Projection to extract the perpendicular component (PEPC) method for extracting kinetics from time-resolved data.

Time-resolved x-ray liquidography (TRXL) is a potent method for investigating the structural dynamics of chemical and biological reactions in the liquid phase. It has enabled the extraction of detailed structural aspects of various dynamic processes, the molecular structures of intermediates, and kinetics of reactions across a wide range of systems, from small molecules to proteins and nanoparticles. Proper data analysis is key to extracting the information of the kinetics and structural dynamics of the studied system encrypted in the TRXL data. In typical TRXL data, the signals from solute scattering, solvent scattering, and solute-solvent cross scattering are mixed in the q-space, and the solute kinetics and solvent hydrodynamics are mixed in the time domain, thus complicating the data analysis. Various methods developed so far generally require prior knowledge of the molecular structures of candidate species involved in the reaction. Because such information is often unavailable, a typical data analysis often involves tedious trial and error. To remedy this situation, we have developed a method named projection to extract the perpendicular component (PEPC), capable of removing the contribution of solvent kinetics from TRXL data. The resulting data then contain only the solute kinetics, and, thus, the solute kinetics can be easily determined. Once the solute kinetics is determined, the subsequent data analysis to extract the structural information can be performed with drastically improved convenience. The application of the PEPC method is demonstrated with TRXL data from the photochemistry of two molecular systems: [Au(CN)2-]3 in water and CHI3 in cyclohexane.

Endoscopy-assisted latissimus dorsi muscle flap harvesting technique for immediate breast reconstruction.

BACKGROUND: The purpose of this study is to investigate the usefulness of endoscopy-assisted latissimus dorsi muscle flap (LDMF) harvesting in immediate breast reconstruction following partial mastectomy. MATERIALS AND METHODS: From November 2016 to December 2019, sixteen female breast cancer patients who underwent immediate breast reconstruction following partial mastectomy underwent LDMF harvesting with endoscopic assistance. This surgical technique was carried out with only one subaxillary skin incision without leaving a scar on the back. Patients' demographic characteristics, histopathologic factors, operative data, postoperative complications, and oncologic safety were collected through electronic chart review. RESULTS: In sixteen patients, LDMFs were harvested successfully using an endoscopy-assisted technique without conversion to an open technique. The mean age of the patients was 48.0±8.0 years, and the mean body mass index was 24.4±3.9kg/m2. The most common histologic subtype was invasive ductal carcinoma, with a mean tumor size of 3.2±2.3cm. In terms of LDMF harvesting time, it took 168.4±44.0minutes. The most common postoperative complication, donor site seroma (75%), was managed non-surgically during the outpatient visit. In terms of cosmetic aspects, we've seen a high level of patient satisfaction, especially with scarring. CONCLUSIONS: Endoscopy-assisted LDMF harvesting technique is safe and useful for breast reconstruction after partial mastectomy. Compared to the conventional open technique, this method does not leave a long scar on the donor site. As a result, it leads to better cosmetic outcomes and improves patient satisfaction.

Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02.

AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

Atypical periprosthetic femoral fracture with stem breakage: a case report.

Although the American Society for Bone and Mineral Research definition of atypical femoral fracture excludes periprosthetic fractures, fractures around the prosthesis with clinical features of atypical femoral fractures have been reported in the literature. All fractures reported thus far have been distal to the prosthetic segment; however, we encountered a case of a stress fracture in the middle of the femoral component segment. An 86-year-old woman with a history of bisphosphonate osteoporosis treatment and revisional total hip arthroplasty visited our outpatient clinic complaining of pain in the left thigh and groin. We diagnosed an incomplete atypical femoral fracture around the hip prosthesis; medical treatment was implemented. Two months later, the patient visited the emergency department with a complete subtrochanteric fracture with stem breakage. Without revision of the broken stem, two plates were applied after reduction. In this case, we recognized the possibility of a stress fracture but overlooked the possibility of stem breakage in an atypical femoral fracture. Even if it is not evident on the radiograph before complete fracture, clinicians should be alert to the signs of stress fracture in the middle of the femoral component segment, as they may be clues to atypical periprosthetic femoral fracture with stem failure. Isolated medical treatment plans are not recommended for incomplete subtrochanteric atypical periprosthetic femoral fracture. Instead, concomitant prophylactic plate fixation is recommended.

