TRPV4 affects visual signals in photoreceptors and rod bipolar cells.

Introduction: Mechanical sensitive channels expressed in mammalian retinas are effectors of elevated pressure stresses, but it is unclear how their activation affects visual function in pressure-related retinal disorders. Methods: This study investigated the role of the transient potential channel vanilloid TRPV4 in photoreceptors and rod bipolar cells (RBCs) with immunohistochemistry, confocal microscopy, electroretinography (ERG), and patch-clamp techniques. Results: TRPV4 immunoreactivity (IR) was found in the outer segments of photoreceptors, dendrites and somas of PKCα-positive RBCs and other BCs, plexiform layers, and retinal ganglion cells (RGCs) in wild-type mice. TRPV4-IR was largely diminished in the retinas of homozygous TRPV4 transgenic mice. Genetically suppressing TRPV4 expression moderately but significantly enhanced the amplitude of ERG a- and b-waves evoked by scotopic and mesopic lights (0.55 to 200 Rh*rod-1 s-1) and photopic lights (105-106 Rh*rod-1 s-1) compared to wild-type mice in fully dark-adapted conditions. The implicit time evoked by dim lights (0.55 to 200 Rh*rod-1 s-1) was significantly decreased for b-waves and elongated for a-waves in the transgenic mice. ERG b-wave evoked by dim lights is primarily mediated by RBCs, and under voltage-clamp conditions, the latency of the light-evoked cation current in RBCs of the transgenic mice was significantly shorter compared to wild-type mice. About 10% of the transgenic mice had one eye undeveloped, and the percentage was significantly higher than in wild-type mice. Conclusions: The data indicates that TRPV4 involves ocular development and is expressed and active in outer retinal neurons, and interventions of TRPV4 can variably affect visual signals in rods, cones, RBCs, and cone ON BCs.

L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction.

BACKGROUND/AIMS: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. METHODS: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H2O2-exposed human kidney cells (HK-2) were treated with LC. RESULTS: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H2O2-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. CONCLUSION: LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

Exogenous pancreatic kininogenase protects against renal fibrosis in rat model of unilateral ureteral obstruction.

Tissue kallikrein has protective function against various types of injury. In this study, we investigated whether exogenous pancreatic kininogenase (PK) conferred renoprotection in a rat model of unilateral ureteral obstruction (UUO) and H2O2-treated HK-2 cells in vitro. SD rats were subjected to UUO surgery, then PK (7.2 U/g per day, ip) was administered for 7 or 14 days. After the treatment, rats were euthanized; the obstructed kidneys were harvested for further examination. We found that PK administration significantly attenuated interstitial inflammation and fibrosis, and downregulated the expression of proinflammatory (MCP-1, TLR-2, and OPN) and profibrotic (TGF-ß1 and CTGF) cytokines in obstructed kidney. UUO-induced oxidative stress, closely associated with excessive apoptotic cell death and autophagy via PI3K/AKT/FoxO1a signaling, which were abolished by PK administration. We further showed that PK administration increased the expression of bradykinin receptors 1 and 2 (B1R and B2R) mRNA and the production of NO and cAMP in kidney tissues. Coadministration with either B1R antagonist (des-Arg9-[Leu8]-bradykinin) or B2R antagonist (icatibant) abrogated the renoprotective effects of PK, and reduced the levels of NO and cAMP in obstructed kidney. In H2O2-treated HK-2 cells, addition of PK (6 pg/mL) significantly decreased ROS production, regulated the expression of oxidant and antioxidant enzymes, suppressed the expression of TGF-ß1 and MCP-1, and inhibited cell apoptosis. Our data demonstrate that PK treatment protects against the progression of renal fibrosis in obstructed kidneys.

Intracellular Dye Microinjection in Retinal Morphological and Communication Studies.

The retina provides an excellent system to analyze neural architecture and communication mechanisms. In retinal physiological, morphological, and developmental studies, intracellular dye microinjection is an extensively applied technique. Dyes and/or chemical compounds are introduced into retinal neurons via iontophoresis injection to identify cell types, communication, and developmental changes. Here, we describe the detailed methods for ejecting the dyes Lucifer yellow and Neurobiotin into retinal neurons through micropipette and concentrate on avoiding the known pitfalls and troubleshooting.

