The Relationship between the Bevel of the Radial Head Epiphysis and the Posterior Synovial Fringe During Rotation of the Elbow: An Ultrasonography Study with Possible Implications Regarding the Pathophysiology of Nursemaid's Elbow.

BACKGROUND: Nursemaid's elbow is the most common upper extremity injury in children under 5 years of age. However, the exact pathomechanism underlying the nursemaid's elbow remains elusive, and approximate one-third of patients present with a nonclassical history. Using a high-frequency ultrasound probe, we attempted to determine the relationship between the anterior edge of the posterior synovial fringe and the peripheral rim of the radial head epiphysis during rotation. It is possible that the primary reason for the nursemaid's elbow is due to the pronator position. METHODS: Twenty-one patients had a history of nursemaid's elbow and had a successful reduction before enrollment in this study. A high-frequency linear array 6 to 24 MHz hockey stick transducer was used to detect small morphologic changes in the peripheral rim of the radial head epiphysis and the posterior synovial fringe during rotation of the capitellum-radial joint. RESULTS: In complete pronation, the anterior edge of the posterior synovial fringe contacts the beveled articular surface of the radial head peripheral rim in all 21 patients. In neutral and complete supination, the anterior edge of the posterior synovial fringe contacts the convexly nonarticular surface of the radial head peripheral rim and extends deep into the foveal radius. The posterior synovial fringe and the capsule-aponeurotic membrane were tightened in passive pronation in all 21 cases. The posterior synovial fringe and the capsule-aponeurosis membrane were all loose in the neutral and supination positions. CONCLUSION: The anterior edge of the posterior synovial fringe touches the beveled peripheral rim of the radial head epiphysis during complete pronation, and the tension of the lateral collateral ligament complex during pronation may further cause unstable conditions of the anterior edge of the posterior synovial fringe. We hypothesized that the beveled peripheral rim of the radial epiphysis and its relationship with the anterior edge of the posterior synovial fringe could be the reason why nursemaid's elbow only occurs while the elbow is in the pronator position.

The Usefulness of Dynamic Ultrasonography in Nursemaid's Elbow: A Prospective Case Series of 13 Patients Reconsideration of the Pathophysiology of Nursemaid's Elbow.

BACKGROUND: Nursemaid's elbow is a common musculoskeletal disorder among children under 5 years of age. However, diagnostic imaging to confirm a nursemaid's elbow diagnosis is still unavailable. Through the use of a high-frequency ultrasound probe, we determined the etiology and possible pathophysiology of nursemaid's elbow. METHODS: Thirteen consecutive patients with the clinical suspicion of nursemaid's elbows were examined. A high-frequency linear array 6 to 24 MHz hockey stick transducer was used to detect small changes (partial eclipse signs) of the radial head in the axial view before and after manipulation. RESULTS: All patients in this study had a successful reduction. A partial eclipse sign was found in all patients before reduction and disappeared after successful reduction. CONCLUSION: These pathologic features detected through high-frequency ultrasonography suggest the role of the escaped posterior synovial fringe in the pathogenesis of the nursemaid's elbow. The specific finding of a "partial eclipse sign" could be a useful additional clue leading to the correct diagnosis of the nursemaid's elbow and may help avoid the unnecessary reduction in patients who do not have a "partial eclipse sign". LEVEL OF EVIDENCE: Level II, diagnostic studies.

Developing three-phase modified bat algorithms to solve medical staff scheduling problems while considering minimal violations of preferences and mean workload.

BACKGROUND: This research studies a medical staff scheduling problem, which includes government regulations and hospital regulations (hard constraints) and the medical staff's preferences (soft constraints). OBJECTIVE: The objective function is to minimize the violations (or dissatisfaction) of medical staff's preferences. METHODS: This study develops three variants of the three-phase modified bat algorithms (BAs), named BA1, BA2, and BA3, in order to satisfy the hard constraints, minimize the dissatisfaction of the medical staff and balance the workload of the medical staff. To ensure workload balance, this study balances the workload among medical staff without increasing the objective function values. RESULTS: Based on the numerical results, the BA3 outperforms the BA1, BA2, and particle swarm optimization (PSO). The robustness of the BA1, BA2, and BA3 is verified. Finally, conclusions are drawn, and directions for future research are highlighted. CONCLUSIONS: The framework of this research can be used as a reference for other hospitals seeking to determine their future medical staff schedule.

The immunologically active oligosaccharides isolated from wheatgrass modulate monocytes via Toll-like receptor-2 signaling.

Wheatgrass is one of the most widely used health foods, but its functional components and mechanisms remain unexplored. Herein, wheatgrass-derived oligosaccharides (WG-PS3) were isolated and found to induce CD69 and Th1 cytokine expression in human peripheral blood mononuclear cells. In particular, WG-PS3 directly activated the purified monocytes by inducing the expression of CD69, CD80, CD86, IL-12, and TNF-α but affected NK and T cells only in the presence of monocytes. After further purification and structural analysis, maltoheptaose was identified from WG-PS3 as an immunomodulator. Maltoheptaose activated monocytes via Toll-like receptor 2 (TLR-2) signaling, as discovered by pretreatment of blocking antibodies against Toll-like receptors (TLRs) and also determined by click chemistry. This study is the first to reveal the immunostimulatory component of wheatgrass with well defined molecular structures and mechanisms.

Oligosaccharide and peptidoglycan of Ganoderma lucidum activate the immune response in human mononuclear cells.

The acid-hydrolyzed fragments of Ganoderma lucidum polysaccharides (GLPS) obtained by Smith degradation were separated by size-exclusion chromatography into two major water-soluble fractions: peptidoglycans (GLPS-SF1) and oligosaccharides (GLPS-SF2). Both fractions induced CD69 in human peripheral blood mononuclear cells (hPB-MNCs), and they displayed distinct immunomodulating properties. GLPS-SF1, with a molecular weight of around 20 kDa, were heterogeneous peptidoglycans composed of glucose/mannose (4:1) that exhibited biological activities with Th1 cytokines IL-12, IL-2, TNF-α, and IFN-γ in hPB-MNCs and stimulated macrophage cytokine expression via Toll-like receptor 4 (TLR4) signaling. For GLPS-SF2, with a molecular weight of around several kilodaltons, its sugar sequence was elucidated by mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy as [-α-1,4-Glc-(ß-1,4-GlcA)(3)-](n). This oligosaccharide displayed specific immune property with low monocyte induction, greatly stimulated cell activation and proliferation of NK and T cells. This oligosaccharide isolated from G. lucidum polysaccharides with internal glucuronic acids/glucose repeat unit in a 3:1 ratio may be responsible for the active stimulation of NK and T cells.

Biodistribution and pharmacokinetics of 188Re-liposomes and their comparative therapeutic efficacy with 5-fluorouracil in C26 colonic peritoneal carcinomatosis mice.

BACKGROUND: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of (188)Re-labeled nanoliposomes ((188)Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. METHODS: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered (188)Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of (188)Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with (188)Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. RESULTS: In biodistribution, the highest uptake of (188)Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of (188)Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of (188)Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the (188)Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with (188)Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). CONCLUSION: The use of (188)Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that (188)Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.

Structure and functions of gamma-dodecalactone isolated from Antrodia camphorata for NK cell activation.

The preserved fungal species Antrodia camphorata has diverse health-promoting effects and has been popularly used in East Asia as a traditional herb. We isolated a volatile compound from the culture medium of A. camphorata and identified it as gamma-dodecalactone (gamma-DDL). Cytomic screening for immune-modulating activity revealed that gamma-DDL can activate human NK cells to express the early activation marker CD69. Further experiments showed that gamma-DDL not only can induce NK cells to express CD69 but also stimulate NK cells to secrete cytotoxic molecules (FasL and granzyme B) and Th1 cytokines (TNF-alpha and INF-gamma). Measuring the distribution of gamma-DDL in the subcellular compartments of NK cells revealed that gamma-DDL has been converted to 4-hydroxydodecanoic acid (an acyclic isomer of gamma-DDL) in a time-dependent manner in the cytoplasm. Synthetic (R,S)-4-hydroxydodecanoic acid activated NK cells to express CD69 mRNA within 10min, in contrast to gamma-DDL, which activated NK cells to express CD69 within 50min. This faster activation suggests that gamma-DDL has converted to 4-hydroxydodecanoic acid and to stimulate the NK cells to express CD69. Optically pure (R)-(+)-4-hydroxydodecanoic acid and (S)-(-)-4-hydroxydodecanoic acid were obtained via: (1) synthesis of its diastereomeric esters of (R,S)-4-hydroxydodecanoic (R)-(-)-2-phenylpropionate; (2) separation of diastereomers via preparative HPLC, and (3) subsequent hydrolysis of the obtained optical pure ester of (R)-(+)-4-hydroxydodecanoic acid (R)-(-)-2-phenylpropionate and (R)-(-)-4-hydroxydodecanoic acid (R)-(-)-2-phenylpropionate, respectively. Further assays of NK cells activation using each enantiomer showed that only the (R)-(+)-4-hydroxydodecanoic acid can activate NK cells.

Cytomic screening of immuno-modulating activity compounds from Calocedrus formosana.

