Abstract Diabetic foot ulceration of the plantar hallux is a challenging condition and can require partial hallux amputation when complicated by infection. Lower extremity biomechanics play an ...important role in the development of hallux ulcers, and hallux rigidus (HR) could influence the outcomes after partial hallux amputation. We hypothesized that radiographic evidence of HR in patients with diabetes would be associated with greater ulcer recurrence and reamputation rates after partial hallux amputation. We performed a retrospective review of all patients with diabetes who had undergone a partial hallux amputation from January 2005 to December 2012. The subjects were divided into 2 cohorts according to the presence or absence of HR identified on preoperative radiographs. Baseline characteristics and outcomes were compared using a 2-sample Student's t test for continuous variables, and categorical variables were compared using the chi-square test for homogeneity and Fisher's exact test. A total of 52 patients were included, with 16 (31%) positive for radiographic evidence of HR at partial hallux amputation. Differences in the patient demographics and comorbidities were not significant between 2 cohorts with and without HR or reamputation. Reamputation was required in 5 subjects (31%) with HR and 2 (6%) without HR ( p = .023). The average follow-up duration was 126 ± 89 weeks. Our results have demonstrated that the reamputation rate after partial hallux amputation is significantly greater in patients with than in those without radiographic evidence of HR. Surgeons should evaluate patients for HR when planning partial hallux amputation and use adjuvant methods of offloading when HR is evident to prevent recurrent ulceration and reamputation.
Kaposi sarcoma (KS) has multiple clinical variants, and most frequently presents on the lower extremities. Anti-human immunodeficiency virus (HIV) therapy has significantly reduced the incidence of ...KS. However, KS is still prevalent in both HIV-infected and HIV-uninfected patients. This case series analysis aims to reveal the clinical presentations, differential diagnosis, and treatment options of KS on the foot and ankle.
Eleven cases of KS involving the foot and ankle were retrieved from our patient database, and their clinicopathologic features were analyzed.
All patients were men, aged 29 to 85 years. Two types of KS were found: classic and acquired immunodeficiency syndrome-associated epidemic. The average ages of classic and epidemic KS were 65.7 and 41.8 years, respectively. Clinically, three patients manifested multiple erythematous or deep violaceous, or blue-violaceous macules on either the dorsal or plantar surfaces of both feet. Eight patients showed exophytic, pyogenic granuloma-like nodules on the plantar surface, heels, and toes. Histologically, all KSs had uniform intervening fascicles of elongated spindle cells with slit-like vascular spaces filled with red blood cells and immunoreactivity with human herpesvirus-8. The patients were treated according to HIV infection status. Human immunodeficiency virus-infected patients were treated with anti-HIV therapy after primary surgical excision or biopsy. Human immunodeficiency virus-negative patients were treated with either surgical excision, Mohs surgery, or a combination of surgical excision and local radiotherapy according to individual patient clinical presentation.
Kaposi sarcoma is still prevalent in both HIV-infected and HIV-uninfected patients with a variety of clinical presentations. Biopsy, with histologic evaluation, in combination with immunohistochemistry is essential for the differential diagnosis. The patient should be treated according their clinical manifestation, staging, comorbidity, and immune function.
A fibro-osseous pseudotumor (FOPT) is a rare, rapidly enlarging, benign soft-tissue neoplasm that presents with localized pain, swelling, and redness. It typically presents in the hands and much less ...frequently in the feet. FOPT is characterized histologically by foci of osseous differentiation within the proliferated fibroblasts. This must be differentiated from other benign and malignant lesions. FOPT of the toes has been described in a few reports, but recurrence, following surgical excision, is extremely rare. Here we report a young, healthy female patient who presented with a rapidly growing FOPT of the left great toe. This unusual case had recurred twice following surgical excision, all within a 2-month period of time. The lesion was again completely excised, with no recurrences at follow-ups of 18 and 36 months. In conclusion, FOPT is a rare soft tissue lesion of the toes. It features fibroblastic proliferation and osseous differentiation, which needs to be differentiated from other benign and malignant tumors. The standard treatment is complete surgical excision with an excellent prognosis.
Structural RNA domains are widely involved in the regulation of biological functions, such as gene expression, gene modification, and gene repair. Activity of these dynamic regions depends ...sensitively on the global fold of the RNA, in particular, on the binding affinity of individual conformations to effector molecules in solution. Consequently, both the 1) structure and 2) conformational dynamics of noncoding RNAs prove to be essential in understanding the coupling that results in biological function. Toward this end, we recently reported observation of three conformational states in the metal-induced folding pathway of the tRNA-like structure domain of Brome Mosaic Virus, via single-molecule fluorescence resonance energy transfer studies. We report herein selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE)-directed structure predictions as a function of metal ion concentrations (Mn+) to confirm the three-state folding model, as well as test 2° structure models from the literature. Specifically, SHAPE reactivity data mapped onto literature models agrees well with the secondary structures observed at 0–10 mM Mg2+, with only minor discrepancies in the E hairpin domain at low Mg2+. SHAPE probing and SHAPE-directed structure predictions further confirm the stepwise unfolding pathway previously observed in our single-molecule studies. Of special relevance, this means that reduction in the metal-ion concentration unfolds the 3′ pseudoknot interaction before unfolding the long-range stem interaction. This work highlights the synergistic power of combining 1) single-molecule Förster resonance energy transfer and 2) SHAPE-directed structure-probing studies for detailed analysis of multiple RNA conformational states. In particular, single-molecule guided deconvolution of the SHAPE reactivities permits 2° structure predictions of isolated RNA conformations, thereby substantially improving on traditional limitations associated with current structure prediction algorithms.
Metabolite-dependent conformational switching in RNA riboswitches is now widely accepted as a critical regulatory mechanism for gene expression in bacterial systems. More recently, similar gene ...regulation mechanisms have been found to be important for viral systems as well. One of the most abundant and best-studied systems is the tRNA-like structure (TLS) domain, which has been found to occur in many plant viruses spread across numerous genera. In this work, folding dynamics for the TLS domain of Brome Mosaic Virus have been investigated using single-molecule fluorescence resonance energy transfer techniques. In particular, burst fluorescence methods are exploited to observe metal-ion (Mn+)-induced folding in freely diffusing RNA constructs resembling the minimal TLS element of brome mosaic virus RNA3. The results of these experiments reveal a complex equilibrium of at least three distinct populations. A stepwise, or consecutive, thermodynamic model for TLS folding is developed, which is in good agreement with the Mn+-dependent evolution of conformational populations and existing structural information in the literature. Specifically, this folding pathway explains the metal-ion dependent formation of a functional TLS domain from unfolded RNAs via two consecutive steps: 1) hybridization of a long-range stem interaction, followed by 2) formation of a 3′-terminal pseudoknot. These two conformational transitions are well described by stepwise dissociation constants for Mg2+ (K1 = 328 ± 30 μM and K2 = 1092 ± 183 μM) and Na+ (K1 = 74 ± 6 mM and K2 = 243 ± 52 mM)-induced folding. The proposed thermodynamic model is further supported by inhibition studies of the long-range stem interaction using a complementary DNA oligomer, which effectively shifts the dynamic equilibrium toward the unfolded conformation. Implications of this multistep conformational folding mechanism are discussed with regard to regulation of virus replication.
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