Parallel plate fixation for distal humeral fracture: Computer simulation to determine the appropriate screw insertion sequence.

BACKGROUND: Parallel plate fixation for distal humeral fractures provides good clinical outcomes. However, few studies have investigated the insertion sequence of the distal screws, although long screw insertion into the distal fragment is technically demanding. The purpose of this study was to investigate a correlation between the insertion sequence of the distal screws and the screw insertion difficulty. METHODS: Medial and lateral anatomical locking plates were closely fitted to the medial and lateral sides of the 10 intact humerus bone models on the computer. Most distal screws have 2 patterns: the screw was inserted from the lateral side first followed by insertion from the medial side (group 1) or from the medial side first followed by insertion from the lateral side (group 2). We calculated the target area wherein the second screw can be inserted. RESULTS: The length of the first most distal screw in group 2 was significantly longer than that in group 1 (58.4 vs. 49.8 mm, p < 0.05). The target areas in both groups were divided into the distal and proximal areas. The distal and proximal areas in group 1 were 91.6 and 61.6 mm2, respectively, and those in group 2 were 191.1 and 11.3 mm2, respectively. The distal area in group 2 was significantly greater than in the other areas (p < 0.05). CONCLUSIONS: In parallel plate fixation for distal humeral fracture, most distal screws could be more easily inserted from the medial side first followed by insertion from the lateral side than from the lateral side first followed by insertion from the medial side.

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide.

The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn(2+), suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn(2+)-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn(2+)-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn(2+)-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.

Anterior impingement test for labral lesions has high positive predictive value.

BACKGROUND: The anterior impingement test is intended to detect anterosuperior acetabular labral lesions. In patients treated for labral lesions its sensitivity is reportedly 95% to 100%, and in a small group of patients undergoing periacetabular osteotomy, its sensitivity was 59% and specificity 100%. However, the sensitivity, specificity, positive predictive value, and negative predict value of this test to detect these labral lesions in unselected patients with hip pain are unknown. QUESTIONS/PURPOSES: We investigated these four parameters (1) in unselected patients with hip pain, and (2) in three subgroups of patients with dysplasia, femoroacetabular impingement (FAI), and with an intact joint space. METHODS: We prospectively studied 69 patients (15 men and 54 women) with a mean age of 57.2 years (range, 27-81 years). One observer performed the anterior impingement test in all patients. We determined the presence or absence of an anterosuperior labral lesion with radial MRI in 107 hips (38 patients in both hips: 14 with pain, and 24 without pain). We also investigated the parameters in the three subgroups which consisted of 60 cases of dysplasia, 27 cases of FAI, and 80 cases with intact joint space; the third subgroup partially overlapped the first and second subgroups. RESULTS: The four parameters in all hips were 50.6% (45/89), 88.9% (16/18), 95.7% (45/47), and 26.7% (16/60), respectively. Parameters in the three subgroups were similar to those of all cases. CONCLUSIONS: Although the sensitivity of the anterior impingement test did not reach a sufficient level for detecting anterosuperior labral lesions, we believe the high positive predictive value makes the test useful. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Arthroscopic Triangular Fibrocartilage Complex Reconstruction Using a Palmaris Longus Tendon Graft.

Patients suffer from persistent ulnar wrist pain and distal radioulnar joint instability because of chronic triangular fibrocartilage complex (TFCC) foveal tear are treated with TFCC reconstruction. We performed an arthroscopic TFCC reconstruction using a palmaris longus tendon graft that provided a minimally invasive procedure. After confirming the TFCC foveal tear and stability between the TFCC remnant and radius, the bone tunnel was made in the ulna from the ulnar shaft to ulnar fovea. The position of the bone tunnel was checked by fluorography and arthroscopy. Curved bendable 18-gauge needles into which 3-0 nylon sutures were inserted in a loop shape were passed through the tunnel from the ulnar side, and both volar-side and dorsal-side TFCC remnants were penetrated. The nylon suture was extracted from the arthroscopic 4/5 portal, and the palmaris longus tendon graft was introduced into the joint. The graft was passed through the TFCC remnant and ulnar bone tunnel from the arthroscopic portal and fixed to the ulna using an interference screw. This procedure was indicated for TFCC foveal tears with intact radial-side TFCC remnants. If the radial-side tear and instability between the TFCC and radius coexist, this technique is contraindicated, and stabilization of both the radial and ulnar sides of the TFCC should be considered. This arthroscopic technique does not violate the distal radioulnar joint capsule, extensor carpi ulnaris tendon, or tendon sheath. In addition, it helps to stabilize the ulnar carpal complex.