Procedures for cytomic screening were developed for identifying compounds with immuno-modulating properties from the crude extracts of natural products. Human peripheral blood mononuclear cells (hPB-MNCs) were first cultured with different natural crude extracts for 12 hours in culture media. By analyzing the expression of early activation CD69 marker, the potential immuno-activating properties of ethanol extracts of Calocedrus formosana were observed. By the double staining of antibodies recognizing CD69 and specific cell type markers, the increase of CD69 expressions was observed in CD3 and CD14 cell populations. To examine the immuno-activating properties in CD3 T cells and CD14 monocytes, the extracts were further purified. From NMR and mass spectra, sugiol was identified as a pure functional compound, and its immuno-enhancing activities were confirmed by CD69 expressions in the affected cell populations. Furthermore, to clarify the sugiol-affected subpopulations in CD3 T cells, CD3 T cell activation in association with increase in CD8 cytotoxic T cells subpopulation was observed. To address the effect of sugiol on each isolated cell population, we found that the expression of CD69, CD80, and CD86 increased in CD14 monocytes upon exposure to sugiol, whereas for CD3 T cells, sugiol failed to induce the expressions of CD69 and CD25. However, T cell activation by co-culturing monocytes and T cells suggests that the sugiol activation of T cells in hPB-MNCs involved the accessory mechanisms of sugiol-primed monocytes. Therefore, cytomic screening as a multiple-parameter screening strategy reveals the plasticity for immuno-functional studies, leading to the applications to discover new drugs of specific immuno-modulating activities.

A screening platform for compounds with potential immuno-regulatory activities using human cord blood mononuclear cells.

A systematic and combinatorial approach was adopted using human umbilical cord blood mononuclear cells (hUCB-MNCs) to screen for potential immuno-regulatory compounds. The hUCB-MNCs contain several types of immunogenic cells, which are a suitable material to mimic the in vivo immuno-response after drug treatment. hUCB-MNCs were treated with various natural products such as quercetin, astaxanthin, caffeic acid, bilobalide, eugenol, rutin and gamma-dodecalactone (gamma-DDL). Phenotypic expression analysis revealed that the subpopulation of CD3(+) T cells, CD56(+) NK cells and CD1a(+) dendritic cells apparently increased after being treated with gamma-DDL for 6 days. The expression of CD56 reached a maximum at 72 h with a dose-dependent relationship. The NK cells activation marker (CD69) also elevated following gamma-DDL treatment. These results demonstrated that the gamma-DDL has immuno-regulatory effects to enhance cord blood NK cells population and bioactivities. Such a high-throughput methodology using hUCB-MNCs may be an effective platform for systematically screening potential immuno-regulatory compounds.

Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue.

Recent studies have shown that adult tissues contain stem/ progenitor cells capable of not only generating mature cells of their tissue of origin but also transdifferentiating themselves into other tissue cells. Murine skin-derived precursor cells, for example, have been described as unique, nonmesenchymal-like stem cells capable of mesodermal and ectodermal neurogenic differentiation. Human-derived skin precursors are less well characterized. In this study, the isolation and characterization of adherent, mesenchymal stem cell-like cells from human scalp tissue (hSCPs) are described. hSCPs initially isolated by both medium-selection (ms-hSCPs) and single-cell (c-hSCPs) methods were cultured in medium containing epidermal growth factor and fibroblast growth factor-beta. Cultured ms-hSCPs and c-hSCPs demonstrated a consistent growth rate, continuously replicated in cell culture, and displayed a stable phenotype indistinguishable from each other. Both hSCPs expressed surface antigen profile (CDw90, SH2, SH4, CD105, CD166, CD44, CD49d-e, and HLA class I) similar to that of bone marrow mesenchymal stem cells (BM-MSCs). The growth kinetics, surface epitopes, and differentiation potential of c-hSCP cells were characterized and compared with BM-MSCs. In addition to differentiation along the osteogenic, chondrogenic, and adipogenic lineages, hSCPs can effectively differentiate into neuronal precursors evident by neurogenic gene expression of glial fibrillary acid protein, NCAM, neuron filament-M, and microtubule-associated protein 2 transcripts. Therefore, hSCPs may potentially be a better alternative of BM-MSCs for neural repairing, in addition to their other mesenchymal regenerative capacity. Our study suggests that hSCPs may provide an alternative adult stem cell resource that may be useful for regenerative tissue repair and autotransplantations.

Atypical slipped capital femoral epiphysis after radiotherapy and chemotherapy.

Atypical slipped capital femoral epiphysis after radiotherapy and chemotherapy is uncommon. Only 32 cases have been reported in the literature. Because patients may have slippage at atypical ages, we report two cases of slipped capital femoral epiphysis in children and review the 32 cases previously reported to heighten clinicians' awareness of this condition in patients who have received radiation and chemotherapy for pelvic tumors. The controversy over prophylactic pinning of the uninvolved hip in radiotherapy-associated slipped capital femoral epiphysis is unresolved. It may be justifiable to fix the nonslipped epiphysis if possible prodromal signs of abnormal radiographic findings are detected. Because radiotherapy and chemotherapy were used in the two children reported, it is not possible to state whether one or both forms of treatment were responsible for the atypical slipped capital femoral epiphysis.