Neurovascular Island Flap for Pulp and Nail Augmentation in Thumb Duplication Reconstruction: A Surgical Method With Long-Term Follow-Up.

PURPOSE: Pulp and nail atrophy and asymmetry are commonly seen in thumb duplication. In hypoplasia of both digits, conventional reconstruction or Bilhaut-Cloquet procedure and its modifications may not be possible or may lead to a poor cosmetic outcome. The purpose of the study was to review a reconstruction technique with a neurovascular island flap developed to improve the aesthetic and functional results of treatment. METHODS: Fourteen patients with thumb duplication aged 8 to 18 months were operated between 2002 and 2013 in our center. All patients had significant hypoplasia and asymmetry of the pulp and nail of the digit planned to be retained. A neurovascular island flap including part of the pulp tissue, nail bed, with or without the associated phalangeal bone, was raised from the planned ablated digit base on its single neurovascular bundle. The nail bed, nail fold, and pulp tissue from the 2 digits were apposed with fine sutures under magnification. All patients were followed to monitor the aesthetic, functional, and radiological outcome. RESULTS: The mean follow-up period was 7 years, 11 months. Thirteen patients underwent the flap procedure and all flaps survived. In 1 patient, the flap procedure was aborted because the vascular pedicle was not well formed. The nail width and pulp circumference were restored to a similar size as the contralateral thumb. CONCLUSIONS: In selected cases of thumb duplication with significant pulp hypoplasia and nail asymmetry, the neurovascular island flap is a safe and effective means to restore size and symmetry. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Depleted Leukocyte Mitochondrial DNA Copy Number Correlates With Unfavorable Left Ventricular Volumetric and Spherical Shape Remodeling in Acute Myocardial Infarction After Primary Angioplasty.

BACKGROUND: Left ventricular (LV) shape influences LV systolic function. It is possible to assess LV shape using 3-D echocardiography sphericity index (SI). Maintaining mitochondrial DNA copy number (MCN) is important for preserving mitochondrial function and LV systolic function after acute myocardial infarction (AMI). Information is limited, however, regarding the relationship between leukocyte MCN and the subsequent change in LV shape after AMI.Methods and Results:Fifty-five AMI patients undergoing primary angioplasty were recruited. Plasma MCN was measured before primary angioplasty using quantitative polymerase chain reaction. 3-D echocardiography measurement of SI was performed at baseline, and at 1-, 3-, and 6-month follow-up. AMI subjects with MCN lower than the median had a higher 6-month SI and LV volume compared with those with higher MCN. Baseline echocardiographic parameters were similar between the 2 groups. MCN was negatively correlated with 3- and 6-month SI, and 3- and 6-month LV volume. On multiple linear regression analysis, baseline plasma MCN could predict LV SI and LV volume at 6 months after primary angioplasty for AMI, even after adjusting for traditional prognostic factors. CONCLUSIONS: In AMI patients, higher plasma leukocyte MCN at baseline was associated with favorable LV shape and remodeling at 6-month follow-up. Plasma leukocyte MCN may provide a novel prognostic biomarker for LV remodeling after AMI.

Outcomes of Thumb Carpometacarpal Joint Osteoarthritis Treated with Arthroscopic Fusion.

Background The thumb carpometacarpal joint (CMCJ) osteoarthritis is one of the most common pathologies in the hand with controversial treatment options. Description of Technique Describe the use of arthroscopic technique for thumb CMCJ arthrodesis and the clinical outcome. Patients and Methods Cases with Eaton III thumb CMCJ osteoarthritis treated with arthroscopic arthrodesis were reviewed. Patient evaluations include: grip strength, pinch strength, range of motion, Kapandji score, Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, and the visual analog scores for pain. All cases were assessed before the surgery and at 3, 6, 12, and 24 months after surgery. Radiographs were reviewed. Results There were total 16 patients with 18 arthrodesis performed. The average age was 62.2 years with M:F ratio of 2:7. The average follow-up time was 57.2 months. There was improvement of pain score as early as at postop 3 months ( p < 0.001) and continued to improve at 6, 12, and 24 months. There was improvement of grip strength and pinch strength at 12 and 24 months (p < 0.001). The DASH score showed improvement as early as at 3 months ( p = 0.012). There was a reduction of Kapandji score and interphalangeal joint motion at 3 months postop, but these returned to normal at 6 months. There was no major complication. There was one case of nonunion (5.6%). Conclusion Arthroscopic arthrodesis is a feasible treatment option and provides excellent pain relief, restore thumb strength and stability, retain functional thumb mobility, and hence improvement in hand function.