Subtrochanteric atypical femoral fracture induced solely by glucocorticoid without bisphosphonate treatment: a case report.

An AFF is a form of stress fracture induced by excessive physiologic repetitive stress over the bone remodeling capacity. Although glucocorticoid administration is a known risk factor for AFF, no case of AFF with glucocorticoid administration as the only risk factor has been previously reported. In this report, we aimed to highlight the risk of AFF associated with long-term administration of glucocorticoids, and the importance of surveillance and correction of risk factors in patients undergoing long-term glucocorticoid therapy. A 58-year-old male patient was diagnosed with subtrochanteric AFF. He had no medical history of any condition that might disrupt bone metabolism and no known risk factors for AFF, except for long-term administration of glucocorticoid. After fixation of the fracture, the glucocorticoid was replaced with an alternative medication. Although AFF is notorious for delayed union or nonunion, complete union of the fracture was obtained at 14 months postoperatively. This case brought to our attention the possibility that glucocorticoids alone may be responsible for inducing AFF and highlighted the importance of regular assessments in case of necessity of glucocorticoid administration. Additionally, correction of risk factors might expedite the union of AFF.

Evaluation of hepatic injury in acute carbon monoxide-poisoned patients in emergency department.

INTRODUCTION: The affinity of hemoglobin for carbon monoxide (CO) is 250 times higher than that for oxygen. Therefore, exposure to CO leads to a reduction in oxygen delivery to tissues, resulting in cellular hypoxia and affects whole body. Hepatic dysfunction in critically ill patients is related to poor outcome, but few studies have been conducted on this subject that occurs after CO poisoning. This study aims to conduct a study of hepatic injury in CO-poisoned patients in emergency department (ED). METHODS: This retrospective observational study collected data from patients who were diagnosed with acute CO poisoning at the ED between June 2011 and May 2018 in local tertiary-care hospital (Wonju, Republic of Korea). The primary end point of this study was to describe the prevalence of hepatic injury in acute CO-poisoned patients. The secondary goals were to investigate the recovery trends of hepatic injury caused by acute CO poisoning and the relation to neurologic outcome and mortality. RESULTS: Eight hundred ninety-four patients were enrolled in the final analysis, 128 cases (14.3%) had subclinical hepatic injury and 15 (1.6%) cases had hepatic injury. The relationship with mortality was not statistically significant. However, the hepatic injury group was higher incidence of intensive care unit admission and other complications. Patients in the hepatic injury group recovered through conservative management within 1 week of being admitted to the ED. CONCLUSIONS: While CO-induced hepatic injury is relatively uncommon, it can be associated with complications and poor neurologic outcome. However, CO-induced hepatic injury was not found to have a statistically significant effect on mortality rate.

Viral antigen nanoparticles for discriminated and quantitative detection of different subtypes of anti-virus immunoglobulins.

The aim of this study is to develop a novel method for the accurate diagnosis of the infection status of viral diseases, which requires discriminated and quantitative detection of different anti-virus immunoglubulin subtypes. Considering hepatitis A as a representative model disease, viral antigen nanoparticles (vAgNPs) were designed and synthesized by genetically presenting hepatitis A virus (HAV) antigens on the surface of human heavy chain ferritin (hFTH) nanoparticles to detect anti-HAV antibodies with discriminating immunoglobulin subtypes M and G (IgM and IgG, respectively). The vAgNPs also display multi-copies of hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is vital for the autonomous generation of quantitatively meaningful detection signals. The quantitative level of anti-HAV IgM or IgG in 30 patient sera was successfully analyzed using the vAgNPs of HAV, which was performed through label-free one-step-immunoassay based on the self-enhancement of optical signals from gold nanoparticles clustered on the viral antigen nanoparticles. The diagnostic performance was compared with that of enzyme-linked immunosorbent assay (ELISA), which did not enable accurate quantitative assay due to the poor linearity between the antibody concentration and detection signal. Furthermore, these vAgNP-based immunoassays did not produce any false negative/positive signals, indicating 100% sensitivity and 100% specificity.

