OBJECTIVE: Spinal instrumentation without fusion often fails due to biological failure of intervertebral joints (spontaneous fusion, degeneration, etc). The purpose of this study is to investigate the influence of fixation rigidity on viability of intervertebral joints. METHODS: Twenty pigs in growing period were subjected to posterior segmental fixation. Twelve were fixed with a rigid fixation system(RF) while eight were fixed with a flexible unconstrained implant(FF). At the time of the surgery, a scoliosis was created to monitor fixation adequacy. The pigs were subjected to periodic radiological examinations and 12pigs (six in RF, six in FF) were euthanized at 12-18months postoperatively for analysis. RESULTS: The initial scoliotic curve was reduced from 31+/-5degrees to 27+/-8degrees in RF group (p=0.37) and from 19+/-4degrees to 17+/-5degrees in FF group (p=0.21). Although severe disc degeneration and spontaneous fusion of facet joints were observed in RF group, disc heights of FF group were well maintained without major signs of degeneration. CONCLUSION: The viability of the intervertebral joints depends on motion spinal fixation. Systems allowing intervertebral micromotion may preserve the viability of intervertebral discs and the facet joint articular cartilages while maintaining a reasonably stable fixation.
Cartilage, Articular ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Joints* ; Scoliosis ; Swine ; Zygapophyseal Joint

No abstract available.
Animals ; Cattle ; Encephalopathy, Bovine Spongiform/epidemiology ; Meat/*analysis ; United States

Approximately 15%−25% of breast lymphatic drainage passes through the internal thoracic (internal mammary) lymphatic system, draining the inner quadrants of the breast. This study aimed to use lymphosonography to identify sentinel lymph nodes (SLNs) in the axillary and internal thoracic lymphatic systems in patients with breast cancer. Seventy-nine patients received subcutaneous ultrasound contrast agent injections around the tumor.Lymphosonography was used to identify SLNs. In 14 of the 79 patients (17.7%), the tumor was located in the inner quadrant of the breast. Lymphosonography identified 217 SLNs in 79 patients, averaging 2.7 SLNs per patient. The 217 identified SLNs in the 79 patients were located in the axillary lymphatic system; none were located in the internal thoracic (internal mammary) lymphatic system, although it was expected in two to four patients (i.e., 4–11 SLNs). These results implied that SLNs associated with breast cancer are predominantly located in the axillary lymphatic system.

A pregnane steroid, 3α-hydroxy-pregn-7-ene-6,20-dione (1), was isolated from a Hydractinia-associated Cladosporium sphaerospermum SW67 by repetitive column chromatographic separation and highperformance liquid chromatography (HPLC) purification. The planar structure of 1 was elucidated from the analysis of the spectroscopic data (1D and 2D NMR spectra) and LC-MS data. The absolute configuration of 1 was determined by interpretation of ROESY spectrum of 1, together with the comparison of reported spectroscopic values in previous studies. To the best of our knowledge, this is the first report of the identification of the pregnane scaffold from C. sphaerospermum, a natural source. Compound 1 was evaluated for its effects on lipid metabolism and adipogenesis during adipocyte maturation and showed that compound 1 substantially inhibited lipid accumulation compared to the control. Consistently, the expression of the adipocyte marker gene (Adipsin) was reduced upon incubation with 1. Further, we evaluated the effects of 1 on lipid metabolism by measuring the transcription of lipolytic and lipogenic genes. The expression of the lipolytic gene ATGL was significantly elevated upon exposure to 1 during adipogenesis, whereas the expression of lipogenic genes FASN and SREBP1 was significantly reduced upon treatment with 1. Thus, our findings provide experimental evidence that the steroid derived from Hydractinia-associated C. sphaerospermum SW67 is a potential therapeutic agent for obesity.

Overactive bladder (OAB) is prevalent in men and women and negatively impacts physical and psychological health. Fluid and caffeine intake modifications, which are lifestyle modification interventions, are simple methods to manage OAB. However, studies that synthesized both interventions and found scientific evidence are scarce. This review aimed to synthesize scientific evidence on whether fluid and caffeine intake modifications are effective for OAB symptoms. PubMed, CINAHL (Cumulative Index for Nursing and Allied Health Literature), Embase, Scopus, the Cochrane Library, KoreaMed, and RISS (Research Information Sharing Service) were used to search for studies and 8 studies were included. The Cochrane risk of bias tool (RoB 2.0) and ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) were used to assess the quality of selected studies. Due to the heterogeneous outcome variables, a meta-analysis was not conducted. Among the 8 included, 7 studies were randomized controlled trials and one was a quasi-experimental study. Four studies assessed urgency. Caffeine reduction was statistically effective for urgency symptoms, but increasing fluid intake was not. Frequency was assessed in 5 studies, which showed decreasing caffeine and fluid intake was effective in treating the symptoms. Urinary incontinence episodes were assessed in 6 studies, and nocturia in 2. Restricting caffeine intake was effective in treating these 2 symptoms, but restricting both caffeine and fluid intake was not. Quality of life (QoL) was examined in 5 studies, and modifying fluid and caffeine intake significantly improved QoL in 2. Although there were limited studies, our review provides scientific evidence that fluid and caffeine intake modification effectively manages OAB symptoms. Further research should examine acceptability and sustainability of interventions in the long-term and enable meta-analysis.

OBJECTIVE: Pedicle screw is gaining popularity in pediatric deformities. However, biological response of actively growing spine to rigid pedicle screw fixation remains unclear. The objective of this study is to determine the biological response of growing spine to rigid segmental fixation. METHODS: Twelve mini pigs in actively growing period were subjected to posterior segmental screw -rod instrumentation spanning nine levels and creation of experimental scoliosis. There was no attempt of posterior arthrodesis. The pigs were subjected to periodic radiological examinations and were euthanized at 18 months for analysis. RESULTS: There was no significant fixation failure despite conspicuous growth of the animals. Initial scoliosis of 31+/-5degrees was reduced to 27+/-8degrees at 18 months, but there was no statistical significance (p=0.37). Though there was no change in length of the implant construct, the vertebrae within the instrumented section showed mean longitudinal growth of 6+/-3 mm (p=0.000). The growth occurred at expense of the disc spaces that progressively narrowed with time. On necropsy, the instrumented region was completely fused posteriorly with crossing of the osseous traberculae across the former facet joints. Intervertebral discs were severely atrophic in all the discs with occasional spontaneous fusion. CONCLUSION: Even in the actively growing spine, the force of growth does not overcome the fixation offered by segmental pedicle screws. Longitudinal growth occurs at the expense of the joint spaces and leads to spontaneous intervertebral fusion. Our results may explain the favorable outcomes in pedicle fixations in pediatric population, showing little implant failure or nonunion.
Animals ; Arthrodesis ; Congenital Abnormalities ; Intervertebral Disc ; Joints ; Scoliosis ; Spine* ; Swine ; Zygapophyseal Joint

BACKGROUND: Pathogenic variants of USH1C, encoding a PDZ-domain-containing protein called harmonin, have been known to cause autosomal recessive syndromic or nonsyndromic hearing loss (NSHL). We identified a causative gene in a large Korean family with NSHL showing a typical pattern of autosomal dominant (AD) inheritance. METHODS: Exome sequencing was performed for five affected and three unaffected individuals in this family. Following identification of a candidate gene variant, segregation analysis and functional studies, including circular dichroism and biolayer interferometry experiments, were performed. RESULTS: A novel USH1C heterozygous missense variant (c.667G>T;p.Gly223Cys) was shown to segregate with the NSHL phenotype in this family. This variant affects an amino acid residue located in the highly conserved carboxylate-binding loop of the harmonin PDZ2 domain and is predicted to disturb the interaction with cadherin-related 23 (cdh23). The affinity of the variant PDZ2 domain for a biotinylated synthetic peptide containing the PDZ-binding motif of cdh23 was approximately 16-fold lower than that of the wild-type PDZ2 domain and that this inaccessibility of the binding site was caused by a conformational change in the variant PDZ2 domain. CONCLUSIONS A heterozygous variant of USH1C that interferes with the interaction between cdh23 and harmonin causes novel AD-NSHL.

KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.

KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.