VP Groups Research Articles

Antibiotic calcium sulphate beads lower the bacterial burden and prevent infection in a mouse model of periprosthetic joint infection.

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. A mouse model of PJI of the knee was used. Mice were randomized into groups with intervention at the time of surgery (postoperative day (POD) 0): a sterile control (SC; n = 6); infected control (IC; n = 15); systemic vancomycin (SV; n = 9); vancomycin powder (VP; n = 21); and vancomycin bead (VB; n = 19) groups. Delayed inoculation was introduced during an arthrotomy on POD 7 with 1 × 105 colony-forming units (CFUs) of a bioluminescent strain of Staphylococcus aureus. The bacterial burden was monitored using bioluminescence in vivo. All mice were killed on POD 21. Implants and soft-tissue were harvested and sonicated for analysis of the CFUs. The mean in vivo bioluminescence in the VB group was significantly lower on POD 8 and POD 10 compared with the other groups. There was a significant 1.3-log10 (95%) and 1.5-log10 (97%) reduction in mean soft-tissue CFUs in the VB group compared with the VP and IC groups (3.6 × 103 vs 7.0 × 104; p = 0.022; 3.6 × 103 vs 1.0 × 105; p = 0.007, respectively) at POD 21. There was a significant 1.6-log10 (98%) reduction in mean implant CFUs in the VB group compared with the IC group (1.3 × 100 vs 4.7 × 101, respectively; p = 0.038). Combined soft-tissue and implant infection was prevented in 10 of 19 mice (53%) in the VB group as opposed to 5 of 21 (24%) in the VP group, 3 of 15 (20%) in the IC group, and 0% in the SV group. In our in vivo mouse model, antibiotic-releasing calcium sulphate beads appeared to outperform vancomycin powder alone in lowering the bacterial burden and preventing soft-tissue and implant infections.

An Analysis of the Neutralizing Antibodies against the Main SARS-CoV-2 Variants in Healthcare Workers (HCWs) Vaccinated against or Infected by SARS-CoV-2.

Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, "breakthrough infections" have been documented in patients with complete primary vaccination courses. Most of the SARS-CoV-2 neutralizing antibodies produced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and the infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of a host. The aim of this study was to compare the titers of neutralizing antibodies (NtAbs) against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). A total of 293 HCWs were enrolled and divided into three cohorts as follows: 91 who had recovered from SARS-CoV-2 infection (nVP); 102 that were vaccinated and became positive after the primary cycle (VP); and 100 that were vaccinated with complete primary cycles and concluded the follow-up period without becoming positive (VN). Higher neutralization titers were observed in the vaccinated subjects' arms compared to the nVP subjects' arms. Differences in neutralization titers between arms for single variants were statistically highly significant (p < 0.001), except for the differences between titers against the Alpha variant in the nVP and in VP groups, which were also statistically significant (p < 0.05). Within the nVP group, the number of subjects with an absence of neutralizing antibodies was high. The presence of higher titers in patients with a complete primary cycle compared to patients who had recovered from infection suggested the better efficacy of artificial immunization compared to natural immunization, and this further encourages the promotion of vaccination even in subjects with previous infections.

A high α1-antitrypsin/interleukin-10 ratio predicts bacterial pneumonia in adults with community-acquired pneumonia: a prospective cohort study

BackgroundCurrent microbiological tests fail to identify the causative microorganism in more than half of all pneumonia cases. We explored biomarkers that could be used for differentiating between bacterial and viral pneumonia in patients with community-acquired pneumonia (CAP).MethodsIn this prospective cohort study conducted in Japan, data obtained from adult patients with bacterial pneumonia, including bacterial and viral coinfections (bacterial pneumonia [BP] group), and purely viral pneumonia (VP group) at diagnosis were analyzed using multivariate logistic regression analysis to identify predictors of bacterial pneumonia. Furthermore, a decision tree was developed using the predictors.ResultsA total of 210 patients were analyzed. The BP and VP groups comprised 108 and 18 patients, respectively. The other 84 patients had no identified causative microorganism. The two groups shared similar characteristics, including disease severity; however, a significant difference (p < 0.05) was observed between the two groups regarding sputum type; sputum volume score; neutrophil counts; and serum levels of interleukin (IL)-8, IL-10, and α1-antitrypsin (AAT). Sputum volume score (p < 0.001), IL-10 (p < 0.001), and AAT (p = 0.008) were ultimately identified as predictors of BP. The area under the curve for these three variables on the receiver operating characteristic (ROC) curve was 0.927 (95% confidence interval [CI]: 0.881–0.974). The ROC curve for sputum volume score and an AAT/IL-10 ratio showed a diagnostic cutoff of 1 + and 65, respectively. Logistic regression analysis using dichotomized variables at the cutoff values showed that the odds ratios for the diagnosis of BP were 10.4 (95% CI: 2.2–50.2) for sputum volume score (absence vs. presence) and 19.8 (95% CI: 4.7–83.2) for AAT/IL-10 ratio (< 65 vs. ≥ 65).ConclusionsConsidering that obtaining a definitive etiologic diagnosis with the current testing methods is difficult and time consuming, a decision tree with two predictors, namely sputum volume and the AAT/IL-10 ratio, can be useful in predicting BP among patients diagnosed with CAP and facilitating the appropriate use of antibiotics.Trial registrationUMIN000034673 registered on November 29, 2018.

