Transarticular screw fixation for atlantoaxial instability - modified Magerl's technique in 38 patients

<p>Abstract</p> <p>Background</p> <p>Symptomatic atlantoaxial instability needs stabilization of the atlantoaxial joint. Among the various techniques described in literature for the fixation of atlantoaxial joint, Magerl's technique of transarticular screw fixation remains the gold standard. Traditionally this technique combines placement of transarticular screws and posterior wiring construct. The aim of this study is to evaluate clinical and radiological outcomes in subjects of atlantoaxial instability who were operated using transarticular screws and iliac crest bone graft, without the use of sublaminar wiring (a modification of Magerl's technique).</p> <p>Methods</p> <p>We evaluated retrospectively 38 subjects with atlantoaxial instability who were operated at our institute using transarticular screw fixation. The subjects were followed up for pain, fusion rates, neurological status and radiographic outcomes. Final outcome was graded both subjectively and objectively, using the scoring system given by Grob et al.</p> <p>Results</p> <p>Instability in 34 subjects was secondary to trauma, in 3 due to rheumatoid arthritis and 1 had tuberculosis. Neurological deficit was present in 17 subjects. Most common presenting symptom was neck pain, present in 35 of the 38 subjects.</p> <p>Postoperatively residual neck and occipital pain was present in 8 subjects. Neurological deficit persisted in only 7 subjects. Vertebral artery injury was seen in 3 subjects. None of these subjects had any sign of neurological deficit or vertebral insufficiency. Three cases had nonunion. At the latest follow up, subjectively, 24 subjects had good result, 6 had fair and 8 had bad result. On objective grading, 24 had good result, 11 had fair and 3 had bad result. The mean follow up duration was 41 months.</p> <p>Conclusions</p> <p>Transarticular screw fixation is an excellent technique for fusion of the atlantoaxial complex. It provides highest fusion rates, and is particularly important in subjects at risk for nonunion. Omitting the posterior wiring construct that has been used along with the bone graft in the traditional Magerl' s technique achieves equally good fusion rates and is an important modification, thereby avoiding the complications of sublaminar wire passage.</p

Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction

Numerical Study of Wind Loads on Y Plan-Shaped Tall Building Using CFD

The increase in the population is at an exponential rate, and the available land is in the form of irregular shapes. That is why irregular shapes are very commonly built. Wind load increases with respect to height, so wind load evolution is necessary for such high-rise structures. Wind forces majorly depend on the plan's cross-sectional shape. Therefore, for an irregular shape, an investigation is needed for tall buildings. This paper demonstrates a detailed study on velocity stream line, external pressure coefficients, pressure distribution on the surfaces of the building and the turbulence kinetic energy for the Y-shaped plan for tall buildings under wind excitation for wind incidence angles of 0o to 180o. k-  turbulence model is utilized to solve the problem using computational fluid dynamics techniques in ANSYS for terrain category II as per IS: 875 (Part3), 2015. Wind ward faces in all building models show positive pressure distribution, while the leeward faces are under the effect of negative pressure distribution. Wind load can be reduced on building models by modifying the corners, such as chamfering, rounding, and double recessed. The variation of pressure distribution on different faces of a "Y" plan shaped tall building for 0° and 180° is investigated using ANSYS CFX, and the pressure contours are plotted for all the faces of different "Y" shaped buildings to compute the effect of corner modification on pressure distribution. In this research, it was found that building models with rounded corners are highly efficient in resisting the wind load. Doi: 10.28991/CEJ-2022-08-02-06 Full Text: PD

Effect of Hyperglycemia on Purinergic and Nitrergic Inhibitory Neuromuscular Transmission in the Antrum of the Stomach: Implications for Fast Gastric Emptying