Relationship between distal radius fracture severity and 25-hydroxyvitamin-D level among perimenopausal and postmenopausal women.

AIMS: Low-energy distal radius fractures (DRFs) are the most common upper arm fractures correlated with bone fragility. Vitamin D deficiency is an important risk factor associated with DRFs. However, the relationship between DRF severity and vitamin D deficiency is not elucidated. Therefore, this study aimed to identify the correlation between DRF severity and serum 25-hydroxyvitamin-D level, which is an indicator of vitamin D deficiency. METHODS: This multicentre retrospective observational study enrolled 122 female patients aged over 45 years with DRFs with extension deformity. DRF severity was assessed by three independent examiners using 3D CT. Moreover, it was categorized based on the AO classification, and the degree of articular and volar cortex comminution was evaluated. Articular comminution was defined as an articular fragment involving three or more fragments, and volar cortex comminution as a fracture in the volar cortex of the distal fragment. Serum 25-hydroxyvitamin-D level, bone metabolic markers, and bone mineral density (BMD) at the lumbar spine, hip, and wrist were evaluated six months after injury. According to DRF severity, serum 25-hydroxyvitamin-D level, parameters correlated with bone metabolism, and BMD was compared. RESULTS: The articular comminuted group (n = 28) had a significantly lower median serum 25-hydroxyvitamin-D level than the non-comminuted group (n = 94; 13.4 ng/ml (interquartile range (IQR) 9.8 to 17.3) vs 16.2 ng/ml (IQR 12.5 to 20.4); p = 0.005). The AO classification and volar cortex comminution were not correlated with the serum 25-hydroxyvitamin-D level. Bone metabolic markers and BMD did not significantly differ in terms of DRF severities. CONCLUSION: Articular comminuted DRF, referred to as AO C3 fracture, is significantly associated with low serum 25-hydroxyvitamin-D levels. Therefore, vitamin D3 supplementation for vitamin D deficiency might prevent articular comminuted DRFs. Nevertheless, further studies must be conducted to validate the results of the current study. Cite this article: Bone Jt Open 2022;3(3):261-267.

Vesicular glutamate transporter 2-immunoreactive synapses onto phrenic motoneurons in the neonatal rat.

The synaptic organization between vesicular glutamate transporter 2 (VGLUT2)-immunoreactive (ir) axon terminals and phrenic motoneurons in the neonatal rat was examined using a combined retrograde tracing and immunohistochemistry for VGLUT2. The phrenic nucleus (PhN) contained large numbers of VGLUT2-ir axon terminals, some of which made axosomatic and axodendritic synapses with PhN motoneurons. These terminals were of asymmetrical type and contained spherical clear synaptic vesicles. The results suggest that in the neonatal rat glutamatergic synapses onto PhN motoneurons exist and mediate excitatory transmission to drive PhN motoneurons.

Anatomical changes of phrenic motoneurons during development.

Although the phrenic motoneurons are relatively well-developed at the time of birth as compared to non-respiratory motoneurons, they show distinct anatomical changes during postnatal development. In the present review we summarize anatomical changes of phrenic motoneurons during pre- and postnatal development. Cell bodies of phrenic motoneurons migrate into the ventromedial region of the ventral horn of C3-C6 by E13-E14 in the rat. During development the sizes and surface areas of phrenic motoneurons are increased with changes in dendritic morphology.

Neuroanatomical and neurochemical organization of projections from the central amygdaloid nucleus to the nucleus retroambiguus via the periaqueductal gray in the rat.

The periaqueductal gray (PAG)-nucleus retroambiguus (NRA) pathway has been known to be involved in the control of vocalization and sexual behavior. To know how the amygdaloid complex influences the PAG-NRA pathway, here we first examined the synaptic organization between the central amygdaloid nucleus (CeA) fibers and the PAG neurons that project to the NRA by using anterograde and retrograde tract-tracing techniques in the rat. After ipsilateral injections of biotinylated dextran amine (BDA) into the CeA and cholera toxin B subunit (CTb) into the NRA, the prominent overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found ipsilaterally in the lateral/ventrolateral PAG, where some of the BDA-labeled terminals made symmetrical synaptic contacts with somata and dendrites of the CTb-labeled neurons. After CTb injection into the lateral/ventrolateral PAG, CTb-labeled neurons were distributed mainly in the medial division of the CeA. After BDA injection into the lateral/ventrolateral PAG, BDA-labeled fibers were distributed mainly in and around the NRA within the medulla oblongata. Using a combined retrograde tracing and in situ hybridization technique, we further demonstrated that more than half of the CeA neurons labeled with Fluoro-Gold (FG) injected into the lateral/ventrolateral PAG were positive for glutamic acid decarboxylase 67 mRNA and that the vast majority of PAG neurons labeled with FG injected into the NRA expressed vesicular glutamate transporter 2 mRNA. The present results suggest that the glutamatergic PAG-NRA pathway is under the inhibitory influence of the GABAergic CeA neurons.

