Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis.

Osteoarthritis (OA) is a debilitating disease in dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA; however, many dogs do not obtain adequate pain relief with an NSAID alone. This pilot study evaluated the systemic anti-inflammatory and mobility enhancing effects of an eggshell membrane-based nutritional supplement in dogs with OA-associated pain and mobility impairment. Twenty-seven dogs with OA-associated pain were enrolled into a randomized, double-masked, placebo-controlled, proof of principle pilot study and received either placebo or an eggshell membrane-based nutritional supplement over a 12-week period. Inflammatory biomarkers (IL-2, IL-6, IL-8, tumor necrosis factor-α, C-reactive protein, S100A12, and N-methylhistamine) were measured at Day 0 and Day 84. Owner questionnaires (CBPI and LOAD) were completed at Day 0, Day 42, and Day 84. Differences between groups over time were calculated. Twenty-two dogs completed the pilot study. Inflammatory biomarker IL-2 decreased in the supplement group, compared to the placebo group. Although small, the difference was statistically significant at an alpha of 0.1 (P=0.069). LOAD scores were numerically lower in the supplement group, but not significantly different from the placebo group at Day 0. Day 84 LOAD scores were significantly lower in the supplement group compared to the placebo group (P=0.034). CBPI results did not show the same pattern. The changes in biomarkers and LOAD scores were small, and do not provide definitive evidence of positive effects. However, these pilot results provide a rationale for performing a larger placebo-controlled study of the potential effects of the eggshell membrane-based nutritional supplement.

Initial evaluation of PetPace activity monitor.

Mobility is considered a vital component of health and quality of life in humans and companion animals. Wearable devices for pets that can monitor activity and other aspects of health are increasingly being marketed to veterinarians and owners, with claims around their ability to monitor aspects of health. However, there is little scientific evidence to support the validity of these claims. To address this, the objective of this study was to assess the correlation of the activity measurement from the PetPace device compared to activity output from Actigraph and the validated Actical device. Ten client-owned, healthy dogs were used for the study. The three devices were mounted simultaneously on a dedicated collar and activity was recorded during a period of 7 days. There were moderate correlations between the Actical and the PetPace (r2=0.59, P=<0.001). There was high correlation between the PetPace and the Actigraph (r2=0.85, P=<0.001) and between the Actical and the Actigraph (r2=0.72, P=<0.001). If the Actical activity counts were limited under 50,000 per hour, there was strong correlation between the Actical and the PetPace (r2=0.71, P=<0.001) and between the Actical and the Actigraph (r2=0.86, P=<0.001). PetPace has a moderate correlation with the most validated activity monitor that has been used in veterinary medicine. Its real-time data acquisition, user friendly interface for owners and cost make this device an attractive tool for monitoring activity in dogs. Further studies maybe needed to evaluate its performance, validity and clinical utility in the field.

The presence of multiple NS5A RASs is associated with the outcome of sofosbuvir and ledipasvir therapy in NS5A inhibitor-naïve patients with chronic HCV genotype 1b infection in a real-world cohort.

It is unclear whether multiple nonstructural (NS) 5A resistance-associated substitutions (RASs) correlate with the outcome of sofosbuvir (SOF) and ledipasvir (LDV) therapy. We investigated the effects of multiple NS5A RASs in NS5A inhibitor-naïve patients with chronic hepatitis C virus genotype 1b infection treated with SOF/LDV. In 313 patients treated with SOF/LDV, we assessed the effects of multiple NS5A RASs on the sustained virological response (SVR). RASs at L28, R30, L31, Q54, P58, Q62, A92, and Y93 in the NS5A region were examined by direct sequencing. The prevalence of RASs was as follows: 2.6% at L28, 8.7% at R30, 6.1% at L31, 48.7% at Q54, 9.9% at P58, 9.9% at Q62, 5.1% at A92, 13.8% at Y93, and 19.2% at L31 or Y93. A total of 133 patients had no RASs. SVR was achieved in 98.7% of the patients. SVR rates significantly differed between patients with and without the L31 or Y93 RAS (93.0% [53/57] vs 100% [250/250], P = .0011). In addition, among patients with the L31 or Y93 RAS, 29.8%, 45.6% and 24.6% had one, two and three or more NS5A RASs, respectively. The SVR rate was significantly lower in patients with the L31 or Y93 RAS with more than three NS5A RASs compared to those with fewer than three NS5A RASs (71.4% [10/14] vs 100% [43/43], P = .0025). Although the prevalence of multiple NS5A RASs at baseline was low in NS5A inhibitor-naïve patients, the presence of multiple NS5A RASs was associated with the effectiveness of SOF/LDV therapy.

Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct-acting antiviral therapy.

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon-free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co-infected patients and 765 patients with resolved HBV infection during and after treatment with direct-acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti-HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)-positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti-HBs titres at baseline with those at post-DAA therapy in 123 patients without HBsAg. There was no significant difference in anti-HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg-negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV-reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.

Renin is activated in monochorionic diamniotic twins with birthweight discordance who do not have twin-to-twin transfusion syndrome.

OBJECTIVE: To assess renin, aldosterone, human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) levels in cord blood from monochorionic diamniotic (MD) twins with a birthweight (BW) discordance that do not satisfy the criteria of twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: Cord blood samples were obtained from 28 MD twins without TTTS. They were divided into two groups on the basis of BW discordance as follows: large (>7.5%) and small (7.5%). Cord blood renin, aldosterone, hANP and BNP levels were measured. RESULT: Renin levels in MD twins with a large BW discordance were significantly higher than those in MD twins with a small BW discordance, with no significant differences in aldosterone, hANP and BNP levels. A significant correlation was found between renin levels and BW discordance. CONCLUSION: Renin is activated in MD twins with a BW discordance of >7.5%, even in non-TTTS.

Antenatal magnesium sulfate and the postnatal response of the ductus arteriosus to indomethacin in extremely preterm neonates.

OBJECTIVE: The aim of this study is to evaluate the influence of antenatal magnesium sulfate (MgSO(4)) treatment on the clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis and on that of symptomatic patent ductus arteriosus (sPDA) to indomethacin treatment in premature neonates. STUDY DESIGN: This is a retrospective study of 160 consecutively admitted neonates with a gestational age of <28 weeks (41 MgSO(4) exposed and 119 controls) who received indomethacin prophylaxis. RESULT: Incidence of early closure of the ductus arteriosus was lower in the MgSO(4)-exposed neonates than in the control group (59 vs 84%, respectively; P=0.002), whereas incidence of an sPDA was higher (46 vs 24%, respectively; P=0.006). Response to indomethacin treatment was similar between the two groups. Logistic regression analysis indicated increased risk of failure of early ductus arteriosus closure following antenatal MgSO(4) treatment (odds ratio, 4.03; P=0.002). CONCLUSION: In extremely preterm neonates, antenatal MgSO(4) treatment reduces clinical responsiveness of the ductus arteriosus to indomethacin prophylaxis but not that of sPDA to indomethacin treatment.

Analysis of autonomic nerve preservation and pouch reconstruction influencing fragmentation of defecation after sphincter-preserving surgery for rectal cancer.

Our questionnaire survey on defecation disorders after rectal cancer surgery revealed that 66.7% of postoperative patients were most annoyed with fragmentation of defecation. Therefore, we performed a change-over-time analysis on the relationship of fragmentation and factors including location of rectal cancer, surgical technique, anastomosis method, pouch reconstruction, extent of lymph node dissection, and degree of pelvic and colonic nerve preservation surrounding the superior mesenteric artery. The fragmentation decreased over time at the postoperative time points of 6 months, 2 and 5 years. A statistical analysis of factors influencing fragmentation revealed that location of cancer, reconstruction technique, anastomosis method and degree of pelvic nerve preservation were significant factors for the entire patient population and that colonic nerve preservation was a significant factor 5 years after surgery. Analysis of patients with lower rectal cancer only showed that in addition to surgical technique and anastomosis method, pouch reconstruction was effective and autonomic nerve preservation was effective 5 years after surgery. As a result, when the anastomotic site was closer to the anus, the frequency of fragmentation increased; we concluded that pouch reconstruction was an effective surgical technique and colonic nerve preservation was effective in the longer term.

Add-on combination therapy with adefovir dipivoxil induces renal impairment in patients with lamivudine-refractory hepatitis B virus.

Combination therapy with adefovir dipivoxil (ADV) and lamivudine (LAM) is recommended for patients infected with LAM-refractory hepatitis B virus (HBV). However, the effects of such therapy on renal function and serum phosphorus levels have not been fully evaluated. Combination therapy with ADV and LAM was given to 37 patients infected with LAM-refractory HBV, including 17 with hepatic cirrhosis. Serum HBV DNA levels decreased to below 2.6 log(10) copies/mL in 23 (62%) of 37 patients at 12 months, 25 (78%) of 32 patients at 24 months, and 16 (84%) of 19 patients at 36 months. Except for one cirrhotic patient, serum alanine aminotransferase levels were below 50 IU/L in all patients during combination therapy. Serum creatinine levels increased in 14 (38%) of 37 patients, and serum phosphate levels decreased to below 2.5 mg/mL in 6 (16%) of 37 patients during combination therapy. Patients who received combination therapy for 36 months or longer had a significantly incidence of elevated serum creatinine levels. Fanconi syndrome occurred in a 57-year-old woman with cirrhosis after ADV was added to LAM. Combination therapy with ADV and LAM can maintain biochemical remission in patients with LAM-refractory HBV. However, the dosing interval of ADV should be adjusted according to renal function and serum phosphate levels in patients receiving long-term treatment.

