Comparison of first, second, and third versus the average of six probe-corneal touches for intraocular measurement of two rebound tonometers in healthy horses.

The aim of this study was to evaluate the intraocular pressure (IOP) measurements obtained from first, second, and third probe-cornea touch (PCT) and compare them with the average of six PCTs using two rebound tonometers in horses. This study enrolled a total of thirty-eight stallions, comprising of 24 Arabian horses and 14 cross-breeds (with an average age of 8 ± 3 years). The IOP measurements of first, second, and third, as well as the average of six PCTs were obtained using either Tonovet (TV) or Tonovet Plus (TV+) rebound tonometers. The mean differences (95% limits of agreement) between the average of six PCTs and the first, second, and third PCTs were 0.1 (-4.8 to 5), 0.2 (-4.8 to 4.5), and 0.2 (-3.6 to 4.0) mmHg with TV, respectively. With TV+, the differences were 0.3 (-6.6 to 7.2), 1.1 (-8.6 to 10.8), and -0.2 (-3.6 to 4.0) mmHg, respectively. Compared to the average of six PCTs, only 89.5%, 92.1%, and 97.4% of IOP measurements obtained from TV and 78.9%, 73.3%, and 65.8% of IOP measurements obtained from TV+ were within 4 mmHg of the average of six PCTs for first, second, and third PCTs, respectively. In conclusion, the measurement of IOP in the first PCT achieved best agreement with the IOP measurement of six average PCTs. Therefore, the first PCT could be considered as an alternative option for measuring IOP in horses when obtaining an average of six PCTs is not feasible.

Deletion of osteopontin or bone sialoprotein induces opposite bone responses to mechanical stimulation in mice.

Osteopontin (OPN) and Bone Sialoprotein (BSP) are co-expressed in bone and display overlapping and complementary physiological properties. Both genes show a rapid expression response to mechanical stimulation. We used mice with single and double deletions (DKO) of BSP and OPN to assess the specificity of their roles in skeletal adaptation to loading. Two-month-old Wild-Type (WT), BSP knockout (BSP-/-), OPN-/- and DKO male mice were submitted to two mechanical stimulation regimen (n = 10 mice/group) respectively impacting trabecular bone (Hypergravity, HG) and cortical bone (Whole Body Vibration, WBV). HG increased trabecular bone volume (BV/TV) in WT femur through reduced resorption, and in BSP-/- mice femur and vertebra through increased bone formation. In contrast, HG increased the turnover of OPN-/- bone, resulting in reduced femur and vertebra BV/TV. HG did not affect DKO bones. Similarly, WBV increased cortical thickness in BSP-/- mice and decreased it in OPN-/-, without affecting structurally WT and DKO bone. Vibrated BSP-/- mice displayed increased endocortical bone formation with a drop in Sclerostin expression, and reduced periosteal osteoclasts with lower Rankl and Cathepsin K expression. In contrast, vibrated OPN-/- endocortical bone displayed decreased formation and increased osteoclast coverage. Therefore, under two regimen (HG and WBV) targeting distinct bone compartments, absence of OPN resulted in bone loss while lack of BSP induced bone gain, reflecting divergent structural adaptations. Strikingly, absence of both proteins led to a relative insensitivity to either mechanical challenge. Interplay between OPN and BSP thus appears as a key element of skeletal response to mechanical stimulation.

The efficacy of the ON-Q elastomeric pump system in post-thoracotomy acute pain control.

OBJECTIVES: We aimed to evaluate the efficacy of continuous local anesthetic infusion to the incision site with the On-Q elastomeric pump system in postoperative acute pain control after thoracotomy. METHODS: A retrospective comparative analysis of of sixty patients who underwent thoracotomy for lung cancer by the same surgical team was performed between January 2016 and December 2017. The patients were divided into two groups according to postoperative pain management, those who were traditionally received tramadolol (15 mg/h) by intravenous continuous infusion (Group IVT, n = 30) and those who were administered continuous local anesthetic (0.5% bupivacaine, 4 ml/h) infusion to the incision site through an elastomeric pump in addition to the traditional treatment (Group LA, n = 30). The primary outcomes were postoperative acute pain scores on the numeric rating scale and postoperative rescue opioid consumption for 72 hours following surgery reported as pethidine equivalents. The secondary outcomes were frequency of analgesia related adverse events/complications, ICU and hospital stay, drug and total hospital cost. RESULTS: The mean pain scores at 2, 12, 24, 48 and 72th hours at rest and during coughing were found to be significantly lower in group LA (p < 0.05). Rescue opioid consumption on postoperative 0, 1, 2 and 3rd days and in total was found to be significantly lower in Group LA (p < 0.05). In Group LA, postoperative length of hospital stay was significantly shorter (5.8 ± 2.1 days vs. 8.0 ± 3.1 days; p = 0.034), drug costs (95.24 vs. 160.08 Euro; p = 0.023) and total hospital costs were lower (434.26 vs. 685.75 Euro; p = 0.014) than Group IVT. CONCLUSIONS: We believe that continuous local anesthetic infusion to the incision site in addition to systemic analgesic treatment for multimodal acute pain management after thoracotomy is an effective and safe method.

