Maximum flexion and lateral rollback revealed better patient satisfaction after total knee arthroplasty.

INTRODUCTION: Patient satisfaction is an important outcome of total knee arthroplasty (TKA). However, we cannot predict how and why patients are satisfied or dissatisfied with TKA. The hypothesis of this study was that patient-reported outcomes (PROs) correlate with in vivo kinematics after TKA. MATERIALS AND METHODS: One hundred knees were analyzed after TKA. The in vivo kinematics of deep knee bending motion were estimated from single-plane fluoroscopy using a two-to-three-dimensional registration technique. Active knee flexion, femoral rotation and rollback were evaluated. The PROs were obtained after surgery using the 2011 Knee Society Scoring System (KSS), and their relationship with in vivo kinematics was determined. RESULTS: The average minimum and maximum flexion were -2.4 ± 7.3° and 113.2 ± 13.6°, respectively. The average femoral rotation was 7.4 ± 3.4°, and the average medial and lateral rollback were 2.4 ± 4.8 mm and 7.2 ± 5.6 mm, respectively. The multiple regression analysis revealed that the maximum flexion angle significantly contributed to symptoms and satisfaction. In addition, lateral rollback was also a significant factor affecting patient satisfaction. Lateral rollback and lateral Anterior-Posterior (AP) position at maximum flexion were correlated with the maximum flexion angle, whereas femoral rotation did not correlate with flexion angles. CONCLUSIONS: Maximum flexion and lateral rollback are important for better patient satisfaction after TKA. To obtain the maximum flexion angle, it was necessary to perform the normal kinematic pattern with a large amount of lateral rollback.

Can we predict 1-year functional outcomes and mortality following hip fracture in middle-aged and geriatric patients at time of admission?

This study's purpose is to determine if patients treated for hip fracture at highest risk for poor functional outcomes, shorter time to death, and death within 1-year can be predicted at the time of admission. We hypothesized that the Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA) tool can be used to predict risk of these variables. Between February 2019-July 2020, 544 patients ≥ 55-years-old were treated for hip fracture [AO/OTA 31A/B, 32A/C]. Each patient's demographics, functional status, and injury details were used to calculate their respective risk (STTGMA) score at time of admission. Patients were divided into risk quartiles by STTGMA score. Patients were contacted by phone to complete EuroQol-5 Dimension (EQ5D-3L) questionnaires on functional status. Comparative analyses were conducted on outcomes and EQ5D-3L questionnaire results. 439 patients (80.7%) had at least 1-year follow-up. 82 patients (18.7%) died within 1-year after hospitalization. Mean STTGMA score was 1.67% ± 4.49%. The highest-risk cohort experienced a 42x (p < 0.01) and 2.5x (p = 0.01) increased rate of 1-year mortality compared to the minimal- and low-risk groups respectively. The highest-risk cohort had the shortest time to death (p = 0.015). The highest-risk cohort had the lowest EQ5D index (p < 0.01) and VAS scores (p < 0.01) along with the highest rate of 30 day readmission (p < 0.01) and the longest length of stay (p < 0.01). The STTGMA tool provides important prognostic information for middle-aged and geriatric hip fracture patients that can help modulate care levels. This information is useful when counseling patients, their families, and caregivers on expected outcomes.

Acute undifferentiated febrile illness: Protocol in emergency department.