Surface mineralized biphasic calcium phosphate ceramics loaded with urine-derived stem cells are effective in bone regeneration.

BACKGROUND: Segmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world. Recent developments in tissue engineering have provided a new treatment for segmental bone defects. Urine-derived stem cells (USCs) can be obtained noninvasively and might be a new kind of seed cells used in bone tissue regeneration. Therefore, the first aim of the present study was to investigate the biological characteristics of USCs. The second aim of the present study was to study the osteogenic effect of surface mineralized biphasic calcium phosphate ceramics (BCPs) loaded with USCs in vitro and in vivo. METHODS: We isolated USCs from the urine of healthy adult donors and evaluated the biological characteristics of USCs in vitro. We mineralized the surface of BCPs by simulated body fluid (SBF). Cell adhesion and proliferation of USCs on the surface mineralized BCPs were evaluated. Osteogenic proteins and genes of USCs on the surface mineralized BCPs were texted by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) assay. Critical-sized segmental bone defects model in New Zealand white rabbits were established and randomly divided into 4 groups (surface mineralized BCPs loaded with USCs, BCPs loaded with USCs, surface mineralized BCPs, and BCPs) based on the implant they received. The therapeutic efficacy of the scaffolds in a large bone defect at post-implantation was evaluated by imaging and histological examination. RESULTS: USCs isolated in our study expressed stem cell-specific phenotypes and had a stable proliferative capacity and multipotential differentiation capability. Surface mineralized BCPs promoted osteogenic proteins and genes expression of USCs without affecting the proliferation of USCs. After 10 weeks, the amount of new bone formation was the highest in the group of surface mineralized BCPs loaded with USCs. CONCLUSION: USCs, from non-invasive sources, have good application prospects in the field of bone tissue engineering. Surface mineralized BCPs can significantly enhance osteogenic potential of USCs without changing biological characteristics of BCPs. Surface mineralized BCPs loaded with USCs are effective in repairing of critical-sized segmental bone defects in rabbits.

[Clinical study of recombinant human erythropoietin combined with iron to correct perioperative anemia in elderly patients with intertrochanteric fractures].

OBJECTIVE: To investigate the effectiveness of recombinant human erythropoietin (rHuEPO) combined with iron in treatment of anemia in elderly patients with intertrochanteric fractures during perioperative period. METHODS: A clinical data of 71 patients with intertrochanteric fractures met the inclusion criteria between April 2016 and October 2017 was retrospectively analyzed. All patients were treated with closed reduction and proximal femoral intramedullary nail fixation. Thirty-one patients were treated with rHuEPO and iron before operation as trial group, and 40 patients were not treated with rHuEPO and iron as control group. There was no significant difference in gender, age, body mass index, cause of injury, fracture side and classification, American Society of Anesthesiologists (ASA) classification, combined medical diseases, time from fracture to admission, preoperative hospital stay, and operation time between the two groups ( P>0.05).The hemoglobin levels before operation and at 1, 3, and 7 days after operation, number of blood transfusion, blood transfusion rate, blood transfusion volume, postoperative hospital stay, complications were recorded and compared. RESULTS: After operation, 8 patients (25.8%) in trial group and 22 patients (55.0%) in control group received blood transfusion; the blood transfusion volume was (1.96±0.85) units in trial group and (3.19±1.61) units in control group. There were significant differences in blood transfusion rate and volume between the two groups ( P<0.05). There was no significant difference in preoperative hemoglobin level between the two groups ( P>0.05). The postoperative hemoglobin level was higher in trial group than in control group, and the difference between the two groups was significant at 7 days ( P<0.05). The postoperative hospital stay was (6.16±3.97) days in trial group and (9.25±4.47) days in control group, showing significant difference between the two groups ( P<0.05). There were 8 patients (25.8%) with pulmonary infection in trial group and 14 (35.0%) in control group after operation; 6 patients (19.4%) with deep venous thrombosis in trial group and 8 (20.0%) in control group. There was no significant difference in the incidences of complications between the two groups ( P>0.05). All patients were discharged from hospital normally, and no one died during hospitalization. CONCLUSION: The application of rHuEPO combined with iron before operation in elderly patients with intertrochanteric fractures can rapidly increase the hemoglobin level after operation, shorten the hospital stay, and do not increase the risk of deep venous thrombosis after operation.

