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1.
J Assoc Physicians India ; 69(2): 49-53, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527811

RESUMO

Introduction: The thyroid hormones perpetuate a fine equilibrium of glucose metabolism. Abnormalities of thyroid function can disrupt this balance leading to glucose metabolism abnormalities and insulin resistance. Objectives: We studied the correlation between insulin resistance and thyroid status in hyperthyroid, euthyroid, and hypothyroid individuals. Methods: In this observational comparative analysis conducted at a tertiary care center, the 3 study groups comprised of 35 patients each with newly detected hyperthyroidism, hypothyroidism and euthyroid individuals. Assays were conducted for serum insulin, thyroid profile, blood sugar and routine biochemistry in the fasting state. The homeostasis model assessment for insulin resistance (HOMA-IR) was used to evaluate insulin resistance. Results: The mean HOMA-IR was highest in patients with hypothyroidism (3.22 ± 2.69) followed by the hyperthyroid group (2.25 ± 1.59). It was lowest in the euthyroid group (0.79 ± 0.58) with the intergroup difference being statistically significant (P<0.001). Hypothyroid patients showed a significant a positive correlation between TSH and HOMA-IR (r=0.945, P=<0.001) whereas hyperthyroid patients showed positive correlation between FT3 and insulin resistance (r=0.706, P<0.001). Conclusion: Thyroid dysfunction is associated with an increase in insulin resistance and glucose abnormalities validating the resultant higher risk of related cardiovascular and metabolic abnormalities observed in these patients.


Assuntos
Resistência à Insulina , Doenças da Glândula Tireoide , Humanos , Índia/epidemiologia , Centros de Atenção Terciária , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia
2.
Neurospine ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33494552

RESUMO

Objective: The conventional criteria for defining the basilar invagination(BI) focus on the relationship of odontoid tip to basion and opisthion, landmarks that are intrinsically variable especially in presence of occipitalised atlas. A universal single reference line is proposed that helps in unequivocally establishing the diagnosis of BI, may be relevant in establishing both Goel's type A and B BI, as well as in differentiating a 'very high' from 'regular' BI. Methods: Study design - case control study. In 268 patients [Group I with BI (n=89) including Goel's type A BI (n=66) and type B BI (n=23)]; and, Group II controls (n=179)], the perpendicular distance between odontoid tip and line subtended between posterior tip of hard palate-internal occipital protuberance (P-IOP line) was measured. Logistic regression analysis determined factors influencing the proposed parameter (p-value<0.05). Results: In patients with a 'very high' BI (n=5), the odontoid tip intersected/or was above the P-IOP line. In patients with a 'regular' BI (n=84), the odontoid tip was 6.56+3.9mm below the P-IOP line; while in controls, this distance was 12.53+4.28 mm (P<0.01). In Goel's type A BI, the distance was 7.01+3.78 mm and in type B BI, it was 5.07+4.19 mm (P=0.004). Receiver-operating characteristic curve (ROC) analysis identified 9.0 mm (8.92 mm-9.15 mm) as the cut-point for diagnosing BI using the odontoid tip-P-IOP line distance as reference. Conclusion: The odontoid tip either intersecting the P-IOP line (very high BI); or being <9mm below the P-IOP line (Type A and B BI), are recommended as highly applicable criteria to establish the diagnosis of BI. This parameter may be useful in establishing the diagnosis in all varieties of BI.

4.
FEBS J ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33264497

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19) that exhibits an overwhelming contagious capacity over other Human Coronaviruses (HCoVs). This structural snapshot describes the structural bases underlying the pandemic capacity of SARS-CoV-2 and explains its fast motion over respiratory epithelia that allow its rapid cellular entry. Based on notable viral spike (S) protein features, we propose that the flat sialic acid-binding domain at the N-terminal domain (NTD) of the S1 subunit leads to more effective first contact and interaction with the sialic acid layer over the epithelium and this, in turn, allows faster viral "surfing" of the epithelium and receptor scanning by SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE-2) protein on the epithelial surface is the primary entry receptor for SARS-CoV-2, and protein-protein interaction assays demonstrate high-affinity binding of the S protein to ACE-2. To date, no high-frequency mutations were detected at the C-terminal domain (CTD) of the S1 subunit in the S protein, where the receptor-binding domain (RBD) is located. Tight binding to ACE-2 by a conserved viral RBD suggests the ACE2-RBD interaction is likely optimal. Moreover, the viral S subunit contains a cleavage site for furin and other proteases, which accelerates cell entry by SARS-CoV-2. The model proposed here describes a structural basis for the accelerated host cell entry by SARS-CoV-2 relative to other HCoVs, and also discusses emerging hypotheses that are likely to contribute to the development of antiviral strategies to combat the pandemic capacity of SARS-CoV-2.