Fever accounts for around 15% of emergency visits in elderly age group and around 5% in adults. The spectrum of etiologies ranges from non-infectious to infectious etiologies. There are very few studies done in the past highlighting the approach of patients with acute febrile illness without any localizing signs and symptoms. OBJECTIVES: The aim of the study was to formulate a targeted approach for evaluation and treatment of patients with acute undifferentiated febrile illness without evidence of localizing symptoms and signs. The secondary objective was to study the etiology and final outcome of patients with acute undifferentiated febrile illness. MATERIALS AND METHODS: A protocol was devised for patients aged more than 18 years, who presented in emergency department with complaints of fever without localizing symptoms or signs of sepsis over a period of 6 months from April 2018 to September 2018. Patient's data were collected retrospectively from the hospital record section. RESULTS: A total of 212 patients of undifferentiated acute febrile illness were enrolled in the study. Maximum number of patients [n = 69 (32.5%)], presented on second day of illness. All the patients presenting within 1 or 2 days of fever experienced defervescence. Out of these 69 patients, 35 (36.4%) were investigated of which in 29 (82.2%) investigations were not found to be useful; 75 (78.1%) patients with 1 or 2 days history of fever improved without investigations. Surprisingly, 54 patients (72%) with 1 or 2 days' history of acute febrile illness experienced defervescence without the need of antibiotics. CONCLUSION: There is an urgent need to devise a standardized protocol for diagnosis and treatment of patients with acute undifferentiated febrile illness in order to avoid unnecessary investigations and antimicrobial use.

Patient function continues to improve over the first five years following tibial plateau fracture managed by open reduction and internal fixation.

AIMS: Tibial plateau fractures are serious injuries about the knee that have the potential to affect patients' long-term function. To our knowledge, this is the first study to use patient-reported outcomes (PROs) with a musculoskeletal focus to assess the long-term outcome, as compared to a short-term outcome baseline, of tibial plateau fractures treated using modern techniques. METHODS: In total, 102 patients who sustained a displaced tibial plateau fracture and underwent operative repair by one of three orthopaedic traumatologists at a large, academic medical centre and had a minimum of five-year follow-up were identified. Breakdown of patients by Schatzker classification is as follows: two (1.9%) Schatzker I, 54 (50.9%) Schatzker II, two (1.9%) Schatzker III, 13 (12.3%) Schatzker IV, nine (8.5%) Schatzker V, and 26 (24.5%) Schatzker VI. Follow-up data obtained included: Visual Analogue Scale (VAS) or Numeric Rating Scale (NRS) pain scores, Short Musculoskeletal Functional Assessment (SMFA), and knee range of movement (ROM). Data at latest follow-up were then compared to 12-month data using a paired t-test. RESULTS: Patient-reported functional outcomes as assessed by overall SMFA were statistically significantly improved at five years (p < 0.001) compared with one-year data from the same patients. Patients additionally reported an improvement in the Standardized Mobility Index (p < 0.001), Standardized Emotional Index (p < 0.001), as well as improvement in Standardized Bothersome Index (p = 0.003) between the first year and latest follow-up. Patient-reported pain and knee ROM were similar at five years to their one-year follow-up. In total, 15 of the patients had undergone subsequent orthopaedic surgery for their knees at the time of most recent follow-up. Of note, only one patient had undergone knee arthroplasty following plateau fixation related to post-traumatic osteoarthritis (OA). CONCLUSION: Knee pain following tibial plateau fracture stabilizes at one year. However, PROs continue to improve beyond one year following tibial plateau fracture, at least in a statistical sense, if not also clinically. Patients displayed statistical improvement across nearly all SMFA index scores at their minimum five-year follow-up compared with their one-year follow-up. Cite this article: Bone Joint J 2020;102-B(5):632-637.

Functional outcome after proximal humerus fracture fixation : understanding the risk factors.

The purpose is to identify risk factors of functional outcome following proximal humerus open reduction and internal fixation. Patients treated for proximal humerus fractures with open reduction and internal fixation were enrolled in a prospective data registry. Patients were evaluated for function using the Disability of the Arm, Shoulder and Hand score for 12 months and as available beyond 12 months. Univariate analyses were conducted to identify variables associated with functional outcome. Significant variables were included in a multivariate regression predicting functional outcome. Demographics and minimum of 12 month follow-up were available for 129 patients (75%). Multiple regression demonstrated postoperative complication (B=8.515 p=0.045), education level (B=-6.269p<0.0005), age (B=0.241p=0.049) and Charlson Comorbidity Index (B=6.578, p=0.001) were all significant predictors of functional outcome. Orthopaedic surgeons can use education level, comorbidities, age, and postoperative complication information to screen patients for worse outcomes, establish expectations, and guide care.

Identification of urinary proteins potentially associated with diabetic kidney disease.

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Although several parameters are used to evaluate renal damage, in many instances, there is no pathological change until damage is already advanced. Mass spectrometry-based proteomics is a novel tool to identify newer diagnostic markers. To identify urinary proteins associated with renal complications in diabetes, we collected urine samples from 10 type 2 diabetes patients each with normoalbuminuria, micro- and macro-albuminuria and compared their urinary proteome with that of 10 healthy individuals. Urinary proteins were concentrated, depleted of albumin and five other abundant plasma proteins and in-gel trypsin digested after prefractionation on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The peptides were analyzed using a nanoflow reverse phase liquid chromatography system coupled to linear trap quadrupole-Orbitrap mass spectrometer. We identified large number of proteins in each group, of which many were exclusively present in individual patient groups. A total of 53 proteins were common in all patients but were absent in the controls. The majority of the proteins were functionally binding, biologically involved in metabolic processes, and showed enrichment of alternative complement and blood coagulation pathways. In addition to identifying reported proteins such as α2-HS-glycoprotein and Vitamin D binding protein, we detected novel proteins such as CD59, extracellular matrix protein 1 (ECM1), factor H, and myoglobin in the urine of macroalbuminuria patients. ECM1 and factor H are known to influence mesangial cell proliferation, and CD59 causes microvascular damage by influencing membrane attack complex deposition, suggestive their biological relevance to DN. Thus, we have developed a proteome database where various proteins exclusively present in the patients may be further investigated for their role as stage-specific markers and possible therapeutic targets.

The use of ultra-low-dose CT scans for the evaluation of limb fractures: is the reduced effective dose using ct in orthopaedic injury (REDUCTION) protocol effective?

AIMS: To evaluate whether an ultra-low-dose CT protocol can diagnose selected limb fractures as well as conventional CT (C-CT). PATIENTS AND METHODS: We prospectively studied 40 consecutive patients with a limb fracture in whom a CT scan was indicated. These were scanned using an ultra-low-dose CT Reduced Effective Dose Using Computed Tomography In Orthopaedic Injury (REDUCTION) protocol. Studies from 16 selected cases were compared with 16 C-CT scans matched for age, gender and type of fracture. Studies were assessed for diagnosis and image quality. Descriptive and reliability statistics were calculated. The total effective radiation dose for each scanned site was compared. RESULTS: The mean estimated effective dose (ED) for the REDUCTION protocol was 0.03 milliSieverts (mSv) and 0.43 mSv (p < 0.005) for C-CT. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the REDUCTION protocol to detect fractures were 0.98, 0.89, 0.98 and 0.89 respectively when two occult fractures were excluded. Inter- and intra-observer reliability for diagnosis using the REDUCTION protocol (κ = 0.75, κ = 0.71) were similar to those of C-CT (κ = 0.85, κ = 0.82). Using the REDUCTION protocol, 3D CT reconstructions were equivalent in quality and diagnostic information to those generated by C-CT (κ = 0.87, κ = 0.94). CONCLUSION: With a near 14-fold reduction in estimated ED compared with C-CT, the REDUCTION protocol reduces the amount of CT radiation substantially without significant diagnostic decay. It produces images that appear to be comparable with those of C-CT for evaluating fractures of the limbs. Cite this article: Bone Joint J 2016;98-B:1668-73.

One-Pot Synthesis of 2,4,5-Trisubstituted Imidazoles via [2 + 2 + 1] Cycloannulation of 1,3-Bishet(aryl)-monothio-1,3-diketones, α-Substituted Methylamines and Sodium Nitrite through α-Nitrosation of Enaminones.