Sphingolipid Metabolism Is Associated with Cardiac Dyssynchrony in Patients with Acute Myocardial Infarction.

AIM: Sphingolipids are a class of complex and bioactive lipids that are involved in the pathological processes of cardiovascular disease. Fabry disease is an X-linked storage disorder that results in the pathological accumulation of glycosphingolipids in body fluids and the heart. Cardiac dyssynchrony is observed in patients with Fabry disease and left ventricular (LV) hypertrophy. However, little information is available on the relationship between plasma sphingolipid metabolites and LV remodelling after acute myocardial infarction (AMI). The purpose of this study was to assess whether the baseline plasma sphingomyelin/acid ceramidase (aCD) ratio predicts LV dyssynchrony at 6M after AMI. METHODS: A total of 62 patients with AMI undergoing primary angioplasty were recruited. Plasma aCD and sphingomyelin were measured prior to primary angioplasty. Three-dimensional echocardiographic measurements of the systolic dyssynchrony index (SDI) were performed at baseline and 6 months of follow-up. The patients were divided into three groups according to the level of aCD and sphingomyelin above or below the median. Group 1 denotes lower aCD and lower sphingomyelin; Group 3 denotes higher aCD and higher sphingomyelin. Group 2 represents different categories of patients with aCD and sphingomyelin. Trend analysis showed a significant increase in the SDI from Group 1 to Group 3. Logistic regression analysis showed that the sphingomyelin/aCD ratio was a significant predictor of a worsening SDI at 6 months. CONCLUSIONS: AMI patients with high baseline plasma sphingomyelin/aCD ratios had a significantly increased SDI at six months. The sphingomyelin/aCD ratio can be considered as a surrogate marker of plasma ceramide load or inefficient ceramide metabolism. Plasma sphingolipid pathway metabolism may be a new biomarker for therapeutic intervention to prevent adverse remodelling after MI.

Improved CaP Nanoparticles for Nucleic Acid and Protein Delivery to Neural Primary Cultures and Stem Cells.

Efficiently delivering exogenous materials into primary neurons and neural stem cells (NSCs) has long been a challenge in neurobiology. Existing methods have struggled with complex protocols, unreliable reproducibility, high immunogenicity, and cytotoxicity, causing a huge conundrum and hindering in-depth analyses. Here, we establish a cutting-edge method for transfecting primary neurons and NSCs, named teleofection, by a two-step process to enhance the formation of biocompatible calcium phosphate (CaP) nanoparticles. Teleofection enables both nucleic acid and protein transfection into primary neurons and NSCs, eliminating the need for specialized skills and equipment. It can easily fine-tune transfection efficiency by adjusting the incubation time and nanoparticle quantity, catering to various experimental requirements. Teleofection's versatility allows for the delivery of different cargos into the same cell culture, whether simultaneously or sequentially. This flexibility proves invaluable for long-term studies, enabling the monitoring of neural development and synapse plasticity. Moreover, teleofection ensures the consistent and robust expression of delivered genes, facilitating molecular and biochemical investigations. Teleofection represents a significant advancement in neurobiology, which has promise to transcend the limitations of current gene delivery methods. It offers a user-friendly, cost-effective, and reproducible approach for researchers, potentially revolutionizing our understanding of brain function and development.

Atypical presentation of forearm compartment syndrome in a case of vascular type Ehlers-Danlos syndrome.

