bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an ORF45-Derived Peptide To Inhibit the Sustained RSK Activation and Lytic Replication of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Li Xiaojuan , Huang Lu , Xiao Yunjun , Yao Xiangyang , Long Xubing , Zhu Fanxiu , Kuang Ersheng
Published: March 2019

ORF45-induced RSK activation plays an essential role in KSHV lytic replication, and ORF45-null or ORF45 F66A mutagenesis that abolishes sustained RSK activation and RSK inhibitors significantly decreases lytic replication, indicating that the ORF45-RSK association is a unique target for KSHV-related diseases. However, the side effects, low affinity, and poor efficacy of RSK modulators limit their clinical application. In this study, we developed a nontoxic cell-permeable ORF45-derived peptide from the RSK-binding region to disrupt ORF45-RSK associations and block ORF45-induced RSK activation without interfering with S6K1 activation. This peptide effectively suppresses spontaneous, hypoxia-induced, or chemically induced KSHV lytic replication and enhances the inhibitory effect of rapamycin on lytic replication and sensitivity to rapamycin in lytic KSHV-infected cells. Our results reveal that the ORF45-RSK signaling axis and KSHV lytic replication can be effectively targeted by a short peptide and provide a specific approach for treating KSHV lytic and persistent infection.
Draft Genome Sequence of
Streptomyces
sp. Strain NL15-2K, a Degrader of Lignin-Derived Aromatic Compounds, Isolated from Forest Soil
Authors: Nishimura Motohiro , Kawakami Susumu , Otsuka Hideaki
Published: March 2019

Streptomyces
sp. strain NL15-2K is a degrader of lignin-derived aromatic compounds and was isolated from a forest soil sample.
Draft Genome Sequence of a Canine Uropathogenic Escherichia coli Strain Isolated in New Zealand
Authors: Le Vuong V. H. , Bruce Ian , Biggs Patrick J. , Rakonjac Jasna
Published: March 2019

Escherichia coli
P50 is a canine uropathogenic isolate sampled in the Wellington region of New Zealand. We report the draft genome sequence of this isolate, which contains characteristic virulence genes for urinary tract infections and is predicted to be capable of causing human infections.
Draft Genome Sequence of
Agrobacterium deltaense
Strain CNPSo 3391, Isolated from a Soybean Nodule in Mozambique
Authors: Scherer Anderson José , Delamuta Jakeline Renata Marçon , Ribeiro Renan Augusto , Chibeba Amaral Machaculeha , Kyei-Boahen Stephen , Nogueira Marco Antonio , Hungria Mariangela
Published: March 2019

Agrobacterium deltaense
strain CNPSo 3391 was isolated from a soybean nodule in Mozambique. Its genome size was estimated at 4,926,588 bp.
Draft Genome Sequence of Halobacillus trueperi SS1, Isolated from Lunsu, a Saltwater Body in the Northwest Himalayas
Authors: Gupta Sonika , Sharma Parul , Dev Kamal , Baumler David J. , Sourirajan Anuradha
Published: March 2019

We report here the genome sequence of halophilic
Halobacillus trueperi
SS1, isolated from the Lunsu saltwater body in India. The bacteria are Gram positive and rod shaped.
Relating knowledge, attitude and practice of antibiotic use to extended-spectrum beta-lactamase-producing Enterobacteriaceae carriage: results of a cross-sectional community survey
Authors: Mo Yin , Seah Ivan , Lye Pei Shi Priscillia , Kee Xiang Lee Jamie , Wong Kien Yee Michael , Ko Kwan Ki Karrie , Ong Rick Twee-Hee , Tambyah Paul A , Cook Alex R
Published: March 2019

Objectives

To study the correlation between knowledge, attitude and practices (KAP) of antibiotic consumption with epidemiology and molecular characteristics of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) carriage, in order to identify modifiable factors and public health interventions to reduce prevalence of multidrug-resistant organism colonisation in the community.

Design

Cross-sectional questionnaire of KAP towards antibiotic use and collection of stool samples or rectal swabs. ESBL-PE isolates obtained underwent whole genome sequencing to identify resistance genes.

Setting

A densely populated community in Singapore.

Participants

There were 693 healthy community-dwelling questionnaire respondents. Out of which, 305 provided stool samples or rectal swabs.

Results

The overall knowledge of antibiotic use was poor (mean score 4.6/10, IQR 3.0–6.0). 80 participants (80/305, 26.2%) carried at least one ESBL-PE isolate. The most common ESBL-PE wasEscherichia colisequence type 131 carrying CTX-M type beta-lactamases (11/71, 15.5%). Living overseas for >1 year (OR 3.3, 95% CI 1.6 to 6.9) but not short-term travel, recent hospitalisation or antibiotic intake was associated with ESBL-PE carriage. Interestingly, higher knowledge scores (OR 2.0, 95% CI 1.03 to 3.9) and having no leftover antibiotics (OR 2.4, 95% CI 1.2 to 4.9) were independent factors associated with ESBL-PE carriage in the multivariate logistic regression model.