An efficient one-pot synthesis of a series of diversely functionalized trisubstituted 4(5)het(aroyl)-2,5(4)-het(aryl)/alkylimidazoles from readily available 1,3-bishet(aryl)monothio-1,3-diketones has been reported. This novel sequential one-pot, three step protocol, wherein three new carbon nitrogen bonds are formed in contiguous fashion, involves in situ generation of enaminones by reaction of monothio-1,3-diketones with α-substituted methylamines, followed by their α-nitrosation with sodium nitrite and subsequent base mediated intramolecular heterocyclization of the resulting α-hydroxyiminoimines to trisubstituted imidazoles in high yields under mild conditions. These newly prepared 4(5)-het(aroyl)-5(4)-het(aryl)/alkylimidazoles are shown to exist as tautomeric mixture, however, their subsequent alkylation with methyl iodide in the presence of potassium carbonate affords 1-N-methy-2,5-bishet(aryl)-4-het(aroyl)imidazoles in highly regioselective fashion in most of the cases. Synthesis of few 4(5)-(2-hydroxyphenyl)-2,5(4)-substituted imidazoles, which are known to be good coordinating ligands, has also been reported. A probable mechanism for the formation of these imidazoles from hydroxyiminoimine intermediates has also been suggested.

Total shoulder arthroplasty for proximal humerus fracture is associated with increased hospital charges despite a shorter length of stay.

BACKGROUND: Operation choice is a complex decision in the surgical management of proximal humerus fractures. Recently, there has been an increase in the use of total shoulder arthroplasty (TSA) for complex fracture patterns. HYPOTHESIS: Patients with proximal humerus fractures who receive TSA are more likely to have higher hospital charges and a prolonged length of stay relative to patients receiving hemiarthroplasty (HA), open reduction with internal fixation (ORIF) or closed reduction with internal fixation (CRIF). MATERIALS AND METHODS: A statewide electronic database was used to identify 13,316 hospital admissions from 2000-2011 were a proximal humerus fracture was surgically managed in an effort to determine the effect of operation choice on cost and length of stay. A univariate analysis was preformed to examine overall trends in surgical management. Additionally, a periodic, multivariate logistic regression analysis was used to determine how operation choice affected the odds of a high cost hospital stay or a prolonged length of stay after controlling for age, comorbidity burden, gender, and insurance type. RESULTS: After controlling for confounding factors, patients receiving total shoulder arthroplasty (TSA) were 2.25 times more likely to have high total hospital charges than patients receiving HA and 3.21 times more likely than patients receiving ORIF. Additionally, TSA was found to be a significant negative predictor of prolonged length of stay (pLOS). HA, ORIF and CRIF did not significantly predict pLOS. DISCUSSION: The use of TSA for acute proximal humerus fractures is associated with increased hospital costs despite a shorter length of stay when compared to other operative choices. As reverse total shoulder arthroplasty becomes more popular for treatment of this injury, it is important that functional outcomes be interpreted in the context of relative cost trade-offs. LEVEL OF EVIDENCE: Level IV.

Púrpura fulminante en relación con septicemia por Streptococcus pneumoniae en un paciente pediátrico asplénico / Purpura Fulminans Associated with Streptococcus pneumoniae Septicemia in an Asplenic Pediatric Patient

La púrpura fulminante es un síndrome rápidamente progresivo de trombosis de pequeños vasos y necrosis hemorrágica de la piel que se acompaña de coagulación intravascular diseminada. Describimos un caso de septicemia por Streptococcus pneumoniae en un niño de 5 años de edad tratado con tacrolimus oral, con una historia médica previa de trasplante de múltiples vísceras y sin bazo, y el desarrollo subsiguiente de púrpura fulminante en su pecho y la parte distal de sus extremidades. La forma aguda infecciosa de púrpura fulminante es debida habitualmente a bacterias gramnegativas. Los casos secundarios a bacterias grampositivas encapsuladas ocurren por lo general cuando los individuos están inmunosuprimidos o presentan asplenia funcional o anatómica. Nuestro paciente presentaba ambas condiciones, lo cual con seguridad aumentó su susceptibilidad, y respondió bien a la terapia antimicrobiana además de a la cobertura profiláctica en el contexto de su inmunosupresión. Revisamos la literatura buscando casos similares debidos a Streptococcus pneumoniae en la población pediátrica y discutimos la etiología y el tratamiento de la púrpura fulminante (AU)

Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans (AU)

Purpura fulminans associated with Streptococcus pneumoniae septicemia in an asplenic pediatric patient.

Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans.

