A new device for efficient preparation of standard antibiotic bead chains and customized antibiotic delivery.

Antibiotic-loaded polymethylmethacrylate (PMMA) beads are widely used in orthopedic practice for the prevention of infections after open fractures and in the management of osteomyelitis. The use of commercial beads is limited by insufficient flexibility, lack of provision for selection of specific antibiotic, and short drug-release time. Further, the manual procedure for the preparation of PMMA beads is slow, and the products are not uniform in size. Uniformity of the bead size is crucial because the placement of oversized beads place at sites with limited space (e.g., narrow medullary canal) is difficult, and their retrieval from such sites is painful to the patient. To overcome the limitations of commercial beads and manually prepared beads, we developed a simple device for the efficient preparation of antibiotic-loaded PMMA beads of uniform sizes. We describe the device, bead preparation, and the characteristics of the beads prepared using our device, and the preliminary clinical results. The beads obtained using this device were relatively small, had excellent flexibility, and were suitable for implantation in small spaces. The device permits the selection of the antibiotic to be loaded on to the beads. The results of preliminary studies of the beads prepared using our device have been positive, highlighting the need for more large-scale and longitudinal investigations.

Epigenetic regulation of lncRNA connects ubiquitin-proteasome system with infection-inflammation in preterm births and preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM. METHODS: Here, we further investigated the relationship of lncRNAs, which are differentially expressed in spontaneous PTB (sPTB) and PPROM placentas and are found to overlap a coding locus, with the differential expression of transcribed mRNAs at the same locus. Ten lncRNAs (five up-regulated and five down-regulated) and the lncRNA-associated 10 mRNAs (six up- and four down-regulated), which were identified by microarray in comparing PPROM vs. sPTB, were then validated by real-time quantitative PCR. RESULTS: A total of 62 (38 up- and 24 down-regulated) and 1,923 (790 up- and 1,133 down-regulated) lncRNAs were identified from placentas of premature labor (sPTB + PPROM), as compared to those from full-term labor (FTB + PROM) and from premature rupture of membranes (PPROM + PROM), as compared to those from non-rupture of membranes (sPTB + FTB), respectively. We found that a correlation existed between differentially expressed lncRNAs and their associated mRNAs, which could be grouped into four categories based on the gene strand (sense or antisense) of lncRNA and its paired transcript. These findings suggest that lncRNA regulates mRNA transcription through differential mechanisms. Differential expression of the transcripts PPP2R5C, STAM, TACC2, EML4, PAM, PDE4B, STAM, PPP2R5C, PDE4B, and EGFR indicated a co-expression among these mRNAs, which are involved in the ubiquitine-proteasome system (UPS), in addition to signaling transduction and beta adrenergic signaling, suggesting that imbalanced regulation of UPS may present an additional mechanism underlying the premature rupture of membrane in PPROM. CONCLUSION: Differentially expressed lncRNAs that were identified from the human placentas of sPTB and PPROM may regulate their associated mRNAs through differential mechanisms and connect the ubiquitin-proteasome system with infection-inflammation pathways. Although the detailed mechanisms by which lncRNAs regulate their associated mRNAs in sPTB and PPROM are yet to be clarified, our findings open a new approach to explore the pathogenesis of sPTB and PPROM.

CRMP2 protein SUMOylation modulates NaV1.7 channel trafficking.

Voltage-gated sodium channel (NaV) trafficking is incompletely understood. Post-translational modifications of NaVs and/or auxiliary subunits and protein-protein interactions have been posited as NaV-trafficking mechanisms. Here, we tested if modification of the axonal collapsin response mediator protein 2 (CRMP2) by a small ubiquitin-like modifier (SUMO) could affect NaV trafficking; CRMP2 alters the extent of NaV slow inactivation conferred by the anti-epileptic (R)-lacosamide, implying NaV-CRMP2 functional coupling. Expression of a CRMP2 SUMOylation-incompetent mutant (CRMP2-K374A) in neuronal model catecholamine A differentiated (CAD) cells did not alter lacosamide-induced NaV slow inactivation compared with CAD cells expressing wild type CRMP2. Like wild type CRMP2, CRMP2-K374A expressed robustly in CAD cells. Neurite outgrowth, a canonical CRMP2 function, was moderately reduced by the mutation but was still significantly higher than enhanced GFP-transfected cortical neurons. Notably, huwentoxin-IV-sensitive NaV1.7 currents, which predominate in CAD cells, were significantly reduced in CAD cells expressing CRMP2-K374A. Increasing deSUMOylation with sentrin/SUMO-specific protease SENP1 or SENP2 in wild type CRMP2-expressing CAD cells decreased NaV1.7 currents. Consistent with a reduction in current density, biotinylation revealed a significant reduction in surface NaV1.7 levels in CAD cells expressing CRMP2-K374A; surface NaV1.7 expression was also decreased by SENP1 + SENP2 overexpression. Currents in HEK293 cells stably expressing NaV1.7 were reduced by CRMP2-K374A in a manner dependent on the E2-conjugating enzyme Ubc9. No decrement in current density was observed in HEK293 cells co-expressing CRMP2-K374A and NaV1.1 or NaV1.3. Diminution of sodium currents, largely NaV1.7, was recapitulated in sensory neurons expressing CRMP2-K374A. Our study elucidates a novel regulatory mechanism that utilizes CRMP2 SUMOylation to choreograph NaV1.7 trafficking.

Hypermethylation of the enolase gene (ENO2) in autism.

UNLABELLED: It has been hypothesized that dysregulation of brain-expressed genes is the major predisposing underlying mechanism for autism. This dysregulation may be mediated by differential methylation of CpG sites within gene promoters, which could be candidate biomarkers and used for early clinical screening of autism. A total of 131 pairs of age- and sex-matched autistic and control subjects were recruited in this study. Peripheral blood cells were analyzed. The first five pairs were randomly applied to array-based genome-wide methylation studies. A neuron-specific gene, ENO2, was found to be hypermethylated in the autistic samples. This difference was validated by bisulfite sequencing PCR (BSP). The differential expression of ENO2 gene was further analyzed with RT-qPCR and ELISA. The hypermethylation of ENO2 within the promoter region was confirmed by BSP to be present in 14.5 % (19/131) of the total of the autistic samples. The mean ENO2 RNA level in these 19 autistic samples was reduced by about 70 % relative to that in controls. The average level of ENO2 protein expression in the 19 autistic samples (15.18 ± 3.51 µg/l) was about half of that in the controls (33.86 ± 8.16 µg/l). CONCLUSION: These findings suggest that reduced ENO2 expression may be a biomarker for a subset of autistic children.

A novel treatment of clavicular nonunion: Combination with PRP, autologous bone grafting, and internal plate fixation.

BACKGROUND: Nonunion is a major concern for orthopedic surgeons, particularly nonunion of the clavicle, which can cause severe pain, loss of full range of motion, poor sleep quality, and loss of strength in the affected individuals. Platelet-rich plasma (PRP), an important biological agent, is widely used in orthopedics. OBJECTIVE: We used a combination of three techniques - the PRP technique, autologous bone grafting technique, and internal plate fixation technique - to ensure adequate internal fixation and enable a bone growth-supportive environment at the fracture site. METHODS: The surgical approach was applied to a patient with clavicle nonunion. RESULTS: Based on postoperative follow-up findings and intraoperative findings at the time of re-removal of the patient's implant, the prognosis at the fracture site was considered satisfactory. CONCLUSION: We observed that the patient treated with this method had favorable clinical outcomes, and we recommend that this technique be used in patients with long-bone nonunion.

Low-energy shock waves promote the cisplatin chemosensitivity of human osteosarcoma MNNG/HOS cells via the P2X7/Akt/mTOR pathway.

Background: The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects. Methods and results: To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors' results showed that 400 SW pulses at 0.21 mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7. Conclusions: For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.

Suppression of pain-related behavior in two distinct rodent models of peripheral neuropathy by a homopolyarginine-conjugated CRMP2 peptide.

The N-type voltage-gated calcium channel (CaV2.2) is a clinically endorsed target in chronic pain treatments. As directly targeting the channel can lead to multiple adverse side effects, targeting modulators of CaV2.2 may prove better. We previously identified ST1-104, a short peptide from the collapsin response mediator protein 2 (CRMP2), which disrupted the CaV2.2-CRMP2 interaction and suppressed a model of HIV-related neuropathy induced by anti-retroviral therapy but not traumatic neuropathy. Here, we report ST2-104 -a peptide wherein the cell-penetrating TAT motif has been supplanted with a homopolyarginine motif, which dose-dependently inhibits the CaV2.2-CRMP2 interaction and inhibits depolarization-evoked Ca(2+) influx in sensory neurons. Ca(2+) influx via activation of vanilloid receptors is not affected by either peptide. Systemic administration of ST2-104 does not affect thermal or tactile nociceptive behavioral changes. Importantly, ST2-104 transiently reduces persistent mechanical hypersensitivity induced by systemic administration of the anti-retroviral drug 2',3'-dideoxycytidine (ddC) and following tibial nerve injury (TNI). Possible mechanistic explanations for the broader efficacy of ST2-104 are discussed.

Incidence, distribution, disease spectrum, and genetic deficits of congenital heart defects in China: implementation of prenatal ultrasound screening identified 18,171 affected fetuses from 2,452,249 pregnancies.

BACKGROUND: Congenital heart defects (CHDs) are the most common birth defects. Assessment of the incidence, distribution, disease spectrum, and genetic deficits of fetal CHDs in China is urgently needed. METHODS: A national echocardiography screening program for fetal CHDs was implemented in 92 prenatal screening-diagnostic centers in China. FINDINGS: A total of 18,171 fetal CHD cases were identified from 2,452,249 pregnancies, resulting in 7·4/1,000 as the national incidence rate of fetal CHD. The incidences of fetal CHD in the six geographical regions, the southern, central, eastern, southwestern, northern, and northwestern, were 7·647 (CI: 7·383-7·915), 7·839 (CI: 7·680-8·000), 7·647 (CI: 7·383-7·915), 7·562 (CI: 7·225-7·907), 5·618 (CI: 5·337-5·906), and 4·716 (CI: 4·341-5·108), respectively, per 1,000 pregnancies. Overall, ventricular septal defect was the most common fetal CHD, accounting for 17.04% of screened pregnancies nationwide, and tetralogy of Fallot, the most common anomaly in the major defect of fetal CHD, was the second most common, accounting for 9.72%. A total of 76.24% cases of fetal CHD were found to be an isolated intracardiac single defect. The remaining 23.76% of cases of fetal CHD had multiple heart defects. Among all extracardiac malformations, the central nervous system (CNS) was the most common tissue with extracardiac anomalies associated with CHD, accounting for 22.89% of fetal CHD cases. Chromosomal karyotyping identified trisomy 18 as the most common chromosomal abnormality in fetal CHD. We also documented that CHD-containing syndromes could be identified with a comprehensive approach integrating prenatal ultrasound, MRI, pathological autopsy, and cytogenetics and molecular genetics. CONCLUSION: Implementation of prenatal echocardiography as a practically feasible platform to screen fetal CHD will reduce the financial and emotional burden of CHD, which may facilitate intrauterine and neonatal intervention of CHD.

A proteomic study of Hutchinson-Gilford progeria syndrome: Application of 2D-chromotography in a premature aging disease.

The Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease characterized by segmental premature aging. Applying a two-dimensional chromatographic proteomic approach, the 2D Protein Fractionation System (PF2D), we identified 30 differentially expressed proteins in cultured HGPS fibroblasts. We categorized them into five groups: methylation, calcium ion binding, cytoskeleton, duplication, and regulation of apoptosis. Among these 30 proteins, 23 were down-regulated, while seven were up-regulated in HGPS fibroblasts as compared to normal fibroblasts. Three differentially expressed cytoskeleton proteins, vimentin, actin, and tubulin, were validated via Western blotting and characterized by immunostaining that revealed densely thickened bundles and irregular structures. Furthermore in the HGPS cells, the cell cycle G1 phase was elongated and the concentration of free cytosolic calcium was increased, suggesting intracellular retention of calcium. The results that we obtained have implications for understanding the aging process.

Reduced expression in preterm birth of sFLT-1 and PlGF with a high sFLT-1/PlGF ratio in extracellular vesicles suggests a potential biomarker.

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases of preterm birth and 38 control cases. Our results showed that both sFLT-1 (P=0.0014) and PlGF (P=0.0032) were significantly downregulated in cases of preterm birth compared to controls, while the sFLT-1/PIGF ratio was significantly (P=0.0008) increased in EVs-EXs, but not in maternal plasma. Our results suggest that this reduced expression of sFLT-1 and PlGF with an elevated sFLT-1/PlGF ratio in EVs-EXs may represent a potential biomarker for prediction of PTB.

Characterization of placental and decidual cell development in early pregnancy loss by single-cell RNA sequencing.

BACKGROUND: Early pregnancy loss (EPL) presents as sporadic or recurrent miscarriage during the first trimester. In addition to chromosomal defects, EPL may result from impairment of the placental-decidual interface at early gestational age due to gene-environmental interactions. METHODS: To better understand the pathogenesis associated with this impairment, cell development in chorionic villi and decidua of different forms of EPL (sporadic or recurrent) was investigated with single-cell RNA sequencing and compared to that of normal first-trimester tissue. RESULTS: Unique gene expression signatures were obtained for the different forms of EPL and for normal tissue and the composition of placental and decidual cell clusters in each form was established. In particular, the involvement of macrophages in the EPL phenotypes was identified revealing an immunoactive state. CONCLUSION: Differential gene expression and unique marker genes among cell clusters from chorionic villi and decidua of miscarried and normal pregnancies, may lead to identification of biomarker for EPL.

Identification of differentially expressed transcripts and translatants targeted by knock-down of endogenous PCBP1.

PCBP1 is a member of the hnRNP family and participates in the regulation of transcription and translation. Previously, we identified transcripts targeted by overexpression of exogenous PCBP1. To further determine if these altered transcripts may also be targeted by a lack of PCBP1, we depleted endogenous PCBP1 in human SH-SY5Y cells. We identified 941 transcripts with the Affymetrix and 1362 with the Agilent expression platforms. There were 375 transcripts identified by both platforms, including 328 down-regulated and 47 up-regulated. The identified transcripts could be grouped into neuronal, cell signaling, metabolic, developmental, and differentiation categories, with pathway involvement in Wnt signaling, TGF beta signaling, translation factors and nuclear receptors. A proteomic profiling study with a two-dimensional chromatographic platform showed global translational changes over a range of isoelectric points (pI)=4.84-8.42. This study identifies the transcripts affected by knock-down of endogenous PCBP1 and compares them to the transcripts affected by overexpression of PCBP1.

Functional outcomes and adverse effects following three interventions for displaced midshaft clavicular fractures: A Bayesian network meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of the most commonly used interventions for clavicle fractures remains controversial. These interventions are: open reduction and plate fixation (ORPF), non-surgical intervention (NSI), and use of an intramedullary nail (IMN). In adult patients with clavicle fractures, choosing which intervention might be best is challenging. MATERIALS AND METHODS: PubMed, Journals@Ovid Full Text, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and Embase were performed to search English-language studies from the inception to February 2020. Randomized controlled trials (RCTs) comparing any of these three interventions were included. Patient and baseline characteristics, nonunion, major complications, Constant-Murley score (CMS), and Disabilities of the Arm, Shoulder and Hand score (DASH) were extracted. Then, we evaluated the functional outcomes and adverse effects after use of these three interventions for the management of displaced midshaft clavicle fractures in a Bayesian network meta-analysis. RESULTS: A Bayesian random-effects model was conducted, and nonunion and major complications were evaluated with: risk ratio (RR) and 95% confidential interval (CI); while CMS and DASH were evaluated with mean differences (MD) and the corresponding 95% confidential interval CI. The rank probability of each endpoint was assessed on the basis of the surface area under the cumulative ranking curve (SUCRA). DISCUSSION: ORPF is most likely to be successful in achieving objective functional outcomes as captured by the CMS, and IMN demonstrates significant efficacy for subjective functional outcomes, as captured by DASH scores. Compared with the other interventions examined, IMN was associated with decreased risk for adverse effects. LEVELS OF EVIDENCE: I; meta-analysis.

Transcriptomics-determined chemokine-cytokine pathway presents a common pathogenic mechanism in pregnancy loss and spontaneous preterm birth.

PROBLEM: Various etiological factors, such as infection and inflammation, may induce the adverse outcomes of pregnancy of miscarriage, stillbirth, or preterm birth. The pathogenic mechanisms associated with these adverse pregnancies are yet unclear. We hypothesized that a common pathogenic mechanism may underlie variant adverse outcomes of pregnancy, which are induced by genetic-environmental factors. The specific objective of the current study is to uncover the common molecular mechanism(s) by identifying the specific transcripts that are present in variant subtypes of pregnancy loss and preterm birth. METHOD OF STUDY: Transcriptomic profiling was performed with RNA expression microarray or RNA sequencing of placentas derived from pregnancy loss (which includes spontaneous miscarriage, recurrent miscarriage, and stillbirth) and spontaneous preterm birth, followed by bioinformatic analysis of multi-omic integration to identify pathogenic molecules and pathways involved in pathological pregnancies. RESULTS: The enrichment of common differentially expressed genes between full-term birth and preterm birth and pregnancy loss of miscarriage and stillbirth revealed different pathophysiological pathway(s), including cytokine signaling dysregulated in spontaneous preterm birth, defense response, graft-versus-host disease, antigen processing and presentation, and T help cell differentiation in spontaneous miscarriage. Thirty-three genes shared between spontaneous preterm birth and spontaneous miscarriage were engaged in pathways of interferon gamma-mediated signaling and of antigen processing and presentation. For spontaneous miscarriage, immune response was enriched in the fetal tissue of chorionic villi and in the maternal facet of the placental sac. The transcript of nerve growth factor receptor was identified as the common molecule that is differentially expressed in all adverse pregnancies: spontaneous preterm birth, stillbirth, spontaneous miscarriage, and recurrent miscarriage. Superoxide dismutase 2 was up-regulated in all adverse outcomes of pregnancy except for recurrent miscarriage. Cytokine-cytokine receptor interaction was the common pathway in spontaneous preterm birth and spontaneous miscarriage. Defense response was enriched in the fetal tissue of miscarriage and in the maternal tissue in spontaneous miscarriage. CONCLUSIONS: Our results indicated that the chemokine-cytokine pathway may play important roles in and function as a common pathogenic mechanism associated with, the different adverse outcomes of pregnancy, which demonstrated that differentially expressed transcripts could result from a common pathogenic mechanism associated with pregnancy loss and spontaneous preterm birth, although individual pregnancy outcomes may differ from each other phenotypically.

(Epi)genetic variants of the sarcomere-desmosome are associated with premature utero-contraction in spontaneous preterm labor.

Spontaneous preterm birth is a syndrome with clinical and genetic heterogeneity. Few studies have focused on the genetic and epigenetic defects and pathogenic mechanisms associated with premature uterine contraction in spontaneous preterm birth. The objective of this study was to investigate the (epi)genetic variations associated with premature uterine contraction of spontaneous preterm birth. A systems biology approach with an integrated multiomic study was employed. Biobanked pregnancy tissues selected from a pregnancy cohort were subjected to genomic, transcriptomic, methylomic, and proteomic studies, with a focus on genetic loci/genes related to uterine muscle contraction, specifically, genes associated with sarcomeres and desmosomes. Thirteen single nucleotide variations and pathogenic variants were identified in the sarcomere gene, TTN, which encodes the protein Titin, from 146 women with spontaneous preterm labor. Differential expression profiles of five long non-coding RNAs were identified from loci that overlap with four sarcomeric genes. Longitudinally, the long non-coding RNA of gene TPM3 that encodes the protein tropomysin 3 was found to significantly regulate the mRNA of TPM3 in the placenta, compared to maternal blood. The majority of genome methylation profiles related to premature uterine contraction were also identified in the CpG promoters of sarcomeric genes/loci. Differential expression profiles of mRNAs associated with premature uterine contraction showed 22 genes associated with sarcomeres and three with desmosomes. The results demonstrated that premature uterine contraction was associated mainly with pathogenic variants of the TTN gene and with transcriptomic variations of sarcomeric premature uterine contraction genes. This association is likely regulated by epigenetic factors, including methylation and long non-coding RNAs.

Comparison of plate fixation vs. intramedullary fixation for the management of mid-shaft clavicle fractures: A systematic review and meta-analysis of randomised controlled trials.

A number of meta-analyses have compared clinical outcomes following plate vs. intramedullary fixation for midshaft clavicle fractures (MSCF), but with conflicting results. There is a requirement for updated level-1 evidence to guide clinicians managing MSCF. The aim of the present systematic review and meta-analysis was to compare clinical outcomes following plate vs. intramedullary fixation of MSCF. The PubMed, Scopus, BioMed Central, Cochrane Central Register of Controlled Trials and Google Scholar databases were searched for records added until 1st July 2019. A total of 10 randomised controlled trials (RCTs) were included. Shoulder function was assessed using the Constant-Murley Shoulder Outcome questionnaire and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). There was no statistically significant difference in Constant-Murley scores between plate and intramedullary fixation [Mean difference (MD)=0.75; 95% CI: -2.49 to 3.99; P=0.65; I2=85%]. Similarly, there was no statistically significant difference in DASH scores between the two groups (MD=1.55; 95% CI: -1.12 to 4.23; P=0.26; I2=89%). There was no statistically significant difference in complications requiring non-routine surgery between plate and intramedullary fixation [risk ratio (RR)=1.80, 95%CI: 0.80-4.05, P=0.15; I2=0%]. There was an increased risk of complications that did not require non-routine surgery with plate fixation as compared to intramedullary fixation (RR=2.38, 95%CI: 1.22-4.62, P=0.01; I2=70%). Plate fixation was also associated with an increased risk of infection and complications of cosmetic dissatisfaction. The present results indicated no difference in long-term functional outcomes between plate and intramedullary fixation of MSCF. Plate fixation was associated with an increased risk of complications not requiring non-routine surgery. Further high-quality RCTs shall strengthen the evidence on this subject.

Staged treatment and internal fixation of floating ankle: A case report and literature review.

RATIONALE: Floating ankle is a rare traumatic condition characterized by a combination of tibial and ipsilateral foot fractures, with the ankle remaining intact. It is usually caused by high-energy trauma and also presents with serious soft tissue damage. Its treatment is mainly restricted to external fixation, which results in poor outcomes. We present a patient with a floating ankle who underwent staged treatment and achieved full internal fixation, subsequently returning to normal activity. PATIENT CONCERNS: A 26 year- old man had an accident with an reel machine and sustained an open fracture on his right lower extremity. DIAGNOSES: Digital radiograph demonstrated a distal tibial fracture, fibular fracture, and multiple metatarsal fractures, which fulfilled the criteria for a floating ankle. INTERVENTIONS: Initial ankle-spanning external fixation was performed. After 21 days, the patient underwent open reduction and internal fixation on his first and fifth metatarsals, and K-wire fixation on his fourth metatarsal. The external fixator was replaced by plaster fixation. Seven days later, the patient underwent internal fixation of his leg, open reduction and internal fixation with plating was applied of the fibular fracture, and minimally invasive plate osteosynthesis of the tibial fracture. OUTCOMES: At 1-year follow-up, bone union was identified by digital radiograph; after 2 years, his ankle function had fully recovered, and he resumed his normal activities. LESSONS: In the staged treatment protocol of the floating ankle, temporary external fixation provided traction and immobilization of the skeletal and soft tissues. Secondary internal fixation maintained the reduction and alignment and allowed early exercise, which is critical to the prognosis of a floating ankle.

Application of Iron Oxide Nanoparticles in the Diagnosis and Treatment of Neurodegenerative Diseases With Emphasis on Alzheimer's Disease.