A study of the incidence of implantation cyst at anastomotic sites after low anterior resection of the rectum with the double stapling technique.

BACKGROUND: The incidence of implantation cyst occurring at sites of anastomosis after low anterior resection of the rectum were studied in two different periods depending on the type of surgical devices used to close the rectal stump. SUBJECTS: The study included 361 patients undergoing the surgery during the first 8-year period between 1996 and 2003 and 87 patients undergoing the surgery during the second 3-year period between 2004 and 2006. RESULTS: Implantation cysts were found in nine (2.5%) of the patients undergoing the surgery during the first period and one of them also had local recurrence. Implantation cysts occurred 9 to 31 months postoperatively (mean, 17.1 +/- 6.9 months). Clinical symptoms were noted in one patient and treatment of the cysts, including local recurrence, was given to two patients. Anastomosis of the distal rectum was performed with the Roticulator or the Access 55 in all patients. Although implantation cysts were found in any patient undergoing surgery during the second period, no statistically significant difference was recognized (p = 0.217). Anastomosis of the distal rectum was performed with the TX30 in all patients. CONCLUSION: The pathogenesis of implantation cysts may be explained by the production of mucus when the mucosal epithelium of the colon is caught under the submucosa, forming a cyst after closure of the rectal stump, and the difference in the incidence rates of implantation cyst was presumably due to the characteristics of the device used and progress of the operative procedure.

Usefulness of Gram staining of tracheal aspirates in initial therapy for ventilator-associated pneumonia in extremely preterm neonates.

OBJECTIVE: To determine the effectiveness of Gram staining of tracheal aspirates for predicting causative microorganisms and guiding appropriate initial antibiotic therapy to treat ventilator-associated pneumonia (VAP) in extremely preterm neonates. STUDY DESIGN: A prospective study was conducted on all episodes of presumed VAP in neonates with a gestational age below 28 weeks at birth. RESULT: Gram-positive cocci and Gram-negative bacilli were the causative microorganisms in 11 and 38 confirmed episodes of VAP, respectively. The sensitivity and specificity of Gram staining were 82 and 100% for Gram-positive VAP and 100 and 82% for Gram-negative VAP, respectively. The initial antibiotic therapies based on Gram-stain findings were appropriate for 96% (47/49) of patients with VAP. CONCLUSION: Gram staining of tracheal aspirates is useful in predicting classes of causative microorganisms and for guiding appropriate initial antibiotic therapy for VAP in extremely preterm neonates.

Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling.

The receptor tyrosine kinase Ror2 regulates cell migration by acting as a receptor or co-receptor for Wnt5a. Although Wnt5a has been implicated in the invasiveness of several types of tumors, the role of Ror2 in tumor invasion remains elusive. Here we show that osteosarcoma cell lines SaOS-2 and U2OS show invasive properties in vitro by activating Wnt5a/Ror2 signaling in a cell-autonomous manner. The suppressed expression of either Wnt5a or Ror2 in osteosarcoma cells inhibits cell invasiveness accompanying decreased invadopodia formation. Gene-expression profiling identified matrix metalloproteinase 13 (MMP-13) as one of the genes whose expression is downregulated in SaOS-2 cells following suppression of Ror2 expression. Reduced expression or activity of MMP-13 suppresses invasiveness of SaOS-2 cells. Moreover, expression of MMP-13 and cell invasiveness by Wnt5a/Ror2 signaling can be abrogated by an inhibitor of the Src-family protein tyrosine kinases (SFKs), suggesting the role of the SFKs in MMP-13 expression through Wnt5a/Ror2 signaling. We further show that activation of an SFK is inhibited by the suppressed expression of Ror2. Collectively, these results indicate that Wnt5a/Ror2 signaling involves the activation of a SFK, leading to MMP-13 expression, and that constitutively active Wnt5a/Ror2 signaling confers invasive properties on osteosarcoma cells in a cell-autonomous manner.

High-resolution analysis of chromosome copy number alterations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified, with single nucleotide polymorphism-typing microarrays.