Conclusions

While the role of trans-border transmission of antimicrobial resistance is well known, we may have to examine the current recommendation that all antibiotics courses have to be completed. Clinical trials to determine the optimum duration of treatment for common infections are critically important.
Effects of home-based cardiac exercise rehabilitation with remote electrocardiogram monitoring in patients with chronic heart failure: a study protocol for a randomised controlled trial
Authors: Li Jiahui , Yang Peng , Fu Dongliang , Ye Xiaojun , Zhang Lifang , Chen Gang , Yang Yiyun , Luo He , Chen Li , Shao Mingjing , Li Chunyan , Liu Yi , Zhou Ying , Jiang Hong , Li Xianlun
Published: March 2019

Introduction

Patients with chronic heart failure (CHF) can benefit from exercise rehabilitation (ER) with significant improvements in exercise capacity, quality of life and reduction in hospitalisations. Despite its reported benefits, only a small number of patients with CHF attend ER due to poor adherence, and improper exercise may even lead to adverse events. Remote ECG monitoring system (REMS) has the potential to overcome these obstacles. We hypothesise that home-based cardiac ER using REMS in CHF patients is effective compared with conventional ER without monitoring.

Methods and analysis

This study is a prospective, randomised, parallel controlled clinical trial designed to evaluate the effectiveness of home-based phase-II ER with REMS in the treatment of CHF with a target enrolment of 120 patients (left ventricular ejection fraction <50%, New York Heart Association (NYHA) classes I to III). Patients are randomised to either REMS rehabilitation group or conventional rehabilitation group in a 1:1 ratio. All patients start an exercise training in a supervised setting and then transition to a home-based regimen. The supervised training phase consists of 12 supervised training sessions, three sessions per week for 4 weeks. During the home exercise phase, patients exercise five times per week for 8 weeks. In the REMS group, patients wear monitors during exercise to ensure that exercise intensity is within the set ranges. REMS will also detect risky arrhythmia and alert the patients and their doctors on time. The training intensity is not monitored in the conventional rehabilitation group. The primary outcome is exercise capacity improvement measured by peak oxygen uptake (VO2peak) (baseline vs 3 m). Secondary outcomes include 6-min walk test, NYHA classes, echocardiographic parameters, cardiac biomarkers, major adverse cardiovascular events, quality of life, psychological well-being and patients’ adherence to the rehabilitation programme.

Ethics and dissemination

This study was approved by Ethics Committee of China-Japan Friendship Hospital for Clinical Research (No. 2018–55 K39). The results of this study will be disseminated via peer-reviewed publications and presentations at conferences.

Trial registration number

ChiCTR-RNR-17012446; Pre-results.
A priori choice of neuraxial labour analgesia and breastfeeding initiation success: a community-based cohort study in an Italian baby-friendly hospital
Authors: Wetzl Roberto Giorgio , Delfino Enrica , Peano Luca , Gogna Daniela , Vidi Yvette , Vielmi Francesca , Bianquin Eleonora , Cerioli Serena , Bettinelli Maria Enrica , Giannì Maria Lorella , Frassy Gabriella , Boris Elena , Arioni Cesare
Published: March 2019

Objective

To investigate whether the nature of the decision about receiving neuraxial labour analgesia is associated with breastfeeding initiation success (BIS), defined as exclusive breastfeeding until discharge associated with postnatal weight loss <7% at 60 hours from birth.

Design

Single-centre community-based cohort study.

Setting

An Italian baby-friendly hospital, from 1 July 2011 to 22 September 2015.

Participants

Inclusion criteria: women vaginally delivering singleton cephalic newborns and willing to breastfeed. Exclusion criteria: women who delivered in uterus-dead fetuses, were single or requested but did not receive neuraxial analgesia. Overall, 775 out of the 3628 enrolled women received neuraxial analgesia.

Results

Compared with women who tried to cope with labour pain, those who decided a priori to receive neuraxial analgesia had less BIS (planned vaginal birth: 2121/3421 (62.0%), vs 102/207 (49.3%; p<0.001; risk difference (RD), 12.7%); actual vaginal birth: 1924/2994 (64.3%), vs 93/189 (49.2%; p<0.001; RD, 15.1%)). Multivariable analyses with antelabour-only confounders confirmed both associations (planned vaginal birth: relative risk (RR), 0.65; 95% CI, 0.48 to 0.87; actual vaginal birth: RR, 0.59; 95% CI, 0.43 to 0.80). Although women who requested analgesia as a last resort had less BIS than did those successfully coping with labour pain in the bivariable analyses (planned vaginal birth: 1804/2853 (63.2%), vs 317/568 (55.8%; p=0.001; RD, 7.4%); actual vaginal birth: 1665/2546 (65.4%), vs 259/448 (57.8%; p=0.002; RD, 7.6%)), multivariable analyses with either antelabour-only or peripartum confounders did not confirm these associations (planned vaginal birth: RR, 0.99; 95% CI, 0.80 to 1.23; actual vaginal birth: RR, 0.90; 95% CI, 0.69 to 1.16).

Conclusions

Compared with trying to cope with labour pain, a priori choice of neuraxial analgesia is negatively associated with BIS. Conversely, compared with having successfully coped with pain, requesting neuraxial analgesia as a last resort is not negatively associated with BIS.
Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum
Authors: Look M. , Chang D. , Sugarbaker P. H.
Published: March 2019

The aim of this study was to review the long-term results of cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Our goal was to identify clinical factors by which to select patients likely to benefit from a comprehensive management plan.

Clinical data of 28 females who underwent surgery were retrieved from a prospective database. Major cytoreductive procedures were possible in 25 patients. Heated intraoperative or early postoperative intraperitoneal chemotherapy was also used where appropriate. The median follow-up after cytoreduction was 26.9 months. The overall median survival after cytoreduction was 45.8 months. The prognostic indicators associated with a statistically significant impact on survival were the prior surgery score (P< 0.001), the completeness of cytoreduction score (CC;P= 0.037), and response to chemotherapy prior to surgery (P= 0.012).

Our findings suggest that cytoreductive surgery can be effective when combined with perioperative intraperitoneal chemotherapy. Results can be improved by excluding cases where CC seems unlikely. Extensive prior surgery without the protection of adjunctive intraperitoneal chemotherapy is associated with a poor prognosis. This may be due to disruption of anatomical planes leading to deep abdominal and pelvic dissemination intractable to further treatment.
Nuclear size, shape, and density in endometrial carcinoma
Authors: Miller J. , Geisler J. P. , Manahan K. J. , Geisler H. E. , Miller G. A. , Zhou Z. , Wiemann M. C. , Crabtree W.
Published: March 2019

Objective

The authors, using image analysis, previously demonstrated nuclear size and summed optical density to be independent prognostic indicators of recurrence in patients with endometrial carcinoma. The same tumors were analyzed by studying the optical features in the G0–G1peak to see if this changed the values found as well as their importance as prognostic features at greater than 5 years of follow-up.

Methods

Tumors from 74 consecutive patients, surgically treated, with endometrial cancer, were evaluated. Survival, depth of invasion, lymphvascular space invasion, FIGO stage, grade, histology were analyzed. DNA index, progesterone receptor status, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD) were evaluated. NUSZ, NUSH, and NUSD were quantified using image analysis.

Results

Fifteen patients died from disease during the observation period of the study. Mean follow-up was 82 months with a median of 84 months. Forty-nine patients had stage I cancers, five stage II, 17 stage III, and three stage IV. NUSZ and NUSD were all significantly different between the original (entire cell cycle) and the re-measured (G0G1only) values (both P < 0.001). Multivariate analysis showed both the original (P= 0.0001) and G0G1-only (P= 0.046) NUSZ and the original (P= 0.0002) and G0G1-only (P= 0.018) NUSD to be independent prognosticators of survival.

Conclusion

Image analysis is able to quantify cellular and nuclear parameters not otherwise quantifiable. NUSD and NUSZ correlated with traditional prognostic indicators, were demonstrated independent predictors of survival at over 5 years of follow-up. Although the re-measured NUSZ and NUSD from only the G0–G1peak were significantly different from the original NUSZ and NUSD, they were not as valuable as prognostic factors. Nuclear size and summed optical density measured from the entire cell cycle are independent prognostic indicators of survival at greater than 5 years of follow-up. Measuring nuclear morphometric features in the G0–G1peak only does not add any new prognostic information.
Primary fallopian tube carcinoma presenting with a sinus in the posterior portion of cervix
Authors: Khan Y. , Haq A. N. , Nasar R.
Published: March 2019

Primary fallopian tube carcinoma is an aggressive but rare tumor. This is an unusual presentation of papilliferous tubal carcinoma presenting with vaginal discharge through a large sinus approximately 2–3 cm in size, located posterior to the neck of cervix. Surgery was undertaken with the initial diagnosis of primary ovarian carcinoma and the fistula was left to heal spontaneously. Surgical resection was followed by adjuvant chemotherapy. The patient is doing well after the therapy.
Rapid growth of myxoid leiomyosarcoma of the vulva during pregnancy: a case report
Authors: Di Gilio A. R. , Cormio G. , Resta L. , Carriero C. , Loizzi V. , Parisi A. M. , Selvaggi L.
Published: March 2019

Smooth muscle tumors arising in the vulva are rare. Leiomyosarcoma is the most common variant of vulvar sarcoma, and very few cases have been reported during pregnancy. A 36-year-old woman presented with a progressively enlarging vulvar mass during pregnancy, diagnosed as a Bartholin's gland cyst. The lesion was resected at 38 weeks of gestation during cesarean section and diagnosis of myxoid leiomyosarcoma of the vulva was made. Six weeks later the patients were referred to our center and submitted to wide vulvar excision with groin lymph node dissection that revealed the presence of a small residual focus of leiomyosarcoma. At 30 months of follow-up the patient was well without any sign of recurrent disease. Leiomyosarcoma should be included in the differential diagnosis of vulvar masses; progressively enlarging vulvar lesion should be biopsied even during pregnancy. Leiomyosarcoma should be considered in the differential diagnosis of vulvar mass.
Influenza syndromic surveillance and vaccine efficacy in the UK Armed Forces, 2017–2018
Authors: Dermont Mark Andrew , Elmer T
Published: March 2019

Introduction

This paper describes the first ever analysis of health data to report influenza vaccine uptake and the effectiveness of the vaccine in preventing general practice presentations for influenza-like illness (ILI) in the UK Armed Forces (UK AF). This was undertaken during the 2017–2018 influenza season.

Methods

Clinical Read codes for ILI and influenza vaccinations were used to generate reports for the period from September 2017 to April 2018. Using a methodology adapted from Public Health England's (PHE) in hours syndromic surveillance, the ILI rate for the UK AF was calculated. Subsequent analysis explored vaccination uptake in target groups and compared the relative risk (RR) of ILI in vaccinated versus unvaccinated Service Personnel (SP).

Results

4234 SPs had a record of ILI between September 2017 and April 2018, with a peak rate of 216 cases per 100 000 PAR. The absolute risk reduction for reporting ILI in vaccinated versus unvaccinated SP was 0.4% (p=0.0031), and the RR was statistically significant at 15% (95% CI 5% to 23 %) lower than in the non-vaccinated PAR. The number needed to vaccinate (NNV) to prevent one presentation of ILI was 241 (95% CI 145 to 714). The 8153 vaccinations recorded for the untrained strength equate to approximately 38% of overall training throughput and 65% of all Army SP recorded as being in phase 1 training at some point during this period.

Conclusions

The relative risk reduction (RRR) for vaccinated personnel was modest and lower than reported elsewhere, but closely compares with ILI rates included in a 2018 Cochrane review. The small RRR and large NNV do not support widening the population of UK AF eligible to receive influenza vaccine. Regimental Medical Officers (RMOs) seeking advice on whether to vaccinate other groups of SP should be aware that this approach offers questionable clinical benefit. The ILI surveillance methodology used in this work could be adapted for syndromic surveillance of other infectious diseases.
Stent assisted coiling versus non-stent assisted coiling for the management of ruptured intracranial aneurysms: a meta-analysis and systematic review
Authors: Zhang Xiaoxi , Zuo Qiao , Tang Haishuang , Xue Gaici , Yang Pengfei , Zhao Rui , Li Qiang , Fang Yibin , Xu Yi , Hong Bo , Huang Qinghai , Liu Jianmin
Published: March 2019

Purpose

To compare the safety and efficiency of stent assisted coiling (SAC) with non-SAC for the management of ruptured intracranial aneurysms.

Methods

A meta-analysis that compared SAC with coiling alone and balloon assisted coiling was conducted by database searching. The primary outcomes of this study were immediate occlusion and progressive thrombosis rate, overall perioperative complication rate, and angiographic recurrence. Secondary outcomes included mortality at discharge, hemorrhagic and ischemic complications, and favorable clinical outcome at discharge and at follow-up.

Results

Eight retrospective cohort studies with 1408 ruptured intracranial aneurysms (SAC=499; non-SAC=909) were included. The SAC group tended to show a lower immediate complete occlusion rate than the non-SAC group (54.3% vs 64.2%; RR 0.90; 95% CI 0.83 to 0.99; I2=17.4%) and achieved a significantly higher progressive complete rate at follow-up (73.4% vs 61.0%; RR 1.30; 95% CI 1.16 to 1.46; I2=40.5%) and a lower recurrence rate (4.8% vs 16.6%; RR 0.28; 95% CI 0.16 to 0.50; I2=0.0%). With respect to safety concerns, overall perioperative complications in the SAC group were significantly higher (20.2% vs 13.1%; RR 1.70; 95% CI 1.36 to 2.11; I2=0.0%). However, no significant difference was found for mortality rate at discharge (6.3% vs 6.2%; RR 1.29; 95% CI 0.86 to 1.94; I2=0.0%), or favorable clinical outcome rate at discharge (73.4% vs 74.2%; RR 0.95; 95% CI 0.88 to 1.02; I2=12.1%) and at follow-up (85.6% vs 87.9%; RR 0.98; 95% CI 0.93 to 1.02; I2=0.0%; P=0.338).

Conclusions

SAC has a lower recurrence rate than non-SAC. Nevertheless, further validation by well designed prospective studies is warranted for determining whether stents improve angiographic outcome without an increased complication rate or unfavorable clinical outcome.
A prospective study of the transradial approach for diagnostic cerebral arteriography
Authors: Zussman Benjamin M , Tonetti Daniel A , Stone Jeremy , Brown Merritt , Desai Shashvat M , Gross Bradley A , Jadhav Ashutosh , Jovin Tudor G , Jankowitz Brian Thomas
Published: March 2019

Background

The transradial approach for cardiac catheterization is associated with improved patient safety and satisfaction in comparison with the transfemoral approach. Prospective data for the transradial approach for cerebral arteriography are lacking.

Objective

To carry out a prospective study of consecutive patients undergoing transradial cerebral arteriography at our institution to evaluate the safety, feasibility, and limitations of this approach.

Methods

Consecutive patients referred for diagnostic cerebral arteriography at an institution with minimal transradial experience were enrolled until 50 right transradial diagnostic cerebral arteriograms were obtained. A procedural staging system was developed and goals of angiography were defined before each procedure. The primary outcome was the ability to achieve the predefined goals using the transradial approach. Secondary outcomes included the technical ability to access and inject each supra-aortic artery of interest and the incidence of complications.

Results

A total of 65 patients were screened; 15 were excluded owing to contraindications and 50 underwent attempted right transradial cerebral arteriography. The primary outcome was achieved in 44 patients (88%). Failures occurred at stage 1 (n=3, 6%), stage 2 (n=1, 2%), stage 3a (n=1, 2%), and stage 3b (n=1, 2%). Crossover to the transfemoral approach occurred in four patients (8%) and the procedure was terminated in two patients (4%). All supra-aortic arteries of interest were accessed and injected, with success rates between 89% and 100% with the exception of the left vertebral artery (successful in 59%). There were no major complications and five minor complications.

Conclusion

Neurointerventionalists attempting the transradial approach can expect to achieve moderate early success and a low complication rate.
In vitro accuracy and inter-observer reliability of CT angiography in detecting intracranial aneurysm enlargement
Authors: Al Kasab Sami , Nakagawa Daichi , Zanaty Mario , Bathla Girish , Policeni Bruno , Soni Neetu , Allan Lauren , Hudson Joseph , Limaye Kaustubh , Ortega-Gutierrez Santiago , Samaniego Edgar A , Hasan David
Published: March 2019

Background and purpose

To evaluate the accuracy and inter-observer variability when CT angiography is used to identify unruptured intracranial aneurysm growth.

Methods

Two silicone phantom models were used in this study. Each phantom had eight aneurysms of variable size. The size and location of aneurysms in phantom 1 were representative of real patient aneurysms who presented to our institution. Phantom 2 contained aneurysms in the same locations, but with enlargement in various directions. Three blinded board-certified neuroradiologists were asked to identify the size of each aneurysm in three dimensions using CT angiography. The individual enlargement detection rates and inter-observer agreement rates of aneurysm enlargement among the three experts were calculated.

Results

The detection rate of aneurysm enlargement in one dimension was 58.3% among the three observers. Accurate detection of enlargement in all dimensions was 12.5% among the three observers. Detection accuracy was not related to the size of enlargement. Significant inter-observer measurement variability was present.

Conclusion

The use of CT angiography was associated with a poor ability to identify aneurysm enlargementaccurately. Further human studies are required to confirm our findings.
Palmar/plantar approach for radiographic‐guided injection of the equine distal interphalangeal joint collateral ligament insertion
Authors: Kirkpatrick C Jordan , Ernst Nicolas S , Trumble Troy N
Published: March 2019

There are limited radiographic‐guided injection techniques of the insertion of the distal interphalangeal joint (DIPJ) collateral ligaments. The objective of this study was to develop and evaluate a palmar/plantar radiographic‐guided injection of the collateral ligament insertion in cadavers. Fifty limbs were used to develop the technique and 24 additional limbs were used to evaluate accuracy. An 18 G, 9 cm spinal needle was placed in the depression between the palmar digital neurovascular bundle and arch of the ungular cartilage with dorsodistal advancement towards the distal phalanx collateral fossa. Radiographs verified ideal needle location on the proximal border of the distal phalanx at the collateral fossa. Dye was injected. Hoof walls were partially removed and collateral ligaments were dissected with needles in place to determine needle and dye location. Accuracy of needle placement into the insertion of the DIPJ collateral ligament was 41/48 (85 per cent), with lower accuracy of dye within the ligament (34/48; 71 per cent). Dye entered the DIPJ in 2/48 injections, but dye entered periligamentous structures in 22/48 (46 per cent) injections. A palmar/plantar radiographic‐guided injection of the insertion of the DIPJ collateral ligament had high accuracy rate with low injection rate of the DIPJ in cadavers.
Synthesis, Characterization and Anti-Microbial Activity of Oxalate-Assisted CO3O4 Nanoparticles Derived from Homogeneous Co-Precipitation Method
Authors: Anuradha C. T. , Raji P.
Published: March 2019

Nano-sized cobalt oxide particles exhibit unique and fascinating physical, chemical and anti-microbial activity owing to their large surface to volume ratio. The study of metal oxide nanoparticles interaction with pathogenic microorganisms is great importance for various biomedical applications. The main purpose of this work is to study the anti-bacterial and anti-fungal behavior of cobalt oxide (CO3O4) nanoparticles against gram-positive and gram-negative bacterial strains and different fungi. The structure and morphology of CO3O4 nanoparticles were characterized by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and UV-Visible Spectroscopy, respectively. The CO3O4 nanoparticles showed a significant anti-bacterial activity against two gram-positive bacteria, Staphylococcusaureus (G[Formula: see text]), Streptococcus mutans (G[Formula: see text]), and two gram-negative bacteria, Klebsilla pneumonia (G[Formula: see text]), E. coli (G[Formula: see text]), and it shows a good anti-fungal activity against the two different fungal i.e., Aspergillus flavus (F) and Aspergillus niger (F), at different solvents. It was noted that synthesized CO3O4 nanoparticles exhibited the solvent-dependent anti-bacterial activity against all tested bacterial strains. CO3O4 NPs could be employed effectively for anti-microbial applications.
Singlet oxygen generation from porphyrin-functionalized hexahedral polysilicon microparticles
Authors: Bruce Gordon , Samperi Mario , Amabilino David B. , Duch Marta , Plaza José A. , Pérez-García Lluïsa
Published: March 2019

The generation of singlet oxygen (SO), primarily by using a combination of light and photosensitizers in the presence of a dissolved gas, finds applications in both chemistry and medicine. The efficiency of its formation can be enhanced by immobilization of the photosensitizers. In this work, we have explored the covalent functionalization in suspension of hexahedral slab-like polysilicon microparticles ( [Formula: see text]P, with a largest dimension of three microns) with a model photosensitizer, 5-(4-isothiocyanatophenyl)-10,15,20-(triphenyl)porphyrin (ITC-P), and evaluated the singlet oxygen generation of this photosensitizer in solution and after immobilization (ITC-P-[Formula: see text]P) in suspension. The SO-detection experiment on the functionalized microparticles was performed using a hydrogel as the matrix supporting the microparticles (to avoid their settling), and revealed that ITC-P-[Formula: see text]Pin suspension is capable of generating SO more efficiently than free ITC-P in solution.
Vitamin D and Infertility: The Evidence
Authors: Hornstein Mark D.
Published: March 2019

Vitamin D is a lipid soluble vitamin synthesized by the skin upon exposure to UV light. Approximately 10–20% of vitamin D comes from dietary sources and 25OH-D is its circulating form. Vitamin D receptors are found in reproductive tissues including ovary, uterus, and endometrium permitting investigators to hypothesize a role for vitamin D in reproduction. Indeed, a number of animal studies provide evidence of vitamin D’s importance in fertility. Studies in humans, however, generally have not supported an effect of vitamin D on fertility outcomes. Several retrospective cohort studies did not demonstrate an association between vitamin D levels and pregnancy. Similarly, one study did not find correlation between anovulatory infertility and vitamin D intake. Very low levels of vitamin D, however, were associated with miscarriage in another study. A large meta-analysis of 11 studies and 2700 women did show an improvement in IVF success rates in those with higher levels of vitamin D. Finally, two small studies on vitamin D supplementation and pregnancy did not show a benefit of increasing vitamin D intake. In conclusion, the literature at best shows a minimal impact of vitamin D on infertility and IVF outcomes.
Loss of myeloid-specific protein phosphatase 2A enhances lung injury and fibrosis and results in IL-10-dependent sensitization of epithelial cell apoptosis
Authors: Sun Lei , Hult Elissa M. , Cornell Timothy T. , Kim Kevin K. , Shanley Thomas P. , Wilke Carol A. , Agarwal Manisha , Gurczynski Stephen J. , Moore Bethany B. , Dahmer Mary K.
Published: March 2019

Protein phosphatase 2A (PP2A), a ubiquitously expressed Ser/Thr phosphatase is an important regulator of cytokine signaling and cell function. We previously showed that myeloid-specific deletion of PP2A (LysMcrePP2A−/−) increased mortality in a murine peritoneal sepsis model. In the current study, we assessed the role of myeloid PP2A in regulation of lung injury induced by lipopolysaccharide (LPS) or bleomycin delivered intratracheally. LysMcrePP2A−/−mice experienced increased lung injury in response to both LPS and bleomycin. LysMcrePP2A−/−mice developed more exuberant fibrosis in response to bleomycin, elevated cytokine responses, and chronic myeloid inflammation. Bone marrow-derived macrophages (BMDMs) from LysMcrePP2A−/−mice showed exaggerated inflammatory cytokine release under conditions of both M1 and M2 activation. Notably, secretion of IL-10 was elevated under all stimulation conditions, including activation of BMDMs by multiple Toll-like receptor ligands. Supernatants collected from LPS-stimulated LysMcrePP2A−/−BMDMs induced epithelial cell apoptosis in vitro but this effect was mitigated when IL-10 was also depleted from the BMDMs by crossing LysMcrePP2A−/−mice with systemic IL-10−/−mice (LysMcrePP2A−/−× IL-10−/−) or when IL-10 was neutralized. Despite these findings, IL-10 did not directly induce epithelial cell apoptosis but sensitized epithelial cells to other mediators from the BMDMs. Taken together our results demonstrate that myeloid PP2A regulates production of multiple cytokines but that its effect is most pronounced on IL-10 production. Furthermore, IL-10 sensitizes epithelial cells to apoptosis in response to myeloid-derived mediators, which likely contributes to the pathogenesis of lung injury and fibrosis in this model.
Expression of soluble receptor for advanced glycation end products is associated with disease severity in congenital diaphragmatic hernia
Authors: Kipfmueller Florian , Heindel Katrin , Geipel Annegret , Berg Christoph , Bartmann Peter , Reutter Heiko , Mueller Andreas , Holdenrieder Stefan
Published: March 2019

Pulmonary hypertension (PH) and lung hypoplasia are major contributors to morbidity and mortality in newborns with congenital diaphragmatic hernia (CDH). The soluble receptor for advanced glycation end products (sRAGE) is a marker of endothelial function and might be associated with disease severity in CDH newborns. In a cohort of 30 CDH newborns and 20 healthy control newborns, sRAGE concentration was measured at birth and at 6 h, 12 h, 24 h, 48 h, and 7–10 days. In healthy newborns, sRAGE was significantly higher at birth and at 48 h compared with CDH newborns (both P < 0.001). Among CDH newborns, sRAGE was significantly lower at birth ( P = 0.033) and at 7–10 days ( P = 0.035) in patients receiving extracorporeal membrane oxygenation (ECMO) compared with patients not receiving ECMO. In contrast, CDH newborns receiving ECMO had significantly higher values at 6 h ( P = 0.001), 12 h ( P = 0.004), and 48 h (0.032). Additionally, sRAGE correlated significantly with PH severity, intensity and duration of mechanical ventilation, and prenatally assessed markers of CDH severity (lung size, liver herniation). The probability to receive ECMO therapy was five times higher in CDH newborns with sRAGE concentrations below the calculated cutoff of 650 pg/ml at birth ( P = 0.002) and nine times higher in CDH newborns with sRAGE concentrations above the cutoff of 3,500 pg/ml at 6 h ( P = 0.001). These findings suggest a potential involvement of sRAGE in the pathophysiology of CDH and may act as a therapeutic target in future treatment approaches.
Exaggerated mechanoreflex in early-stage type 1 diabetic rats: role of Piezo channels
Authors: Grotle Ann-Katrin , Garcia Elizabeth A. , Harrison Michelle L. , Huo Yu , Crawford Charles K. , Ybarbo Kai M. , Stone Audrey J.
Published: March 2019

Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the mechanoreflex, which is commonly stimulated by stretching the Achilles tendon, contributes to this abnormal response. Furthermore, the role of mechano-gated Piezo channels, found on thin-fiber afferent endings, in evoking the mechanoreflex in T1DM is also unknown. Therefore, in male and female streptozotocin (STZ, 50 mg/kg)-induced T1DM and healthy control (CTL) rats, we examined the pressor and cardioaccelerator responses to tendon stretch during the early stage of the disease. To determine the role of Piezo channels, GsMTx-4, a selective Piezo channel inhibitor, was injected into the arterial supply of the hindlimb. At 1 wk after STZ injection in unanesthetized, decerebrate rats, we stretched the Achilles tendon for 30 s and measured pressor and cardioaccelerator responses. We then compared pressor and cardioaccelerator responses to tendon stretch before and after GsMTx-4 injection (10 µg/100 ml). We found that the pressor (change in mean arterial pressure) response [41 ± 5 mmHg ( n = 15) for STZ and 18 ± 3 mmHg ( n = 11) for CTL ( P < 0.01)] and cardioaccelerator (change in heart rate) response [18 ± 4 beats/min for STZ ( n = 15) and 8 ± 2 beats/min ( n = 11) for CTL ( P < 0.05)] to tendon stretch were exaggerated in STZ rats. Local injection of GsMTx-4 attenuated the pressor [55 ± 7 mmHg ( n = 6) before and 27 ± 9 mmHg ( n = 6) after GsMTx-4 ( P < 0.01)], but not the cardioaccelerator, response to tendon stretch in STZ rats and had no effect on either response in CTL rats. These data suggest that T1DM exaggerates the mechanoreflex response to tendon stretch and that Piezo channels play a role in this exaggeration.
Antenatal betamethasone augments early rise in pulmonary perfusion at birth in preterm lambs: role of ductal shunting and right ventricular outflow distribution
Authors: Smolich Joseph J. , Kenna Kelly R. , Mynard Jonathan P.
Published: March 2019

The glucocorticosteroid betamethasone is routinely administered via maternal intramuscular injection to enhance fetal lung maturation before anticipated preterm birth. Although antenatal betamethasone increases fetal pulmonary arterial (PA) blood flow, whether this agent alters the contribution of 1) right ventricular (RV) output or 2) left-to-right shunting across the ductus arteriosus to rises in PA blood flow after preterm birth is unknown. To address this question, anesthetized control ( n = 7) and betamethasone-treated ( n = 7) preterm fetal lambs (gestation 127 ± 1 days, means ± SD) were instrumented with aortic, pulmonary, and left atrial catheters as well as ductus arteriosus and left PA flow probes to calculate RV output, with hemodynamics measured for 30 min after cord clamping and mechanical ventilation. Mean PA blood flow was higher in betamethasone-treated than in control lambs over the initial 10 min after birth ( P < 0.05). This higher PA flow was accompanied by 1) a greater pulmonary vascular conductance ( P ≤ 0.025), 2) a larger proportion of RV output passing to lungs ( P ≤ 0.01), despite a fall in this output, and 3) earlier reversal and a greater magnitude ( P ≤ 0.025) of net ductal shunting, due to the combination of higher left-to-right ( P ≤ 0.025) and lesser right-to-left phasic shunting ( P ≤ 0.025). These results suggest that antenatal betamethasone augments the initial rise in PA blood flow after birth in preterm lambs, with this augmented rise supported by the combination of 1) a greater redistribution of RV output toward the lungs and 2) a faster and larger reversal in net ductal shunting underpinned not only by greater left-to-right, but also by lesser right-to-left phasic shunting.
Potassium-sparing effects of furosemide in mice on high-potassium diets
Authors: Wang Bangchen , Sansom Steven C.
Published: March 2019

In individuals on a regular “Western” diet, furosemide induces a kaliuresis and reduction in plasma K concentration by inhibiting Na reabsorption in the thick ascending limb of Henle’s loop, enhancing delivery of Na to the aldosterone-sensitive distal nephron. In the aldosterone-sensitive distal nephron, the increased Na delivery stimulates K wasting due to an exaggerated exchange of epithelial Na channel-mediated Na reabsorption of secreted K. The effects of furosemide are different in mice fed a high-K, alkaline (HK) diet: the large-conductance Ca-activated K (BK) channel, in conjunction with the BK β4-subunit (BK-α/β4), mediates K secretion from intercalated cells (IC) of the connecting tubule and collecting ducts. The urinary alkaline load is necessary for BK-α/β4-mediated K secretion in HK diet-fed mice. However, furosemide acidifies the urine by increasing vacuolar ATPase expression and acid secretion from IC, thereby inhibiting BK-α/β4-mediated K secretion and sparing K. In mice fed a low-Na, high-K (LNaHK) diet, furosemide causes a greater increase in plasma K concentration and reduction in K excretion than in HK diet-fed mice. Micropuncture of the early distal tubule of mice fed a LNaHK diet, but not a regular or a HK diet, reveals K secretion in the thick ascending limb of Henle’s loop. The sites of action of K secretion in individuals consuming a high-K diet should be taken into account when diuretic agents known to waste K with low or moderate K intakes are prescribed.
Both fast and slow learning processes contribute to savings following sensorimotor adaptation
Authors: Coltman Susan K. , Cashaback Joshua G. A. , Gribble Paul L.
Published: March 2019

Recent work suggests that the rate of learning in sensorimotor adaptation is likely not fixed, but rather can change based on previous experience. One example is savings, a commonly observed phenomenon whereby the relearning of a motor skill is faster than the initial learning. Sensorimotor adaptation is thought to be driven by sensory prediction errors, which are the result of a mismatch between predicted and actual sensory consequences. It has been proposed that during motor adaptation the generation of sensory prediction errors engages two processes (fast and slow) that differ in learning and retention rates. We tested the idea that a history of errors would influence both the fast and slow processes during savings. Participants were asked to perform the same force field adaptation task twice in succession. We found that adaptation to the force field a second time led to increases in estimated learning rates for both fast and slow processes. While it has been proposed that savings is explained by an increase in learning rate for the fast process, here we observed that the slow process also contributes to savings. Our work suggests that fast and slow adaptation processes are both responsive to a history of error and both contribute to savings.

NEW & NOTEWORTHY We studied the underlying mechanisms of savings during motor adaptation. Using a two-state model to represent fast and slow processes that contribute to motor adaptation, we found that a history of error modulates performance in both processes. While previous research has attributed savings to only changes in the fast process, we demonstrated that an increase in both processes is needed to account for the measured behavioral data.
Basolateral amygdala neurons are activated during threat expectation
Authors: Amir Alon , Kyriazi Pinelopi , Lee Seung-Chan , Headley Drew B. , Paré Denis
Published: March 2019

Fear conditioning studies have led to the view that the amygdala contains neurons that signal threat and in turn elicit defensive behaviors through their brain stem and hypothalamic targets. In agreement with this model, a prior unit-recording study in rats performing a seminaturalistic foraging task revealed that many lateral amygdala (LA) neurons are predator responsive. In contrast, our previous study emphasized that most basolateral (BL) amygdala neurons are inhibited at proximity of the predator. However, the two studies used different methods to analyze unit activity, complicating comparisons between them. By applying the same method to the sample of BL neurons we recorded previously, the present study revealed that most principal cells are inhibited by the predator and only 4.5% are activated. Moreover, two-thirds of these cells were also activated by nonthreatening stimuli. In fact, fitting unit activity with a generalized linear model revealed that the only task variables associated with a prevalent positive modulation of BL activity were expectation of the predator’s presence and whether the prior trial had been a failure or success. At odds with the threat-coding model of the amygdala, actual confrontation with the predator was usually associated with a widespread inhibition of principal BL neurons.

NEW & NOTEWORTHY The basolateral amygdala (BL) is thought to contain neurons that signal threat, in turn eliciting defensive behaviors. In contrast, the present study reports that very few principal BL cells are responsive to threats and that most of them are also activated by nonthreatening stimuli. Yet, expectation of the threat’s presence was associated with a prevalent positive modulation of BL activity; actual confrontation with the threat was associated with a widespread inhibition.
Oral LPS Dosing Induces Local Immunological Changes in the Pancreatic Lymph Nodes in Mice
Authors: Kihl Pernille , Krych Lukasz , Deng Ling , Kildemoes Anna Overgaard , Laigaard Ann , Hansen Lars Hestbjerg , Hansen Camilla Hartmann Friis , Buschard Karsten , Nielsen Dennis Sandris , Hansen Axel Kornerup
Published: March 2019

Lacking the initial contact between the immune system and microbial-associated molecular patterns (MAMPs), such as lipopolysaccharides (LPS), early in life, may be regarded as one of the causal factors of the increasing global increase in the incidence of autoimmune diseases, such as type 1 diabetes (T1D). Previously, a reduced incidence of T1D accompanied by dramatically increased abundances of both the mucin-metabolising bacterium Akkermansia muciniphila, and LPS-carrying Proteobacteria was observed, when vancomycin was given to pups of nonobese diabetic (NOD) mice. While the T1D incidence reducing effect of A. muciniphila has been shown in further studies, little is known as to whether the increased abundance of LPS-carrying bacteria also has a protective effect. Therefore, we fed NOD pups with Eschericia coli LPS orally from birth to weaning, which decreased the gene expressions of TNFα, IL-10, IL-6, IFNγ, IL-1β, IL-2, IL-4, and FoxP3 in the pancreatic lymph nodes, while the same gene expression profile in the spleen was unaffected. However, no significant difference in the incidence of T1D, gut microbiota composition, or ileum expression of the genetic markers of gut permeability, Claudin8, Occludin, Zonulin-1 (Tjp1), Claudin15, Muc1, and Muc2 were observed in relation to LPS ingestion. It is, therefore, concluded that early life oral E. coli LPS has an impact on the local immune response, which, however, did not influence T1D incidence in NOD mice later in life.
Contrast-Enhanced EUS for Differential Diagnosis of Pancreatic Masses: A Meta-Analysis
Authors: Mei Sibin , Wang Mengyu , Sun Leimin
Published: March 2019

Background. Though methods for the diagnosis of pancreatic masses are various, such as ultrasonography (US), computed tomography (CT), endoscopic ultrasonography (EUS), and contrast-enhanced computed tomography (CE-CT), their sensitivity, specificity, and accuracy are not quite satisfying. Contrast-enhanced endoscopic ultrasonography (CE-EUS), as a new technique, has its own unique advantages in diagnosing pancreatic disease. However, its sensitivity, specificity, and accuracy are still controversial. Objective. To evaluate the accuracy of CE-EUS for differential diagnosis between benign and malignant pancreatic mass lesions. Design. Eighteen relevant articles systemically searched from PubMed, Web of Science, Ovid, Scopus, and MEDLINE were selected. The pooled results were calculated in a fixed effects model. Main Outcome Measurement. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative likelihood ratio, diagnostic odds ratio (OR), and summary receiver operating characteristic (SROC) curve. Results. The pooled sensitivity, specificity, and diagnostic odds ratio of CE-EUS for the differential diagnosis of pancreatic adenocarcinomas were 0.91 (95% confidence interval (CI), 0.89-0.93), 0.86 (95% CI, 0.83-0.89), and 69.50 (95% CI, 48.89-98.80), respectively. The SROC area under the curve was 0.9545. The subgroup analysis based on excluding the outliers showed that the heterogeneity was eliminated and the pooled sensitivity and specificity were 0.92 (95% CI, 0.90-0.93) and 0.87 (95% CI, 0.84-0.89), respectively. The SROC area under the curve was 0.9569. Conclusion. CE-EUS is a useful method to distinguish pancreatic adenocarcinoma from other pancreatic diseases. Compared with EUS elastography, it has higher specificity. However, it is still not superior to pathological diagnosis for the identification of pancreatic carcinomas.