Traumatic brain injury (TBI) results in complex pathological reactions, the initial lesion worsened by secondary inflammation and edema. Angiotensin II (Ang II) is produced in the brain and Ang II receptor type 1 (AT 1 R) overstimulation produces vasoconstriction and inflammation. Ang II receptor blockers (ARBs) are neuroprotective in models of stroke but little is known of their effect when administered in TBI models. We therefore performed controlled cortical impact (CCI) injury on mice to investigate whether the ARB candesartan would mitigate any effects of TBI. We administered candesartan or vehicle to mice 5 h before CCI injury. Candesartan treatment reduced the lesion volume after CCI injury by approximately 50%, decreased the number of dying neurons, lessened the number of activated microglial cells, protected cerebral blood flow (CBF), and reduced the expression of the cytokine TGFb1 while increasing expression of TGFb3. Candesartan-treated mice also showed better motor skills on the rotarod 3 days after injury, and improved performance in the Morris water maze 4 weeks after injury. These results indicate that candesartan is neuroprotective, reducing neuronal injury, decreasing lesion volume and microglial activation, protecting CBF and improving functional behavior in a mouse model of TBI. Co-treatment with a peroxisome proliferator-activated receptor-gamma (PPARg) antagonist significantly reduced some of the beneficial effects of candesartan after CCI, suggesting that PPARg activation may contribute to part or to all of the neuroprotective effect of candesartan. Overall, our data suggest that ARBs with dual AT 1 R-blocking and PPARg activation properties may have therapeutic value in treating TBI.
Thoracic pedicle screws have become the spinal anchor of choice because of the superior biomechanics of this technique. It is widely used for the treatment of scoliosis, spinal deformity (such as kyphosis), trauma, tumors, infection, and other pathologies. The technique demands precision as malposition can result in spinal cord or visceral injury with potential catastrophic consequences (death or paralysis). There have been many published articles looking at the anatomy and the anatomic variation in various populations according to race, age, deformity, etc. Lenke and others have developed start point guidelines that seem to have reasonable validity. There are two basic screw trajectories:The straightforward technique.The anatomic trajectory. The straightforward technique parallels the superior end plate of the instrumented vertebra. It has the best insertional torque. The anatomic trajectory bisects the sagittal axis of the pedicle, typically 15° cranial to caudal, and has the largest available bone channel. The accuracy of placement is a debated topic. There are several meta-analyses and systematic reviews that address this question. However, there are a variety of definitions of acceptable compared with optimal placement. The current gold standard for judging screw placement is the use of computed tomography; however, it carries a substantial radiation burden to the patient, which must be considered. There are a myriad of described techniques, including freehand (anatomically based), fluoroscopy-guided, and three-dimensional (3-D) image-guided methods. All have their advantages and disadvantages. Surgeons must find the technique that is safe and reliable in their hands. The procedure is performed with the following steps:Preoperative planning is done by initially looking at plain radiographs and by assessing bending radiographs and preoperative computed tomography scans, if available.The patient is placed on a Jackson table, which is radiolucent and allows easy access for C-arm or O-arm technology.Locate the start point around the thoracic level (T12, T8, etc.); a review of the Lenke start point map is helpful.Create the dorsal cortical hole, which is best done with a small pilot hole; we recommend the use of a 3-mm high-speed burr (Midas Rex; Medtronic).Create a track within the pedicle by probing with either a navigated probe or a Lenke-style freehand probe.Confirm the accuracy of the screw tract placement, which can be done by palpation although it is not 100% reliable.Place the screw after tapping 1 mm less than the nominal screw diameter.Confirm the accuracy of screw placement with fluoroscopy or plain radiographs; 3-D intraoperative imaging is the most reliable technique, but it also exposes the patient to the most radiation.Confirm the neurological status of the patient by monitoring the motor evoked potential signals after screw placement.Close the wound after the screws have been checked with intraoperative 2-D or 3-D imaging to ensure that they have not cut or plowed out. The results of thoracic pedi...
Importance The rise of novel, more infectious SARS-CoV-2 variants has made clear the need to rapidly deploy large-scale testing for COVID-19 to protect public health. However, testing remains limited due to shortages of personal protective equipment (PPE), naso- and oropharyngeal swabs, and healthcare workers. Simple test methods are needed to enhance COVID-19 screening. Here, we describe a simple, and inexpensive spit-test for COVID-19 screening called Patient Self-Collection of Sample-CoV2 (PSCS-CoV2). Objective To evaluate an affordable and convenient test for COVID-19. Methods The collection method relies on deep throat sputum (DTS) self-collected by the subject without the use of swabs, and was hence termed the Self-Collection of Sample for SARS-CoV-2 (abbreviated PSCS-CoV2). We used a phenol-chloroform extraction method for the viral RNA. We then tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction with primers against at least two coding regions of the viral nucleocapsid protein (N1 and N2 or E) of SARS-CoV-2. We evaluted the sensitivity and specificity of our protocol. In addition we assess the limit of detection, and efficacy of our Viral Inactivating Solution. We also evaluated our protocol, and pooling strategy from volunteers on a local college campus. Results We show that the PSCS-CoV2 method accurately identified 42 confirmed COVID-19 positives, which were confirmed through the nasopharyngeal swabbing method of an FDA approved testing facility. For samples negative for COVID-19, we show that the cycle threshold for N1, N2, and RP are similar between the PSCS-CoV2 and nasopharynx swab collection method (n = 30). We found a sensitivity of 100% (95% Confidence Interval [CI], 92-100) and specifity of 100% (95% CI, 89-100) for our PSCS-CoV2 method. We determined our protocol has a limit of detection of 1/10,000 for DTS from a COVID-19 patient. In addition, we show field data of the PSCS-CoV2 method on a college campus. Ten of the twelve volunteers (N1 < 30) that we tested as positive were subsequently tested positive by an independent laboratory. Finally, we show proof of concept of a pooling strategy to test for COVID-19, and recommend pool sizes of four if the positivity rate is less than 15%. Conclusion and Relevance We developed a DTS-based protocol for COVID-19 testing with high sensitivity and specificity. This protocol can be used by non-debilitated adults without the assistance of another adult, or by non-debilitated children with the assistance of a parent or guardian. We also discuss pooling strategies based on estimated positivity rates to help conserve resources, time, and increase throughput. The PSCS-CoV2 method can be a key component of community-wide efforts to slow the spread of COVID-19.
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