5.
Molecules ; 25(24)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33322198

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.


Assuntos
Glicoproteína da Espícula de Coronavírus , /genética , Animais , /metabolismo , Gatos , Bovinos , Cães , Humanos , Pan troglodytes , Domínios Proteicos , /metabolismo , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
6.
Life Sci ; : 118676, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33129880

RESUMO

Angiotensin-converting enzyme 2 (ACE 2) is a membrane-bound enzyme that cleaves angiotensin II (Ang II) into angiotensin (1-7). It also serves as an important binding site for SARS-CoV-2, thereby, facilitating viral entry into target host cells. ACE 2 is abundantly present in the intestine, kidney, heart, lungs, and fetal tissues. Fetal ACE 2 is involved in myocardium growth, lungs and brain development. ACE 2 is highly expressed in pregnant women to compensate preeclampsia by modulating angiotensin (1-7) which binds to the Mas receptor, having vasodilator action and maintain fluid homeostasis. There are reports available on Zika, H1N1 and SARS-CoV where these viruses have shown to produce fetal defects but very little is known about SARS-CoV-2 involvement in pregnancy, but it might have the potential to interact with fetal ACE 2 and enhance COVID-19 transmission to the fetus, leading to fetal morbidity and mortality. This review sheds light on a path of SARS-CoV-2 transmission risk in pregnancy and its possible link with fetal ACE 2.

7.
Bioorg Chem ; 104: 104326, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33142431

RESUMO

SARS-CoV-2 (COVID-19) epidemic has created an unprecedented medical and economic crisis all over the world. SARS-CoV-2 is found to have more contagious character as compared to MERS-CoV and is spreading in a very fast manner all around the globe. It has affected over 31 million people all over the world till date. This virus shares around 80% of genome similarity with SARS-CoV. In this perspective, we have explored three major targets namely; SARS-CoV-2 spike (S) protein, RNA dependent RNA polymerase, and 3CL or Mpro Protease for the inhibition of SARS-CoV-2. These targets have attracted attention of the medicinal chemists working on computer-aided drug design in developing new small molecules that might inhibit these targets for combating COVID-19 disease. Moreover, we have compared the similarity of these target proteins with earlier reported coronavirus (SARS-CoV). We have observed that both the coronaviruses share around 80% similarity in their amino acid sequence. The key amino acid interactions which can play a crucial role in designing new small molecule inhibitors against COVID-19 have been reported in this perspective. Authors believe that this study will help the medicinal chemists to understand the key amino acids essential for interactions at the active site of target proteins in SARS-CoV-2, based on their similarity with earlier reported viruses. In this review, we have also described the lead molecules under various clinical trials for their efficacy against COVID-19.

8.
Soft Matter ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155586

RESUMO

Macromolecular crowding and the presence of surfaces can significantly impact the spatial organization of biopolymers. While the importance of crowding-induced depletion interactions in biology has been recognized, much remains to be understood about the effect of crowding on biopolymers such as DNA plasmids. A fundamental problem highlighted by recent experiments is to characterize the impact of crowding on polymer-polymer and polymer-surface interactions. Motivated by the need for quantitative insight, we studied flexible ring polymers in crowded environments using Langevin dynamics simulations. The simulations demonstrated that crowding can lead to compaction of isolated ring polymers and enhanced interactions between two otherwise repulsive polymers. Using umbrella sampling, we determined the potential of mean force (PMF) between two ring polymers as a function of their separation distance at different volume fractions of crowding particles, φ. An effective attraction emerged at φ ≈ 0.4, which is similar to the degree of crowding in cells. Analogous simulations showed that crowding can lead to strong adsorption of a ring polymer to a wall, with an effective attraction to the wall emerging at a smaller volume fraction of crowders (φ ≈ 0.2). Our results reveal the magnitude of depletion interactions in a biologically-inspired model and highlight how crowding can be used to tune interactions in both cellular and cell-free systems.

