Craniocervical Junction Syndrome: Anatomy of the Craniocervical and Atlantoaxial Junctions and the Effect of Misalignment on Cerebrospinal Fluid Flow

The craniocervical junction (CCJ) is comprised of the inferior surface of the skull, the atlas and axis, as well as muscles and connective tissues that attach the skull to the cervical spine. The CCJ encloses the central nervous system (CNS), encephalic vasculature and the cerebrospinal fluid (CSF) system. The CCJ spans the brainstem to the spinal cord, including the vascular system as well as connecting the cerebrospinal fluid (CSF) cisterns within the skull to the CSF channels in the spinal canal. Malformation and misalignment of the craniocervical junction can cause a constellation of cerebral and other neurological signs and symptoms collectively called craniocervical syndrome (CCS). The signs and symptoms of craniocervical junction syndrome may be due to mechanical strain causing deformation of dura mater, vasculature and other structures of the cranial vault resulting in irritation of and dysfunction of affected tissues. Deformation of the CCJ may also obstruct blood and CSF flow. Chronic ischemia, edema and hydrocephalus can cause degenerative cascades that can in turn lead to neurodegenerative diseases

Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-l, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity, The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication

Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis

Introduction Telomeres, are composed of tandem repeat sequences located at the ends of chromosomes and are required to maintain genomic stability. Telomeres can become shorter due to cell division and specific lifestyle factors. Critically shortened telomeres are linked to cellular dysfunction, senescence and aging. A number of studies have used low resolution techniques to assess telomere length in the placenta. In this study, we applied Single Telomere Length Analysis (STELA) which provides high-resolution chromosome specific telomere length profiles to ask whether we could obtain more detailed information on the length of individual telomeres in the placenta. Methods Term placentas (37–42 weeks) were collected from women delivering at University Hospital of Wales or Royal Gwent Hospital within 2 h of delivery. Multiple telomere-length distributions were determined using STELA. Intraplacental variation of telomere length was analysed (N = 5). Telomere length distributions were compared between labouring (N = 10) and non-labouring (N = 11) participants. Finally, telomere length was compared between female (N = 17) and male (N = 20) placenta. Results There were no significant influences of sampling site, mode of delivery or foetal sex on the telomere-length distributions obtained. The mean telomere length was 7.7 kb ranging from 5.0 kb to 11.7 kb across all samples (N = 42) and longer compared with other human tissues at birth. STELA also revealed considerable telomere length heterogeneity within samples. Conclusions We have shown that STELA can be used to study telomere length homeostasis in the placenta regardless of sampling site, mode of delivery and foetal sex. Moreover, as each amplicon is derived from a single telomeric molecule, from a single cell, STELA can reveal the full detail of telomere-length distributions, including telomeres within the length ranges observed in senescent cells. STELA thus provides a new tool to interrogate the relationship between telomere length and pregnancy complications linked to placental dysfunction

Telomere length heterogeneity in placenta revealed with high-resolution telomere length analysis

Introduction Telomeres, are composed of tandem repeat sequences located at the ends of chromosomes and are required to maintain genomic stability. Telomeres can become shorter due to cell division and specific lifestyle factors. Critically shortened telomeres are linked to cellular dysfunction, senescence and aging. A number of studies have used low resolution techniques to assess telomere length in the placenta. In this study, we applied Single Telomere Length Analysis (STELA) which provides high-resolution chromosome specific telomere length profiles to ask whether we could obtain more detailed information on the length of individual telomeres in the placenta. Methods Term placentas (37–42 weeks) were collected from women delivering at University Hospital of Wales or Royal Gwent Hospital within 2 h of delivery. Multiple telomere-length distributions were determined using STELA. Intraplacental variation of telomere length was analysed (N = 5). Telomere length distributions were compared between labouring (N = 10) and non-labouring (N = 11) participants. Finally, telomere length was compared between female (N = 17) and male (N = 20) placenta. Results There were no significant influences of sampling site, mode of delivery or foetal sex on the telomere-length distributions obtained. The mean telomere length was 7.7 kb ranging from 5.0 kb to 11.7 kb across all samples (N = 42) and longer compared with other human tissues at birth. STELA also revealed considerable telomere length heterogeneity within samples. Conclusions We have shown that STELA can be used to study telomere length homeostasis in the placenta regardless of sampling site, mode of delivery and foetal sex. Moreover, as each amplicon is derived from a single telomeric molecule, from a single cell, STELA can reveal the full detail of telomere-length distributions, including telomeres within the length ranges observed in senescent cells. STELA thus provides a new tool to interrogate the relationship between telomere length and pregnancy complications linked to placental dysfunction

An Absolute Flux Density Measurement of the Supernova Remnant Casseopia A at 32 GHz

We report 32 GHz absolute flux density measurements of the supernova remnant Cas A, with an accuracy of 2.5%. The measurements were made with the 1.5-meter telescope at the Owens Valley Radio Observatory. The antenna gain had been measured by NIST in May 1990 to be $0.505 \pm 0.007 \frac{{\rm mK}}{{\rm Jy}}$. Our observations of Cas A in May 1998 yield $S_{cas,1998} = 194 \pm 5 {\rm Jy}$. We also report absolute flux density measurements of 3C48, 3C147, 3C286, Jupiter, Saturn and Mars.Comment: 30 pages, 4 figures; accepted for publication by AJ. Revised systematic error budget, corrected typos, and added reference

Surgical repair of truncal valve regurgitation†

OBJECTIVES Truncal valve regurgitation remains a short- and long-term risk factor for patients with truncus arteriosus. There are limited data available on techniques and outcomes of truncal valve repair (TVR). The aim of this study was to report our experience with TVR in patients of all ages. METHODS From 1997 to 2012, 36 patients (13 neonates, 30 children and 3 adults) underwent TVR for significant regurgitation. RESULTS There were 3 early deaths (8%), all of which were in neonates. Twenty-two patients had a quadricuspid, 13 a tricuspid and 1 a bicuspid truncal valve before repair. Valve repair improved regurgitation in 31 of 36 repairs. The median regurgitation decreased from moderate-severe to mild (P < 0.001). During a mean follow-up of 38.3 ± 44.9 months (range 1 month—15 years), there was 1 late death, 16 patients required reoperation on the truncal valve and 1 required a second reoperation. Freedom from reoperation was 91.4 ± 4.8% at 1 year, 55.0 ± 10.4% at 5 and 22.9 ± 12.2% at 10 years. A quadricuspid valve after repair tended to worsen freedom from reoperation (P = 0.15), and tricuspidization tended to improve freedom from reoperation (P = 0.19). Neonatal repair (hazards ratio (HR) 4.1, P = 0.03) and leaflet thinning (HR 22.5, P = 0.002) were independent predictors of reoperation. CONCLUSIONS Valve repair for truncal valve regurgitation is feasible, with good results. Surgical creation of a tricuspid truncal valve seems to provide the best outcomes in this challenging populatio

Digital tracking algorithm reveals the influence of structural irregularities on joint movements in the human cervical spine

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.clinbiomech.2018.04.015 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Background Disc height loss and osteophytes change the local mechanical environment in the spine; while previous research has examined kinematic dysfunction under degenerative change, none has looked at the influence of disc height loss and osteophytes throughout movement. Methods Twenty patients with pain related to the head, neck or shoulders were imaged via videofluoroscopy as they underwent sagittal-plane flexion and extension. A clinician graded disc height loss and osteophytes as “severe/moderate”, “mild”, or “none”. A novel tracking algorithm quantified motions of each vertebra. This information was used to calculate intervertebral angular and shear displacements. The digital algorithm made it practical to track individual vertebrae in multiple patients through hundreds of images without bias. Findings Cases without height loss/osteophytes had a consistent increase in intervertebral angular displacement from C2/C3 to C5/C6, like that of healthy individuals, and mild height losses did not produce aberrations that were systematic or necessarily discernable. However, joints with moderate to severe disc height loss and osteophytes exhibited reduced range of motion compared to adjacent unaffected joints in that patient and corresponding joints in patients without structural irregularities. Interpretation Digitally-obtained motion histories of individual joints allowed anatomical joint changes to be linked with changes in joint movement patterns. Specifically, disc height loss and osteophytes were found to influence cervical spine movement in the sagittal plane, reducing angular motions at affected joints by approximately 10% between those with and without height loss and osteophytes. Further, these joint changes were associated with perturbed intervertebral angular and shear movements.Natural Sciences and Engineering Research Council (NSERC) Discovery Grant

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals