Hyperbranched polymers (HBPs) have drawn great interest in the biomedical field on account of their special morphology, low viscosity, self-regulation, and facile preparation methods. Moreover, their large intramolecular cavities, high biocompatibility, biodegradability, and targeting properties render them very suitable for anti-tumor drug delivery. Recently, exploiting the specific characteristics of the tumor microenvironment, a range of multifunctional HBPs responsive to the tumor microenvironment have emerged. By further introducing various types of drugs through physical embedding or chemical coupling, the resulting HBPs based delivery systems have played a crucial part in improving drug stability, increasing effective drug concentration, decreasing drug toxicity and side effects, and enhancing anti-tumor effect. Here, based on different types of tumor microenvironment stimulation signals such as pH, redox, temperature, etc., we systematically review the preparation and response mechanism of HBPs, summarize the latest advances in drug delivery applications, and analyze the challenges and future research directions for such nanomaterials in biomedical clinical applications.

OBJECTIVE: Few studies have prospectively evaluated the diagnostic accuracy and temporal impact of ultrasound in the emergency department (ED) in a randomized manner. In this study, we aimed to perform a randomized, standard therapy controlled evaluation of the diagnostic accuracy and temporal impact of a standardized ultrasound strategy, versus standard care, in patients presenting to the ED with acute dyspnea.METHODS: The patients underwent a standardized ultrasound examination that was blinded to the team caring for the patient. Ultrasound results remained blinded in patients randomized to the treating team but were unblinded in the interventional cohort. Scans were performed by trained emergency physicians. The gold standard diagnosis (GSDx) was determined by two physicians blinded to the ultrasound results. The same two physicians reviewed all data >30 days after the index visit.RESULTS: Fifty-nine randomized patients were enrolled. The mean±standard deviation age was 54.4±11 years, and 37 (62%) were male. The most common GSDx was acute heart failure with reduced ejection fraction in 13 (28.3%) patients and airway diseases such as acute exacerbation of asthma or chronic obstructive pulmonary disease in 10 (21.7%). ED diagnostic accuracy, as compared to the GSDx, was 76% in the ultrasound cohort and 79% in the standard care cohort (P=0.796). Compared with the standard care cohort, the final diagnosis was obtained much faster in the ultrasound cohort (mean±standard deviation: 12±3.2 minutes vs. 270 minutes, P<0.001).CONCLUSION: A standardized ultrasound approach is equally accurate, but enables faster ED diagnosis of acute dyspnea than standard care.
Asthma ; Cohort Studies ; Diagnosis ; Diagnostic Imaging ; Dyspnea ; Emergencies ; Emergency Service, Hospital ; Heart Failure ; Humans ; Male ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; Ultrasonography

The role of extracellular vesicles (EV) in osteoarthritis has become the focus of much research. These vesicles were isolated from several cell types found in synovial joint including chondrocytes and synovium. As articular cartilage is an avascular tissue surrounded by synovial fluid, it is believed that EV might play a crucial role in the homeostasis of cartilage and also could hold key information in the pathogenesis of osteoarthritis. This is thought to be due to activation of pro-inflammatory factors leading to a catabolic state and degradation of cartilage. In addition, due to the nature of articular cartilage lacking neuronal innervation, knowledge of EV can contribute to identification of novel biomarkers in this debilitating condition. This can be either directly isolated from aspirate of synovial fluid or from peripheral blood. Finally, EVs are known to shuttle important signalling molecules which can be utilised as unique modality in transferring therapeutic compounds in a cell free manner.

There is an enduring disconnect between the routine surveillance of mosquitoes that transmit dengue viruses and control activities to limit disease spread. A great variety of methods used to collect vector surveillance data exists globally, with program design typically influenced by historical, socio-cultural and cost factors. Surveillance data can be expensive to collect, meaning that without demonstration of its usefulness in directing mosquito control it may be deprioritized or even abandoned. Given that universally prescribed surveillance methods are unlikely to be sustainable and successful, we propose that strategies be designed according to the local terroir of dengue transmission. Strategy design should consider not only costs, but the amenability of workers and the public to various methods, the utility of methods for directing control and reducing disease, and the underlying spatial structure of the vector populations locally. A process of evaluating each of these factors should precede strategy design and be part of on-going review processes. In the case that the usefulness of vector surveillance cannot be demonstrated, then it may be argued that resources could be allocated to other aspects of disease control.

