. Complementation groups XP-A and XP-D are most frequently associated with neurological disorders. Design/methods This is a retrospective review of patients with XP who were evaluated at NIH from 1986 to 2015 and had nerve conduction studies (NCS). In the complementation groups with peripheral neuropathy, further comparisons of the NCS were made with audiological, brain imaging, neuropsychological assessments that were also performed on most of the patients. Limited neuropathology of XP-A and XP-D patients were examined.. Results The 33 patients had NCS: XP-A (9 patients), XP-C (7 patients), XP-D (10 patients), XP-E (1 patient), XP-V (4 patients), and XP-unknown (2 patients). Peripheral neuropathy based on nerve conduction studies was documented only in two complementation groups: 78% (7/9) of XP-A patients had a sensorimotor neuropathy while 50% (5/10) of XP-D patients had a sensory neuropathy only. Analysis of sural sensory nerve amplitude in both complementation groups XP-A and XP-D correlated with sensorineural hearing loss (SNHL), MRI/CT severity, and Full-scale Intelligence Quotient (IQ). Analysis of fibular motor nerve amplitude in complementation XP-A correlated with SNHL and MRI/CT severity. Limited follow-up studies showed gradual loss of NCS responses compared to an earlier and more rapid progression of the hearing loss. Conclusions Despite similar brain imaging and audiological findings patients, XP-A and XP-D complementation groups differ in the type of neuropathy, sensorimotor versus sensory alone. A few cases suggest that sensorineural hearing loss may precede abnormal NCS in XP and therefore serve as valuable clinical indicators of XP patients that will later develop peripheral neuropathy.

scholarly journals Barriers to Development of an App for Improving Staff-Family Communication at Israeli Geriatric Facilities

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 192-193
Author(s):  
Rinat Cohen ◽  
Gal Maydan ◽  
Shai Brill ◽  
Jiska Cohen-Mansfield
Keyword(s):  
Mobile App ◽  
Institutional Review Boards ◽  
Staff Members ◽  
Institutional Review ◽  
Implementation Planning ◽  
Institutional Adoption ◽  
Communication Needs ◽  
The University ◽  
And Control ◽  
To Receive

Abstract Family caregivers (FCs) of institutionalized noncommunicative older persons reported multiple unmet communication needs focusing on the need to receive reliable and regular updates on the patient’s condition. We have developed a mobile app for improving communication between FCs and healthcare professionals (HPs), based on 152 interviews with FCs and 13 discussion groups with HPs from four Israeli geriatric facilities. Both parties participated in app planning, tailoring it to their needs and abilities. App use implementation encountered major obstacles including the bureaucratic process concerning signing contracts between the university and software development firms, which hindered the process for a full year; data security department required disproportionate security levels that interfered with user experience and delayed the development process; the study’s definition varied across different ethics/Helsinki committees (Institutional Review Boards; IRBs), which led to different demands, e.g., insurance for medical clinical trials although no drugs or medical device were involved; lack of cooperation by mid-level staff members despite the institutional adoption of the app project; low utilization by HPs resulted in FCs not receiving timely responses. Despite these and other obstacles, we tested app use for 15 months in one facility in a pre-post-design with intervention and control groups, and we have since begun testing it in another facility. FCs who had used the app had positive feedback and wished to continue using it. App use optimization requires implementation planning, assimilating changes in each facility’s work procedures and HP’s engagement and motivation and thus depends on institutional procedures and politics.

MRI Research Proposals Involving Child Subjects: Concerns Hindering Research Ethics Boards from Approving Them and a Checklist to Help Evaluate Them

2011 ◽  
Vol 20 (1) ◽  
pp. 115-129 ◽  
Author(s):  
J. DEBORAH SHILOFF ◽  
BRYAN MAGWOOD ◽  
KRISZTINA L. MALISZA
Keyword(s):  
United States ◽  
Research Ethics ◽  
Gold Standard ◽  
The United States ◽  
Institutional Review Boards ◽  
Scientific Review ◽  
Initial Development ◽  
Institutional Review ◽  
Research Ethics Boards ◽  
A Current

The process of research is often lengthy and can be extremely arduous. It may take many years to proceed from the initial development of an idea through to the comparison of the new modalities against a current gold-standard practice. Each step along the way involves rigorous scientific review, where protocols are scrutinized by multiple scientists not only in the specific field at hand but related fields as well. In addition to scientific review, most countries require a further review by a panel that will specifically address the ethics of the proposed research. In Canada, those panels are referred to as Research Ethics Boards (REB), with the United States counterparts known as Institutional Review Boards (IRB).

scholarly journals UV-induced Hyperphosphorylation of Replication Protein A Depends on DNA Replication and Expression of ATM Protein

2001 ◽  
Vol 12 (5) ◽  
pp. 1199-1213 ◽  
Author(s):  
Gregory G. Oakley ◽  
Lisa I. Loberg ◽  
Jiaqin Yao ◽  
Mary A. Risinger ◽  
Remy L. Yunker ◽  
...  
Keyword(s):  
Dna Replication ◽  
Uv Radiation ◽  
Excision Repair ◽  
Genetic Disorder ◽  
Protein A ◽  
Dna Recombination ◽  
Delayed Response ◽  
Replication Intermediates

Exposure to DNA-damaging agents triggers signal transduction pathways that are thought to play a role in maintenance of genomic stability. A key protein in the cellular processes of nucleotide excision repair, DNA recombination, and DNA double-strand break repair is the single-stranded DNA binding protein, RPA. We showed previously that the p34 subunit of RPA becomes hyperphosphorylated as a delayed response (4–8 h) to UV radiation (10–30 J/m2). Here we show that UV-induced RPA-p34 hyperphosphorylation depends on expression of ATM, the product of the gene mutated in the human genetic disorder ataxia telangiectasia (A-T). UV-induced RPA-p34 hyperphosphorylation was not observed in A-T cells, but this response was restored by ATM expression. Furthermore, purified ATM kinase phosphorylates the p34 subunit of RPA complex in vitro at many of the same sites that are phosphorylated in vivo after UV radiation. Induction of this DNA damage response was also dependent on DNA replication; inhibition of DNA replication by aphidicolin prevented induction of RPA-p34 hyperphosphorylation by UV radiation. We postulate that this pathway is triggered by the accumulation of aberrant DNA replication intermediates, resulting from DNA replication fork blockage by UV photoproducts. Further, we suggest that RPA-p34 is hyperphosphorylated as a participant in the recombinational postreplication repair of these replication products. Successful resolution of these replication intermediates reduces the accumulation of chromosomal aberrations that would otherwise occur as a consequence of UV radiation.

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