A 30-year-old Chinese man with vascular type Ehlers-Danlos Syndrome presents with spontaneous right forearm compartment syndrome due to pseudoaneurysms along the radial artery. Emergency fasciotomy and reconstruction of the radial artery with a saphenous vein graft were performed. Genetic test showed a heterozygous DNA change c. 1852 G > C in COL3A1 gene.

Dysregulated proteostasis network in neuronal diseases.

Long-term maintenance of synaptic connections is important for brain function, which depends on varying proteostatic regulations to govern the functional integrity of neuronal proteomes. Proteostasis supports an interconnection of pathways that regulates the fate of proteins from synthesis to degradation. Defects in proteostatic signaling are associated with age-related functional decline and neurodegenerative diseases. Recent studies have advanced our knowledge of how cells have evolved distinct mechanisms to safely control protein homeostasis during synthesis, folding and degradation, and in different subcellular organelles and compartments. Neurodegeneration occurs when these protein quality controls are compromised by accumulated pathogenic proteins or aging to an irreversible state. Consequently, several therapeutic strategies, such as targeting the unfolded protein response and autophagy pathways, have been developed to reduce the burden of misfolded proteins and proved useful in animal models. Here, we present a brief overview of the molecular mechanisms involved in maintaining proteostatic networks, along with some examples linking dysregulated proteostasis to neuronal diseases.

Humerus Diaphyseal Stress Fracture in a Teenage Tennis Athlete: Case Report.

A teenage male tennis player had chronic pain in his dominant arm during tennis practice. Magnetic resonance imaging (MRI) suggested humerus diaphyseal stress injury. After 4 weeks, he became asymptomatic and resumed playing. However, pain recurred after 3 days. A new MRI revealed a diaphyseal undisplaced humerus fracture and significant bone marrow edema. The patient remained in rest for 4 weeks. After that, strengthening exercises were introduced and return to training was allowed after 12 weeks. Even if asymptomatic, we suggest that these patients should not return to play before 12 weeks, depending on the physical exam and imaging findings.

Endothelial IL-1R1 is a critical mediator of EAE pathogenesis.

Interleukin-1 (IL-1) has been implicated in the disease progression of multiple sclerosis (MS). In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), the induction of disease is significantly attenuated in mice lacking the type I IL-1 receptor (IL-1R1). In this study, we created a transgenic mouse (eIL-1R1 kd) in which IL-1R1 expression is knocked down specifically in endothelial cells. Induction of EAE in eIL-1R1 kd mice results in a decrease in incidence, severity and delayed onset of EAE. In addition, eIL-1R1 kd mice show significant decrease in VCAM-1 expression and diminished CD45(+) and CD3(+) infiltrating leukocytes in the spinal cord in animals challenged with EAE. Further, IL-1 and IL-23 stimulate IL-17 production by splenocytes from both wild type and the eIL-1R1 kd animals. Similarly, IL-1 and IL-23 synergistically stimulate splenocytes proliferation in these two strains of animals. After immunization with MOG(79-96), although eIL-1R1 kd mice displayed greatly reduced clinical scores, their splenocytes produced IL-17 and proliferated in response to a second MOG challenge, similar to wild type animals. These findings indicate a critical role for endothelial IL-1R1 in mediating the pathogenesis of EAE, and describe a new model that can be used to study endothelial IL-1R1.

Treatment of Dangling-Type Thumb Polydactyly: Suture Ligation vs. Surgical Excision.

Background: To review the cases of dangling-type thumb polydactyly treated with suture ligation vs surgical excision. Methods: Cases of dangling-type thumb polydactyly treated in 2 different hospitals from 1994 to 2014 were recruited. Group 1 includes cases treated with suture ligation in hospital 1; Group 2 includes cases treated with surgical excision in hospital 2. The demographics data, early clinical outcomes and early complications were retrieved from clinical notes. All cases were contacted for a final assessment. Results: There were 23 cases recruited in group 1 and 26 cases recruited in group 2. The mean age at the time of procedure was 15.9 days (group 1) vs. 14 months (group 2). The infection rate was comparable in both groups (4.35% vs. 3.85%). 12 cases in group 1 and 14 cases in group 2 completed a final assessment. Residual tissue is common in group 1 (58.5%) and 4 cases (33.3%) required revision surgery. No case in group 2 had residual tissue and none require revision surgery. There was no painful neuroma in both groups and all patients achieved normal thumb and hand functions. The parental satisfaction score was 7.8 (group 1) and 8.8 (group 2) with no statistical difference (p = 0.061). Conclusions: Suture ligation and surgical excision are safe and effective treatment options for dangling-type thumb polydactyly. Both methods received comparable parental satisfaction. However, residual tissue is common after suture ligation while this problem is not observed after surgical excision.

Endogenous Expression of G-CSF in Rat Dorsal Root Ganglion Neurons after Nerve Injury.

Granulocyte colony-stimulating factor (G-CSF) has been reported to modulate pain function following nerve injury. However, the expression of endogenous G-CSF in the dorsal root ganglion (DRG) and the response to nerve injury remain unclear. In the present study, we demonstrated that G-CSF and G-CSFR are mainly expressed in both small- and medium-diameter DRG neurons in rats and are responsible for transmitting pain responses. G-CSF and G-CSFR were co-expressed in certain nociceptive DRG neurons. In addition, G-CSF was expressed in satellite glial cells around large-diameter DRG neurons. After sciatic nerve injury, the number of G-CSF-positive DRG neurons was increased in both the ipsilateral and contralateral lesion sites in rats. However, G-CSF expression in satellite glial cells was not affected by nerve injury. To clarify the role of G-CSF in pain, exogenous G-CSF was administered to a rat model of neuropathic pain induced by partial sciatic nerve transaction (PST). Our results indicate that treatment with G-CSF did not attenuate but exacerbated neuropathic pain. In summary, G-CSF may directly activate sensory neurons and contribute to nociceptive signaling.

COUP-TFI specifies the medial entorhinal cortex identity and induces differential cell adhesion to determine the integrity of its boundary with neocortex.

Development of cortical regions with precise, sharp, and regular boundaries is essential for physiological function. However, little is known of the mechanisms ensuring these features. Here, we show that determination of the boundary between neocortex and medial entorhinal cortex (MEC), two abutting cortical regions generated from the same progenitor lineage, relies on COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I), a patterning transcription factor with graded expression in cortical progenitors. In contrast with the classical paradigm, we found that increased COUP-TFI expression expands MEC, creating protrusions and disconnected ectopic tissue. We further developed a mathematical model that predicts that neuronal specification and differential cell affinity contribute to the emergence of an instability region and boundary sharpness. Correspondingly, we demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. Thus, we conclude that a sharp boundary requires a subtle interplay between patterning transcription factors and differential cell affinity.

Type IIIB and IV hypoplastic thumb reconstruction with non-vascularized fourth metatarsal.

We treated 16 patients with 17 hypoplastic thumbs (eight Type IIIB and nine Type IV) using a non-vascularized fourth metatarsal transfer with a rotational flap and multi-staged reconstruction. The average age at the first operation was 24 months. The average follow-up time was 46 months. All patients achieved reasonable hand function and were able to use the reconstructed thumb to grip small and large objects. The operated thumb achieved an average Kapandji score of 6.7 and average pinch strength of 0.9 kg. There were two cases of graft nonunion. All parents are satisfied with the function and appearance of the reconstructed thumb and donor foot. We conclude that non-vascularized fourth metatarsal transfer is a feasible reconstruction method for patients with Types IIIB and IV hypoplastic thumbs. The reconstruction allows for the preservation of a 5-digit hand with reasonable function and appearance and minimal donor site morbidity, although long-term growth of the metatarsals still need to be monitored.Level of evidence: IV.

Cloning, expression and purification of Bacillus cereus endochitinase in the Escherichia coli AD494(DE3)pLysS expression system.

A chitinase gene from Bacillus cereus was cloned and expressed in Escherichia coli. The purified recombinant chitinase had much higher (128 fold) specificity to pNP-beta-(GlcNAc)(3) than to pNP-beta-(GlcNAc), suggesting endochitinase. Thirty-three amino acids in the N-terminal were recognized and cut off during expression, which consequently made the M(r) not correspond to that predicted.

CPEB4-Dependent Neonate-Born Granule Cells Are Required for Olfactory Discrimination.

The rodent olfactory bulb (OB) contains two distinct populations of postnatally born interneurons, mainly granule cells (GCs), to support local circuits throughout life. During the early postnatal period (i.e., 2 weeks after birth), GCs are mostly produced locally from progenitor cells in the OB with a proportion of them deriving from proliferating cells in the rostral migratory stream (RMS). Afterward, the replenishment of GCs involves differentiated neuroblasts from the subventricular zone (SVZ) in a process known as adult neurogenesis. Although numerous studies have addressed the role of SVZ-born GCs in olfactory behaviors, the function of GCs produced early postnatally in the OB remains elusive. Our previous study demonstrated that the translational regulator, cytoplasmic polyadenylation element-binding protein 4 (CPEB4), is a survival factor exclusively for neonate-born but not SVZ/adult-derived GCs, so CPEB4-knockout (KO) mice provide unique leverage to study early postnatal-born GC-regulated olfactory functions. CPEB4-KO mice with hypoplastic OBs showed normal olfactory sensitivity and short-term memory, but impaired ability to spontaneously discriminate two odors. Such olfactory dysfunction was recapitulated in specific ablation of Cpeb4 gene in inhibitory interneurons but not in excitatory projection neurons or SVZ-derived interneurons. The continuous supply of GCs from adult neurogenesis eventually restored the OB size but not the discrimination function in 6-month-old KO mice. Hence, in the early postnatal OB, whose function cannot be replaced by adult-born GCs, construct critical circuits for odor discrimination.

Swimming as Treatment of Scapular Dyskinesis.

Scapular dyskinesis is quite frequent and can lead to shoulder pain. The diagnosis is essentially clinical. The main cause is muscle imbalance, between the trapezius, rhomboids, and pectoralis minor. In these cases, rehabilitation is the best treatment. We present a case of a young male patient with dyskinesis due to axonal involvement of the long thoracic nerve and paresis of the anterior serratus muscle. After a swimming program to increase muscular strength and imbalance, he experienced pain reduction and functional recovery of the upper limb, with reduction of the winged scapula.

Endothelial-specific knockdown of interleukin-1 (IL-1) type 1 receptor differentially alters CNS responses to IL-1 depending on its route of administration.

Interleukin-1 (IL-1) has been implicated as a critical mediator of neuroimmune communication. In the brain, the functional receptor for IL-1, type 1 IL-1 receptor (IL-1R1), is localized primarily to the endothelial cells. In this study, we created an endothelial-specific IL-1R1 knockdown model to test the role of endothelial IL-1R1 in mediating the effects of IL-1. Neuronal activation in the hypothalamus was measured by c-fos expression in the paraventricular nucleus and the ventromedial preoptic area. In addition, two specific sickness symptoms, febrile response and reduction of locomotor activity, were studied. Intracerebroventricular injection of IL-1 induced leukocyte infiltration into the CNS, activation of hypothalamic neurons, fever, and reduced locomotor activity in normal mice. Endothelial-specific knockdown of IL-1R1 abrogated all these responses. Intraperitoneal injection of IL-1 also induced neuronal activation in the hypothalamus, fever, and reduced locomotor activity, without inducing leukocyte infiltration into the brain. Endothelial-specific knockdown of IL-1R1 suppressed intraperitoneal IL-1-induced fever, but not the induction of c-fos in hypothalamus. When IL-1 was given intravenously, endothelial knockdown of IL-1R1 abolished intravenous IL-1-induced CNS activation and the two monitored sickness symptoms. In addition, endothelial-specific knockdown of IL-1R1 blocked the induction of cyclooxygenase-2 expression induced by all three routes of IL-1 administration. These results show that the effects of intravenous and intracerebroventricular IL-1 are mediated by endothelial IL-1R1, whereas the effects of intraperitoneal IL-1 are partially dependent on endothelial IL-1R1.