GABAergic neurons in the ventrolateral subnucleus of the nucleus tractus solitarius are in contact with Kölliker-Fuse nucleus neurons projecting to the rostral ventral respiratory group and phrenic nucleus in the rat.

After ipsilateral injections of biotinylated dextran amine (BDA) into the ventrolateral subnucleus of the nucleus tractus solitarius (vlNTS) and Fluoro-gold (FG) into the rostral ventral respiratory group (rVRG) region or into the phrenic nucleus (PhN) region in the rat, an overlapping distribution of BDA-labeled axon terminals and FG-labeled neurons was found in the Kölliker-Fuse (KF) nucleus ipsilateral to the injection sites. Using retrograde tracing combined with immunohistochemistry for glutamic acid decarboxylase isoform 67 (GAD67), we indicated that as many as 40% of the vlNTS neurons projecting to the KF were immunoreactive for GAD67. Using a combination of anterograde and retrograde tracing techniques, and immunohistochemistry for GAD67, we further demonstrated that the vlNTS axon terminals with GAD67 immunoreactivity established close contact to the rVRG- or PhN-projecting KF neurons. The present results suggest that GABAergic vlNTS fibers may exert inhibitory influences on the rVRG- as well as PhN-projecting KF neurons and these circuits may be involved in the respiratory reflexes such as the Hering-Breuer reflex.

Suture Fixation Using Polyblend Polyethylene Sutures With Hydroxyapatite Block for an Intra-articular Depression Fracture of the Pisiform Bone.

Few cases in which open reduction and internal fixation was performed for displaced pisiform fractures have been reported. We present a new surgical technique for the treatment of depressed intra-articular pisiform fractures. First, the depressed fragment was reduced by pushing the bone tamp. Then, the fracture void resulting from the reduction of the depressed fragment was filled with a shaped hydroxyapatite block. Finally, the fragments were sutured using braided polyblend polyethylene sutures. The postoperative radiography could achieve a well-reduced articular facet, and this procedure had a good clinical outcome.

Immunoglobulin G4-Related Disease of the Hip.

The authors report a case of immunoglobulin G4-related disease (IgG4-RD) of the hip. A 60-year-old man diagnosed with osteoarthritis of the right hip was referred to the authors' outpatient clinic for surgical intervention. Laboratory test results revealed elevated C-reactive protein and serum IgG levels. A subsequent laboratory test revealed an IgG4 level of 318 mg/dL. Magnetic resonance imaging revealed an abnormal mass in the right hip joint. The authors suspected IgG4-RD of the hip. The mass was resected during total hip arthroplasty. Immunohistochemical analysis for IgG revealed positive staining of many plasma cells. Most of the IgG-positive plasma cells were positive for IgG4, and the ratio of IgG4/IgG-positive cells was 51%. This case met all criteria for IgG4-RD; thus, the authors made a definitive diagnosis of IgG4-RD of the hip. The C-reactive protein level decreased to a negative value, and the IgG level decreased to a normal range at 3 weeks postoperatively. The IgG4 level gradually decreased to 152 mg/dL at 5 months postoperatively. This is the first reported case of IgG4-RD of the hip joint. [Orthopedics. 2018; 41(6):e876-e879.].

Time-Dependent Recovery of Human Synovial Membrane Mesenchymal Stem Cell Function After High-Dose Steroid Therapy: Case Report and Laboratory Study.