BACKGROUND: The purpose of this study was to evaluate the functional outcomes, infection rate, and complications associated with shoulder arthroplasty for sequelae of prior septic arthritis. METHODS: This is a retrospective cohort study of 17 patients who underwent shoulder arthroplasty for sequelae of septic arthritis. Patients were analyzed for patient-reported outcomes, complications, and reoperations. RESULTS: The 17 patients in this cohort were an average age of 65.4 ± 12.2 years old, were 58.8% male, and had an average body mass index of 27.9 ± 4.1 kg/m2. These patients underwent 14 reverse shoulder arthroplasties (RSAs; 11 after antibiotic spacer placement), one anatomic total shoulder arthroplasty after antibiotic spacer placement, and two hemiarthroplasties (both after antibiotic spacer placement). Two patients underwent reoperation (dislocated RSAs). There were four complications (23.5%): two RSA dislocations, one acromial stress fracture, and one atraumatic rotator cuff tear after hemiarthroplasty. There were no cases of postoperative wound complications or infection. At an average of 4.1 ± 1.8 years of follow-up for all 17 of 17 cases, the average visual analogue scale pain score was 4.6 ± 2.3, average Single Assessment Numeric Evaluation Score was 59.3 ± 23.7, average American Shoulder and Elbow Surgeons Score was 57.6 ± 15.5, and average Simple Shoulder Test was 6.9 ± 2.6 based on “yes” responses. CONCLUSIONS: Shoulder arthroplasty after septic arthritis had inconsistent functional outcomes and high complication rates but no reinfection.
Arthritis, Infectious ; Arthritis, Reactive* ; Arthroplasty* ; Body Mass Index ; Cohort Studies ; Dislocations ; Elbow ; Follow-Up Studies ; Fractures, Stress ; Hemiarthroplasty ; Humans ; Male ; Reoperation ; Retrospective Studies ; Rotator Cuff ; Shoulder* ; Surgeons ; Tears ; Wounds and Injuries

OBJECTIVE: Clinicopathological studies over the last decade have broadened the clinical spectrum of progressive supranuclear palsy (PSP) to include several distinct clinical syndromes. We examined the cognitive profiles of patients with PSP-Richardson's syndrome (PSP-RS) and two atypical ‘brainstem predominant' PSP phenotypes (PSP-parkinsonism, PSP-P; and PSP-pure akinesia with gait freezing, PSP-PAGF) using a comprehensive neuropsychological battery. METHODS: Fourteen patients diagnosed as PSP-RS, three patients with PSP-P and four patients with PSP-PAGF were assessed using a comprehensive battery of neuropsychological tests.
Cognition ; Executive Function ; Freezing ; Gait ; Humans ; Neuropsychological Tests ; Neuropsychology ; Paralysis ; Phenotype ; Prospective Studies ; Supranuclear Palsy, Progressive

BACKGROUND: Antibiotic spacers in shoulder periprosthetic joint infection deliver antibiotics locally and provide temporary stability. The purpose of this study was to evaluate differences between stemmed and stemless spacers. METHODS: All spacers placed from 2011 to 2013 were identified. Stemless spacers were made by creating a spherical ball of cement placed in the joint space. Stemmed spacers had some portion in the humeral canal. Operative time, complications, reimplantation, reinfection, and range of motion were analyzed. RESULTS: There were 37 spacers placed: 22 were stemless and 15 were stemmed. The stemless spacer population was older (70.9 ± 7.8 years vs. 62.8 ± 8.4 years, p = 0.006). The groups had a similar percentage of each gender (stemless group, 45% male vs. stemmed group, 40% male; p = 0.742), body mass index (stemless group, 29.1 ± 6.4 kg/m² vs. stemmed group, 31.5 ± 8.3 kg/m²; p = 0.354) and Charlson Comorbidity Index (stemless group, 4.2 ± 1.2 vs. stemmed group, 4.2 ± 1.7; p = 0.958). Operative time was similar (stemless group, 127.5 ± 37.1 minutes vs. stemmed group, 130.5 ± 39.4 minutes). Two stemless group patients had self-resolving radial nerve palsies. Within the stemless group, 15 of 22 (68.2%) underwent reimplantation with 14 of 15 having forward elevation of 109°± 23°. Within the stemmed group, 12 of 15 (80.0%, p = 0.427) underwent reimplantation with 8 of 12 having forward elevation of 94°± 43° (range, 30° to 150°; p = 0.300). Two stemmed group patients had axillary nerve palsies, one of which self-resolved but the other did not. One patient sustained dislocation of reverse shoulder arthroplasty after reimplantation. One stemless group patient required an open reduction and glenosphere exchange of dislocated reverse shoulder arthroplasty at 6 weeks after reimplantation. CONCLUSIONS: Stemmed and stemless spacers had similar clinical outcomes. When analyzing all antibiotic spacers, over 70% were converted to revision arthroplasties. The results of this study do not suggest superiority of either stemmed or stemless antibiotic spacers.
Anti-Bacterial Agents ; Arthroplasty* ; Body Mass Index ; Comorbidity ; Dislocations ; Humans ; Joints ; Male ; Operative Time ; Paralysis ; Prosthesis-Related Infections ; Radial Nerve ; Range of Motion, Articular ; Replantation ; Shoulder*