Surgical management of anorectal foreign bodies.

PURPOSE: Anorectal foreign bodies (AFBs) inserted into anus constitute one of the most important problems needing surgical emergency due to its complications. We describe our experience in the diagnosis and treatment of AFBs retained in the rectosigmoid colon. MATERIALS AND METHODS: Between the years 2006 and 2015, a total of 11 patients diagnosed with AFBs were admitted to an emergency room and general surgery clinics. They were diagnosed and treated in four different hospitals in four different cities in Turkey. Information on the AFBs, clinical presentation, treatment strategies, and outcomes were documented. We retrospectively reviewed the medical records of these unusual patients. RESULTS: Eleven patients were involved in this study. All patients were male with their mean age was 49.81 (range, 23-71) years. The time of the presentation to the removal of the foreign bodies ranged between 2 h and 96 h with a mean of 19.72 h. Ten patients inserted AFBs in the anus with the purpose of eroticism but one patient's reason to relieve constipation. The objects were one body spray can, two bottles, three dildos, two sticks, one water hose, one corncob, and one pointed squash. Three objects were removed transanally after anal dilatation under general anesthesia. Eight of the patients required laparotomy (milking, primary suture, and colostomy). Five of the patients had perforation of the rectosigmoid colon. Abdominal abscess complicated extraction in one patient after the postoperative period. The hospitalization time of the patients was 6.18 (1-16) days. None of the patients died. CONCLUSIONS: A careful assessment is a key point for the correct diagnosis and treatment of AFBs. Clinical conditions of patients and type of AFBs are important in the choice of treatment strategy. If the AFBs are large, proximally migrated or the patients with an AFB have acute abdomen due to perforation, pelvic abscess, obstruction, or bleeding, surgery is needed as soon as possible. There are different types of surgical approaches such as less invasive transanal extraction under anesthesia and more invasive abdominal routes such as laparotomy or laparoscopy. The stoma can be done if there is colonic perforation. In the management of AFBs, the priority must be less invasive methods as possible.

A hybrid reference-guided de novo assembly approach for generating Cyclospora mitochondrion genomes.

Cyclospora cayetanensis is a coccidian parasite associated with large and complex foodborne outbreaks worldwide. Linking samples from cyclosporiasis patients during foodborne outbreaks with suspected contaminated food sources, using conventional epidemiological methods, has been a persistent challenge. To address this issue, development of new methods based on potential genomically-derived markers for strain-level identification has been a priority for the food safety research community. The absence of reference genomes to identify nucleotide and structural variants with a high degree of confidence has limited the application of using sequencing data for source tracking during outbreak investigations. In this work, we determined the quality of a high resolution, curated, public mitochondrial genome assembly to be used as a reference genome by applying bioinformatic analyses. Using this reference genome, three new mitochondrial genome assemblies were built starting with metagenomic reads generated by sequencing DNA extracted from oocysts present in stool samples from cyclosporiasis patients. Nucleotide variants were identified in the new and other publicly available genomes in comparison with the mitochondrial reference genome. A consolidated workflow, presented here, to generate new mitochondrion genomes using our reference-guided de novo assembly approach could be useful in facilitating the generation of other mitochondrion sequences, and in their application for subtyping C. cayetanensis strains during foodborne outbreak investigations.

Postmarketing Safety Study Tool: A Web Based, Dynamic, and Interoperable System for Postmarketing Drug Surveillance Studies.

Postmarketing drug surveillance is a crucial aspect of the clinical research activities in pharmacovigilance and pharmacoepidemiology. Successful utilization of available Electronic Health Record (EHR) data can complement and strengthen postmarketing safety studies. In terms of the secondary use of EHRs, access and analysis of patient data across different domains are a critical factor; we address this data interoperability problem between EHR systems and clinical research systems in this paper. We demonstrate that this problem can be solved in an upper level with the use of common data elements in a standardized fashion so that clinical researchers can work with different EHR systems independently of the underlying information model. Postmarketing Safety Study Tool lets the clinical researchers extract data from different EHR systems by designing data collection set schemas through common data elements. The tool interacts with a semantic metadata registry through IHE data element exchange profile. Postmarketing Safety Study Tool and its supporting components have been implemented and deployed on the central data warehouse of the Lombardy region, Italy, which contains anonymized records of about 16 million patients with over 10-year longitudinal data on average. Clinical researchers in Roche validate the tool with real life use cases.