Angioimmunoblastic T-cell lymphoma (AILT) and peripheral T-cell lymphoma, unspecified (PTCL-u) are relatively frequent subtypes of T- or natural killer cell lymphoma. To characterize the structural anomalies of chromosomes associated with these disorders, we here determined chromosome copy number alterations (CNAs) and loss of heterozygosity (LOH) at >55,000 single nucleotide polymorphism loci for clinical specimens of AILT (n=40) or PTCL-u (n=33). Recurrent copy number gain common to both conditions was detected on chromosomes 8, 9 and 19, whereas common LOH was most frequent for a region of chromosome 2. AILT- or PTCL-u-specific CNAs or LOH were also identified at 21 regions, some spanning only a few hundred base pairs. We also identified prognosis-related CNAs or LOH by several approaches, including Cox's proportional hazard analysis. Among the genes that mapped to such loci, a poor prognosis was linked to overexpression of CARMA1 at 7p22 and of MYCBP2 at 13q22, with both genes being localized within regions of frequent copy number gain. For a frequent LOH region at 2q34, we also identified IKAROS family zinc-finger 2 cDNAs encoding truncated proteins. Our data indicate that AILT and PTCL-u consist of heterogeneous subgroups with distinct transforming genetic alterations.

[Pleomorphic carcinoma of the lung; report of a case].

A 66-year-old female complained of cough, and was referred to our hospital. Chest radiography and computed tomography (CT) showed a tumor mass near the right hilum and atelectasis of the middle lobe. Bronchoscopy revealed a whitish polypoid tumor obstructing the middle lobe bronchus. Histology by punch biopsy suggested adenocarcinoma Right upper and middle lobectomy was performed, due to the direct invasion of the tumor from the middle lobe to the upper lobe. Histological findings showed adenocarcinoma comprised of spindle cell component, finally diagnosing as pleomorphic carcinoma of the lung. After the operation, systemic chemotherapy, including paclitaxel and carboplatin was performed. About 42 months after operation, the patient died of multiple brain metastases.

Serum level of advanced glycation end-products (AGEs) is an independent determinant of plasminogen activator inhibitor-1 (PAI-1) in nondiabetic general population.

Glucose can react nonenzymatically with amino groups of proteins to form senescent macroprotein derivatives termed advanced glycation end-products (AGEs). Recently, AGEs have been shown to play an important role in atherosclerosis even in nondiabetic subjects. However, the molecular mechanism underlying this is not fully understood. We have now investigated whether serum AGE level was an independent determinant of plasminogen activator inhibitor-1 (PAI-1), a major physiological inhibitor of fibrinolysis, in nondiabetic general population. One-hundred and eighty-six nondiabetic Japanese subjects underwent a complete history and physical examination, determination of blood chemistries, PAI-1, and AGEs. Uni- and multivariate analyses were applied for the determinants of PAI-1 levels. The average PAI-1 levels were 29.7+/-23.8 ng/ml in males and 21.8+/-17.1 ng/ml in females, respectively. Univariate regression analysis showed that PAI-1 levels were associated with age (inversely, p=0.003), male (p=0.003), body mass index (BMI) (p<0.001), HDL-cholesterol (inversely, p<0.001), triglycerides (p<0.001), fasting plasma glucose (p<0.001), insulin (p<0.001), uric acids (p<0.001), AGEs (p=0.037), and alcohol intake (p<0.001). By the use of multiple regression analyses, BMI (p<0.001), male (p=0.003), fasting plasma glucose (p=0.005), age (inversely, p=0.017), and AGEs (p=0.034) remained significant. The present study is the first demonstration that serum AGE level was one of the independent determinants of PAI-1 in nondiabetic general population. The AGE-associated thrombogenic abnormality may be involved in atherogenesis in nondiabetic subjects.

Modification of submerged membrane bioreactors (MBRS) by inserting baffles: pilot scale study.

Submerged membrane bioreactors (MBRs) have been gaining in popularity in various types of wastewater treatment. One drawback of submerged MBRs is difficulty in removing nitrogen as they are accompanied with intensive aeration inside the reactor and therefore principally operated under aerobic conditions. In order to address this problem, a simple modification for submerged MBRs, insertion of baffles to create alternative aerobic/anoxic conditions, was proposed. In this study, the performance of the proposed baffled membrane bioreactor (BMBR) was investigated based on a pilot-scale experiment using a real municipal wastewater. With appropriate operating conditions, the BMBR could remove more than 70% of total nitrogen contained in the feed water without any external carbon source. The BMBR demonstrated a good treatment performance in terms of TOC and phosphorus removal as well. Increase of trans-membrane pressure difference was subtle, which might be attributed to the alternative creation of aerobic/anoxic conditions.