Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice.

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR.

Clinical evidence of chemical radiculopathy.

It is universally accepted that an anatomic abnormality such as a herniated disc or spinal stenosis can lead to radicular leg pain. There is some controversy as to whether radicular pain can be caused by a non-structural, solely biochemical disorder. Prior studies using biochemical analysis of inflammatory mediators of the disc or surrounding structures have enumerated many possible biochemical mediators of radicular pain. However, such studies have not definitively demonstrated whether these inflammatory mediators are the causes of radicular pain or whether these mediators are simply products of the degenerative cascade. The purpose of this paper is to report upon patients who satisfy strict criteria affirming a diagnosis of radiculopathy in the presence of normal imaging studies. The study was designed as a prospective case series of patients fulfilling inclusion and exclusion criteria at a university hospital outpatient physiatric spine practice. Inclusion criteria consisted of symptoms of extremity pain greater than axial pain, examination findings demonstrating a new myotomal deficit that correlates with the root level predicted by the dermatomal pain distribution, and failure to improve after at least 4 weeks of active physical therapy. Magnetic resonance imaging void of local nerve root pathology as per review by the first author and the interpreting radiologist was required. Each patient had to have a positive electromyographic study for an acute radiculopathy. Each patient had to have a positive fluoroscopically guided diagnostic selective nerve root block. In summary, this paper provides clinical evidence that anatomic abnormalities are not required to cause radiculopathy, thus implying that a biochemical etiology is likely to play a significant role in radiculopathy and radicular pain.

Anatomy of the intervertebral foramen.

The intervertebral foramen serves as the doorway between the spinal canal and periphery. It lies between the pedicles of neighboring vertebrae at all levels in the spine. A number of categorization schemes have been attempted to describe the boundaries of the intervertebral foramen. No uniform agreement has been made on which classification best describes this area. Studies of the nerve root canals have clearly noted variations in the angle of take-off from the thecal sac, length of the nerve root, and placement of the dorsal root ganglion from different lumbar levels. The nerve root canal receives a dual blood supply from central and peripheral sources. The dorsal root ganglion also has a dual vascular supply that aids in preventing damage to this vital foraminal structure. The presence of ligamentous structures within the foramen has been demonstrated by a number of recent studies. These ligaments serve a protective and organizational role for the neurovascular structures of the foramen. A thorough knowledge of the intervertebral foramen will allow the understanding of the pathological and degenerative changes that cause compression or injury to these foraminal structures.

Painless foot drop: an atypical etiology of a common presentation.

Weakness of the dorsiflexor muscles of the foot is a relatively common presentation. In most cases, the etiology involves a peripheral injury to the common peroneal nerve. These patients usually present with lower motor neuron findings on evaluation. In contrast, if upper motor neuron findings were present a central lesion should be suspected and appropriate imaging studies are performed. We describe a patient with painless foot drop and lower motor findings on examination that was diagnosed with multiple sclerosis. This case demonstrates that multiple sclerosis can masquerade as a peripheral process in some patients.