A focused update on preventing ceramic fractures in hip arthroplasty: is the 'cup' half full?

Ceramic bearings have several desirable properties, such as resistance to wear, hardness, and biocompatibility, that favour it as an articulating surface in hip arthroplasty. However, ceramic fracture remains a concern. We have reviewed the contemporary literature, addressing the factors that can influence the incidence of ceramic bearing surface fracture. Cite this article: Bone Joint J 2019;101-B:897-901.

Serum ammonia as an early predictor of in-hospital mortality in patients with glufosinate poisoning.

BACKGROUND: The mortality rate associated with human glufosinate poisoning is high. We evaluated the usefulness of serum ammonia and sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores for early prediction of in-hospital mortality in glufosinate ammonium poisoning. METHODS: A prospectively collected pesticide poisoning registry at a single academic medical center was retrospectively analyzed. Data were collected from consecutive patients diagnosed with glufosinate ammonium poisoning between May 2007 and February 2018. The initial serum ammonia level was defined as the highest serum ammonia level measured within 12 h after emergency department (ED) arrival. The SOFA and APACHE II scores were calculated using data obtained within the first 12 h after ED arrival. The patients were divided into survivor and nonsurvivor groups by in-hospital death status. RESULTS: In total, 110 patients were included. Ten patients (9.1%) died in the hospital despite treatment. Median initial serum ammonia level was significantly higher in the nonsurvivor group than in the survivor group (219 (range: 158-792) versus 100.5 (range: 25-317) µg/dL, p < 0.001). Median SOFA and APACHE II scores in the survivor and nonsurvivor groups were 2 (range: 0-10) versus 5 (range: 1-8) (p = 0.044) and 7 (range: 0-28) versus 16 (range: 8-22) (p = 0.001), respectively. In the multiple logistic regression analysis, the initial serum ammonia level was the only independent predictor (cutoff value: 151 µg/dL). CONCLUSION: An initial serum ammonia level >151 µg/dL was an independent early predictor of in-hospital mortality in glufosinate ammonium poisoning.

The usefulness of the SOFA and APACHE II scoring systems for the early prediction of mortality in patients with dapsone poisoning.

The rate of mortality from dapsone poisoning is high because of the long absorption half-life of dapsone. This study aimed to evaluate the usefulness of the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scoring systems for the early prediction of mortality in patients with dapsone poisoning. This is a retrospective and observational study of consecutive patients diagnosed with dapsone poisoning. The SOFA and APACHE II scores were obtained within the first 24 h of admission. Patients were divided into survivor and non-survivor groups. In total, 106 patients were included. The SOFA scores of the survivor and non-survivor groups were 1 (0-8) and 4 (1-10), respectively (p < 0.001). The APACHE II scores of the survivor and non-survivor groups were 9 (1-25) and 14 (3-23), respectively (p < 0.001). Based on these scores and in-hospital mortality cases, the standardized mortality ratios for the APACHE II and SOFA were 1.00 (95% confidence interval (CI): 0.64-1.48) and 1.00 (95% CI: 0.64-1.49), respectively. In the model adjusted for clinically important variables and variables with significant differences between the survivor and non-survivor groups, the area under the curve of the SOFA (0.907; 95% CI: 0.834-0.955) was significantly higher than that of the APACHE II (0.793; 95% CI: 0.703-0.867) (p = 0.008). The SOFA and APACHE II score systems had good discrimination and satisfactory calibration performance in patients with dapsone poisoning. However, the SOFA score was a more useful method in predicting mortality than the APACHE II score.

Ultrasound-guided versus blind temporomandibular joint injections: a pilot cadaveric evaluation.