9.
J Trace Elem Med Biol ; 62: 126633, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32818862

RESUMO

Experimentally, it has been proved that cadmium served as an effective carcinogen and able to induce tumors in rodents in a dose-specific manner. However, systemic evaluation of cadmium exposure for the transformation of prostatic hyperplasia into prostate cancer (PCa) is still unclear. In the present study, an attempt has been made to establish cadmium-induced human prostate carcinogenesis using an in vitro model of BPH cells. Wide range of cadmium concentrations, i.e., 1 nM, 10 nM, 100 nM and 1µM, were chronically exposed to the human BPH cells for transformation into PCa and monitored using cell and molecular biology approaches. After eight weeks of exposure, the cells showed subtle morphological changes and shifts of cell cycle in the G2M phase. Significant increase in expression of prostatic genes AR, PSA, ER-ß, and 5αR with increased nuclear localization of AR and pluripotency markers Cmyc, Klf4 indicated the carcinogenic effect of Cd. Further, the BPH cells exposed to Cd showed a substantial increase in the secretion of MMP-2 and MMP-9, influencing migratory potential of the cells along with decreased expression of the p63 protein which further strengthen the progression towards carcinogenesis and aggressive tumor studies. Data from the present study state that Cd exhibited marked invasiveness in BPH cells. These observations established a connecting link of BPH towards PCa pathogenesis. Further, the study will also help in investigating the intricate pathways involved in cancer progression.

10.
ACS Nano ; 14(7): 7760-7782, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32571007

RESUMO

The current global health threat by the novel coronavirus disease 2019 (COVID-19) requires an urgent deployment of advanced therapeutic options available. The role of nanotechnology is highly relevant to counter this "virus" nano enemy. Nano intervention is discussed in terms of designing effective nanocarriers to counter the conventional limitations of antiviral and biological therapeutics. This strategy directs the safe and effective delivery of available therapeutic options using engineered nanocarriers, blocking the initial interactions of viral spike glycoprotein with host cell surface receptors, and disruption of virion construction. Controlling and eliminating the spread and reoccurrence of this pandemic demands a safe and effective vaccine strategy. Nanocarriers have potential to design risk-free and effective immunization strategies for severe acute respiratory syndrome coronavirus 2 vaccine candidates such as protein constructs and nucleic acids. We discuss recent as well as ongoing nanotechnology-based therapeutic and prophylactic strategies to fight against this pandemic, outlining the key areas for nanoscientists to step in.


Assuntos
Infecções por Coronavirus/prevenção & controle , Vacinação em Massa/métodos , Nanotecnologia/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/uso terapêutico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Humanos , Vacinação em Massa/efeitos adversos , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Vacinas Virais/imunologia
11.
Mol Cell Biochem ; 471(1-2): 129-142, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32504365

RESUMO

Activation of epithelial-AR signaling is identified as the major cause of hyperproliferation of the cells during benign and malignant prostate conditions. However, the contribution of stromal-AR is also precarious due to its secretory actions that contribute to the progression of benign and malignant tumors. The present study was aimed to understand the influence of stromal-AR mediated actions on epithelial cells during BPH condition. The secretome (conditioned media-CM) was collected from AR agonist (testosterone-propionate-TP) and antagonist (Nilutamide-Nil) treated BPH patient-derived stromal cells and exposed to BPH epithelial cells. Epithelial cells exhibited increased cell proliferation with the treatment of CM derived from TP-treated stromal cells (TP-CM) but did not support the clonogenic growth of BPH epithelial cells. However, CM derived from Nil-treated stromal cells (Nil-CM) depicted delayed and aggressive BPH epithelial cell proliferation with increased clonogenicity of BPH epithelial cells. Further, decreased AR levels with increased cMyc transcripts and pAkt levels also validated the clonogenic transformation under the paracrine influence of inhibition of stromal-AR. Moreover, the CM of stromal-AR activation imparted positive regulation of basal/progenitor pool through LGR4, ß-Catenin, and ΔNP63α expression. Hence, the present study highlighted the restricted disease progression and retains the basal/progenitor state of BPH epithelial cells through the activation of stromal-AR. On the contrary, AR-independent aggressive BPH epithelial cell growth due to paracrine action of loss stromal-AR directs us to reform AR pertaining treatment regimes for better clinical outcomes.

