A clinical review of hand manifestations of cervical myelopathy, cervical radiculopathy, radial, ulnar, and median nerve neuropathies.

Cervical spondylotic myelopathy (CSM) is defined as compression of the spinal cord in the neck, resulting in problems with fine motor skills, hand numbness, pain or stiffness of the neck, and difficulty walking due to loss of balance. Brachial plexus (BP) neuropathies arise due to compression to any distal branches arising from C5-T1, whereas cervical radiculopathy involves compression at the nerve root in the neck. Such conditions can present with variable degrees of musculoskeletal pain, weakness, sensory changes, and reflex changes. The pronounced convergence in symptomatic manifestation within these conditions can pose a formidable challenge to clinicians, particularly in primary care. Thus, the primary objective of this paper is to enhance clarity and distinction among these pathological conditions. This objective is pursued through comprehensive delineation of the dermatomal and myotomal distributions characteristic of each condition. Furthermore, a meticulous examination is undertaken to elucidate physical indicators and maneuvers that exhibit a notably high sensitivity in detecting these conditions. Accurate diagnosis and treatment of each nerve pathology is important as long-term spinal cord compression and its roots may result in permanent disability and severely impact one's quality of life. As such, this systematic review serves as a guide that aids clinicians in differentiating the aforementioned conditions based on anatomy, physical exam findings, and imaging studies. Furthermore, this study aims to outline common peripheral nerve neuropathies in the upper extremities and ways to mitigate these pathologies using the least to most invasive treatment modalities.

Does pes anserinus tenotomy affect surgical site infection rate in operative tibial plateau fractures?

PURPOSE: To assess if pes anserinus tenotomy (PAT) during definitive open reduction and internal fixation (ORIF) of tibial plateau fractures is associated with a decreased risk of surgical site infection (SSI) and other postoperative complications. METHODS: A retrospective review of all adults who underwent ORIF for tibial plateau fractures from April 2005 to February 2022 at single level 1 trauma center was performed. Patients who had a medial approach to the plateau with minimum three-month follow-up were required for inclusion. All patients with fasciotomy for compartment syndrome or with traumatically avulsed or damaged pes anserinus prior to ORIF were excluded. Two groups were created: those who received a pes anserinus tenotomy with repair (PAT group) and those whose pes anserinus were spared and left intact (control group). Patient demographics, injury and operative characteristics, and surgical outcomes were compared. The primary outcomes were rates of deep and superficial SSI. RESULTS: The PAT group had significantly lower rates of deep SSI (9.2% vs. 19.7%, P = 0.009), superficial SSI (14.2% vs. 26.5%), P = 0.007), and any SSI (15.8% vs. 28.9%, P = 0.005). Multiple logistic regression showed that heart failure (aOR = 7.215, 95% CI 2.291-22.719, P < 0.001), and presence of open fracture (aOR = 4.046, 95% CI 2.074-7.895, P < 0.001) were independently associated with increased odds of deep SSI, while PAT was associated with a decreased odds of deep SSI (aOR = 0.481, 95% CI 0.231-0.992, P = 0.048). PAT had significantly lower rates of unplanned return to the operating room (20.8% vs. 33.7%, P = 0.010) and implant removal (10.0% vs. 18.0%, P = 0.042). CONCLUSION: While these data do not allow for discussion of functional recovery or strength, pes anserinus tenotomy was independently associated with significantly lower rates of infection, unplanned operation, and implant removal. LEVEL OF EVIDENCE: Level III.

Medical Students' Perceptions of Orthopedics as a Career for Women.

OBJECTIVES: To determine potential factors influencing female medical students' interest and subsequent application to orthopedics, and to evaluate female and male medical students' perceptions of women in the field of orthopedics. METHODS: An institutional review board-approved survey was distributed in March 2020 and subsequently in April 2022 to medical students in the classes of 2023 and 2024 at the University of Alabama at Birmingham Heersink School of Medicine. Study data were collected and managed using REDCap electronic data capture. An e-mail link to the REDCap survey was sent to students across the southeast region of the United States, followed by three reminder e-mails. All 25 allopathic medical schools in the southeastern United States with an Orthopedics Interest Group listed on their institution's Web site were invited to participate in the study. Nine Orthopedics Interest Group leaders interested in participating were asked to provide the researchers with a list of fourth-year medical students who attended an event hosted by that group (215). A total of 39 respondents who completed the survey were included in this study. RESULTS: Overall, the majority of students (n = 35, 90%) believed that women faced more barriers to a career in orthopedics than did men. The most significant barriers to women entering the field of orthopedics were the perceived expectations of an orthopedic surgeon (n = 34, 87%), difficulty balancing career and family (n = 28, 72%), and demanding schedule (n = 13, 33%). CONCLUSIONS: This study demonstrates that both male and female medical students believe there are significant additional barriers to success for women in the field. Study participants report that expectations set by physicians, other healthcare professionals, and patients contribute to creating greater barriers that deter medical students interested in orthopedics from ultimately applying to the specialty.