Age-related percutaneous penetration part 2: effect of age on dermatopharmacokinetics and overview of transdermal products.

Transdermal drug delivery allows for a constant rate of drug administration and prolonged action, which can be beneficial to elderly patients who are often polymedicated. Several studies have compared dermatopharmacokinetics in the young and elderly with conflicting results. Despite the potential limitations of age-related changes in skin factors and cutaneous metabolism, marketed transdermal products generally do not report age-related differences in pharmacokinetics. This overview discusses the current data, summarizes marketed product findings and highlights the importance of further studies to evaluate age-related dermatopharmacokinetics.

Age-related percutaneous penetration part 1: skin factors.

Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.

Primary cutaneous follicle center lymphoma in the setting of chronic lymphocytic leukemia.

Primary cutaneous malignancies arising in association with chronic lymphocytic leukemia (CLL) are notable for their atypical clinical and histological presentation. We report a 69-year-old man with a 17-year history of CLL who presented for evaluation of a well-defined red to violaceous nodule with a central depressed scar on the left lower extremity. Microscopic examination of a punch biopsy revealed an infiltrate of predominantly small lymphocytes with scattered large, atypical epithelioid cells. Immunohistochemical stains revealed diffuse positive staining of the lesional cells with CD20+ and bcl-6+ and focal positive staining with bcl-2+ (negative CD10 and CD23), findings which, in conjunction with the histology, were most compatible with a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). A review of the clinical charts revealed several prior biopsies with varied diagnoses. In light of the most recent biopsy findings, all previous biopsies were re-reviewed and interpreted as PCFCL arising in the setting of CLL. Features contributing to the diagnostic conundrum in this case included an atypical clinical and histological presentation, lack of pertinent clinical history and multiple presentations at different institutions.

Do postsurgical interventions optimize ultimate scar cosmesis.

Keloids and other scars are different manifestations of the normal wound healing process. If located in visible areas, scars may have a psychological impact that could affect the quality of life of the scar-bearing population. Good preoperatory planning including hiding incisions in natural anatomical landmarks or placing them parallel to relaxed skin tension lines are among the techniques used to improve the cosmesis of scars. Once a prominent or noticeable scar has developed, multiple therapeutic modalities can be applied including surgical excision, although high recurrence rates precludes its use as monotherapy. Several advanced surgical correction techniques including Z-plasty and W-plasty may be useful in repositioning scars. Other modalities that have been reported to improve scar cosmesis include cryosurgery, radiotherapy, lasers, and skin substitute grafts. Adjuvant postsurgical treatment modalities have reduced dramatically the recurrence rates associated with the removal of the scar. In this review of the literature the authors discuss evidence based data related to the abovementioned modalities and other topical and intralesional therapies including occlusion, compression, silicone, corticosteroids, interferons, imiquimod, resiquimod, tacrolimus, 5-fluorouracil, retinoids, as well as the role of several over-the-counter agents such as onion extract, vitamin E and the combination of hydrocortisone, vitamin E and silicone. Finally, they address newer modalities including vascular endothelial growth factor inhibitor, transforming growth factor-3, interleukin-10, mannose-6-phosphate, UVA-1, narrowband UVB, intense pulsed light and photodynamic therapy. Ultimately, the decision of choosing the most appropriate postexcisional management treatment should be taken by physicians on a case-by-case basis in order to obtain the best cosmetically acceptable results.

Design and engineering of an O(2) transport protein.

The principles of natural protein engineering are obscured by overlapping functions and complexity accumulated through natural selection and evolution. Completely artificial proteins offer a clean slate on which to define and test these protein engineering principles, while recreating and extending natural functions. Here we introduce this method with the design of an oxygen transport protein, akin to human neuroglobin. Beginning with a simple and unnatural helix-forming sequence with just three different amino acids, we assembled a four-helix bundle, positioned histidines to bis-histidine ligate haems, and exploited helical rotation and glutamate burial on haem binding to introduce distal histidine strain and facilitate O(2) binding. For stable oxygen binding without haem oxidation, water is excluded by simple packing of the protein interior and loops that reduce helical-interface mobility. O(2) affinities and exchange timescales match natural globins with distal histidines, with the remarkable exception that O(2) binds tighter than CO.

Structure and phospholipase function of peroxiredoxin 6: identification of the catalytic triad and its role in phospholipid substrate binding.

Peroxiredoxin 6 (Prdx6) is a bifunctional protein with glutathione peroxidase and phospholipase A(2) (PLA(2)) activities, and it alone among mammalian peroxiredoxins can hydrolyze phospholipids. After identifying a potential catalytic triad (S32, H26, D140) from the crystal structure, site-specific mutations were used to evaluate the role of these residues in protein structure and function. The S32A mutation increased Prdx6 alpha-helical content, whereas secondary structure was unchanged by mutation to H26A and D140A. Lipid binding by wild-type Prdx6 to negatively charged unilamellar liposomes showed an apparent rate constant of 11.2 x 10(6) M(-1) s(-1) and a dissociation constant of 0.36 microM. Both binding and PLA(2) activity were abolished in S32A and H26A; in D140A, activity was abolished but binding was unaffected. Overoxidation of the peroxidatic C47 had no effect on lipid binding or PLA(2) activity. Fluorescence resonance energy transfer from endogenous tryptophanyls to lipid probes showed binding of the phospholipid polar head in close proximity to S32. Thus, H26 is a site for interfacial binding to the liposomal surface, S32 has a key role in maintaining Prdx6 structure and for phospholipid substrate binding, and D140 is involved in catalysis. This putative catalytic triad plays an essential role for interactions of Prdx6 with phospholipid substrate to optimize the protein-substrate complex for hydrolysis.

Inhibition of hemoglobin S polymerization in vitro by a novel 15-mer EF-helix beta73 histidine-containing peptide.

Our mutational studies on Hb S showed that the Hb S beta73His variant (beta6Val and beta73His) promoted polymerization, while Hb S beta73Leu (beta6Val and beta73Leu) inhibited polymerization. On the basis of these results, we speculated that EF-helix peptides containing beta73His interact with beta4Thr in Hb S and compete with Hb S, resulting in inhibition of Hb S polymerization. We, therefore, studied inhibitory effects of 15-, 11-, 7-, and 3-mer EF-helix peptides containing beta73His on Hb S polymerization. The delay time prior to Hb S polymerization increased only in the presence of the 15-mer His peptide; the higher the amount, the longer the delay time. DIC image analysis also showed that the fiber elongation rate for Hb S polymers decreased with increasing concentration of the 15-mer His peptide. In contrast, the same 15-mer peptide containing beta73Leu instead of His and peptides shorter than 11 amino acids containing beta73His including His alone showed little effect on the kinetics of polymerization and elongation of polymers. Analysis by protein-chip arrays showed that only the 15-mer beta73His peptide interacted with Hb S. CD spectra of the 15-mer beta73His peptide did not show a specific helical structure; however, computer docking analysis suggested a lower energy for interaction of Hb S with the 15-mer beta73His peptide compared to peptides containing other amino acids at this position. These results suggest that the 15-mer beta73His peptide interacts with Hb S via the beta4Thr in the betaS-globin chain in Hb S. This interaction may influence hydrogen bond interaction between beta73Asp and beta4Thr in Hb S polymers and interfere in hydrophobic interactions of beta6Val, leading to inhibition of Hb S polymerization.

Sevoflurane-induced structural changes in a four-alpha-helix bundle protein.

The mechanisms whereby volatile general anesthetics reversibly alter protein function in the central nervous system remain obscure. Using three different spectroscopic approaches, evidence is presented that binding of the modern general anesthetic sevoflurane to the hydrophobic core of a model four-alpha-helix bundle protein results in structural changes. Aromatic residues in the hydrophobic core reorient into new environments upon anesthetic binding, and the protein as a whole becomes less dynamic and exhibits structural tightening. Comparable structural changes in the predicted in vivo protein targets, such as the gamma-aminobutyric acid type A receptor and the N-methyl-D-aspartate receptor, may underlie some, or all, of the behavioral effects of these widely used clinical agents.