Preventing intraperitoneal adhesions with ethyl pyruvate and hyaluronic acid/carboxymethylcellulose: a comparative study in an experimental model.

OBJECTIVE: To compare the effectiveness of ethyl pyruvate (EP) with that of hyaluronic acid+carboxymethyl cellulose (Seprafilm) for the prevention of intraperitoneal adhesions. Seprafilm has been shown to be effective in many experimental and clinical studies. STUDY DESIGN: Thirty rats were divided into three groups at random, and uterine horn abrasion was performed by laparotomy. One group received no treatment (control group), one group received a single intraperitoneal dose of EP 50mg/kg (EP group), and a 2×1-cm patch of Seprafilm was applied in the third group (Seprafilm group). All rats were killed 14 days after surgery. Macroscopic and histopathological evaluation were performed by a surgeon and a pathologist who were blinded to group allocation. Histopathologically, inflammation, fibroblastic activity, foreign body reaction, collagen proliferation, vascular proliferation, Masson-Trichrome score, matrix metalloproteinase-2 score and vascular endothelial growth factor score were studied. RESULTS: Median macroscopic intraperitoneal adhesion scores for the control, EP and Seprafilm groups were 2.8, 1.2 and 1.1, respectively. Multiple comparisons between groups showed a significant difference (p<0.05). In binary comparisons, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.05). No significant difference was found between the adhesion scores for the EP group and the Seprafilm group (p>0.05). After histopathological evaluation, significant differences in all parameters were found between the groups (p<0.05). In the paired comparison, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.0167), but no significant difference was found between the EP group and the Seprafilm group (p>0.0167). CONCLUSIONS: In comparison with the untreated control group, EP and Seprafilm were found to reduce the formation of intraperitoneal adhesions. No significant difference was found between EP and Seprafilm.

The effect of silymarin on mesenteric ischemia-reperfusion injury.

OBJECTIVE: To examine the effect of silymarin (SM), a mixture of flavonoids and polyphenols extracted from Silybum marianum, on mesenteric ischemia-reperfusion (I-R) injury in a rat model. MATERIALS AND METHODS: Fifty rats were randomly divided into 5 groups (n = 10). Group 1 was sham operated, while groups 2-5 were subjected to mesenteric I-R lasting 1 h. Group 2 received isotonic sodium chloride, group 3 received SM (100 mg/kg/day) for 7 days before I-R, group 4 received SM for 7 days after I-R, and group 5 received SM for 7 days both before and after I-R. The rats were sacrificed by exsanguination in groups 1-3 at the 24th hour and groups 4 and 5 were sacrificed on the 7th day of reperfusion. Blood and intestinal specimens were taken for biochemical and pathological evaluations. RESULTS: Serum superoxide dismutase (SOD) and heat shock protein 70 levels were significantly higher in group 2 (5.24 ± 1.76 U/l and 261.4 ± 16.8 ng/ml) compared to the sham group (2.08 ± 1.76 U/l and 189.9 ± 28.7 ng/ml) (p < 0.001 and p < 0.0001, respectively). However, SOD activity and the extent and severity of the histopathological lesions were significantly less in groups 3 [3.11 ± 1.18 U/l, 1.0 (range 0.0-2.0)], 4 [2.15 ± 0.87 U/l, 1.0 (range 1.0-3.0)], and 5 [1.80 ± 0.61 U/l, 0.5 (range 0.0-2.0)], treated with SM, than in group 2 [5.24 ± 1.76 U/l, 2.0 (range 2.0-3.0)] (p = 0.002, p < 0.001, and p = 0.0001; p < 0.001, p = 0.007, and p = 0.0001, respectively). Also, TNF-α levels were lower in the SM-supplemented groups compared to group 2. Serum thiobarbituric acid-reactive substance concentrations were low in the pre-/posttreatment groups treated with SM compared to group 2. No statistical difference was observed for protein carbonyls between the groups. CONCLUSION: Our findings suggest that SM therapy may attenuate the oxidative and intestinal damage induced by I-R injuries.

Benign posterior mediastinal neurogenic tumors: results of a comparative study into video-assisted thoracic surgery and thoracotomy (13 years' experience).

OBJECTIVE: Mediastinal neurogenic tumors originate from the nerve tissues of the thorax and are generally located in the posterior mediastinum. The present study was performed to compare the results of thoracotomy with those of video-assisted thoracic surgery (VATS) for the surgical treatment of posterior mediastinal neurogenic tumors. METHODS: Twenty patients who underwent surgical resection for posterior neurogenic tumors between January 1996 and January 2009 were examined retrospectively. Thirteen (65%) patients were treated by thoracotomy (group T) and VATS was used in seven (35%) patients (group V). RESULTS: The duration of surgery was shorter in group V (83.5 ± 19 min) than in group T (124.6 ± 16.6 min; P < 0.0001). Chest drains were withdrawn earlier in group V (after 1 day) than in group T (1.6 ± 0.5 days; P = 0.005). The hospital stay was shorter for group V (1 day) compared with group T (3 ± 0.9 days; P < 0.0001) and group V required fewer analgesics than group T (P < 0.0001). CONCLUSION: VATS is the preferred treatment for posterior neurogenic tumors that show no preoperative signs of malignancy and do not involve the medulla spinalis.