Erythroid differentiation in mouse erythroleukemia cells depends on Tmod3-mediated regulation of actin filament assembly into the erythroblast membrane skeleton.

Erythroid differentiation (ED) is a complex cellular process entailing morphologically distinct maturation stages of erythroblasts during terminal differentiation. Studies of actin filament (F-actin) assembly and organization during terminal ED have revealed essential roles for the F-actin pointed-end capping proteins, tropomodulins (Tmod1 and Tmod3). Tmods bind tropomyosins (Tpms), which enhance Tmod capping and F-actin stabilization. Tmods can also nucleate F-actin assembly, independent of Tpms. Tmod1 is present in the red blood cell (RBC) membrane skeleton, and deletion of Tmod1 in mice leads to a mild compensated anemia due to mis-regulated F-actin lengths and membrane instability. Tmod3 is not present in RBCs, and global deletion of Tmod3 leads to embryonic lethality in mice with impaired ED. To further decipher Tmod3's function during ED, we generated a Tmod3 knockout in a mouse erythroleukemia cell line (Mel ds19). Tmod3 knockout cells appeared normal prior to ED, but showed defects during progression of ED, characterized by a marked failure to reduce cell and nuclear size, reduced viability, and increased apoptosis. Tmod3 does not assemble with Tmod1 and Tpms into the Triton X-100 insoluble membrane skeleton during ED, and loss of Tmod3 had no effect on α1,ß1-spectrin and protein 4.1R assembly into the membrane skeleton. However, F-actin, Tmod1 and Tpms failed to assemble into the membrane skeleton during ED in absence of Tmod3. We propose that Tmod3 nucleation of F-actin assembly promotes incorporation of Tmod1 and Tpms into membrane skeleton F-actin, and that this is integral to morphological maturation and cell survival during erythroid terminal differentiation.

A Plausible Pipeline to Diversifying Orthopaedics: Premedical Programming.

OBJECTIVE: To determine whether premedical programming can address the interest level and perception of barriers to women in orthopaedics held by female high school and medical students. DESIGN: A thirteen-question paper-based survey was distributed among the high school and medical school participants prior to the January 2020 Perry Outreach Program and Medical Student Outreach Program. After a day of participation in mock procedures and speaker sessions, participants subsequently completed another survey of seven-questions. SETTING: The Perry Outreach Program and Medical Student Outreach Program were conducted at the University of Alabama at Birmingham campus. PARTICIPANTS: Participants consisted of high school and medical school women hailing from the Birmingham metropolitan area, who had signed up for the Perry programs via email, outreach to local high schools, and social media interest pages. Participant sampling was stratified by race and level of education (high school vs. medical school). RESULTS: A total of 36 women, 18 high school and 18 medical school, attended the Perry Initiative events and responded to the pre-event and post-event surveys. Before the Perry Initiative programs, all participants felt women faced more barriers than men in pursuing a career in orthopaedics. Participation in the Perry Initiative event increased average interest in orthopaedics by 28% among high school and 11% among medical school students. CONCLUSIONS: Prior to the Perry Initiative, 31% percent of the total attendees reported knowing a female orthopaedist. The Perry Initiative improved perceptions of both high school and medical students regarding the ability of women to have a work/life balance, family life, and children during orthopaedics residency. Medical student participation in the events led to a decreased belief in barriers regarding schedule, family life, perceptions of an orthopaedic surgeon, and perceptions of peers within healthcare setting.

Spironolactone Reduces Aortic Stiffness in Patients With Resistant Hypertension Independent of Blood Pressure Change.

Background Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase-contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P<0.001) and pulsatility and distensibility increased (15.9%±5.3% to 22.1%±7.9%, P<0.001; and 0.28%±0.10%/mm Hg to 0.40%±0.14%/mm Hg, P<0.001, respectively) following 6 months of spironolactone. Conclusions Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

Purification and immunogenicity of hemagglutinin from highly pathogenic avian influenza virus H5N1 expressed in Nicotiana benthamiana.

Highly pathogenic avian influenza (HPAI) H5N1 is an ongoing global health concern due to its severe sporadic outbreaks in Asia, Africa and Europe, which poses a potential pandemic threat. The development of safe and cost-effective vaccine candidates for HPAI is considered the best strategy for managing the disease and addressing the pandemic preparedness. The most potential vaccine candidate is the antigenic determinant of influenza A virus, hemagglutinin (HA). The present research was aimed at developing optimized expression in Nicotiana benthamiana and protein purification process for HA from the Malaysian isolate of H5N1 as a vaccine antigen for HPAI H5N1. Expression of HA from the Malaysian isolate of HPAI in N. benthamiana was confirmed, and more soluble protein was expressed as truncated HA, the HA1 domain over the entire ectodomain of HA. Two different purification processes were evaluated for efficiency in terms of purity and yield. Due to the reduced yield, protein degradation and length of the 3-column purification process, the 2-column method was chosen for target purification. Purified HA1 was found immunogenic in mice inducing H5 HA-specific IgG and a hemagglutination inhibition antibody. This paper offers an alternative production system of a vaccine candidate against a locally circulating HPAI, which has a regional significance.

Production of Functionally Active and Immunogenic Non-Glycosylated Protective Antigen from Bacillus anthracis in Nicotiana benthamiana by Co-Expression with Peptide-N-Glycosidase F (PNGase F) of Flavobacterium meningosepticum.

Bacillus anthracis has long been considered a potential biological warfare agent, and therefore, there is a need for a safe, low-cost and highly efficient anthrax vaccine with demonstrated long-term stability for mass vaccination in case of an emergency. Many efforts have been made towards developing an anthrax vaccine based on recombinant protective antigen (rPA) of B. anthracis, a key component of the anthrax toxin, produced using different expression systems. Plants represent a promising recombinant protein production platform due to their relatively low cost, rapid scalability and favorable safety profile. Previous studies have shown that full-length rPA produced in Nicotiana benthamiana (pp-PA83) is immunogenic and can provide full protection against lethal spore challenge; however, further improvement in the potency and stability of the vaccine candidate is necessary. PA of B. anthracis is not a glycoprotein in its native host; however, this protein contains potential N-linked glycosylation sites, which can be aberrantly glycosylated during expression in eukaryotic systems including plants. This glycosylation could affect the availability of certain key epitopes either due to masking or misfolding of the protein. Therefore, a non-glycosylated form of pp-PA83 was engineered and produced in N. benthamiana using an in vivo deglycosylation approach based on co-expression of peptide-N-glycosidase F (PNGase F) from Flavobacterium meningosepticum. For comparison, versions of pp-PA83 containing point mutations in six potential N-glycosylation sites were also engineered and expressed in N. benthamiana. The in vivo deglycosylated pp-PA83 (pp-dPA83) was shown to have in vitro activity, in contrast to glycosylated pp-PA83, and to induce significantly higher levels of toxin-neutralizing antibody responses in mice compared with glycosylated pp-PA83, in vitro deglycosylated pp-PA83 or the mutated versions of pp-PA83. These results suggest that pp-dPA83 may offer advantages in terms of dose sparing and enhanced immunogenicity as a promising candidate for a safe, effective and low-cost subunit vaccine against anthrax.

Controlled release of an anthrax toxin-neutralizing antibody from hydrolytically degradable polyethylene glycol hydrogels.

In this study, hydrophilic and hydrolytically degradable poly (ethylene glycol) (PEG) hydrogels were formed via Michael-type addition and employed for sustained delivery of a monoclonal antibody against the protective antigen of anthrax. Taking advantage of the PEG-induced precipitation of the antibody, burst release from the matrix was avoided. These hydrogels were able to release active antibodies in a controlled manner from 14 days to as long as 56 days in vitro by varying the polymer architectures and molecular weights of the precursors. Analysis of the secondary and tertiary structure and the in vitro activity of the released antibody showed that the encapsulation and release did not affect the protein conformation or functionality. The results suggest the promise for developing PEG-based carriers for sustained release of therapeutic antibodies against toxins in various applications.

A plant-produced protective antigen vaccine confers protection in rabbits against a lethal aerosolized challenge with Bacillus anthracis Ames spores.

The potential use of Bacillus anthracis as a bioterrorism weapon threatens the security of populations globally, requiring the immediate availability of safe, efficient and easily delivered anthrax vaccine for mass vaccination. Extensive research efforts have been directed toward the development of recombinant subunit vaccines based on protective antigen (PA), the principal virulence factor of B. anthracis. Among the emerging technologies for the production of these vaccine antigens is our launch vector-based plant transient expression system. Using this system, we have successfully engineered, expressed, purified and characterized full-length PA (pp-PA83) in Nicotiana benthamiana plants using agroinfiltration. This plant-produced antigen elicited high toxin neutralizing antibody titers in mice and rabbits after two vaccine administrations with Alhydrogel. In addition, immunization with this vaccine candidate protected 100% of rabbits from a lethal aerosolized B. anthracis challenge. The vaccine effects were dose-dependent and required the presence of Alhydrogel adjuvant. In addition, the vaccine antigen formulated with Alhydrogel was stable and retained immunogenicity after two-week storage at 4°C, the conditions intended for clinical use. These results support the testing of this vaccine candidate in human volunteers and the utility of our plant expression system for the production of a recombinant anthrax vaccine.