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse.

In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Here, we demonstrate that T-box transcription factor T-brain 1 (Tbr1) is expressed in two groups of morphologically and functionally distinct RGCs: the orientation-selective J-RGCs and a group of OFF-sustained RGCs with symmetrical dendritic arbors. When Tbr1 is genetically ablated during retinal development, these two RGC groups cannot develop. Ectopically expressing Tbr1 in M4 ipRGCs during development alters dendritic branching and density but not the inner plexiform layer stratification level. Our data indicate that Tbr1 plays critical roles in regulating the formation and dendritic morphogenesis of specific RGC types.

Shen-Kang protects against tacrolimus-induced renal injury.

BACKGROUND/AIMS: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. METHODS: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor ß1 [TGF-ß1] and TGF-ß inducible gene-h3 [ßig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. RESULTS: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-ß1/Smad2/3, ßig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio). CONCLUSION: SK protects against TAC-induced renal injury.

Admission prevalence of deep vein thrombosis in elderly Chinese patients with hip fracture and a new predictor based on risk factors for thrombosis screening.

BACKGROUND: Elderly hip fracture (HF) patients are at very high risk of developing deep vein thrombosis (DVT), which increases their perioperative mortality. However, data focusing on the admission prevalence of DVT in elderly Chinese patients with hip fracture are limited. Venography and ultrasonography are not suitable for most elderly HF patients; there is also controversy about the prognostic value of D-dimer in elderly patients. Thus, our primary goal was to clarify the prevalence of and risk factors for DVT in elderly Chinese HF patients at admission. Our secondary goal was to evaluate the diagnostic value of a new predictor of DVT based on the risk factors for elderly HF patients. METHODS: This retrospective study was conducted in the West China Hospital, Sichuan University. Between January 2015 and January 2017, 248 elderly Chinese HF patients (> 60 years) were enrolled in this study. The subjects were diagnosed with DVT using ultrasonography or venography. All the patients' clinical data were obtained, including demographic variables, medical history, comorbidities, and laboratory results. A stepwise multiple logistic regression analysis was used to identify the risk factors contributing to the occurrence of DVT. The value of the new DVT predictor was calculated using a formula based on the coefficient regression and independent variables. A receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of different factors. RESULTS: Of the study patients, 74 (29.8%) were diagnosed with DVT, including sixty-five (87.8%) with distal peripheral, five (6.8%) with proximal central and four (5.4%) with mixed DVT. A multivariate logistic regression analysis showed that five risk factors increased the occurrence of DVT at admission, including gender, age, time from injury to admission, fibrinogen, and D-dimer. The new DVT predictor was calculated using the following formula: 1.131× (female = 1, male = 0) + 0.071 × age (years) + 0.571 × time from injury to admission (days) + 1.028 × fibrinogen(g/L) + 0.123 × D-dimer(g/L). The diagnostic value of the new predictor was highest among those risk predictors whose AUC (area under the ROC curves) value was 0.852. CONCLUSIONS: The results of this study revealed a high prevalence of DVT in elderly Chinese HF patients at admission. Moreover, the new predictor, based on risk factors, was a good method to improve the diagnosis of DVT.

[Perioperative treatment progress of Parkinson's disease with hip fracture].

Objective: To review the progress of perioperative treatments for patients of Parkinson's disease and hip fractures. Methods: The related literature of treatments for patients of Parkinson's disease and hip fractures were reviewed and analyzed from the aspects such as the perioperative management, selection of operation ways, and prognosis. Results: The patients of Parkinson's disease are more likely to sustain hip fractures because of postural instability and osteoporosis. The perioperative treatments for patients of Parkinson's disease and hip fractures should be determined by orthopedists, neurologist, anesthesiologist, and physical therapist. There is still controversy about the selection of operation and surgical approach. And the prognosis of patients of Parkinson's disease and hip fractures are associated with the severity of Parkinson's disease. Conclusion: There are few clinical studies about the patients of Parkinson's disease and hip fractures. The mid-term and long-term functional outcomes of patients of Parkinson's disease and hip fractures are unsufficient. And the best treatments of patients of Parkinson's disease and hip fractures need to be further explored.

[The application and research progress of in-situ tissue engineering technology in bone and cartilage repair].

Objective: To review the application and research progress of in-situ tissue engineering technology in bone and cartilage repair. Methods: The original articles about in-situ tissue engineering technology in bone and cartilage repair were extensively reviewed and analyzed. Results: In-situ tissue engineering have been shown to be effective in repairing bone defects and cartilage defects, but biological mechanisms are inadequate. At present, most of researches are mainly focused on animal experiments, and the effect of clinical repair need to be further studied. Conclusion: In-situ tissue engineering technology has wide application prospects in bone and cartilage tissue engineering. However, further study on the mechanism of related cytokines need to be conducted.

[Application of cell sheet technology in bone and cartilage tissue engineering].

Objective: To review the progress of cell sheet technology and its application in bone and cartilage engineering. Methods: The recent literature concerning the cell sheet technology used in treatment of bone and cartilage defects was extensively reviewed and summarized. Results: Cell sheet built through many different ways can protect extracellular matrix from proteolytic enzymes. As a three-dimensional structure, cell sheet can repair bone and cartilige defects via folding, wrapping scaffold, or be created by the layering of individual cell sheets. Conclusion: The cell sheet technology would have a very broad prospects in bone and cartilage tissue engineering in future.

Postoperative occipital neuralgia in posterior upper cervical spine surgery: a systematic review.

Postoperative occipital neuralgia (PON) after upper cervical spine surgery can cause significant morbidity and may be overlooked. The causes, presentation, diagnosis, management, prognosis, and prevention of PON were reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. English-language studies and case reports published from inception to 2017 were retrieved. Data on surgical procedures, incidence, cause of PON, management, outcomes, and preventive technique were extracted. Sixteen articles, including 591 patients, were selected; 93% of the patients with PON underwent C1 lateral mass screw (C1LMS) fixation, with additional 7% who underwent occipitocervical fusion without C1 fixation. PON had an incidence that ranged from 1 to 35% and was transient in 34%, but persistent in 66%. Five articles explained the possible causes. The primary presentation was constant or paroxysmal burning pain located mainly in the occipital and upper neck area and partially extending to the vertical, retroauricular, retromandibular, and forehead zone. Treatment included medications, nerve block, revision surgery, and nerve stimulation. Two prospective studies compared the effect of C2 nerve root transection on PON. PON in upper cervical spine surgery is a debilitating complication and was most commonly encountered by patients undergoing C1LMS fixation. The etiology of PON is partially clear, and the pain could be persistent and hard to cure. Reducing the incidence of PON can be realized by improving technique. More high-quality prospective studies are needed to define the effect of C2 nerve root transection on PON.

Cervical intradural disc herniation: A systematic review.

BACKGROUND: Cervical intradural disc herniation (CIDH) is rare, and diagnosis and treatment are challenging. We conducted a systematic review and meta-analysis of the literature on the diagnosis and treatment of CIDH. METHOD: The presentation, imaging manifestations, diagnosis, management, prognosis and possible pathogenesis were reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies and case reports published from inception to 2017 were retrieved. Data on presentation, imaging characteristics, diagnosis, management, outcomes and pathogenesis were extracted. RESULTS: Twenty articles involving 23 patients were selected. The most common involved level was C5-6 (43.5%), followed by C6-7 (30.4%), C4-5 (13%), and C3-4 (13%). Spontaneous IDH occurred in 61% of the patients, and relevant cervical trauma was present in 39%. Brown-Sequard's syndrome (56.5%), quadriparesis (34.8%), and radiculopathy (8.7%) were the main presentations. Magnetic resonance imaging (MRI) was the most commonly used diagnostic technique, and the "halo" and "Y-sign" were strong indicators of CIDH. Three (13%) patients were diagnosed as having CIDH preoperatively, and 87% were confirmed intraoperatively. All patients underwent surgical intervention primarily (73.9%) through an anterior approach. Neurological function improved postoperatively in all patients but one. Dural and arachnoid mater tears were managed by direct suture or covering with a substitute, and only one patient sustained cerebrospinal fluid (CSF) leakage after surgery. CONCLUSION: IDH mostly involves the lower cervical spine. More than half of the patients had spontaneous CIDH, and some had a relevant cervical trauma history. BSS was the main presentation. It is difficult to diagnose CIDH depending on clinical presentations and radiographic findings. Surgery was an effective treatment for CIDH and can provide a definitive diagnosis. With meticulous management of dural and arachnoid tears, the postoperative incidence of CSF leakage was found to be low.

Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response.

The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

Iatrogenic Vertebral Artery Injury During Anterior Cervical Spine Surgery: A Systematic Review.

BACKGROUND: Iatrogenic vertebral artery injury (VAI) during anterior cervical surgery is rare but potentially catastrophic. METHODS: Causes, presentation, diagnosis, management, prognosis, and prevention of VAI were reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English language studies and case reports published from 1980 to 2017 were retrieved. Data on diagnosis, surgical procedures and approach, site and cause of VAI, management, outcomes, and vertebral artery (VA) status were extracted. RESULTS: In 25 articles including 54 patients, VAI was diagnosed during or after surgery commonly indicated for cervical degenerative diseases (64%), tumors (14%), and trauma (9%). The incidence of VAI for each side was similar regardless of approach. Common presentations were unexpected copious surgical bleeding, delayed hemorrhage of pseudoaneurysm with neck swelling, dyspnea, hypotension, and cervical bruits caused by arteriovenous fistula. Causes included drilling (61%), instrumentation (16%), and soft tissue retraction (8%). Direct exposure or angiography confirmed VAI. Ten patients had VA anomalies; collateral status was verified in 9 before definitive treatment. Tamponade was adopted for urgent hemostasis in most cases but with a high incidence of pseudoaneurysm (48%). Unknown VA status increased occlusion risk and neurologic sequelae (41%). VA repair and stent placement had excellent outcomes. CONCLUSIONS: Extensive lateral decompression, loss of landmarks, and anatomic variations or pathologic status of VA increased VAI risk. Evaluation of collateral vessels before definitive treatment helped determine appropriate management and avoid neurologic sequelae. Tamponade was not recommended as definitive treatment. Meticulous preoperative evaluation, cautious intraoperative manipulation, and real-time radiographic guidance reduced VAI risk.

Wavy multistratified amacrine cells in the monkey retina contain immunoreactive secretoneurin.

The goals of this study were to describe the morphology, neurotransmitter content and synaptic connections of neurons in primate retinas that contain the neuropeptide secretoneurin. Amacrine cells were labeled with antibodies to secretoneurin in macaque and baboon retinas. Their processes formed three distinct plexuses in the inner plexiform layer: one in the outermost stratum, one in the center and one in the innermost stratum. In light microscopic double immunolabeling experiments, GABA was colocalized with secretoneurin in these cells, but glycine transporter 1 and Substance P were not. ON bipolar cell axon terminals labeled with antibody to the cholecystokinin precursor, G6-gly, have ON responses to stimulation of short wavelength sensitive (S) cones. Axons of these bipolar cells made contacts with amacrine cell dendrites containing secretoneurin. Secretoneurin-IR amacrine cells also made contacts with retinal ganglion cell dendrites labeled with antibody to the photopigment melanopsin, which have OFF responses to stimulation of S cones. Using electron microscopic immunolabeling, 436 synapses from macaque retina were analyzed. Axons from bipolar cells were identified by their characteristic synaptic ribbons; their synaptic densities were asymmetric like those of excitatory synapses in the brain. Amacrine cells made and received conventional synapses with symmetric synaptic densities, like those of inhibitory synapses in the brain. Ganglion cell dendrites were identified by their absence of presynaptic specializations; they received inputs from both amacrine cells and bipolar cells. The majority of inputs to the secretoneurin-IR amacrine cells were from other amacrine cells, but they also received 21% of their input from bipolar cells. They directed most of their output, 54%, to amacrine cells, but there were many synapses onto bipolar cell axons and ganglion cell dendrites, as well. The synaptic connections were very similar in the three plexuses with one notable exception; output synapses to bipolar cells were significantly less common in the innermost one, where the S-ON bipolar cells terminate. Taken together, these findings suggest that the secretoneurin-IR amacrine cells in primates receive excitatory input from S-ON bipolar cells and, in turn, inhibit intrinsically photosensitive retinal ganglion cells.

Role of magnetic resonance imaging versus ultrasound for detection of plantar plate tear.

BACKGROUND: Plantar plate tears could be the reason of forefoot pain, affecting foot function. Magnetic resonance imaging (MRI) and ultrasound (US) were commonly used for the diagnosis of plantar plate tears. The decision of whether to use MRI or US carried some controversy. Our study aimed to find out the diagnostic accuracy of MRI versus US for plantar plate tears. METHODS: The database of the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and relative orthopedic meetings until May 2016 were searched. Studies involved in the diagnostic detection of MRI or ultrasound for plantar plate tears with surgical criteria as the reference test were included. Data was analyzed by meta-analysis. We compared sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and summary receiver operating characteristic (sROC) plot of both MRI and US. RESULTS: Seven studies involving 246 plantar plate tears were included. The MRI showed more diagnostic accuracy than US for the detection of plantar plate tears. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of MRI were 95%, 54%, 2.08, and 0.08, respectively, while the same values for US were 93%, 33%, 1.20, and 0.35, respectively. And the sROC showed more superior diagnostic accuracy than the US. CONCLUSION: The current result suggests that MRI has better accuracy than US for detection of plantar plate tears.

Wide-field diffuse amacrine cells in the monkey retina contain immunoreactive Cocaine- and Amphetamine-Regulated Transcript (CART).

The goals of this study were to localize the neuropeptide Cocaine- and Amphetamine-Regulated Transcript (CART) in primate retinas and to describe the morphology, neurotransmitter content and synaptic connections of the neurons that contain it. Using in situ hybridization, light and electron microscopic immunolabeling, CART was localized to GABAergic amacrine cells in baboon retinas. The CART-positive cells had thin, varicose dendrites that gradually descended through the inner plexiform layer and ramified extensively in the innermost stratum. They resembled two types of wide-field diffuse amacrine cells that had been described previously in macaque retinas using the Golgi method and also A17, serotonin-accumulating and waterfall cells of other mammals. The CART-positive cells received synapses from rod bipolar cell axons and made synapses onto the axons in a reciprocal configuration. The CART-positive cells also received synapses from other amacrine cells. Some of these were located on their primary dendrites, and the presynaptic cells there included dopaminergic amacrine cells. Although some CART-positive somas were localized in the ganglion cell layer, they did not contain the ganglion cell marker RNA binding protein with multiple splicing (RBPMS). Based on these results and electrophysiological studies in other mammals, the CART-positive amacrine cells would be expected to play a major role in the primary rod pathway of primates, providing feedback inhibition to rod bipolar cells.

Nicotinic and muscarinic acetylcholine receptors shape ganglion cell response properties.

The purpose of this study was to evaluate the expression patterns of nicotinic and muscarinic ACh receptors (nAChRs and mAChRs, respectively) in relation to one another and to understand their effects on rabbit retinal ganglion cell response properties. Double-label immunohistochemistry revealed labeled inner-retinal cell bodies and complex patterns of nAChR and mAChR expression in the inner plexiform layer. Specifically, the expression patterns of m1, m4, and m5 muscarinic receptors overlapped with those of non-α7 and α7 nicotinic receptors in presumptive amacrine and ganglion cells. There was no apparent overlap in the expression patterns of m2 muscarinic receptors with α7 nicotinic receptors or of m3 with non-α7 nicotinic receptors. Patch-clamp recordings demonstrated cell type-specific effects of nicotinic and muscarinic receptor blockade. Muscarinic receptor blockade enhanced the center responses of brisk-sustained/G4 On and G4 Off ganglion cells, whereas nicotinic receptor blockade suppressed the center responses of G4 On-cells near the visual streak but enhanced the center responses of nonstreak G4 On-cells. Blockade of muscarinic or nicotinic receptors suppressed the center responses of brisk-sustained Off-cells and the center light responses of subsets of brisk-transient/G11 On- and Off-cells. Only nicotinic blockade affected the center responses of G10 On-cells and G5 Off-cells. These data indicate that physiologically and morphologically identified ganglion cell types have specific patterns of AChR expression. The cholinergic receptor signatures of these cells may have implications for understanding visual defects in disease states that result from decreased ACh availability.