Neurodegenerative diseases are characterized by chronic progressive degeneration of the structure and function of the nervous system, which brings an enormous burden on patients, their families, and society. It is difficult to make early diagnosis, resulting from the insidious onset and progressive development of neurodegenerative diseases. The drugs on the market cannot cross the blood-brain barrier (BBB) effectively, which leads to unfavorable prognosis and less effective treatments. Therefore, there is an urgent demand to develop a novel detection method and therapeutic strategies. Recently, nanomedicine has aroused considerable attention for diagnosis and therapy of central nervous system (CNS) diseases. Nanoparticles integrate targeting, imaging, and therapy in one system and facilitate the entry of drug molecules across the blood-brain barrier, offering new hope to patients. In this review, we summarize the application of iron oxide nanoparticles (IONPs) in the diagnosis and treatment of neurodegenerative disease, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We focus on IONPs as magnetic resonance imaging (MRI) contrast agents (CAs) and drug carriers in AD. What most neurodegenerative diseases have in common is that hall marker lesions are represented by protein aggregates (Soto and Pritzkow, 2018). These diseases are of unknown etiology and unfavorable prognosis, and the treatments toward them are less effective (Soto and Pritzkow, 2018). Such diseases usually develop in aged people, and early clinical manifestations are atypical, resulting in difficulty in early diagnosis. Recently, nanomedicine has aroused considerable attention for therapy and diagnosis of CNS diseases because it integrates targeting, imaging, and therapy in one system (Gupta et al., 2019). In this review article, we first introduce the neurodegenerative diseases and commonly used MRI CAs. Then we review the application of IONPs in the diagnosis and treatment of neurodegenerative diseases with the purpose of assisting early theranostics (therapy and diagnosis).

Modified tension band wiring of patellar fracture as a technique to minimize postoperative complications: A case report.

RATIONALE: Tension band wiring is the most widely accepted technique for the treatment of patellar fractures but the technique is associated with common complications like wire migration, prominence, and breakage. To reduce these complications, we developed and propose a modified technique that has a superior biomechanical strength and a potential to reduce such postoperative complications. PATIENT CONCERNS: The patient presented with pain and mild swelling in his left knee after he slipped on the floor and fell on his left knee. He has no significant past medical or surgical history. The patient took the tension band wiring as the first choice because of the wide acceptance. But he worried about the complications. DIAGNOSES: X-ray showed a transverse fracture of the left patella with an inferior pole occult fracture. INTERVENTIONS: The patient was operated with a modified technique of the classic tension band wiring for patellar fractures. In our 4-step procedure, double tension cerclage wires were wrapped under the exposed ends of the Kirschner wires (K-wires) and the tendons in figure-of-8 fashion. The aim was to increase the biomechanical strength so that when one of the tension wires fail, the other one can hold the fragments together. OUTCOMES: The patient recovered very well and without any complications. The patient was followed-up for 1 year and the fracture has united very well, with satisfying knee range of motion. LESSONS: From this case study, we can detect the biomechanical advantages of our technique which can increase the stability of the fracture and that allows early functional exercise and additionally the micromotion at the fracture site has a beneficial effect of fracture union. Based on the perfect outcomes, our technique is worthy of clinical application.

Nasal delivery of a CRMP2-derived CBD3 adenovirus improves cognitive function and pathology in APP/PS1 transgenic mice.

Calcium dysregulation is a key pathological event in Alzheimer's disease (AD). In studying approaches to mitigate this calcium overload, we identified the collapsin response mediator protein 2 (CRMP2), an axonal guidance protein that participates in synapse dynamics by interacting with and regulating activity of N-methyl-D-aspartate receptors (NMDARs). We further identified a 15 amino acid peptide from CRMP2 (designated CBD3, for calcium-binding domain 3), that reduced NMDAR-mediated Ca2+ influx in cultured neurons and post-synaptic NMDAR-mediated currents in cortical slices. Whether targeting CRMP2 could be therapeutically beneficial in AD is unknown. Here, using CBD3, we tested the utility of this approach. Employing the APP/PS1 mouse model of AD which demonstrates robust pathophysiology including Aß1-42 deposition, altered tau levels, and diminished cognitive functions, we asked if overexpression of CBD3 could rescue these events. CBD3 was engineered into an adeno-associated vector and nasally delivered into APP/PS1 mice and then biochemical (immunohistochemistry, immunoblotting), cellular (TUNEL apoptosis assays), and behavioral (Morris water maze test) assessments were performed. APP/PS1 mice administered adeno-associated virus (AAV, serotype 2) harboring CBD3 demonstrated: (i) reduced levels of Aß1-42 and phosphorylated-tau (a marker of AD progression), (ii) reduced apoptosis in the hippocampus, and (iii) reduced cognitive decline compared with APP/PS1 mice or APP/PS1 administered a control virus. These results provide an instructive example of utilizing a peptide-based approach to unravel protein-protein interactions that are necessary for AD pathology and demonstrate the therapeutic potential of CRMP2 as a novel protein player in AD.