Background: Hyperglycemia has been reported to enhance vagovagal reflex that causes the release of inhibitory neurotransmitter, nitric oxide (NO), at the neuromuscular junction in the antrum to relax the antrum and slow gastric emptying by stimulating glucose-sensitive afferent neurons. However, hyperglycemia has also been reported to cause fast gastric emptying that may be due to suppression of the inhibitory motor neurons. Aims The purpose of the present study was to investigate changes in inhibitory neuromuscular transmission in the gastric antrum due to hyperglycemia. Methods: Inhibitory electrical junction potentials were recorded from gastric antral muscle strips, using intracellular electrodes under non-adrenergic, non-cholinergic conditions. Studies were performed in non-hyperglycemic NOD (NH-NOD), NOD mice as they develop hyperglycemia (H-NOD) and their age-matched controls. The purinergic inhibitory junction potential (pIJP) and nitrergic IJP (nIJP) were isolated pharmacologically. Results: The control pIJP was large, around −18 mV and nIJP was small, around −9 mV. In NH-NOD the IJPs were not affected, but in H-NOD pIJP was nearly abolished and nIJP was significantly reduced. In H-NOD mice, membrane hyperpolarization caused by exogenous α,β-MeATP or diethylenetriamine NO adduct was similar to that in wild-type controls (P > 0.05). H-NOD smooth muscles were significantly depolarized as compared to NH-NOD smooth muscles. Conclusion: These observations show that hyperglycemia causes suppression of purinergic and nitrergic transmission by acting on the motor neurons that form the last neuron in the vagovagal circuit. Moreover, the loss the neurotransmission is due to a defect in neurotransmitter release rather than a defect in signal transduction. Hyperglycemia also causes depolarization of smooth muscles that may increase their excitability

Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential

BACKGROUND: In cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells. RESULTS: We designed siRNAs against two different regions of telomerase gene and evaluated their effect on telomere length, proliferative potential, and gene expression in Barrett's adenocarcinoma SEG-1 cells. The mixture of siRNAs in nanomolar concentrations caused a loss of telomerase activity that appeared as early as day 1 and was essentially complete at day 3. Inhibition of telomerase activity was associated with marked reduction in median telomere length and complete loss of detectable telomeres in more than 50% of the treated cells. Telomere loss caused senescence in 40% and apoptosis in 86% of the treated cells. These responses appeared to be associated with activation of DNA sensor HR23B and subsequent activation of p53 homolog p73 and p63 and E2F1. Changes in these gene regulators were probably the source of observed up-regulation of cell cycle inhibitors, p16 and GADD45. Elevated transcript levels of FasL, Fas and caspase 8 that activate death receptors and CARD 9 that interacts with Bcl10 and NFKB to enhance mitochondrial translocation and activation of caspase 9 were also observed. CONCLUSION: These studies show that telomerase siRNAs can cause effective suppression of telomerase and telomere shortening leading to both cell cycle arrest and apoptosis via mechanisms that include up-regulation of several genes involved in cell cycle arrest and apoptosis. Telomerase siRNAs may therefore be strong candidates for highly selective therapy for chemoprevention and treatment of Barrett's adenocarcinoma

Imaging of Nitric Oxide in Nitrergic Neuromuscular Neurotransmission in the Gut

Background: Numerous functional studies have shown that nitrergic neurotransmission plays a central role in peristalsis and sphincter relaxation throughout the gut and impaired nitrergic neurotransmission has been implicated in clinical disorders of all parts of the gut. However, the role of nitric oxide (NO) as a neurotransmitter continues to be controversial because: 1) the cellular site of production during neurotransmission is not well established; 2) NO may interacts with other inhibitory neurotransmitter candidates, making it difficult to understand its precise role. Methodology/Principal Findings: Imaging NO can help resolve many of the controversies regarding the role of NO in nitrergic neurotransmission. Imaging of NO and its cellular site of production is now possible. NO forms quantifiable fluorescent compound with diaminofluorescein (DAF) and allows imaging of NO with good specificity and sensitivity in living cells. In this report we describe visualization and regulation of NO and calcium ($Ca^{2+}$) in the myenteric nerve varicosities during neurotransmission using multiphoton microscopy. Our results in mice gastric muscle strips provide visual proof that NO is produced de novo in the nitrergic nerve varicosities upon nonadrenergic noncholinergic (NANC) nerve stimulation. These studies show that NO is a neurotransmitter rather than a mediator. Changes in NO production in response to various pharmacological treatments correlated well with changes in slow inhibitory junction potential of smooth muscles. Conclusions/Significance: Dual imaging and electrophysiologic studies provide visual proof that during nitrergic neurotransmission NO is produced in the nerve terminals. Such studies may help define whether NO production or its signaling pathway is responsible for impaired nitrergic neurotransmission in pathological states

