Optimization of Surface Display of DENV2 E Protein on a Nanoparticle to Induce Virus Specific Neutralizing Antibody Responses.

The dengue virus (DENV) causes over 350 million infections, resulting in ∼25,000 deaths per year globally. An effective dengue vaccine requires generation of strong and balanced neutralizing antibodies against all four antigenically distinct serotypes of DENV. The leading live-attenuated tetravalent dengue virus vaccine platform has shown partial efficacy, with an unbalanced response across the four serotypes in clinical trials. DENV subunit vaccine platforms are being developed because they provide a strong safety profile and are expected to avoid the unbalanced immunization issues associated with live multivalent vaccines. Subunit vaccines often lack immunogenicity, requiring either a particulate or adjuvanted formulation. Particulate formulations adsorbing monomeric DENV-E antigen to the particle surface incite a strong immune response, but have no control of antigen presentation. Highly neutralizing epitopes are displayed by DENV-E quaternary structures. To control the display of DENV-E and produce quaternary structures, particulate formulations that covalently attach DENV-E to the particle surface are needed. Here we develop a surface attached DENV2-E particulate formulation, as well as analysis tools, using PEG hydrogel nanoparticles created with particle replication in nonwetting templates (PRINT) technology. We found that adding Tween-20 to the conjugation buffer controls DENV-E adsorption to the particle surface during conjugation, improving both protein stability and epitope display. Immunizations with the anionic but not the cationic DENV2-E conjugated particles were able to produce DENV-specific and virus neutralizing antibody in mice. This work optimized the display of DENV-E conjugated to the surface of a nanoparticle through EDC/NHS chemistry, establishing a platform that can be expanded upon in future work to fully control the display of DENV-E.

A Review of 1228 In-Office Hand Surgery Procedures With Wide Awake Local Anesthesia No Tourniquet (WALANT) at a Single Private Practice.

BACKGROUND: This study examined the complication rate of Wide Awake Local Anesthesia No Tourniquet (WALANT) technique in the clinic setting with field sterility at a single private practice. We hypothesized that WALANT is safe and effective with a low complication rate. METHODS: This retrospective chart review included 1228 patients who underwent in-office WALANT hand procedures at a single private practice between 2015 and 2022. Patients were divided into groups based on type of procedure: carpal tunnel release, A1 pulley release, first dorsal compartment release, extensor tendon repair, mass excision, foreign body removal, and needle aponeurotomy. Patient demographics and complications were recorded; statistical comparisons of cohort demographics and risk factors for complications were completed, and P < .05 was considered significant for all statistical comparisons. RESULTS: The overall complication rate for all procedures was 2.77% for 1228 patients including A1 pulley release (n = 962, 2.7%), mass excision (n = 137, 3.7%), extensor tendon repair (n = 23, 4.3%), and first dorsal compartment release (n = 22, 8.3%). Carpal tunnel release, foreign body removal, and needle aponeurotomy groups experienced no complications. No adverse events (e.g. vasovagal reactions, digital ischemia, local anesthetic toxicity, inadequate vasoconstriction) were observed in any group. Patients with known autoimmune disorders and those who were currently smoking had a statistically significant higher complication rate. CONCLUSIONS: Office-based WALANT procedures with field sterility are safe and effective for treating common hand maladies and have a similar complication profile when compared to historical controls from the standard operating room in an ambulatory center or hospital.

Popliteal Artery Entrapment within a Tibial Plateau Fracture: A Case Report.

CASE: Tibial plateau fractures can be associated with arterial injuries or dysvascular limbs, particularly in settings of trauma. Dysvascular limb in the setting of fracture is commonly due to dissection of the artery. Entrapment of the artery within the fracture is rare. We report a 48-year-old man who presented with left popliteal entrapment within a left tibial plateau fracture status-post external fixation and stent placement in the popliteal artery. CONCLUSION: Findings from this case highlight entrapment of an artery as a mechanism of a dysvascular limb in the setting of high-energy lower-extremity fractures and specifically for tibial plateau fractures.

Parsonage-Turner Syndrome After SARS-CoV-2 BNT162b2 Vaccine: A Case Report.

CASE: Parsonage-Turner syndrome, also known as brachial neuritis or neuralgic amyotrophy, is characterized by sudden-onset pain and subsequent weakness of the shoulder. Known precipitating factors include viral and bacterial infections and certain immunizations. Isolated cases after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We report the case of a 66-year-old woman with right shoulder dysfunction and medial scapular winging after immunization with the SARS-CoV-2 BNT162b2 vaccine (Pfizer). CONCLUSION: After physical therapy, the patient resumed her normal activities of daily living. Findings from this case represent the first known documentation of Parsonage-Turner syndrome after SARS-CoV-2 BNT162b2 vaccination.

Complex Focal Pain Syndrome: An Unusual Variant of Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain condition that is often overlooked by clinicians and typically occurs within an entire limb. There is considerable clinical variability in presentation among patients with CRPS. We report a case of extremely focal CRPS localized to the left small finger (LSF) following crush injury. A 48-year-old right-handed male presented with LSF stiffness and severe pain of three months' duration following crush injury. He endorsed severe allodynia and minimal flexion at the proximal interphalangeal and distal interphalangeal joints of the LSF. Physical examination was significant for overt shininess and edema isolated to the LSF. X-ray performed at the time of injury and three months after were devoid of any fracture or dislocation. Chronic focal pain syndrome (CFPS) may be a subset of CRPS that has yet to be documented in the literature.

Management of asymptomatic pulmonary vein aneurysm.

Aneurysm of a pulmonary vein is a rare vascular anomaly that is usually discovered incidentally as a pulmonary nodule or mediastinal mass. Most patients do not have any symptoms but some patients can present with dyspnea, hemoptysis, or cerebral thromboembolism. Proper diagnosis is crucial as to avoid unnecessary testing or surgical procedures. We highlight a case of an asymptomatic 59-year-old female with a pulmonary vein aneurysm presenting as a 1.5 cm right infrahilar nodule on contrast-enhanced CT during evaluation for acute cholecystitis. Further investigation with MRA revealed that it was vascular in nature, and pulmonary angiography showed dilation of the right inferior pulmonary vein with no communication to the pulmonary artery. On serial imaging, there has been no change in the size of the aneurysm. A small non-enlarging pulmonary vein aneurysm should be managed expectantly.

Sex Differences in the Impact of Shift Work Schedules on Pathological Outcomes in an Animal Model of Ischemic Stroke.

Circadian clock desynchronization has been implicated in the pathophysiology of cardiovascular disease and related risk factors (eg, obesity, diabetes). Thus, we examined the extent to which circadian desynchronization exacerbates ischemic stroke outcomes and whether its detrimental effects on stroke severity and functional impairments are further modified by biological sex. Circadian entrainment of activity rhythms in all male and female rats was observed during exposure to a fixed light-dark (LD) 12:12 cycle but was severely disrupted when this LD cycle was routinely shifted (12 h advance/5 d) for approximately 7 weeks. In contrast to the regular estrous cycles in fixed LD animals, cyclicity was abolished and persistent estrus was evident in all shifted LD females. The disruption of estrous cyclicity in shifted LD females was associated with a significant increase in serum estradiol levels relative to that observed in fixed LD controls. Circadian rhythm disruption exacerbated stroke outcomes in both shifted LD male and female rats and further amplified sex differences in stroke impairments. In males, but not females, circadian disruption after exposure to the shifted LD cycle was marked by high rates of mortality. In surviving females, circadian desynchronization after exposure to shifted LD cycles produced significant increases in stroke-induced infarct volume and sensorimotor deficits with corresponding decreases in serum IGF-1 levels. These results suggest that circadian rhythm disruption associated with shift work schedules or the irregular nature of our everyday work and/or social environments may interact with other nonmodifiable risk factors such as biological sex to modulate the pathological effects of stroke.