BACKGROUND: The use of mesenchymal stem cells from various tissue sources to repair injured tissues has been explored over the past decade in large preclinical models and is now moving into the clinic. PURPOSE: To report the case of a patient who exhibited compromised mesenchymal stem cell (MSC) function shortly after use of high-dose steroid to treat Bell's palsy, who recovered 7 weeks after therapy. STUDY DESIGN: Case report and controlled laboratory study. METHODS: A patient enrolled in a first-in-human clinical trial for autologous implantation of a scaffold-free tissue engineered construct (TEC) derived from synovial MSCs for chondral lesion repair had a week of high-dose steroid therapy for Bell's palsy. Synovial tissue was harvested for MSC preparation after a 3-week recovery period and again at 7 weeks after therapy. RESULTS: The MSC proliferation rates and cell surface marker expression profiles from the 3-week sample met conditions for further processing. However, the cells failed to generate a functional TEC. In contrast, MSCs harvested at 7 weeks after steroid therapy were functional in this regard. Further in vitro studies with MSCs and steroids indicated that the effect of in vivo steroids was likely a direct effect of the drug on the MSCs. CONCLUSION: This case suggests that MSCs are transiently compromised after high-dose steroid therapy and that careful consideration regarding timing of MSC harvest is critical. CLINICAL RELEVANCE: The drug profiles of MSC donors and recipients must be carefully monitored to optimize opportunities to successfully repair damaged tissues.

First-in-Human Pilot Study of Implantation of a Scaffold-Free Tissue-Engineered Construct Generated From Autologous Synovial Mesenchymal Stem Cells for Repair of Knee Chondral Lesions.

BACKGROUND: Articular cartilage has limited healing capacity, owing in part to poor vascularity and innervation. Once injured, it cannot be repaired, typically leading to high risk for developing osteoarthritis. Thus, cell-based and/or tissue-engineered approaches have been investigated; however, no approach has yet achieved safety and regenerative repair capacity via a simple implantation procedure. PURPOSE: To assess the safety and efficacy of using a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stem cells (MSCs) for effective cartilage repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Five patients with symptomatic knee chondral lesions (1.5-3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove were included. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed up to 24 months postoperatively. The primary outcome was the safety of the procedure. Secondary outcomes were self-assessed clinical scores, arthroscopy, tissue biopsy, and magnetic resonance image-based estimation of morphologic and compositional quality of the repair tissue. RESULTS: No adverse events were recorded, and self-assessed clinical scores for pain, symptoms, activities of daily living, sports activity, and quality of life were significantly improved at 24 months after surgery. Secure defect filling was confirmed by second-look arthroscopy and magnetic resonance imaging in all cases. Histology of biopsy specimens indicated repair tissue approaching the composition and structure of hyaline cartilage. CONCLUSION: Autologous scaffold-free TEC derived from synovial MSCs may be used for regenerative cartilage repair via a sutureless and simple implantation procedure. Registration: 000008266 (UMIN Clinical Trials Registry number).

Glutamatergic neurons in the Kölliker-Fuse nucleus project to the rostral ventral respiratory group and phrenic nucleus: a combined retrograde tracing and in situ hybridization study in the rat.

Kölliker-Fuse nucleus (KF) neurons are considered to excite motoneurons in the phrenic nucleus (PhN) during inspiration through its projection to the PhN and/or to the rostral ventral respiratory group (rVRG), which in turn projects to the PhN, probably by releasing glutamate from their axon terminals. Using a combined retrograde tracing and in situ hybridization technique, here we demonstrate that most of the KF neurons projecting to the PhN and rVRG contain vesicular glutamate transporter 2 (VGLUT2) mRNA but not glutamic acid decarboxylase 67 (GAD67) mRNA, providing definitive evidence that these neurons are glutamatergic. Together with previous data by Stornetta et al. [Stornetta, R.L., Sevigny, C.P., Guyenet, P.G., 2003b. Inspiratory argumenting bulbospinal neurons express both glutamatergic and enkephalinergic phenotypes. J. Comp. Neurol. 455, 113-124], indicating that PhN-projecting rVRG neurons are VGLUT2 mRNA-positive, the present results suggest that the glutamatergic KF-PhN pathway and/or the glutamatergic KF-rVRG-PhN pathway transmit excitatory outputs of KF neurons to the PhN neurons during inspiration.

A disynaptic pathway from the central amygdaloid nucleus to the paraventricular hypothalamic nucleus via the parastrial nucleus in the rat.