Percutaneous Functional Spinal Unit Cementoplasty versus Posterior Spinal Fixation with Vertebroplasty for Symptomatic Chronic Osteoporotic Vertebral Fractures: A Retrospective Study with a 2-Year Follow up

Purpose To compare the clinical efficacy of percutaneous functional spinal unit cementoplasty (PFSUP) and posterior spinal fixation combined with vertebroplasty (PSF + VP) for the treatment of symptomatic chronic osteoporotic vertebral fractures (SCOVFs). Method Thirty-one patients with SCOVFs were included in this retrospective study and divided into PFSUP (n = 14) and PSF + VP (n = 17) groups. Visual analog scores (VAS) and Oswestry Disability Index (ODI) were recorded before and after surgery and at the last follow-up. Besides, the local kyphosis angle (LKA) and sagittal vertical axis (SVA) were measured. The operation duration, number of X-ray exposures, amount of blood loss, bed rest duration, hospitalization duration, and presence of complications were recorded. Result The VAS, ODI, LKA, and SVA after surgery and at the last follow-up were significantly improved in both groups compared to preoperative measurements. The PFSUP group experienced shorter operation duration (78.2 ± 13.1 vs. 124.7 ± 14.7, p < 0.001), less blood loss (31.1 ± 8.1 vs. 334.7 ± 70.9, p < 0.001), more X-ray exposures (92.1 ± 14.3 vs. 29.4 ± 5.5, p < 0.001), shorter bed rest duration (12.4 ± 3.8 vs. 43.4 ± 10.0, p < 0.001), shorter hospitalization (6.6 ± 2.4 vs. 10.9 ± 2.7, p < 0.001), lower complication rate (28.5% vs. 64.7%, p < 0.05), and higher cement leakage rate (42.9% vs. 5.8%, p < 0.05) than the PSF + VP group. Conclusion During the treatment of SCOVFs, the combination of PFSUP and PSF + VP can restore spinal stability, improve kyphosis, and relieve pain. PFSUP can reduce blood loss and complications, early mobilization, and shorten the hospital stay, but it is associated with a higher cement leakage rate and more radiation exposure.

Safety and immunogenicity of a ChAdOx1 vaccine against Rift Valley fever in UK adults: an open-label, non-randomised, first-in-human phase 1 clinical trial

Rift Valley fever is a viral epidemic illness prevalent in Africa that can be fatal or result in debilitating sequelae in humans. No vaccines are available for human use. We aimed to evaluate the safety and immunogenicity of a non-replicating simian adenovirus-vectored Rift Valley fever (ChAdOx1 RVF) vaccine in humans. We conducted a phase 1, first-in-human, open-label, dose-escalation trial in healthy adults aged 18-50 years at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Participants were required to have no serious comorbidities or previous history of receiving an adenovirus-based vaccine before enrolment. Participants were non-randomly allocated to receive a single ChAdOx1 RVF dose of either 5 × 109 virus particles (vp), 2·5 × 1010 vp, or 5 × 1010 vp administered intramuscularly into the deltoid of their non-dominant arm; enrolment was sequential and administration was staggered to allow for safety to be assessed before progression to the next dose. Primary outcome measures were assessment of adverse events and secondary outcome measures were Rift Valley fever neutralising antibody titres, Rift Valley fever GnGc-binding antibody titres (ELISA), and cellular response (ELISpot), analysed in all participants who received a vaccine. This trial is registered with ClinicalTrials.gov (NCT04754776). Between June 11, 2021, and Jan 13, 2022, 15 volunteers received a single dose of either 5 × 109 vp (n=3), 2·5 × 1010 vp (n=6), or 5 × 1010 vp (n=6) ChAdOx1 RVF. Nine participants were female and six were male. 14 (93%) of 15 participants reported solicited local adverse reactions; injection-site pain was the most frequent (13 [87%] of 15). Ten (67%) of 15 participants (from the 2·5 × 1010 vp and 5 × 1010 vp groups only) reported systemic symptoms, which were mostly mild in intensity, the most common being headache (nine [60%] of 15) and fatigue (seven [47%]). All unsolicited adverse events reported within 28 days were either mild or moderate in severity; gastrointestinal symptoms were the most common reaction (at least possibly related to vaccination), occurring in four (27%) of 15 participants. Transient decreases in total white cell, lymphocyte, or neutrophil counts occurred at day 2 in some participants in the intermediate-dose and high-dose groups. Lymphopenia graded as severe occurred in two participants in the 5 × 1010 vp group at a single timepoint, but resolved at the subsequent follow-up visit. No serious adverse events occurred. Rift Valley fever neutralising antibodies were detectable across all dose groups, with all participants in the 5 × 1010 vp dose group having high neutralising antibody titres that peaked at day 28 after vaccination and persisted through the 3-month follow-up. High titres of binding IgG targeting Gc glycoprotein were detected whereas those targeting Gn were comparatively low. IFNγ cellular responses against Rift Valley fever Gn and Gc glycoproteins were observed in all participants except one in the 5 × 1010 vp dose group. These IFNγ responses peaked at 2 weeks after vaccination, were highest in the 5 × 1010 vp dose group, and tended to be more frequent against the Gn glycoprotein. ChAdOx1 RVF was safe, well tolerated, and immunogenic when administered as a single dose in this study population. The data support further clinical development of ChAdOx1 RVF for human use. UK Department of Health and Social Care through the UK Vaccines Network, Oak Foundation, and the Wellcome Trust. For the Swahili translation of the abstract see Supplementary Materials section.

Oral administration of Synechococcus sp. PCC7942 trans-vp19 and trans-vp (19+28) genes improve the immune and antioxidant capacity in Procambarus clarkii under white spot syndrome virus stress

This study aimed to evaluate antioxidant capacity and protection from white spot syndrome virus (WSSV) challenge of Procambarus clarkii fed trans-vp19 and trans-vp (19 + 28) genes of Synechococcus sp. PCC7942 (Syn7942). P. clarkii were fed transgenic cyanobacteria continuously for 7 days, and then infected with WSSV after 12 h starvation. The daily mortality in each group was measured for 10 days and hepatopancreas and muscle of P. clarkii were examined for enzymes phenoloxidase (PO) activity, catalase (CAT) activity, glutathione peroxidase (GSH-px) activity, and malondialdehyde (MDA) concentration after immunization and viral challenge at different times. Compared with the WSSV-infected crayfish in positive control group (challenge and no vaccination) and wild type group (challenge, feeding wild-type Syn7942), vp19 group (challenge, feeding Syn7942 trans-vp19 gene) and vp (19 + 28) group [challenge, feeding Syn7942 trans-vp (19 + 28) genes] significantly improved the survival rate from 0% to 60% and 56.7%, respectively. Consistently, significantly greater PO, CAT, and GSH-px activity and significantly lower MDA concentration in the vp19 and vp (19 + 28) groups compared to the control group. These results demonstrate that the trans-vp19 and trans-vp (19 + 28) gene of Syn7942 significantly facilitated the immune and antioxidant capacity of crayfish. Therefore, the trans-vp19 and trans-vp (19 + 28) genes of Syn7942 could provide protection for crayfish as an anti-WSSV oral medication.

Changes of Brain Structures and Psychological Characteristics in Predatory, Affective Violent and Nonviolent Offenders.

Purpose: Violent subjects were demonstrated to exhibit abnormal brain structures; however, the brain changes may be different between criminals committing affective (VA), predatory violence (VP), and non-violence (NV). Therefore, the purpose of this study was to compare the differences in brain structures and psychological characteristics between VA, VP, and NV offenders. Methods: Twenty male criminal subjects (7 VP; 6 VA; and 7 NV) offenders; and twenty age-matched male healthy non-criminals were enrolled in this study. All subjects received psychological assessments as well as magnetic resonance imaging scans of the brain. Analysis of variance (ANOVA) was performed to understand the differences among four groups with Bonferroni correction. The voxel-based morphometry and voxel-wise diffusion tensor imaging analyses were performed to compare the gray matter (GM) volume and white matter (WM) integrity between the groups. In significant regions, a Spearman correlation analysis was performed to understand the relationship between the brain changes and psychological scores. Results: The ANOVA analysis showed that AUDIT scores were significantly different among four groups, but no significant group difference was noted after Bonferroni correction. The imaging comparisons further demonstrated that the VP and NV offenders exhibited significant alterations of WM and GM tissues in the rectus and superior temporal gyrus, respectively. In addition, the VP offenders exhibited greater GM volumes than VA offenders in the right middle frontal gyrus, and NV offenders had greater GM volumes than VP offenders in the bilateral thalamus. Conclusion: We concluded that the VA, VP, and NV groups exhibited different degrees of alterations in GM and WM tissues in regions involved in emotion and cognition.

Characteristic Clinical and Dermoscopic Features of Nonvolar Poroma.

A poroma typically presents as a solitary, pink-to-red papule or nodule in acral volar areas. However, in nonvolar areas, this typical clinical feature (TCF) can be difficult to identify. We aimed to compare clinical and dermoscopic characteristics between nonvolar poroma (NVP) and volar (ie, typical) poroma (VP). We assessed the clinical and dermoscopic characteristics of 40 patients with poromas who were divided into the NVP and VP groups. Of the 40 patients, 20 (50.0%) were allocated to the NVP group and 20 (50.0%) to the VP group. Pigmented variants were more common in the NVP group than in the VP group (60.0% vs 5.0%). The TCF of poroma was observed less frequently in the NVP than the VP group (45.0% vs 85.0%). Approximately one-third (30.0%) of patients with NVP received an initial clinical diagnosis of skin cancer. Dermoscopic patterns associated with melanoma or basal cell carcinoma were more common in the NVP group than in the VP group (65% vs 30%). Skin cancer-associated clinicodermoscopic features were more frequently observed in patients with NVP, who simultaneously lost dermoscopic patterns associated to poromas and acquired those associated with skin cancer, than those with VP.

Effects of Synechococcus sp. PCC 7942 harboring vp19, vp28, and vp (19 + 28) on the survival and immune response of Litopenaeus vannamei infected WSSV

This study aimed to assess the effect of oral administration of Synechococcus sp. PCC 7942 harboring vp19, vp28, and vp(19 + 28)against infection by white spot syndrome virus (WSSV) on juveniles of Litopenaeus vannamei. L. vannamei was orally administrated by feeding with different mutants of Synechococcus for 10 days, and then challenged with WSSV. The cumulative mortality of vp19, vp28, vp (19 + 28) groups was lower than that of the positive control group (57.8%, 62.2%, 71.1%, respectively); vp (19 + 28) group had a better protection rate than vp19 and vp28 groups. The analysis of shrimp immunological parameters showed that, after WSSV injection, the activity of superoxide dismutase, phenol oxidase, catalase, and lysozyme in the hepatopancreas of vp19, vp28, and vp (19 + 28) groups was higher than in the positive group; at the same time, growth performances of L. vannamei of experimental groups were better than control groups. Results showed that the Synechococcus mutants harboring vp19, vp28, and vp (19 + 28) could be used both as drug and feed to also enhance the defensive ability of juvenile shrimp against WSSV infection by increasing the activity of immune related enzymes.

Characterisation of brain volume and microstructure at term-equivalent age in infants born across the gestational age spectrum.

BackgroundRisk of morbidity differs between very preterm (VP; <32 weeks' gestational age (GA)), moderate preterm (MP; 32–33 weeks' GA), late preterm (LP; 34–36 weeks' GA), and full-term (FT; ≥37 weeks' GA) infants. However, brain structure at term-equivalent age (TEA; 38–44 weeks) remains to be characterised in all clinically important GA groups. We aimed to compare global and regional brain volumes, and regional white matter microstructure, between VP, MP, LP and FT groups at TEA, in order to establish the magnitude and anatomical locations of between-group differences.MethodsStructural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid (CSF), subcortical grey matter, brainstem and cerebellum. Global tissue volumes were analysed, and additionally, cortical grey matter and white matter volumes were analysed at the regional level using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Statistical analyses involved examining the overall effect of GA group on global volumes (using linear regressions) and regional volumes and microstructure (using non-parametric permutation testing), as well performing post-hoc comparisons between the GA sub-groups.ResultsOn global analysis, cerebrospinal fluid (CSF) volume was larger in all preterm sub-groups compared with the FT group. On regional analysis, volume was smaller in parts of the temporal cortical grey matter, and parts of the temporal white matter and corpus callosum, in all preterm sub-groups compared with the FT group. FA was lower, and RD and MD were higher in voxels located in much of the white matter in all preterm sub-groups compared with the FT group. The anatomical locations of group differences were similar for each preterm vs. FT comparison, but the magnitude and spatial extent of group differences was largest for the VP, followed by the MP, and then the LP comparison. Comparing within the preterm groups, the VP sub-group had smaller frontal and temporal grey and white matter volume, and lower FA and higher MD and RD within voxels in the approximate location of the corpus callosum compared with the MP sub-group. There were few volume and microstructural differences between the MP and LP sub-groups.ConclusionAll preterm sub-groups had atypical brain volume and microstructure at TEA when compared with a FT group, particularly for the CSF, temporal grey and white matter, and corpus callosum. In general, the groups followed a gradient, where the differences were most pronounced for the VP group, less pronounced for the MP group, and least pronounced for the LP group. The VP sub-group was particularly vulnerable compared with the MP and LP sub-groups.

An assessment of the microbial quality of “döner kebab” during cold storage: Effects of different packaging methods and microwave heating before consumption

AbstractIn the current study, döner kebabs packed with different packaging methods (air packaging [AP], modified atmosphere packaging [MAP], vacuum packaging [VP] and sous vide packaging [SVP]) were evaluated for their microbial quality during storage at 4 °C. In addition, the effect of microwave heating before consumption on the microbial quality of döner kebabs was also investigated. Total mesophilic aerobic bacteria and total psycrophilic aerobic bacteria counts of döner kebabs increased during storage and reached to 6.48, 8.27, 8.15, 3.96 and 5.58, 8.53, 8.63, &lt;1.00 log cfu/g in AP (9th day), MAP (29th day), VP (29th day) and SVP (99th day) groups, respectively. Although coliform, Escherichia coli and Staphylococcus aureus counts of döner kebabs were below 3 MPN/g, 3 MPN/g, 2 log cfu/g in all groups, respectively; no Clostridium perfringens and Listeria monocytogenes was detected in any of the groups during storage. Microwave heating was found effective on reducing the microbial load of döner kebabs. It was concluded that without any additional preservation techniques, the SVP prolonged the shelf life of döner kebabs more than 20, 6, and 5 times comparing to AP, MAP, and VP groups, respectively.Practical applicationsDöner kebab is a meat product which is very convenient for microbial growth due to its nutritional and chemical composition. Döner kebab that cannot be sold immediately after production causes high economic losses since the shelf life of döner kebab is very short after cooking. Therefore, it requires additional preservation techniques in order to prevent the economic losses after cooking and to have the opportunity of secure serving of it where döner kebab oven is not present. In the current study, sous vide (SV) applied döner kebabs protected their microbiological quality at least 100 days at 4 °C without any additional preservation techniques and application of SV after cooking provided döner kebabs with a longer shelf life comparing to air packaging, modified atmosphere packaging and vacuum packaging methods. Besides, microwave heating was applied to döner kebabs in order to simulate the conditions of consumption. Microwave heating before consumption significantly reduced the microbial load of döner kebabs.

Effect of dexmedetomidine on visceral pain in rats: the role of α2 adrenergic receptors in locus coeruleus

Objective To evaluate the effect of dexmedetomidine on visceral pain in rats and the role of α2 adrenergic receptors in locus coeruleus (LC). Methods Thirty-two healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 4 groups (n=8 each) using a random number table method: control group (group C), visceral pain group (group VP), dexmedetomidine group (group DEX) and α2-adrenergic receptor antagonist atipamezole group (group AP). α2-adrenergic receptor antagonist atipamezole 522 μg/kg was intramuscularly injected in group AP, and the equal volume of normal saline was given instead in C, VP and DEX groups.At 10 min after intramuscular injection, dexmedetomidine 10 μg/kg was injected via the tail vein in DEX and AP groups, and the equal volume of normal saline was given instead in C and VP groups.VP, DEX and AP groups received intraperitoneal injection of 0.9% acetic acid 10 ml/kg to make the visceral pain model at 15 min after injection via the tail vein.The cumulative visceral pain score was recorded within 60 min after acetic acid injection.The number of c-fos positive cells in LC was detected by immunohistochemistry, and the content of norepinephrine (NA) in the spinal cord were detected by enzyme-linked immunosorbent assay at 2 h after acetic acid injection. Results Compared with group C, the cumulative visceral pain scores, the number of c-fos positive cells in LC and content of NA in the spinal cord were significantly increased in VP, DEX and AP groups (P<0.05). Compared with group VP, the cumulative visceral pain scores, the number of c-fos positive cells in LC and content of NA in the spinal cord were significantly decreased in DEX and AP groups (P<0.05). Compared with group DEX, the cumulative visceral pain scores, the number of c-fos positive cells in LC and content of NA in the spinal cord were significantly increased in group AP (P<0.05). Conclusion Dexmedetomidine can alleviate visceral pain in rats, and the mechanism is partially related to activating α2 adrenergic receptors in LC. Key words: Dexmedetomidine; Visceral; Pain; Locus coeruleus; Receptors, adrenergic alpha-2

Effect of dexmedetomidine pretreatment on inflammatory visceral pain in rats

Objective To investigate the effect of dexmedetomidine pretreatment on inflammatory visceral pain in rats. Methods Forty healthy male Wistar rats, weighing 200-300 g, aged 6-8 weeks, were divided into 5 groups (n=8 each) using a random number table method: control group (group C), visceral pain group (group VP), dexmedetomidine 1 μg/kg group (group Dex1), dexmedetomidine 5 μg/kg group (group Dex2) and dexmedetomidine 10 μg/kg group (group Dex3). The model of inflammatory visceral pain was established by intraperitoneally injecting 0.9% acetic acid 10 ml/kg in VP, Dex1, Dex2 and Dex3 groups, and the equal volume of normal saline was given instead in group C. At 15 min before intraperitoneal injection, dexmedetomidine 1, 5 and 10 μg/kg were injected via the tail vein in Dex1, Dex2 and Dex3 groups, respectively, and the equal volume of normal saline was given instead in C and VP groups.Behavioral changes of rats were observed within 60 min after the model was established, and visceral pain index (VPI) was calculated.Blood samples were collected from the hearts at 180 min after establishing the model for determination of tumor necrosis factor-alpha (TNF-α) concentrations in serum.The animals were then sacrificed, and colons were obtained for examination of pathological changes with a light microscope. Results Compared with group C, the VPI and serum TNF-α concentrations were significantly increased in VP and Dex1-2 groups, and the serum TNF-α concentrations were significantly increased (P 0.05). Compared with group VP, the VPI and serum TNF-α concentrations were significantly decreased (P<0.05), and the pathological changes of colon tissues were significantly attenuated in group Dex1-3.Compared with group Dex1, the VPI and serum TNF-α concentrations were significantly decreased (P<0.01), and the pathological changes of colon tissues were significantly attenuated in Dex2-3 groups.Compared with group Dex2, the VPI and serum TNF-α concentrations were significantly decreased (P<0.01), and the pathological changes of colon tissues were significantly attenuated in group Dex3. Conclusion Dexmedetomidine pretreatment can mitigate inflammatory visceral pain in rats. Key words: Dexmedetomidine; Visceral pain; Inflammation

Correlations of MMP-1, MMP-3, and MMP-12 with the degree of atherosclerosis, plaque stability and cardiovascular and cerebrovascular events.

We analyzed the effects of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-12 on the degree of carotid atherosclerosis (CAS) and plaque stability, and investigated their correlations with cardiovascular and cerebrovascular events (CCEs). Two hundred CAS patients were enrolled. Carotid intima-media thickness (IMT) was measured using ultrasonic examination. Patients were divided into the no plaque group (NP group), stable plaque group (SP group), and vulnerable plaque group (VP group). The Crouse method was used for the evaluation of plaque scores. Additionally, 60 healthy subjects were enrolled as the control group. Serum triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were analyzed. The serum protein levels of MMP-1, MMP-3, and MMP-12 were measured by western blotting. The frequency of CCEs within 2 years was recorded, and its correlation with MMP-1, MMP-3, and MMP-12 was analyzed. The CAS plaque scores in the SP and VP groups were significantly increased compared with the NP group, and the difference between the SP and VP groups was significant. The levels of TC, TG, LDL-C, and HDL-C of CAS patients were significantly increased compared with those in the control group, but the differences in these indexes between the patient groups were not significant. Western blotting showed that the levels of MMP-1, MMP-3, and MMP-12 in the patient groups were significantly increased compared with those in the control group, and the protein levels in the VP group were significantly higher than those in the SP and NP groups. Additionally, the levels of MMP-1, MMP-3, and MMP-12 had significantly positive correlations with the occurrence of CCEs in CAS patients. In conclusion, MMP-1, MMP-3, and MMP-12 are positively correlated with CCEs in CAS patients. They can be used as markers for the clinical diagnosis and prognosis of CAS.

Structure-function relationship of the human external anal sphincter.

Obstetrical external anal sphincter (EAS) injury and subsequent dysfunction are leading risk factors for femalefecal incontinence (FI). Limited knowledge of the EAS structure-function relationship hinders treatment optimization. We directly measured functionally relevant intrinsicparameters of human EAS and tested whether vaginal delivery alters the EAS structure-function relationship. Major predictors of in vivo EAS function were compared between specimens procured from vaginally nulliparous (VN, n=5) and vaginally parous (VP, n=7) cadaveric donors: operational sarcomere length (Ls), which dictates force-length relationship; physiological cross-sectional area (PCSA), which determines isometric force-generating capacity; fiber length (Lfn), responsible for muscle excursion and contractile velocity; and muscle stiffness. Data were analyzed using unpaired and paired t tests, α<0.05. Results are presented as mean±SEM. The VN and VP (median parity 3) groups were similar in age and BMI. No gross anatomical defects were identified. EAS Ls (2.36±0.05μm) was shorter than the optimal Lso (2.7μm), at which contractile force is maximal, P=0.0001. Stiffness was lower at Ls than Lso (5.4±14kPa/μm vs 35.3±12kPa/μm, P<0.0001). This structural design allows active and passive tension to increase with EAS stretching. EAS relatively long Lfn (106±24.8mm) permits rapid contraction without decreased force, whereas intermediate PCSA (1.3±0.3cm2) is conducive to maintaining resting tone. All parameters were similar between groups. This first direct examination of human EAS underscores how EAS intrinsic design matches its intended function. Knowledge of the EAS structure-function relationship is important for understanding the pathogenesis of FI and the optimization of treatments for EAS dysfunction.

Ventriculoatrial versus ventriculoperitoneal shunt complications in idiopathic normal pressure hydrocephalus

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a devastating condition that affects the elderly population. Although ventriculoatrial (VA) shunts can be used to manage iNPH, concerns for associated cardiopulmonary and renal complications have decreased their use. However, the rate of these complications is not well understood within this population of patients. Patients and methodsA retrospective review of the electronic medical records of patients diagnosed with iNPH by the senior author between 1993 and 2015 was performed. Demographic information and baseline symptoms were assessed. Complications including infection, shunt obstruction, overdrainage, cardiopulmonary events, renal dysfunction, and shunt revision were recorded. Complication rates were compared between VA and VP shunted patients. Statistical analysis using Chi-square test, Fisher’s exact test, logistic regression, Wald t-test, Poisson regression, ANOVA, and ANCOVA was performed. Results496 Patients, including 150 receiving VA shunts and 346 receiving VP shunts, were included in the study. The median age was 74 and 73 for VA and VP shunted patients, respectively, with slight male predominance in both (58.0% and 58.4% for VA and VP groups, respectively). A total of 36.0% of VA shunted patients and 42.5% of VP shunted patients experienced at least one post-operative complication. Overdrainage was the most commonly experienced complication in both VA (27.4%) and VP patients (19.9%). Infection occurred in only 2.0% of patients, and renal complications occurred in 1.3%. No patients had cardiopulmonary complications. VA shunted patients were significantly less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients (p=0.008 and <0.001, respectively). Only dizziness and gait disturbance at baseline were correlated with a shorter time to revision in VA shunted patients (p=0.002 for both). ConclusionAlthough cardiopulmonary and renal complications are serious concerns associated with VA shunt placement, they were uncommon in patients with iNPH. VA shunted patients were less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients. Therefore, VA shunts should be considered as an alternative primary treatment option in the iNPH population.

Analysis of the sacroiliac joint vacuum phenomenon in paediatric patients.

To assess the incidence of the sacroiliac joint vacuum phenomenon (SIJ VP) in paediatric patients and the relationship between the presence of VP and clinical factors such as age, sex and body mass index (BMI). We retrospectively reviewed clinical data and imaging findings of 60 patients who underwent abdominopelvic CT (AP CT) between January and June 2015. Patients were divided into VP group and non-VP group based on the presence/absence of VP, and the groups were compared. In addition, other degenerative changes in the SIJ were recorded. The SIJ VP was detected in 19 (31.6%) patients. There were no significant differences in sex distribution between VP and non-VP groups (p = 0.781). The age of the VP group was significantly higher than that of the non-VP group (p < 0.001). After adjusting the BMI for age, there was no significant association between high BMI and the presence of SIJ VP (p = 0.326). Other degenerative changes were not noted in any of the patients. The SIJ VP is not an uncommon finding in paediatric patients. The prevalence of SIJ VP in paediatric patients is similar to its prevalence in adults. The SIJ VP is related to patient age, but not to sex or BMI in children and young adolescents. Advances in knowledge: AP CT can provide information about the SIJ, if it is required to assess the SIJ in paediatric patients.

Improving the Quality of Fresh Rainbow Trout by Sage Essential Oil and Packaging Treatments

AbstractThe present study aimed to investigate the effect of addition of sage oil in different packaging conditions on the quality of fresh trout fillets during storage at 4C. Six different treatments were tested: A; (without sage oil, air packaged), A1; (added sage oil 2% v/wt, air packaged), A2; (added sage oil 4% v/wt, air packaged), VP; (without sage oil, vacuum packaged), VP1 (added sage oil 2% v/wt, vacuum packaged) and VP2 (added sage oil 4% v/wt, vacuum packaged). The results indicated that total mesophilic aerobe, psychrophile, yeast–mold and lipolytic bacteria reached higher populations in A, A1 and A2 groups (as compared to VP groups). In addition, significant differences were determined among groups in terms of total volatile basic nitrogen, Thiobarbituric acid, peroxide value and free fatty acid values (P &lt; 0.05) during the storage period. Based primarily on sensory evaluation, the use of VP, VP1 and VP2 extended the shelf life of fresh trout by ca. 14, 19 and 29 days, respectively.Practical ApplicationsEssential oils derived from spices and herbs have a wide application in food flavoring and preservation. Moreover, antimicrobial and antioxidant activities of essential oils are well‐known. We hypothesized that vacuum packaged fresh trout with the addition of sage oil would increase shelf life. This work demonstrates that sage essential oil together with vacuum packaging treatments could be used to improving the quality of fresh rainbow trout.

Effect of Lyophilized Water Extract of U rtica dioica L. on the Shelf Life of Vacuum-Packaged Beef Steaks

In this research, the effects of lyophilized Urtica dioica L. water extract (LUDWE) on the shelf life of vacuum-packaged beef steaks were evaluated. For this purpose, beef steaks were arranged as control (vacuum packaging, VP), 150 ppm LUDWE + VP, 300 ppm LUDWE + VP and 450 ppm LUDWE + VP, and were stored at 2 ± 0.5C for 21 days. During storage, psychrotrophic bacteria, lactic acid bacteria, Pseudomonas, Enterobacteriaceae counts, pH, color and thiobarbituric acid reactive substances (TBARS) values of beef steaks were determined. By adding LUDWE in the beef steaks, TBARS values decreased (P < 0.01), and minimum values were determined in 450 ppm LUDWE + VP groups (P < 0.05). Depending on the increase in the LUDWE level, psychrotrophic (P < 0.01), Pseudomonas (P < 0.01), Enterobacteriaceae (P < 0.01) and lactic acid bacteria (P < 0.01) counts decreased, and the highest counts of these parameters were determined in the control group. LUDWE also had significant effects on L* (P < 0.01), a* (P < 0.01) and b* (P < 0.01) values of vacuum-packaged beef steaks. Practical Applications Beef steak is more susceptible to microbial spoilage and lipolytic reactions; these can lead to a shorter shelf life with potential risks for human health during storage at low temperatures. In beef steaks, lipid oxidation can be decreased and spoilage bacterial counts can be suppressed using natural antioxidants and antimicrobials such as lyophilized Urtica dioica L. water extract (LUDWE). This work clearly showed that LUDWE could be used as a good natural antioxidant and antimicrobial agent in fresh meat products such as beef steaks.