Plasma basic fibroblast growth factor and bone marrow fibrosis in clonal myeloproliferative disorders.

Basic fibroblast growth factor (bFGF) is an important growth factor involved in clonal hematopoietic expansion, neoangiogenesis, and bone marrow fibrosis, all of which are important pathobiologic features of clonal chronic myeloproliferative disorders (CMPD) and myelodysplastic syndromes (MDS). The aim of this study was to assess circulating bFGF concentrations in patients with CMPD and MDS with respect to the presence of bone marrow fibrosis in histopathologic examination. The study group comprised 18 patients with CMPD (six female, 12 male; median age 50 years), seven patients with MDS (one female, six male; median age 66 years) and 10 healthy adults as controls (four female, six male; median age 29 years). CMPD group included six chronic myelogenous leukemia (CML), seven essential thrombocythemia (ET), three polycythemia vera (PV), two agnogenic myeloid metaplasia (AMM). All seven MDS patients were the FAB subtype of refractory anemia (RA). Bone marrow biopsy sections stained with hematoxylin and eosin (H & E) and for reticulin were examined for the presence of fibrosis. The median plasma bFGF level was 18.2 pg/ml (interquartile range, IQR: 15.2-26.7) in patients with CMPD, 18.0 pg/ml (IQR: 15.8-26.4) in patients with MDS, 13.6 pg/ml (IQR: 9.9-20.0) in the control group. The bFGF levels were significantly higher in patients with CMPD in comparison with the healthy control group (P = 0.031). Circulating bFGF tended to be significantly lower in relation to the development of marrow fibrosis (P = 0.028). The complicated interactions of bFGF and fibrosis in the context of CMPD may be either 'cause' or 'effect'. The bFGF might represent an important link between angiogenesis, fibrosis, and clonal neoplastic hematopoiesis during the development of CMPD.

Clathrin-independent endocytosis of GABA(A) receptors in HEK 293 cells.

The endocytosis of GABA(A) receptors was investigated in HEK 293 cells expressing receptor alpha1beta2- and alpha1beta2gamma2-subunit combinations. For assessment of internalized receptors by radioimmunoassay or immunofluorescence, a triple c-myc epitope was introduced into the amino terminus of the beta2 subunit. An assay based on biotin inaccessibility was used for alpha1 subunits. GABA(A) alpha1beta2- and alpha1beta2gamma2-subunit receptors were internalized with a t(1/2) of 5.5 min at 37 degrees C. With both subunit combinations, phorbol 12-myristate 3-acetate enhanced internalization by nearly 100%. Treatment of the cells with hypertonic sucrose prevented both the basal and phorbol ester-induced endocytosis of GABA(A) receptors. GF 109203X, an inhibitor of protein kinase C, blocked the stimulation by phorbol ester but had no detectable effect on basal receptor endocytosis. Coexpression with a dominant-negative mutant of dynamin (K44A) led to a 100% enhancement of GABA(A) receptor internalization, while the endocytosis of beta(2)-adrenergic receptors was completely prevented. The results indicate that the endocytosis of GABA(A) alpha1beta2-subunit receptors in HEK cells is constitutive, positively modulated by activation of protein kinase C, and occurs by a mechanism that requires neither the participation of a GABA(A) receptor gamma2 subunit nor a clathrin-mediated pathway.

The SEL-12 presenilin mediates induction of the Caenorhabditis elegans uterine pi cell fate.

During Caenorhabditis elegans hermaphrodite development, the anchor cell induces the vulva and the uterine pi cells whose daughters connect to the vulva, thereby organizing the uterine-vulval connection. Both the initial selection of a single anchor cell during the anchor cell vs. ventral uterine precursor cell decision and the subsequent induction of the pi cell fate by the anchor cell are mediated by the lin-12 gene. Members of the presenilin gene family can cause early onset Alzheimer's disease when mutated and are also required for LIN-12/Notch signaling during development. We have shown that, in C. elegans, mutation of the sel-12-encoded presenilin results in pi cell induction defects. By contrast, other lin-12-mediated cell fate decisions occur normally in sel-12 mutants due to the redundant function of a second C. elegans presenilin called HOP-1. We found that the sel-12 egg-laying defect was partially rescued by expression of the sel-12 gene in the pi cells. sel-12-mediated pi cell fate specification provides a useful system for the analysis of presenilin function at single cell resolution.