12.
Sci Rep ; 10(1): 8537, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444778

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by metastasis, drug resistance and high rates of recurrence. With a lack or targeted therapies, TNBC is challenging to treat and carries a poor prognosis. Patients with TNBC tumors expressing high levels of ERK2 have a poorer prognosis than those with low ERK2-expressing tumors. The MAPK pathway is often found to be highly activated in TNBC, however the precise functions of the ERK isoforms (ERK1 and ERK2) in cancer progression have not been well defined. We hypothesized that ERK2, but not ERK1, promotes the cancer stem cell (CSC) phenotype and metastasis in TNBC. Stable knockdown clones of the ERK1 and ERK2 isoforms were generated in SUM149 and BT549 TNBC cells using shRNA lentiviral vectors. ERK2 knockdown significantly inhibited anchorage-independent colony formation and mammosphere formation, indicating compromised self-renewal capacity. This effect correlated with a reduction in migration and invasion. SCID-beige mice injected via the tail vein with ERK clones were employed to determine metastatic potential. SUM149 shERK2 cells had a significantly lower lung metastatic burden than control mice or mice injected with SUM149 shERK1 cells. The Affymetrix HGU133plus2 microarray platform was employed to identify gene expression changes in ERK isoform knockdown clones. Comparison of gene expression levels between SUM149 cells with ERK2 or ERK1 knockdown revealed differential and in some cases opposite effects on mRNA expression levels. Those changes associated with ERK2 knockdown predominantly altered regulation of CSCs and metastasis. Our findings indicate that ERK2 promotes metastasis and the CSC phenotype in TNBC.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/secundário , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos SCID , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Células-Tronco Neoplásicas/metabolismo , Prognóstico , RNA Interferente Pequeno/genética , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Drug Dev Ind Pharm ; 46(6): 878-888, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32338544

RESUMO

Nanoparticles have emerged as an important carrier system to treat wounds as they permit the topical administration of an antimicrobial drug in a sustained and effective manner. On the other hand, if active excipients are added during the formulation, such as chitosan or graphene oxide, the developed Nano formulation could significantly improve its potential for chronic wound healing. Given that, we have conceived the fabrication and evaluation of rosmarinic acid loaded chitosan encapsulated graphene nanoparticles (RA-CH-G-NPOs) formulation to enhance wound healing capacity. The prepared nanoparticles were characterized by particle size, Zeta potential, FT-IR, SEM, TEM and AFM. It was observed the average diameter of RA-CH-G-NPOS is around 417.5 ± 18.3 nm and showed sustained release behavior. Optimized RA-CH-G-NPOs were incorporated into Carbopol gel and evaluated for drug content, pH, in vitro release, texture analysis, and viscosity. The antibacterial activity of optimized formulation was examined as a minimum inhibitory concentration against Staphylococcus aureus. The fabricated RA-CH-G-NPOs were than evaluated for in vitro antimicrobial activity by microdilution assay The combination of RA, Chitosan and Graphene oxide (GO) showed higher antibacterial activity of 0.0038 ± 0.2 mg/mL. Further, these nanoparticles were evaluated in- vivo for wound healing efficacy in Sprague Dawley rats. Histopathological evaluations demonstrated that RA-CH-G-NPOs showed significantly enhanced wound contraction, enhanced cell adhesion, epithelial migration, and high hydroxyproline content leading to faster and more efficient collagen synthesis as compared to plain carbopol, plain RA and controls. Hence the topical administration of fabricated RA-CH-G-NPOs appears to be an interesting and suitable strategy for the treatment of chronic wounds.

14.
Neurol India ; 68(2): 316-324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189696

RESUMO

Background and Purpose: The purpose of this study is to evaluate posterior cerebral artery (PCA) aneurysms along with the efficacy, safety, procedural, and clinical outcome of the endovascular management of these aneurysms. We studied different techniques of endovascular treatment such as selective aneurysmal coiling, parent artery occlusion, and stent-assisted coiling in PCA aneurysms. Methods: From 2010 to 2017, 11 patients (8 females, 3 males) harboring a PCA aneurysm were treated via an endovascular approach. Seven of eleven aneurysms were saccular in nature; four were fusiform shaped. All aneurysms were treated using detachable coils either by selective obliteration of the aneurysm sac or by parent artery occlusion. In one patient, stent-assisted coiling of PCA aneurysm was done, and in one patient, flowdivertor along with few coils used to treat the aneurysm. Results: Five of the eleven aneurysms were successfully treated with preservation of the parent artery, and the other six were treated with aneurysm coiling along with parent vessel occlusion. Of the six where parent vessel occlusion was done, one developed transient hemiparesis which recovered on follow-up and none developed significant disabling vision abnormality. No mortality was noted. Conclusion: Aneurysms of the PCA are rare compared with other locations in the intracranial circulation. These aneurysms can effectively be treated by permanent occlusion of the parent artery even in this era of flowdivertors - however, in these cases, thorough knowledge of PCA segmental anatomy is crucial in order to select the site of occlusion and to avoid major neurological deficits.

16.
AAPS PharmSciTech ; 20(2): 50, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30617637

RESUMO

Gene therapy involving p11 cDNA has been thought to be a futuristic approach for the effective management of depression as the existing treatment regimen presents many issues regarding late onset of action, patient withdrawal and their side effects. For the effective transfection of p11 gene intracellularly, two cationic lipids based on phospholipid DOPE conjugated to basic amino acids histidine and arginine were synthesised, used for liposome formulation and evaluated for their ability as gene delivery vectors. They were further converted using IGF-II mAb into immunoliposomes for CNS targeting and mAb conjugation to liposomes were characterised by SDS-PAGE. They were further analysed by in vitro characterisation studies that include erythrocyte aggregation study, electrolyte-induced study, heparin compatibility study and serum stability studies. SHSY5Y cells were used for conducting cytotoxicity of synthesised lipids and live imaging of cell uptake for 25 min. Finally, the brain distribution studies and western blot were carried out in animals to evaluate them for their BBB permeation ability and effects on p11 protein which is believed to be a culprit. These formulated liposomes from synthesised lipids offer a promising approach for the treatment of depression.


Assuntos
Encéfalo/metabolismo , Peptídeos Penetradores de Células/genética , Depressão/genética , Terapia Genética/métodos , Fator de Crescimento Insulin-Like II/genética , Nanopartículas/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/metabolismo , Depressão/metabolismo , Depressão/terapia , Marcação de Genes/métodos , Técnicas de Transferência de Genes , Humanos , Fator de Crescimento Insulin-Like II/administração & dosagem , Fator de Crescimento Insulin-Like II/metabolismo , Lipossomos/química , Masculino , Camundongos , Nanopartículas/administração & dosagem , Ratos , Ratos Sprague-Dawley
17.
Front Genet ; 10: 1322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32038704

RESUMO

The prevalence of tickborne diseases worldwide is increasing virtually unchecked due to the lack of effective control strategies. The transmission dynamics of tickborne pathogens are influenced by the tick microbiome, tick co-infection with other pathogens, and environmental features. Understanding this complex system could lead to new strategies for pathogen control, but will require large-scale, high-resolution data. Here, we introduce Project Acari, a citizen science-based project to assay, at single-tick resolution, species, pathogen infection status, microbiome profile, and environmental conditions of tens of thousands of ticks collected from numerous sites across the United States. In the first phase of the project, we collected more than 2,400 ticks wild-caught by citizen scientists and developed high-throughput methods to process and sequence them individually. Applying these methods to 192 Ixodes scapularis ticks collected in a region with a high incidence of Lyme disease, we found that 62% were colonized by Borrelia burgdorferi, the Lyme disease pathogen. In contrast to previous reports, we did not find an association between the microbiome diversity of a tick and its probability of carrying B. burgdorferi. However, we did find undescribed associations between B. burgdorferi carriage and the presence of specific microbial taxa within individual ticks. Our findings underscore the power of coupling citizen science with high-throughput processing to reveal pathogen dynamics. Our approach can be extended for massively parallel screening of individual ticks, offering a powerful tool to elucidate the ecology of tickborne disease and to guide pathogen-control initiatives.

18.
Neurospine ; 16(2): 317-324, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30531656

RESUMO

OBJECTIVE: The sacroiliac joint can be a primary source of pain or part of multifactorial syndromes. As there is no single historical, physical examination-based, or radiological feature that definitively establishes a diagnosis of sacroiliac joint pain, diagnostic blocks are regarded as the gold standard. The primary aim of this randomized trial was to compare the posteroanterior approach with the classic oblique approach for sacroiliac joint injection based on an assessment of procedure times and patient-reported pain outcomes in subjects scheduled for fluoroscopically-guided sacroiliac joint injections. METHODS: Thirty patients were randomized into 2 groups of 15 patients each. The endpoints measured included the total length of procedure time, fluoroscopic time, needling time (length of time the needle was maneuvered), and pre- and postprocedure visual analogue scale pain scores. RESULTS: The posteroanterior approach was significantly shorter in terms of procedure time (p=0.03) and needling time (p=0.01) than the oblique approach. Adjusting for body mass index, the mean procedure and needling times were significantly shorter in the posteroanterior group than in the oblique group. CONCLUSION: This study of the posteroanterior approach for fluoroscopic-guided sacroiliac joint injection observed shorter times for fluoroscopy, needling, and the overall procedure than were recorded for the widely prevalent oblique approach. This may translate to lower radiation exposure, lower procedural costs, and enhanced ergonomics of fluoroscopicallyguided sacroiliac joint injections.

19.
Neurospine ; 15(4): 383-387, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30531654

RESUMO

OBJECTIVE: Lower back pain (LBP) is a worldwide health problem, and magnetic resonance imaging (MRI) is a common modality used to aid in its diagnosis. Although specific guidelines for assessing the necessity of MRI usage exist, the use of MRI as the initial imaging method for LBP seems to be more common than necessary in general practice. METHODS: We conducted a retrospective chart review of 313 patients who had undergone MRI of the lumbosacral spine during 2014-2015. We recorded and compared various factors, including age, sex, body mass index, current smoking status, race, symptoms, MRI findings, and progression to surgery within the next year. All rates were compared according to whether the MRI results showed radiographically significant findings (MRI-positive) or not (MRI-negative) using the chi-square or Fisher exact tests (if the expected cell count was <5). All analyses were performed using SAS version 9.4. RESULTS: There were no statistically significant differences in the rates of each symptom between the MRI-positive and MRI-negative groups, which accounted for 58.5% (183 of 313) and 41.5% (130 of 313) of the MRIs, respectively. The difference in the rate of surgery in the next year (18% among MRI-positive patients and 8.5% among MRI-negative patients) was found to be statistically significant (p<0.05). CONCLUSION: Based on our findings, 41.5% of patients underwent lumbar MRI unnecessarily and 81% of patients with positive MRIs did not have surgery within the next year. Further physician training is needed to avoid unnecessary investigations and expenditures.

20.
ACS Synth Biol ; 7(5): 1251-1258, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29687993

RESUMO

Recent superresolution microscopy studies in E. coli demonstrate that the cytoplasm has highly variable local concentrations where macromolecular crowding plays a central role in establishing membrane-less compartmentalization. This spatial inhomogeneity significantly influences molecular transport and association processes central to gene expression. Yet, little is known about how macromolecular crowding influences gene expression bursting-the episodic process where mRNA and proteins are produced in bursts. Here, we simultaneously measured mRNA and protein reporters in cell-free systems, showing that macromolecular crowding decoupled the well-known relationship between fluctuations in the protein population (noise) and mRNA population statistics. Crowded environments led to a 10-fold increase in protein noise even though there were only modest changes in the mRNA population and fluctuations. Instead, cell-like macromolecular crowding created an inhomogeneous spatial distribution of mRNA ("spatial noise") that led to large variability in the protein production burst size. As a result, the mRNA spatial noise created large temporal fluctuations in the protein population. These results highlight the interplay between macromolecular crowding, spatial inhomogeneities, and the resulting dynamics of gene expression, and provide insights into using these organizational principles in both cell-based and cell-free synthetic biology.


Assuntos
Substâncias Macromoleculares/metabolismo , Proteínas/metabolismo , RNA Mensageiro/metabolismo , Biologia Sintética/métodos , Sistema Livre de Células , Expressão Gênica , Genes Reporter , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Biossíntese de Proteínas , Proteínas/genética , RNA Mensageiro/genética
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