Temporomandibular disorders are painful conditions that require precise injection therapy in selected patients. This pilot cadaveric study was undertaken to compare the accuracy of temporomandibular joint (TMJ) injection between the anatomical landmark-based (blind) technique and an ultrasound-guided technique. TMJ injections using the blind technique or the ultrasound-guided technique were performed in 10 non-embalmed cadavers. After dissection, the accuracy of the TMJ injections was found to be significantly greater for the ultrasound-guided injections than for the blind technique (blind 55% vs. ultrasound 95%, P=0.008). For injections into the upper joint space of the TMJ, the success rate of the injection was comparable for the two techniques (blind 80% vs. ultrasound 100%, P=0.474). However, ultrasound-guided injections into the lower joint space had a much higher success rate than the blind technique (blind 30% vs. ultrasound 90%, P=0.020). The blind technique was associated with a considerable proportion of failed or inappropriate injections, especially for lower joint space injections. Ultrasound-guided TMJ injections were accomplished with a higher accuracy than the conventional blind technique, especially in the case of injections targeting the lower joint space of the TMJ.

Performance of point-of-care diagnosis of AIDS: label-free one-step-immunoassay vs. lateral flow assay.

The objective of this study is to develop an accurate, rapid, simple, and label-free assay technology that enables point-of-care diagnosis of AIDS. For this, 3-dimensional (3D) probes to sensitively detect anti-HIV antibodies were designed and synthesized by genetically presenting a HIV antigen (gp41) on the surface of engineered human ferritin nanoparticles. The 3D probes also present multi-copies of the hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is essential for the generation and self-enhancement of assay signals. The developed new assay technology (named "one-step-immunoassay") quickly produced clear optical signals through a simple and convenient one-step procedure. The diagnostic performance of the one-step-immunoassay was compared with that of the conventional lateral flow assay (LFA) using 30 AIDS patient and 20 healthy sera. The sensitivity of LFA was only 63% when a single antigen (gp41) was used but enhanced to 90% when three different antigens (gp41, p24, and gp120) were used together as the assay probes. In contrast, the one-step-immunoassay using only gp41 produced strong optical signals within 15 min without causing any false negative/positive signals, showing 100% sensitivity and 100% specificity and holding promising potential for clinical point-of-care diagnosis of AIDS.

The usefulness of diffusion-weighted magnetic resonance imaging performed in the acute phase as an early predictor of delayed neuropsychiatric sequelae in acute carbon monoxide poisoning.

Delayed onset of neuropsychiatric symptoms after apparent recovery from acute carbon monoxide (CO) poisoning has been described as delayed neuropsychiatric sequelae (DNS). No previous study has determined whether early use of diffusion-weighted magnetic resonance imaging (DWI) can predict which patients will develop DNS in the acute CO poisoning. This retrospective observational study was performed on adult patients with acute CO poisoning consecutively treated over a 17-month period. All included patients with acute CO poisoning underwent DWI to evaluate brain injury within 72 h after CO exposure. DWI was evaluated as follows: (1) presence of pathology, (2) number of pathologies, (3) asymmetry, and (4) location of pathology. Patients were divided into two groups. The DNS group was composed of patients with delayed sequelae, while the non-DNS group included patients with no sequelae. A total of 102 patients with acute CO poisoning were finally enrolled in this study. DNS developed in 10 patients (9.8%). Between the DNS group and the non-DNS group, presence of pathology on DWI and initial Glasgow Coma Scale (GCS) showed significant difference. There was also a statistical difference between the non-DNS group and DNS group in terms of CO exposure time, troponin I, rhabdomyolysis, acute kidney injury, and pneumonia. The presence of pathology in DWI and initial GCS (cutoff: <12) at the emergency department served as an early predictors of DNS.

The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: A prospective observational study.

Glufosinate ammonium poisoning can cause neurological complications even after a symptom-free period. We prospectively investigated the predictors of neurologic complications in acute glufosinate ammonium poisoning and the change of serum ammonia level as a predictor of patient's presence and recovery of neurologic complication. This prospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between September 2014 and June 2016. Serum ammonia was serially measured. The patients were divided into two groups: the neurologic complication group and the nonneurologic complication group. We also defined 25 other insecticide- or herbicide-poisoned patients as controls. The neurologic complication group included 18 patients (72.0%). The latency period for neurologic complications was within 48-h postingestion. The peak ammonia level was statistically higher in the neurologic complication group than in the control group ( p < 0.001) and the nonneurologic complication groups ( p = 0.001). There was a statistical difference between the nonneurologic complication group and the neurologic complication group ( p = 0.0085) in terms of ingested amount. The peak ammonia was the only predictor for the development of neurologic complications (the optimal cutoff: 90 µg/dL). In patients with mental changes, the mean serum ammonia levels before and after recovery of the mental changes were statistically different ( p = 0.0019). In acute glufosinate ammonium poisoning, serial serum ammonia level measurements are needed and a serum peak ammonia level greater than 90 µg/dL is a predictor of neurologic complications. Also, it is important to treat the hyperammonemia in acute glufosinate ammonium poisoning.

Serum neuron-specific enolase as an early predictor of delayed neuropsychiatric sequelae in patients with acute carbon monoxide poisoning.

Delayed onset of neuropsychiatric symptoms after apparent recovery from acute carbon monoxide (CO) poisoning has been described as delayed neuropsychiatric sequelae (DNS). To date, there have been no studies on the utility of serum neuron-specific enolase (NSE), a marker of neuronal cell damage, as a predictive marker of DNS in acute CO poisoning. This retrospective observational study was performed on adult patients with acute CO poisoning consecutively treated over a 9-month period. Serum NSE was measured after emergency department arrival, and patients were divided into two groups. The DNS group comprised patients with delayed sequelae, while the non-DNS group included patients with none of these sequelae. A total of 98 patients with acute CO poisoning were enrolled in this study. DNS developed in eight patients. The median NSE value was significantly higher in the DNS group than in the non-DNS group. There was a statistical difference between the non-DNS group and the DNS group in terms of CO exposure time, Glasgow Coma Scale (GCS), loss of consciousness, creatinine kinase, and troponin I. GCS and NSE were the early predictors of development of DNS. The area under the curve according to the receiver operating characteristic curves of GCS, serum NSE, and GCS combined with serum NSE were 0.922, 0.836, and 0.969, respectively. In conclusion, initial GCS and NSE served as early predictors of development of DNS. Also, NSE might be a useful additional parameter that could improve the prediction accuracy of initial GCS.

Drug repurposing from the perspective of pharmaceutical companies.

Drug repurposing holds the potential to bring medications with known safety profiles to new patient populations. Numerous examples exist for the identification of new indications for existing molecules, most stemming from serendipitous findings or focused recent efforts specifically limited to the mode of action of a specific drug. In recent years, the need for new approaches to drug research and development, combined with the advent of big data repositories and associated analytical methods, has generated interest in developing systematic approaches to drug repurposing. A variety of innovative computational methods to enable systematic repurposing screens, experimental as well as through in silico approaches, have emerged. An efficient drug repurposing pipeline requires the combination of access to molecular data, appropriate analytical expertise to enable robust insights, expertise and experimental set-up for validation and clinical development know-how. In this review, we describe some of the main approaches to systematic repurposing and discuss the various players in this field and the need for strategic collaborations to increase the likelihood of success in bringing existing molecules to new indications, as well as the current advantages, considerations and challenges in repurposing as a drug development strategy pursued by pharmaceutical companies. LINKED ARTICLES: This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

Size-separated particle fractions of stainless steel welding fume particles - A multi-analytical characterization focusing on surface oxide speciation and release of hexavalent chromium.

Welding fume of stainless steels is potentially health hazardous. The aim of this study was to investigate the manganese (Mn) and chromium (Cr) speciation of welding fume particles and their extent of metal release relevant for an inhalation scenario, as a function of particle size, welding method (manual metal arc welding, metal arc welding using an active shielding gas), different electrodes (solid wires and flux-cored wires) and shielding gases, and base alloy (austenitic AISI 304L and duplex stainless steel LDX2101). Metal release investigations were performed in phosphate buffered saline (PBS), pH 7.3, 37°, 24h. The particles were characterized by means of microscopic, spectroscopic, and electroanalytical methods. Cr was predominantly released from particles of the welding fume when exposed in PBS [3-96% of the total amount of Cr, of which up to 70% as Cr(VI)], followed by Mn, nickel, and iron. Duplex stainless steel welded with a flux-cored wire generated a welding fume that released most Cr(VI). Nano-sized particles released a significantly higher amount of nickel compared with micron-sized particle fractions. The welding fume did not contain any solitary known chromate compounds, but multi-elemental highly oxidized oxide(s) (iron, Cr, and Mn, possibly bismuth and silicon).

