79 research outputs found
New Perspectives on Iran: The Path to Progressive Family Law Before the Islamic Revolution
A progressive Iranian women\u27s rights movement has slipped through the cracks of mainstream scholarship. In the 1960s, Iranian women rallied for progressive family law reforms; their efforts culminated in the Family Protection Law of 1967. This note provides an alternative view of the women\u27s rights movement in the Middle East and highlights how a social movement gave rise to comprehensive and progressive family law reform. Over the last century, Iran has been under authoritarian rule, first in the form of a monarchy and now in a theocracy. In spite of this, Iranian women have been steadfast in the fight for freedom. In 2022, Iranian women of all ages, faiths, and socioeconomic backgrounds have led an unprecedented uprising against their government. For the first time since 1979, there is hope for democracy in Iran. This note shines a light on the road to restoring women\u27s rights in Iran
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Subacute Presentation of Central Cord Syndrome Resulting from Vertebral Osteomyelitis and Discitis: A Case Report
Introduction: Central cord syndrome (CCS) is a clinical syndrome of motor weakness and sensory changes. While CCS is most often associated with traumatic events. There have been few documented cases being caused by abscesses resulting from osteomyelitis.Case Report: A 56-year-old male presented to a regional trauma center complaining of excruciating neck and bilateral upper extremity pain. Computed tomography of the cervical and thoracic regions revealed severe discitis and osteomyelitis of the fourth and fifth cervical (C4-C5) with near-complete destruction of the C4 vertebral body, as well as anterolisthesis of C4 on C5 causing compression of the central canal. Empiric intravenous (IV) antibiotic therapy with ampicillin/sulbactam and vancomycin was initiated, and drainage of the abscess was scheduled. After the patient refused surgery, he was planned to be transferred to a skilled nursing facility to receive a six-week course of IV vancomycin therapy. A month later, patient returned to emergency department with the same complaint due to non-compliance with antibiotic therapy.Discussion: Delayed diagnosis and treatment of osteomyelitis can result in devastating neurological sequelae, and literature supports immediate surgical debridement. Although past evidence has suggested surgical intervention in similar patients with presence of abscesses, this case may suggest that antibiotic treatment may be an alternative approach to the management of CCS due to an infectious etiology. However, the patient had been non-compliant with medication, so it is unknown whether there was definite resolution of the condition.Conclusion: In patients presenting with non-traumatic central cord syndrome, it is vital to identify risk factors for infection in a thoroughly obtained patient history, as well as to maintain a low threshold for diagnostic imaging
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Safety and Efficacy of Hospital Utilization of Tranexamic Acid in Civilian Adult Trauma Resuscitation
Introduction: Patients with trauma-induced coagulopathies may benefit from the use of antifibrinolytic agents, such as tranexamic acid (TXA). This study evaluated the safety and efficacy of TXA in civilian adults hospitalized with traumatic hemorrhagic shock.Methods: Patients who sustained blunt or penetrating trauma with signs of hemorrhagic shock from June 2014 through July 2018 were considered for TXA treatment. A retrospective control group was formed from patients seen in the same past five years who were not administered TXA and matched based on age, gender, Injury Severity Score (ISS), and mechanism of injury (blunt vs penetrating trauma). The primary outcome of this study was mortality measured at 24 hours, 48 hours, and 28 days. Secondary outcomes included total blood products transfused, hospital length of stay (LOS), intensive care unit LOS, and adverse events. We conducted three pre-specified subgroup analyses to assess outcomes of patients, including (1) those who were severely injured (ISS >15), (2) those who sustained significant blood loss (â„10 units of total blood products transfused), and (3) those who sustained blunt vs penetrating trauma.Results: Propensity matching yielded two cohorts: the hospital TXA group (n = 280) and a control group (n = 280). The hospital TXA group had statistically lower mortality at 28 days (1.1% vs 5%, odds ratio [OR] [0.21], (95% confidence interval [CI], 0.06, 0.72)) and used fewer units of blood products (median = 4 units, interquartile range (IQR) = [1, 10] vs median=7 units, IQR = [2, 12.5] for the hospital TXA and control groups, respectively, (95% CI for the difference in median, -3 to -1). There were no statistically significant differences between groups with regard to 24-hour mortality (1.1% vs 1.1%, OR = 1, 95% CI, 0.20, 5.00), 48-hour mortality (1.1% vs 1.4%, OR [0.74], 95% CI, 0.17, 3.37), hospital LOS (median= 9 days, IQR = (5, 16) vs median =12 days IQR = (6, 22.5) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-5 to 0)), and incidence of thromboembolic events (eg, deep vein thrombosis, pulmonary embolism) during hospital stay (0.7% vs 0.7% for the hospital TXA and control group, respectively, OR [1], 95% CI, 0.14 to 7.15). We conducted subgroup analyses on patients with ISS>15, patients transfused with â„10 units of blood products, and blunt vs penetrating trauma. The results indicated lower 28-day mortality for ISS>15 (1.8% vs 7.1%, OR [0.23], 95% CI, 0.06 to 0.81) and blunt trauma (0.6% vs 6.3%, OR [0.09], 95% CI, 0.01 to 0.75); fewer units of blood products for penetrating trauma (median = 2 units, IQR = (1, 8) vs median = 8 units, IQR = (5, 15) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-6 to -3)), and ISS>15 (median = 7 units, IQR = (2, 14) vs median = 8.5 units, IQR = (4, 16) for the hospital TXA and control groups, respectively, 95% CI for the difference in median, -3 to 0).Conclusion: The current study demonstrates a statistically significant reduction in mortality after TXA administration at 28 days, but not at 24 and 48 hours, in patients with traumatic hemorrhagic shock
Use of p53-Silenced Endothelial Progenitor Cells to Treat Ischemia in Diabetic Peripheral Vascular Disease.
Background Peripheral vascular disease is a major diabetes mellitusârelated complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53â and p21âsilenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53â and p21âsilenced EPCs could improve collateral vessel formation and blood flow in diabetic vasoâocclusive peripheral vascular disease mouse models. Methods and Results We transplanted p53 and p21KO mouse EPCs (mEPCs) into streptozotocinâinduced diabetic (type 1 diabetes mellitus model) C57BL/6J and db/db (B6.BKS(D)âLeprdb/J) (type 2 model) postâfemoral artery occlusion. Similarly, Adâp53âsilenced and Adâp21âsilenced human EPCs (CD34+) cells were transplanted into streptozotocinâinduced diabetic NOD.CB17âPrkdcscid/J mice. We measured blood flow at 3, 7, and 10 days and hindlimb muscles were obtained postsacrifice for mRNA estimation and CD31 staining. Enhanced blood flow was noted with delivery of p53 and p21KO mEPCs in streptozotocinâinduced diabetic C57BL/6J mice. Similar results were obtained when human Adâp53shEPCs(CD34+) and Adâp21shEPCs(CD34+) were transplanted into streptozotocinâinduced nonobese diabetic severe combined immunodeficiency mice. Gene expression analysis of p53 and p21KO EPCs transplanted hindlimb muscles showed increased expression of endothelial markers such as endothelial nitric oxide synthase, vascular endothelial growth factor A, and platelet endothelial cell adhesion molecule 1. Similarly, quantitative reverse transcriptase polymerase chain reaction of human Adâp53shEPCs (CD34+)â and Adâp21shEPCs (CD34+)âtransplanted hindlimb muscles also showed increased expression of endothelial markers such as vascular endothelial growth factor A, noted primarily in the p53âsilenced EPCs group. However, such beneficial effect was not noted in the db/db type 2 diabetic mouse models. Conclusions Transient silencing of p53 using adenoviral vector in EPCs may have a therapeutic role in diabetic peripheral vascular disease
Phytochemical screening and in vitro antimicrobial activity of Bougainvillea spectabilis flower extracts
Various flower extracts (Chloroform, ethyl acetate, ethanol and water) of Bougainvillea spectabilis were screened for their phytochemical constituents and also investigated for their antimicrobial activities. Phytochemical screening of flower extracts revealed the presence of alkaloids, flavonoides, phlobatannins and terpenoids. Steroids, phenol, tannins, cardinolides and volatile oils were absent in all the extracts. All flower extracts of B. spectabilis inhibited the growth of few of the bacterial and fungal strains tested with varied effectiveness. The maximum antibacterial activities were observed in ethanol and water extracts. The maximum antifungal activities were observed in chloroform and ethanol extracts. Thus the bioactive natural products in flower extracts of Bougainvillea spectabilis can be used in the development of new pharmaceuticals that address unmet therapeutic use
The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial.
AIMS: Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients.
METHODS: In 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg. Subjects aged 40-70 years with diabetes for \u3câ10 years, with no known cardiovascular disease, BMI 25-39.9, HbA1C 6-9% were included. We evaluated EPCs number, function, surface markers and gene expression, in addition to arterial stiffness, blood biochemistries, resting energy expenditure, and body composition parameters. A mixed model regression to examine saxagliptin vs placebo, accounting for within-subject autocorrelation, was done with SAS (pâ\u3câ0.05).
RESULTS: Although there was no significant increase in CD34+ cell number, CD31+ cells percentage increased. Saxagliptin increased migration (in response to SDF1α) with a trend of higher colony formation count. MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells, indicating a functional improvement. Gene expression analysis showed an upregulation in CD34+ cells for antioxidant SOD1 (pâ\u3câ0.05) and a downregulation in CD34- cells for IL-6 (pâ\u3câ0.01). For arterial stiffness, both augmentation index and systolic blood pressure measures went down in saxagliptin subjects (pâ\u3câ0.05).
CONCLUSION: Saxagliptin, in combination with metformin, can help improve endothelial dysfunction in early diabetes before macrovascular complications appear. Trial registration Trial is registered under clinicaltrials.gov, NCT02024477
The P72R Polymorphism in R248Q/W p53 Mutants Modifies the Mutant Effect on Epithelial to Mesenchymal Transition Phenotype and Cell Invasion via CXCL1 Expression
High-grade serous carcinoma (HGSC), the most lethal subtype of epithelial ovarian cancer (EOC), is characterized by widespread TP53 mutations (\u3e90%), most of which are missense mutations (\u3e70%). The objective of this study was to investigate differential transcriptional targets affected by a common germline P72R SNP (rs1042522) in two p53 hotspot mutants, R248Q and R248W, and identify the mechanism through which the P72R SNP affects the neomorphic properties of these mutants. Using isogenic cell line models, transcriptomic analysis, xenografts, and patient data, we found that the P72R SNP modifies the effect of p53 hotspot mutants on cellular morphology and invasion properties. Most importantly, RNA sequencing studies identified CXCL1 a critical factor that is differentially affected by P72R SNP in R248Q and R248W mutants and is responsible for differences in cellular morphology and functional properties observed in these p53 mutants. We show that the mutants with the P72 SNP promote a reversion of the EMT phenotype to epithelial characteristics, whereas its R72 counterpart promotes a mesenchymal transition via the chemokine CXCL1. These studies reveal a new role of the P72R SNP in modulating the neomorphic properties of p53 mutants via CXCL1, which has significant implications for tumor invasion and metastasis
Anaesth Crit Care Pain Med
Objective To develop French guidelines on the management of patients with severe abdominal trauma. Design A consensus committee of 20 experts from the French Society of Anaesthesiology and Critical Care Medicine (SociĂ©tĂ© française dâanesthĂ©sie et de rĂ©animation, SFAR), the French Society of Emergency Medicine (SociĂ©tĂ© française de mĂ©decine dâurgence, SFMU), the French Society of Urology (SociĂ©tĂ© française dâurologie, SFU) and from the French Association of Surgery (Association française de chirurgie, AFC), the Val-de-GrĂące School (Ăcole du Val-De-GrĂące, EVG) and the Federation for Interventional Radiology (FĂ©dĂ©ration de radiologie interventionnelle, FRI-SFR) was convened. Declaration of all conflicts of interest (COI) policy by all participants was mandatory throughout the development of the guidelines. The entire guideline process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for assessment of the available level of evidence with particular emphasis to avoid formulating strong recommendations in the absence of high level. Some recommendations were left ungraded. Methods The guidelines are divided in diagnostic and, therapeutic strategy and early surveillance. All questions were formulated according to Population, Intervention, Comparison, and Outcomes (PICO) format. The panel focused on three questions for diagnostic strategy: (1) What is the diagnostic performance of clinical signs to suggest abdominal injury in trauma patients? (2) Suspecting abdominal trauma, what is the diagnostic performance of prehospital FAST (Focused Abdominal Sonography for Trauma) to rule in abdominal injury and guide the prehospital triage of the patient? and (3) When suspecting abdominal trauma, does carrying out a contrast enhanced thoraco-abdominal CT scan allow identification of abdominal injuries and reduction of mortality? Four questions dealt with therapeutic strategy: (1) After severe abdominal trauma, does immediate laparotomy reduce morbidity and mortality? (2) Does a âdamage control surgeryâ strategy decrease morbidity and mortality in patients with a severe abdominal trauma? (3) Does a laparoscopic approach in patients with abdominal trauma decrease mortality or morbidity? and (4) Does non-operative management of patients with abdominal trauma without bleeding reduce mortality and morbidity? Finally, one question was formulated regarding the early monitoring of these patients: In case of severe abdominal trauma, which kind of initial monitoring does allow to reduce the morbi-mortality? The analysis of the literature and the recommendations were conducted following the GRADEÂź methodology. Results The SFAR/SFMU Guideline panel provided 15 statements on early management of severe abdominal trauma. After three rounds of discussion and various amendments, a strong agreement was reached for 100% of recommendations. Of these recommendations, five have a high level of evidence (Grade 1±), six have a low level of evidence (Grade 2±) and four are expert judgments. Finally, no recommendation was provided for one question. Conclusions Substantial agreement exists among experts regarding many strong recommendations for the best early management of severe abdominal trauma
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Designing and Developing the Mobile Gravity Suit for Long-Duration Spaceflight
Spaceflight Associated Neuro-ocular Syndrome, bone decalcification, and muscle atrophy are among the most prevalent risks associated with long-duration spaceflight. Implementing the lower body negative pressure (LBNP) technique is a potential countermeasure for these risks. LBNP counteracts head-ward fluid shifts and generates ground-reaction forces (GRFs). GRFs are beneficial for maintaining bones and muscles by generating gravitational-like loads we experience on Earth. Currently, LBNP devices are large/bulky and require the subject to maintain a stationary position. However, the mobile Gravity Suit I designed is relatively small, untethered, and flexible. It is hypothesized that by designing and developing a mobile Gravity Suit, we can generate greater GRFs than an LBNP chamber. Static LBNP chambers achieve only one GRF on the subject. This can be expressed as AW(LBNP) = GRF, where Aw = cross-sectional area (CSA) of waist seal. However, the mobile Gravity Suit may achieve an additional GRF using the following equation, (AF + AW)LBNP = GRF, where AF = CSA of subjectâs feet. The additional force can be further expressed as F1 + F2 = AF(LBNP), where F1 = spinal loading force, F2 = waist shear force, and AF(LBNP) = the total downward foot force. While lying supine, GRF data were recorded in both devices using foot sole sensors and a weigh scale. The data show that the Gravity Suit generated a mean maximum bodyweight of 125% +/- 22% whereas the LBNP chamber generated 91% +/- 24%. The mobile Gravity Suit demonstrates higher percent of bodyweight, due to the suit's novel biomechanical design
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