The proposal that diabetes plays a role in the development of heart failure is supported by the increased risk associated with this disease, even after correcting for all other known risk factors. However, the precise mechanisms contributing to the condition referred to as diabetic cardiomyopathy have remained elusive, as does defining the disease itself. Decades of study have defined numerous potential factors that each contribute to disease susceptibility, progression, and severity. Many recent detailed reviews have been published on mechanisms involving insulin resistance, dysregulation of microRNAs, and increased reactive oxygen species, as well as causes including both modifiable and non-modifiable risk factors. As such, the focus of the current review is to highlight aspects of each of these topics and to provide specific examples of recent advances in each area.
Diabetic Cardiomyopathies ; Disease Susceptibility ; Energy Metabolism ; Heart Failure ; Insulin Resistance ; Metabolic Diseases ; MicroRNAs ; Mitochondria, Heart ; Reactive Oxygen Species ; Risk Factors ; Stress, Physiological

BACKGROUND: Different implant designs are utilized in reverse shoulder arthroplasty. The purpose of this systematic review was to evaluate the results of reverse shoulder arthroplasty using a traditional (Grammont) prosthesis and a lateralized prosthesis for the treatment of cuff tear arthropathy and massive irreparable rotator cuff tears. METHODS: A systematic review of the literature was performed via a search of two electronic databases. Two reviewers evaluated the quality of methodology and retrieved data from each included study. In cases where the outcomes data were similar between studies, the data were pooled using frequency-weighted mean values to generate summary outcomes. RESULTS: Thirteen studies met the inclusion and exclusion criteria. Demographics were similar between treatment groups. The frequency-weighted mean active external rotation was 24° in the traditional group and 46° in the lateralized group (p = 0.0001). Scapular notching was noted in 44.9% of patients in the traditional group compared to 5.4% of patients in the lateralized group (p = 0.0001). The rate of clinically significant glenoid loosening was 1.8% in the traditional group and 8.8% in the lateralized group (p = 0.003). CONCLUSIONS: Both the traditional Grammont and the lateralized offset reverse arthroplasty designs can improve pain and function in patients with diagnoses of cuff tear arthropathy and irreparable rotator cuff tear. While a lateralized design can result in increased active external rotation and decreased rates of scapular notching, there may be a higher rate of glenoid baseplate loosening.
Adult ; Aged ; Aged, 80 and over ; *Arthroplasty, Replacement/adverse effects/instrumentation/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Prosthesis Design ; Rotator Cuff/*surgery ; *Shoulder Prosthesis/adverse effects/statistics & numerical data ; Treatment Outcome

Hamamelis japonica (Hamamelidaceae), widely known as Japanese witch hazel, is a deciduous flowering shrub that produces compact clumps of yellow or orange-red flowers with long and thin petals. As a part of our ongoing search for phenolic constituents from this plant, eleven phenolic constituents including six flavonol glycosides, a chalcone glycoside, two coumaroyl flavonol glycosides and two galloylated compounds were isolated from the flowers. Their structures were elucidated as methyl gallate (1), myricitrin (2), hyperoside (3), isoquercitrin (4), quercitrin (5), spiraeoside (6), kaempferol 4'-O-beta-glucopyranoside (7), chalcononaringenin 2'-O-beta-glucopyranoside (8), trans-tiliroside (9), cis-tiliroside (10), and pentagalloyl-O-beta-D-glucose (11), respectively. These structures of the compounds were identified on the basis of spectroscopic studies including the on-line LCNMR- MS and conventional NMR techniques. Particularly, directly coupled LC-NMR-MS afforded sufficient structural information rapidly to identify three flavonol glycosides (2 - 4) with the same molecular weight in an extract of Hamamelis japonica flowers without laborious fractionation and purification step. Cytotoxic effects of all the isolated phenolic compounds were evaluated on HCT116 human colon cancer cells, and pentagalloyl-O-beta-D-glucose (11) was found to be significantly potent in inhibiting cancer cell growth.
Asian Continental Ancestry Group ; Chalcone ; Colonic Neoplasms ; Flowers* ; Glycosides ; Hamamelis* ; Humans ; Molecular Weight ; Phenol* ; Plants