Quorum Sensing Disruption in Vibrio harveyi Bacteria by Clay Materials.

This work describes the use of clay minerals as catalysts for the degradation of quorum sensing molecule N-(3-oxooctanoyl)-dl-homoserine lactone. Certain clay minerals as a result of their surface properties and porosity can catalytically degrade the quorum sensing molecule into smaller fragments. The disruption of quorum sensing by clay in a growing Gram-negative Vibrio harveyi bacteria culture was also studied by monitoring luminescence and population density of the bacteria, wherein quenching of bacterial quorum sensing activity was observed by means of luminescence reduction. The results of this study show that food-grade clays can be used as biocatalysts in disrupting bacterial activity in various media.

RBPMetaDB: a comprehensive annotation of mouse RNA-Seq datasets with perturbations of RNA-binding proteins.

RNA-binding proteins (RBPs) may play a critical role in gene regulation in various diseases or biological processes by controlling post-transcriptional events such as polyadenylation, splicing and mRNA stabilization via binding activities to RNA molecules. Owing to the importance of RBPs in gene regulation, a great number of studies have been conducted, resulting in a large amount of RNA-Seq datasets. However, these datasets usually do not have structured organization of metadata, which limits their potentially wide use. To bridge this gap, the metadata of a comprehensive set of publicly available mouse RNA-Seq datasets with perturbed RBPs were collected and integrated into a database called RBPMetaDB. This database contains 292 mouse RNA-Seq datasets for a comprehensive list of 187 RBPs. These RBPs account for only ∼10% of all known RBPs annotated in Gene Ontology, indicating that most are still unexplored using high-throughput sequencing. This negative information provides a great pool of candidate RBPs for biologists to conduct future experimental studies. In addition, we found that DNA-binding activities are significantly enriched among RBPs in RBPMetaDB, suggesting that prior studies of these DNA- and RNA-binding factors focus more on DNA-binding activities instead of RNA-binding activities. This result reveals the opportunity to efficiently reuse these data for investigation of the roles of their RNA-binding activities. A web application has also been implemented to enable easy access and wide use of RBPMetaDB. It is expected that RBPMetaDB will be a great resource for improving understanding of the biological roles of RBPs.Database URL: http://rbpmetadb.yubiolab.org.

Structure-based protein engineering for alpha-amylase inhibitory activity of plant defensin.

The structure of a novel plant defensin isolated from the seeds of the mung bean, Vigna radiate, has been determined by (1)H nuclear magnetic resonance spectroscopy. The three-dimensional structure of VrD2, the V. radiate plant defensin 2 protein, comprises an alpha-helix and one triple-stranded anti-parallel beta-sheet stabilized by four disulfide bonds. This protein exhibits neither insecticidal activity nor alpha-amylase inhibitory activity in spite of showing a similar global fold to that of VrD1, an insecticidal plant defensin that has been suggested to function by inhibiting insect alpha-amylase. Our previous study proposed that loop L3 of plant defensins is important for this inhibition. Structural analyses and surface charge comparisons of VrD1 and VrD2 revealed that the charged residues of L3 correlate with the observed difference in inhibitory activities of these proteins. A VrD2 chimera that was produced by transferring the proposed functional loop of VrD1 onto the structurally equivalent loop of VrD2 supported this hypothesis. The VrD2 chimera, which differs by only five residues compared with VrD2, showed obvious activity against Tenebrio molitor alpha-amylase. These results clarify the mode of alpha-amylase inhibition of plant defensins and also represent a possible approach for engineering novel alpha-amylase inhibitors. Plant defensins are important constituents of the innate immune system of plants, and thus the application of protein engineering to this protein family may provide an efficient method for protecting against crop losses.