DNA index determination with Automated Cellular Imaging System (ACIS) in Barrett's esophagus: Comparison with CAS 200

BACKGROUND: For solid tumors, image cytometry has been shown to be more sensitive for diagnosing DNA content abnormalities (aneuploidy) than flow cytometry. Image cytometry has often been performed using the semi-automated CAS 200 system. Recently, an Automated Cellular Imaging System (ACIS) was introduced to determine DNA content (DNA index), but it has not been validated. METHODS: Using the CAS 200 system and ACIS, we compared the DNA index (DI) obtained from the same archived formalin-fixed and paraffin embedded tissue samples from Barrett's esophagus related lesions, including samples with specialized intestinal metaplasia without dysplasia, low-grade dysplasia, high-grade dysplasia and adenocarcinoma. RESULTS: Although there was a very good correlation between the DI values determined by ACIS and CAS 200, the former was 25% more sensitive in detecting aneuploidy. ACIS yielded a mean DI value 18% higher than that obtained by CAS 200 (p < 0.001; paired t test). In addition, the average time required to perform a DNA ploidy analysis was shorter with the ACIS (30–40 min) than with the CAS 200 (40–70 min). Results obtained by ACIS gave excellent inter-and intra-observer variability (coefficient of correlation >0.9 for both, p < 0.0001). CONCLUSION: Compared with the CAS 200, the ACIS is a more sensitive and less time consuming technique for determining DNA ploidy. Results obtained by ACIS are also highly reproducible

Comparison of DNA histograms by standard flow cytometry and image cytometry on sections in Barrett's adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare DNA histograms obtained by standard flow cytometry (FC) and high fidelity image cytometry on sections (ICS) in normal gastrointestinal mucosa and Barrett's adenocarcinoma (BAC).</p> <p>Methods</p> <p>Archival formalin-fixed paraffin-embedded tissue blocks of 10 normal controls from 10 subjects and 42 BAC tissues from 17 patients were examined. DNA FC was performed using standard techniques and ICS was carried out by Automated Cellular Imaging System (ACIS). DNA ploidy histograms were classified into diploid with peak DNA index (DI) at 0.9–1.1, and aneuploid with peak DI > 1.1. DI values of aneuploid peaks were determined. Additionally, for DNA ICS, heterogeneity index (HI) representing DNA content heterogeneity, and histograms containing cells with DI > G2 were also identified.</p> <p>Results</p> <p>All control samples were diploid by both FC and ICS analyses. In BAC, FC showed diploid peaks in 29%, diploid peaks with additional aneuploid or tetraploid peaks in 57%, and 14% of the samples, respectively. In contrast, ICS showed aneuploid peaks in all the cases with peak DI > 1.25; 37 cases had peak DI between 1.25 and 2.25; and 5 cases had peak DI > 2.25. HI values (mean ± SD) were 11.3 ± 1.1 in controls and 32.4 ± 8.5 in BAC (p < 0.05). Controls had no G2 exceeding cells. However, 19/37 (51%) of the cases with primary peak DI < 2.25 had cells exceeding 9N.</p> <p>Conclusion</p> <p>ICS detects DNA aneuploidy in all BAC samples while FC missed the diagnosis of aneuploidy in 29%. In addition, ICS provides more information on HI and G2 exceeding rates.</p