Teriparatide therapy for severe, refractory osteoradionecrosis of the jaw.

Although osteoradionecrosis (ORN) is a serious complication of craniofacial radiotherapy, the current management methods remain suboptimal. Teriparatide (TPTD), a recombinant human parathyroid hormone (1-34), has shown beneficial effects on osseous regeneration in medication-related osteonecrosis of the jaw or periodontitis. However, TPTD therapy in irradiated bones has not been indicated yet because of the theoretical risk of osteosarcoma seen in rat models. Hence, we first report here two patients with tongue cancer with late-emerging ORN who were successfully treated with TPTD for 4-6 months with serum calcium and vitamin D supplementation. In contrast to the usual progress of ORN, the bone defect regenerated well and bone turnover markers including serum C-terminal telopeptide of type 1 collagen and osteocalcin were restored with TPTD therapy. Our experience might suggest that TPTD therapy with careful monitoring can provide an effective treatment option for patients with ORN in select refractory cases, with the benefits outweighing the potential risks.

Changes in the pressure distribution by wrist angle and hand position in a wrist splint.

The study was conducted to provide basic data to develop a system that distributes pressure over a broader area by measuring and analyzing pressures in various wrist angles and hand positions while wearing a wrist splint. With 0, 15, 30, and 45 degrees of wrist extension, full-finger extension and finger flexion, pressure distribution changes were measured three times. Average peak pressure was analyzed and mean value picture (MVP) in zones 3-5 was calculated. A one-way Anova was conducted to identify changes in pressure distribution by wrist angle and hand position. Mean peak pressure values (kPa) in zones 3-5 changed depending on the wrist angle. Peak pressures (kPa) changed significantly in 15, 30, and 45 degrees wrist extension, depending on the hand position. Since pressure distributions differ depending the wrist angle and hand position (finger flexion), it is necessary to consider how pressure varies in each wrist position and to provide information on postures that should be avoided during tasks and occupational activities based on various wrist angles or hand positions.

Signal self-enhancement by coordinated assembly of gold nanoparticles enables accurate one-step-immunoassays.

Current immunoassays are in general performed through time-consuming multi-step procedures that depend on the use of premade signal-producing reporters and often cause assay inaccuracy. Here we report an advanced immunoassay technology that resolves the delayed, complex, and inaccurate assay problems of conventional immunoassays. We have developed an accurate, rapid, simple, and label-free one-step-immunoassay based on the self-enhancement of sensitive immunoassay signals in an assay solution. The nano-scale protein particles (hepatitis B virus capsid and human ferritin heavy chain particles) were genetically engineered to present many well-oriented antibody (or antigen) probes and multi-copies of poly-histidine peptides on their surface, resulting in the construction of 3-dimensional (3D) bioprobes that chemisorb gold ions via coordination bonding and sensitively detect both antigen and antibody analytes. Systematic numerical and experimental analyses show that the signal self-enhancement happens through two coupled reactions under reducing conditions: (1) 3D bioprobe-based sensitive immuno-detection of analytes and (2) coordinated assembly of free and chemisorbed gold nanoparticles around the 3D bioprobe-analyte-associated complexes, which is followed by the quick generation of apparent optical signals. This advanced one-step-immunoassay was successfully applied to diagnostic assays requiring high accuracy and/or speed, i.e. diagnosis of acute myocardial infarction and hepatitis C through detecting a cardiac protein (troponin I) and anti-hepatitis C virus antibodies in patient sera, indicating that it is applicable to the accurate and rapid detection of both antigen and antibody markers of a wide range of diseases.