The organization of projections from the central amygdaloid nucleus (CeA) to the paraventricuilar hypothalamic nucleus (PVH) has been studied in order to understand the anatomical substrates of amygdaloid modulation of endocrine and autonomic functions, and a hypothesis that the bed nucleus of the stria terminalis (BST) may act as a relay site between the CeA and PVH has been proposed. Using anterograde and retrograde tract-tracing methods, in the rat, we first indicated that neurons in the parastrial nucleus (PS), where projection fibers from the central amygdaloid nucleus (CeA) terminated, sent their axons to the paraventricular hypothalamic nucleus (PVH). We further demonstrated that the CeA terminals formed symmetrical synaptic contacts with somata and dendrites of the PVH-projecting PS neurons, and that the PS received CeA fibers predominantly from the lateral part and sent large numbers of projection fibers to almost all the subdivisions of the PVH. Using anterograde tracing combined with the postembedding immunogold method, we finally revealed that nearly all the CeA terminals in the PS were immunoreactive for gamma-aminobutyric acid. The present data suggest that output signals from the CeA are transmitted disynaptically to the PVH neurons via the PS neurons and modulate PVH neuron activity by way of disinhibition.

A potential contribution of tenascin-X to blood vessel formation in peripheral nerves.

Tenascin-X (TNX), an extracellular matrix protein, is abundantly expressed in peripheral nerves. However, the physiological role of TNX in peripheral nerves remains unknown. In this study, we found that actin levels in sciatic nerves of TNX-deficient mice were markedly decreased. Since actin was highly expressed in endothelial cells in wild-type sciatic nerves, we assessed morphological alterations of blood vessels in TNX-null sciatic nerves. The density of blood vessels was significantly decreased and the size of blood vessels was larger than those in wild-type sciatic nerves. Immunofluorescence showed that TNX was expressed by Schwann cells and fibroblasts in sciatic nerves. The results suggest that TNX secreted from Schwann cells and/or fibroblasts is involved in blood vessel formation in peripheral nerves.

Characterization of Mesenchymal Stem Cell-Like Cells Derived From Human iPSCs via Neural Crest Development and Their Application for Osteochondral Repair.

Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs) are a promising cell source for the repair of skeletal disorders. Recently, neural crest cells (NCCs) were reported to be effective for inducing mesenchymal progenitors, which have potential to differentiate into osteochondral lineages. Our aim was to investigate the feasibility of MSC-like cells originated from iPSCs via NCCs for osteochondral repair. Initially, MSC-like cells derived from iPSC-NCCs (iNCCs) were generated and characterized in vitro. These iNCC-derived MSC-like cells (iNCMSCs) exhibited a homogenous population and potential for osteochondral differentiation. No upregulation of pluripotent markers was detected during culture. Second, we implanted iNCMSC-derived tissue-engineered constructs into rat osteochondral defects without any preinduction for specific differentiation lineages. The implanted cells remained alive at the implanted site, whereas they failed to repair the defects, with only scarce development of osteochondral tissue in vivo. With regard to tumorigenesis, the implanted cells gradually disappeared and no malignant cells were detected throughout the 2-month follow-up. While this study did not show that iNCMSCs have efficacy for repair of osteochondral defects when implanted under undifferentiated conditions, iNCMSCs exhibited good chondrogenic potential in vitro under appropriate conditions. With further optimization, iNCMSCs may be a new source for tissue engineering of cartilage.

Topographical projection from the hippocampal formation to the amygdala: a combined anterograde and retrograde tracing study in the rat.

The hippocampal formation and amygdala are responsible for regulating emotion, learning, and behavior. The hippocampal projection to the amygdala has been demonstrated to originate in the subiculum and adjacent portion of field CA1 of the Ammon's horn (Sub/CA1) in the rat; however, the topographical organization of this pathway is still understudied. To make it clear, we performed anterograde and retrograde tracing with biotinylated dextran amine (BDA) and cholera toxin B subunit (CTb), respectively, in the rat. A series of BDA experiments revealed that the temporal-to-septal axis of origin determined a medial-to-lateral axis of termination in the amygdala. Briefly, the temporal region of the Sub/CA1 projects preferentially to the medial amygdaloid region including the medial, intercalated, and basomedial nuclei and the amygdalohippocampal transition area, and progressively more septal portions of the Sub/CA1 distribute their efferents in more lateral regions of the amygdala. Sub/CA1 fibers distributed in the central amygdaloid nucleus were relatively few. Retrograde tracing with CTb confirmed this topography and revealed little hippocampal innervation of the central nucleus of the amygdala. These observations suggest that distinct Sub/CA1 regions arranged along the longitudinal hippocampal axis may influence distinct modalities of the amygdala function.