Teaching vaccine development in schools: Learnings from a survey and curriculum design for a course

Although vaccines are being developed and administered to people for more than a century, the understanding of the steps involved in vaccine development is a relatively new subject to the general public. During the current pandemic, there has been an explosion of non-validated news about COVID-19 and vaccines. To enhance the understanding of this critical societal science, there is an urgent need to teach these topics in the early education systems. Defining the essential subjects and courses for high school and developing syllabi for undergraduate courses in immunology and vaccinology can be difficult, as students choose diverse career options after their studies. To define these curricula, understanding the current level of awareness regarding vaccinology and immunology among students becomes essential. Thus, we have undertaken an exploratory survey of 650 high school and undergraduate college students in India on their awareness of the processes of vaccine development. Our results confirmed our hypothesis that there is a very limited understanding of this topic among school-going students. In this article, we propose an outline for a course for teaching in high schools. We recommend that this course should be interdisciplinary and a mix and match of majors and minors. It should train students with soft skills and prepare them for their careers in biomedical research

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Open-door expansile cervical laminoplasty

Open-door expansile laminoplasty is a practical surgical technique for the treatment of cervical myelopathy secondary to cervical spinal stenosis. Laminoplasty procedures were first described in the late 1970s and have undergone numerous modifications. The current article reviews the indications, techniques, and outcome data for cervical laminoplasty. Complications of laminoplasty and comparison to laminectomy outcomes are also discussed

Transplantation of human bone marrow–derived stromal cells into the contused spinal cord of nude rats Laboratory investigation

Object Human bone marrow stromal cells (hMSCs) constitute a potential source of pluripotent stem cells. In the present study, hMSCs were transplanted into an area of spinal cord contusion in nude rats to determine their survival, differentiation, potential for neuroprotection, and influence on axonal growth and functional recovery. Methods Twenty-nine animals received 6 × 105 hMSCs in 6 μl medium 1 week after a contusion, while 14 control animals received an injection of 6 μl medium alone. Basso–Beattie–Bresnahan (BBB) tests were performed weekly. The spinal cords were collected at 6 weeks posttransplantation for histological analysis and assessment of tissue injury. Results Immunostaining with anti–human mitochondria antibody and pretransplantation labeling with green fluorescent protein demonstrated that the grafted hMSCs survived and were capable of achieving a flattened appearance in the grafted area; however, none of the transplanted cells stained positively for human-specific neuronal, anti–neurofilament H or glial fibrillary acidic protein within the sites of engraftment. While neuronal or astrocytic differentiation was not seen, cells lining blood vessels in the vicinity of the transplant stained positively for anti–human endothelium CD105 antibody. Staining for anti–neurofilament H antibody demonstrated abundant axonlike structures around the transplanted area in the hMSC group. Tissue sparing analysis showed that animals with grafted hMSCs had a smaller area of contusion cyst compared with controls, but there was no significant difference between the two groups in BBB scores. Conclusions The grafted hMSCs survived for ≥ 6 weeks posttransplantation, although they did not differentiate into neural or glial cells. Cells with human endothelial characteristics were observed. Spinal cord–injured rats grafted with hMSCs had smaller contusion cavities, which did not have a significant influence on functional recovery

Modification of Wright's technique for placement of bilateral crossing C2 translaminar screws: technical note

Several relatively new screw techniques have been described that rigidly capture the posterior elements of C2. The previously described procedures of axis fixation are technically demanding and place the vertebral artery at some risk. A novel and less technically demanding technique of obtaining C-2 translaminar screws has been recently described. Although the risk of vertebral artery injury has been essentially eliminated, the authors recognize that neurologic injury from breakthrough of the inner cortex of the lamina by the drill or screw is still a possibility. Describe and illustrate a modified C2 translaminar technique and review the results of patients who have undergone the surgery. The current modification of the C2 translaminar screw technique was designed to reduce the risk of inadvertent screw placement within the spinal canal. A techniques paper combined with a retrospective clinical review of patients undergoing the surgery. Patients undergoing posterior instrumented fusion surgery of the cervical spine, which incorporates C2 posterior elements using the translaminar technique. Radiographic analysis of the fusion construct incorporating the C2 translaminar screws. We have modified the previously described technique of C-2 translaminar screw placement with the addition of “exit” cortical windows to assure bicortical, intralaminar screw placement. The results of the first six patients with an average follow-up of 12 months demonstrated this method to be safe and effective in fixating the axis. We have made a simple modification of Wright's elegant technique with the addition of “exit” windows at the facet-laminar junctions. This gives us the assurance that the C2 screw has not entered the spinal canal by directly visualizing the tip of the screw exiting the outer cortices of the lamina before leaving the operating room

Surgical Management of Giant Aneurysms of the Middle Cerebral Artery

The middle cerebral artery (MCA) is the most common location for giant aneurysms of the anterior circulation. The contemporary management of giant aneurysms of the MCA lies largely in the surgical domain. Clipping is the first surgical option for these aneurysms. In about half the cases, the aneurysm neck is amenable to clipping, usually in conjunction with aneurysmorraphy. However, clipping is unsuitable for aneurysms without a well-defined neck or for fusiform giant aneurysms. For these cases, indirect treatment options include aneurysm trapping or proximal occlusion. Although frequently an M4 and occasionally an M3 branch can be sacrificed without the need for a distal bypass, we always recommend distal bypass whenever M1 or M2 must be sacrificed. There are several choices for distal bypass, but we prefer a high-flow bypass with a saphenous vein or radial artery graft whenever M1 is sacrificed and usually when M2 is occluded. With M3 or M4 occlusion, a low-flow superficial temporal artery distal bypass usually suffices. Recurring themes in the surgical treatment of these lesions are preservation of lenticulostriate perforators and keeping vessel reconstructions as simple as possible to reduce the length of temporary occlusion

UDP-glucose dehydrogenase (UGDH) activity is suppressed by peroxide and promoted by PDGF in fibroblast-like synoviocytes: Evidence of a redox control mechanism

UDP-glucose dehydrogenase (UGDH) generates essential precursors of hyaluronic acid (HA) synthesis, however mechanisms regulating its activity are unclear. We used enzyme histostaining and quantitative image analysis to test whether cytokines that stimulate HA synthesis upregulate UGDH activity. Fibroblast-like synoviocytes (FLS, from N = 6 human donors with knee pain) were cultured, freeze-thawed, and incubated for 1 hour with UDP-glucose, NAD+ and nitroblue tetrazolium (NBT) which allows UGDH to generate NADH, and NADH to reduce NBT to a blue stain. Compared to serum-free medium, FLS treated with PDGF showed 3-fold higher UGDH activity and 6-fold higher HA release, but IL-1beta/TGF-beta1 induced 27-fold higher HA release without enhancing UGDH activity. In selected proliferating cells, UGDH activity was lost in the cytosol, but preserved in the nucleus. Cell-free assays led us to discover that diaphorase, a cytosolic enzyme, or glutathione reductase, a nuclear enzyme, was necessary and sufficient for NADH to reduce NBT to a blue formazan dye in a 1-hour timeframe. Primary synovial fibroblasts and transformed A549 fibroblasts showed constitutive diaphorase/GR staining activity that varied according to supplied NADH levels, with relatively stronger UGDH and diaphorase activity in A549 cells. Unilateral knee injury in New Zealand White rabbits (N = 3) stimulated a coordinated increase in synovial membrane UGDH and diaphorase activity, but higher synovial fluid HA in only 2 out of 3 injured joints. UGDH activity (but not diaphorase) was abolished by N-ethyl maleimide, and inhibited by peroxide or UDP-xylose. Our results do not support the hypothesis that UGDH is a rate-liming enzyme for HA synthesis under catabolic inflammatory conditions that can oxidize and inactivate the UGDH active site cysteine. Our novel data suggest a model where UGDH activity is controlled by a redox switch, where intracellular peroxide inactivates, and high glutathione and diaphorase promote UGDH activity by maintaining the active site cysteine in a reduced state, and by recycling NAD+ from NADH

In situ enzyme staining reaction conditions.

In situ enzyme staining reaction conditions.</p