Reduced Dose-Intensity Subcutaneous Bortezomib Plus Prednisone (VP) Or Plus Cyclophosfamide (VCP) Or Plus Melphalan (VMP) For Newly Diagnosed Multiple Myeloma Patients Older Than 75 Years Of Age

BackgroundFrail patients represent 30% of the myeloma population, and are more susceptible to adverse events (AEs) with subsequent treatment discontinuations that significantly affect efficacy and dose-intensity. This community-based, phase II, multicenter trial aims to assess the efficacy and safety of 3 reduced-dose intensity subcutaneous (sc) bortezomib-based treatments in newly diagnosed elderly multiple (MM) patients. MethodsPatients with symptomatic, measurable MM, older than 75 years were enrolled. No exclusion criteria were planned in the protocol, to avoid patient selection bias. Patients with abnormal cardiac, pulmonary, renal or hepatic function were included.Treatment consisted of nine 28-day cycles with sc bortezomib 1.3 mg/m2 days 1, 8, 15, 22 plus oral prednisone 50 mg every other day (VP) or VP plus oral cyclophosphamide 50 mg every other day (VCP) or oral melphalan 2 mg every other day (VMP) for 28 days, followed by maintenance with sc bortezomib every 2 weeks until progression.A geriatric assessment was performed, including the Charlson index for estimating comorbidities, the Activity of Daily Living (ADL) and the Instrumental Activity of Daily Living (IADL) questionnaires to assess self-care and independence status. Combining these factors with age, patients were classified as fit (<80 years, ADL= 6, IADL=8, Charlson score= 0), unfit (fit patients >80 years or ADL=5, IADL=6-7, Charlson score=1), or frail (unfit patients >80 years or ADL≤4, IADL ≤5 and Charlson score ≥2). ResultsA total of 152 patients were enrolled, including 51 patients in the VP, 51 in the VCP and 50 in the VMP group. Median age was 78 years and 30% of patients were older than 80 years. Overall, 53%, 47% and 32% of the patients had ISS stage III disease, 21%, 20% and 24% had an unfavourable FISH profile [at least one chromosomal abnormality: del17, or t(4;14), or t(14;16)], and 88%, 84% and 78% were defined as unfit/frail in the VP, VCP, and VMP groups, respectively.Patients received a median of 9 treatment cycles and 44% of patients started maintenance. All three induction regimens exhibited substantial activity, with an overall response rate (≥partial response) of 67% in the VP, 63% in the VCP, and 80% in the VMP group. After a median follow-up of 17 months, median progression-free survival (PFS) was 14, 16 and 16 months and 1-year overall survival (OS) estimates were 80%, 82% and 80% in the VP, VCP and VMP group, respectively.The incidence of Serious Adverse Events (SAEs) was 22%, 20% and 30% and the discontinuation rate due to AEs was 14%, 16% and 26% in the VP, VCP and VMP groups, respectively. The most common non hematologic grade ≥3 AEs were infections (12%), cardiovascular events (8%), and neurologic events (7%), including 5% of peripheral neuropathy.According to the geriatric classification, and specifically in the fit, unfit and frail patients, the overall response rate was 92%, 67% and 65%, the 1 year OS was 100%, 88% and 73%, rate of SAEs was 4%, 22%, 30% and discontinuation due to toxicity was 40%, 58% and 67%, respectively. ConclusionsIn this community-based population of elderly newly diagnosed MM patients low-dose intensity VP, VCP and VMP showed similar PFS and OS estimates, while SAEs and discontinuations were higher with VMP, suggesting that a melphalan-free regimen should be preferred in these patients. Geriatric assessment is mandatory, since both efficacy and toxicities are significantly different in fit, unfit and frail patients.Table 1VP (N=51)VCP (N=51)VMP (N=50)Overall response rate67%63%80%At least 1 Serious Adverse Event22%20%30%Discontinuation rate for toxicity14%16%26%Median progression-free survival14 months16 months16 months1-year overall survival80%82%80% Disclosures:Larocca:Janssen and Cilag: Honoraria. Cavallo:Janssen-Cilag: Honoraria. Caravita:Janssen-Cilag: Honoraria. Petrucci:Janssen-Cilag: Honoraria. Sonneveld:Janssen-Cilag: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Janssen-Cilag: Research Funding; Millenium: Research Funding; Onyx: Research Funding; Celgene: Research Funding. Boccadoro:Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Research Funding; Janssen-Cilag: Consultancy. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria.