Cervical length measurement by transvaginal sonography in predicting preterm labour in low risk women

Background: Preterm birth is the leading cause of perinatal morbidity and mortality. Transvaginal sonographic measurement of the cervix is a reliable alternative method for the assessment of cervical length as it allows better quality and more accurate visualization of the uterine cervix. Several studies have reported that cervical assessment on transvaginal sonography may be useful in the prediction of preterm delivery. The objective of this study was to assess cervical length at 20 to 24 weeks of gestation in low risk women and correlate with the gestational age at delivery.Methods: A prospective cohort study conducted in a tertiary care Military Hospital in Pune, India. 354 asymptomatic low risk antenatal women with gestational age of 20 to 24 weeks were studied. Cervical assessment with transvaginal sonography for the measurement of cervical length was performed using a 10 MHz transvaginal probe.Results: 7 percent women delivered preterm. The incidence of short cervix in low risk women was only 0.56%. 100% women with short cervix delivered preterm and, only 6.9% patients who had cervical length more than 25 mm delivered preterm. Cervical length 25 mm has got sensitivity and NPV of 100% and a specificity of 93.46%. However, the PPV was only 8%.Conclusions: The study reported significant inverse relation between short cervix and the occurrence of preterm delivery. Our findings suggest that cervical length can be used as a screening method for preterm labour in low risk women. However strong evidences from large randomized control trials would be required to assess its cost-effectiveness.

Axonal Ensheathment and Septate Junction Formation in the Peripheral Nervous System of Drosophila

Axonal insulation is critical for efficient action potential propagation and normal functioning of the nervous system. I

Nodes of Ranvier Act as Barriers to Restrict Invasion of Flanking Paranodal Domains in Myelinated Axons

Accumulation of voltage gated sodium (Nav) channels at nodes of Ranvier is paramount for action potential propagation along myelinated fibers, yet the mechanisms governing nodal development, organization and stabilization remain unresolved. Here, we report that genetic ablation of the neuron-specific isoform of Neurofascin (NfascNF186) in vivo results in nodal disorganization, including loss of Nav channel and ankyrin-G (AnkG) enrichment at nodes in the peripheral (PNS) and central (CNS) nervous systems. Interestingly, the presence of paranodal domains failed to rescue nodal organization in the PNS and the CNS. Most importantly, using ultrastructural analysis, we demonstrate that the paranodal domains invade the nodal space in NfascNF186 mutant axons and occlude node formation. Our results suggest that NfascNF186-dependent assembly of the nodal complex acts as a molecular boundary to restrict the movement of flanking paranodal domains into the nodal area, thereby facilitating the stereotypic axonal domain organization and saltatory conduction along myelinated axons

Spatiotemporal ablation of myelinating glia-specific neurofascin (Nfasc NF155 ) in mice reveals gradual loss of paranodal axoglial junctions and concomitant disorganization of axonal domains

The evolutionary demand for rapid nerve impulse conduction led to the process of myelination-dependent organization of axons into distinct molecular domains. These domains include the node of Ranvier flanked by highly specialized paranodal domains where myelin loops and axolemma orchestrate the axoglial septate junctions. These junctions are formed by interactions between a glial isoform of neurofascin (NfascNF155) and axonal Caspr and Cont. Here we report the generation of myelinating glia-specific NfascNF155 null mouse mutants. These mice exhibit severe ataxia, motor paresis, and death before the third postnatal week. In the absence of glial NfascNF155, paranodal axoglial junctions fail to form, axonal domains fail to segregate, and myelinated axons undergo degeneration. Electrophysiological measurements of peripheral nerves from NfascNF155 mutants revealed dramatic reductions in nerve conduction velocities. By using inducible PLP-CreER recombinase to ablate NfascNF155 in adult myelinating glia, we demonstrate that paranodal axoglial junctions disorganize gradually as the levels of NfascNF155 protein at the paranodes begin to drop. This coincides with the loss of the paranodal region and concomitant disorganization of the axonal domains. Our results provide the first direct evidence that the maintenance of axonal domains requires the fence function of the paranodal axoglial junctions. Together, our studies establish a central role for paranodal axoglial junctions in both the organization and the maintenance of axonal domains in myelinated axons

No effect of genetic deletion of contactin-associated protein (CASPR) on axonal orientation and synaptic plasticity

Myelinated axons are endowed with a specialized domain structure that is essential for saltatory action potential conduction. The paranodal domain contains the axoglial junctions and displays a unique ultrastructure that resembles the invertebrate septate junctions (SJs). Biochemical characterizations of the paranodal axoglial SJs have identified several molecular components that include Caspr and contactin (Cont) on the axonal side and neurofascin 155 kDa (NF155) isoform on the glial side. All these proteins are essential for the formation of the axoglial SJs. Based on the interactions between Caspr and Cont and their colocalization in the CA1 synaptic areas, it was proposed that the synaptic function of Cont requires Caspr. Here we have extended the phenotypic analysis of CASPR mutants to address further the role of Caspr at the axoglial SJs and also in axonal orientation and synaptic plasticity. We report that, in CASPR mutants, the smooth endoplasmic reticulum (SER) forms elongated membranous complexes that accumulate at the nodal/ paranodal region and stretch into the juxtaparanodal region, a defect that is consistent with the paranodal disorganization. We show that the cerebellar microorganization is unaffected in CASPR mutants. We also demonstrate that Caspr function is not essential for normal CA1 synaptic transmission and plasticity. Taken together with previous findings, our results highlight that the Caspr/ Cont complex is essential for the formation of axoglial SJs, whereas Cont may regulate axonal orientation and synaptic plasticity independent of its association with Caspr

Cysteamine Attenuates the Decreases in TrkB Protein Levels and the Anxiety/Depression-Like Behaviors in Mice Induced by Corticosterone Treatment

OBJECTIVE: Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders. MATERIALS AND METHODS: We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure. RESULTS: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine. CONCLUSIONS: The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders

Long-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortex

Objective: Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under longterm continuous glucocorticoid exposure has not been elucidated. Material and Methods: We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. Results: We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. Conclusions: The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecula

Plasma BDNF Levels Vary in Relation to Body Weight in Females

Brain derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression as well as neuropsychiatric and neurodegenerative disorders. Recent studies show a role of BDNF in energy metabolism and body weight regulation. We examined BDNF levels in plasma and cerebrospinal fluid (CSF) samples from age matched elderly depressed and control subjects. Also, the association of BDNF levels with age, gender, body weight, body mass index (BMI), and cognitive performance was evaluated. We did not find any significant differences in plasma and CSF BDNF levels between depressed and control subjects. Plasma BDNF levels were negatively correlated with age (but not with BMI and body weight), when analyses were performed including both depressed and control subjects. A significant reduction in plasma BDNF levels was observed in females as compared to male subjects, and the change in BDNF levels were significantly and positively related to body weight in females. Furthermore, significant increases in Total Recall and Delayed Recall values were found in females as compared to males. In conclusion, the lower BDNF levels observed in females suggest that changes in peripheral BDNF levels are likely secondary to an altered energy balance. However, further studies using larger sample size are warranted

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability