bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition
Authors: Pianko Matthew J. , Devlin Sean M. , Littmann Eric R. , Chansakul Aisara , Mastey Donna , Salcedo Meghan , Fontana Emily , Ling Lilan , Tavitian Elizabet , Slingerland John B. , Slingerland Ann E. , Clurman Annelie , Gomes Antonio L. C. , Taur Ying , Pamer Eric G. , Peled Jonathan U. , van den Brink Marcel R. M. , Landgren Ola , Lesokhin Alexander M.
Published: October 2019

Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+. Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry–based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD− patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD− and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.
Suitable reference genes determination for real-time PCR using induced sputum samples
Authors: Moermans Catherine , Deliege Esteban , Pirottin Dimitri , Poulet Christophe , Guiot Julien , Henket Monique , da Silva Jane , Louis Renaud
Published: October 2019

Induced sputum is a non-invasive method of collecting cells from airways. Gene expression analysis from sputum cells has been used to understand the underlying mechanisms of airway diseases such as asthma or chronic obstructive pulmonary disease (COPD). Suitable reference genes for normalisation of target mRNA levels between sputum samples have not been defined so far.

The current study assessed the expression stability of nine common reference genes in sputum samples from 14 healthy volunteers, 12 asthmatics and 12 COPD patients.

Using three different algorithms (geNorm, NormFinder and BestKeeper), we identified HPRT1 and GNB2L1 as the most optimal reference genes to use for normalisation of quantitative reverse transcriptase (RT) PCR data from sputum cells. The higher expression stability of HPRT1 and GNB2L1 were confirmed in a validation set of patients including nine healthy controls, five COPD patients and five asthmatic patients. In this group, the RNA extraction and RT-PCR methods differed, which attested that these genes remained the most reliable whatever the method used to extract the RNA, generate complementary DNA or amplify it.

Finally, an example of relative quantification of gene expression linked to eosinophils or neutrophils provided more accurate results after normalisation with the reference genes identified as the most stable compared to the least stable and confirmed our findings.
Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea
Authors: Eastwood Peter R. , Barnes Maree , MacKay Stuart G. , Wheatley John R. , Hillman David R. , Nguyên Xuân-Lan , Lewis Richard , Campbell Matthew C. , Pételle Boris , Walsh Jennifer H. , Jones Andrew C. , Palme Carsten E. , Bizon Alain , Meslier Nicole , Bertolus Chloé , Maddison Kathleen J. , Laccourreye Laurent , Raux Guillaume , Denoncin Katleen , Attali Valérie , Gagnadoux Frédéric , Launois Sandrine H.
Published: October 2019

Background and aim

Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severityviagenioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNSviaa small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system.

Methods

This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea–hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, numberNCT03048604.

Results

22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m−2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h−1, a mean change of 10.8 events·h−1(p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h−1, a mean change of 9.3 events·h−1(p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period.

Conclusions

Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.
RNA-Seq analysis of Clerodendrum inerme (L.) roots in response to salt stress
Authors: Xiong Yuping , Yan Haifeng , Liang Hanzhi , Zhang Yueya , Guo Beiyi , Niu Meiyun , Jian Shuguang , Ren Hai , Zhang Xinhua , Li Yuan , Zeng Songjun , Wu Kunlin , Zheng Feng , Teixeira da Silva Jaime A. , Ma Guohua
Published: October 2019

Background

Clerodendrum inerme (L.) Gaertn, a halophyte, usually grows on coastal beaches as an important mangrove plant. The salt-tolerant mechanisms and related genes of this species that respond to short-term salinity stress are unknown for us. The de novo transcriptome of C. inerme roots was analyzed using next-generation sequencing technology to identify genes involved in salt tolerance and to better understand the response mechanisms of C. inerme to salt stress.

Results

Illumina RNA-sequencing was performed on root samples treated with 400 mM NaCl for 0 h, 6 h, 24 h, and 72 h to investigate changes in C. inerme in response to salt stress. The de novo assembly identified 98,968 unigenes. Among these unigenes, 46,085 unigenes were annotated in the NCBI non-redundant protein sequences (NR) database, 34,756 sequences in the Swiss-Prot database and 43,113 unigenes in the evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) database. 52 Gene Ontology (GO) terms and 31 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were matched to those unigenes. Most differentially expressed genes (DEGs) related to the GO terms “single-organism process”, “membrane” and “catalytic activity” were significantly enriched while numerous DEGs related to the plant hormone signal transduction pathway were also significantly enriched. The detection of relative expression levels of 9 candidate DEGs by qRT-PCR were basically consistent with fold changes in RNA sequencing analysis, demonstrating that transcriptome data can accurately reflect the response of C. inerme roots to salt stress.

Conclusions

This work revealed that the response of C. inerme roots to saline condition included significant alteration in response of the genes related to plant hormone signaling. Besides, our findings provide numerous salt-tolerant genes for further research to improve the salt tolerance of functional plants and will enhance research on salt-tolerant mechanisms of halophytes.
The efficacy and safety of continuous versus single-injection popliteal sciatic nerve block in outpatient foot and ankle surgery: a systematic review and meta-analysis
Authors: Ma Hsuan-Hsiao , Chou Te-Feng Arthur , Tsai Shang-Wen , Chen Cheng-Fong , Wu Po-Kuei , Chen Wei-Ming
Published: October 2019

Background

Continuous popliteal sciatic nerve block (CPSNB) has been performed in outpatient foot and ankle surgery as a regional anesthesia method to relieve postoperative pain. Its efficacy as well as safety is yet to be established. There are two purposes of this study: (1) to validate the efficacy of CPSNB with regards to better pain relief and reduced analgesics consumption; (2) to assess the safety of CPSNB.

Methods

We performed a comprehensive literature review on Web of Science, the Cochrane Library, PubMed and Embase and only included randomized controlled trials (RCTs). Five RCTs that compared the efficacy and safety of CPSNB with the single-injection popliteal sciatic nerve block group were included. The primary outcome parameters were visual analog scale (VAS) scores at postoperative 24, 48 and 72 h. The secondary outcome parameters were amount of oral analgesics consumed, overall patient satisfaction and need of admission after surgery. A sensitivity analysis was performed to explore the consistency of the results.

Results

In comparison with the single-injection group, CPSNB was associated with a lower VAS score at postoperative 24 and 48 h (p < 0.05). There were no neuropathic symptoms or infection events after the nerve block. However, there were several minor complications associated with the pump and catheter system, with drug leakage being the most common complication (N = 26 of 187, 13.9%).

Conclusion

CPSNB is an effective method in pain management for outpatient foot and ankle surgery. Both methods appear to be safe as none of the patients experienced neuropathic symptoms or infection. Further studies with larger sample size are needed to compare the risk of major complications between the two methods.

Level of evidence

I; meta-analysis.
In vivo immobilization of an organophosphorus hydrolyzing enzyme on bacterial polyhydroxyalkanoate nano-granules
Authors: Li Ru , Yang Jian , Xiao Yunzhu , Long Lijuan
Published: October 2019

Background

Polyhydroxyalkanoate (PHA) are nano-granules naturally produced by bacteria. Two types of proteins, PHA synthase (PhaC) and phasins (PhaPs), are attached to the PHA surface by covalent and hydrophobic interactions. Utilizing these anchored proteins, functionalized PHA nano-granules displaying proteins of interest can be easily prepared by fermentation.

Results

In this study, a one-step fabrication method was developed for stable and efficient immobilization of an organophosphorus degrading enzyme on PHA nano-granules. The nano-biocatalysts were produced in recombinant Escherichia coli cells into which the polyhydroxyalkanoate synthesis pathway from Cupriavidus necator had been introduced. Two different strategies, covalent attachment and hydrophobic binding, were investigated by fusing bacterial organophosphorus anhydride hydrolase (OPAA4301) with PhaC and PhaP, respectively. Using both methods, the tetrameric enzyme successfully self-assembled and was displayed on the PHA surface. The display density of the target fused enzyme was enhanced to 6.8% of total protein on decorated PHA by combination of covalent and non-covalent binding modes. Immobilization of the enzyme on PHA granules resulted in higher catalytic efficiency, increased stability and excellent reusability. The kcat values of the immobilized enzymes increased by threefold compared to that of the free enzyme. The pH stability under acidic conditions was significantly enhanced, and the immobilized enzyme was stable at pH 3.0–11.0. Furthermore, more than 80% of the initial enzyme activity retained after recycling ten times.

Conclusions

This study provides a promising approach for cost-efficient in vivo immobilization of a tetrameric organophosphorus degrading enzyme. The immobilization process expands the utility of the enzyme, and may inspire further commercial developments of PHA nano-biocatalysts. As revealed by our results, combination of covalent and non-covalent binding is recommended for display of enzymes on PHA granules.
Mevalonate production from ethanol by direct conversion through acetyl-CoA using recombinant Pseudomonas putida, a novel biocatalyst for terpenoid production
Authors: Yang Jeongmo , Son Ji Hee , Kim Hyeonsoo , Cho Sukhyeong , Na Jeong-geol , Yeon Young Joo , Lee Jinwon
Published: October 2019

Background

Bioethanol is one of the most representative eco-friendly fuels developed to replace the non-renewable fossil fuels and is the most successful commercially available bio-conversion technology till date. With the availability of inexpensive carbon sources, such as cellulosic biomass, bioethanol production has become cheaper and easier to perform, which can facilitate the development of methods for converting ethanol into higher value-added biochemicals. In this study, a bioconversion process using Pseudomonas putida as a biocatalyst was established, wherein ethanol was converted to mevalonate. Since ethanol can be converted directly to acetyl-CoA, bypassing its conversion to pyruvate, there is a possibility that ethanol can be converted to mevalonate without producing pyruvate-derived by-products. Furthermore, P. putida seems to be highly resistant to the toxicity caused by terpenoids, and thus can be useful in conducting terpenoid production research.

Results

In this study, we first expressed the core genes responsible for mevalonate production (atoB, mvaS, and mvaE) in P. putida and mevalonate production was confirmed. Thereafter, through an improvement in genetic stability and ethanol metabolism manipulation, mevalonate production was enhanced up to 2.39-fold (1.70 g/L vs. 4.07 g/L) from 200 mM ethanol with an enhancement in reproducibility of mevalonate production. Following this, the metabolic characteristics related to ethanol catabolism and mevalonate production were revealed by manipulations to reduce fatty acid biosynthesis and optimize pH by batch fermentation. Finally, we reached a product yield of 0.41 g mevalonate/g ethanol in flask scale culture and 0.32 g mevalonate/g ethanol in batch fermentation. This is the highest experimental yield obtained from using carbon sources other than carbohydrates till date and it is expected that further improvements will be made through the development of fermentation methods.

Conclusion

Pseudomonas putida was investigated as a biocatalyst that can efficiently convert ethanol to mevalonate, the major precursor for terpenoid production, and this research is expected to open new avenues for the production of terpenoids using microorganisms that have not yet reached the stage of mass production.
Designer bioemulsifiers based on combinations of different polysaccharides with the novel emulsifying esterase AXE from Bacillus subtilis CICC 20034
Authors: Tao Weiyi , Lin Junzhang , Wang Weidong , Huang He , Li Shuang
Published: October 2019

Background

Bioemulsifiers are surface-active compounds, which exhibit advantages including low toxicity, higher biodegradability and biocompatibility over synthetic chemical surfactants. Despite their potential benefits, some obstacles impede the practical applications of bioemulsifiers, including low yields and high purification costs. Here, we aimed to exploit a novel protein bioemulsifier with efficient emulsifying activity and low-production cost, as well as proposed a design-bioemulsifier system that meets different requirements of industrial emulsification in the most economical way.

Results

The esterase AXE was first reported for its efficient emulsifying activity and had been studied for possible application as a protein bioemulsifier. AXE showed an excellent emulsification effect with different hydrophobic substrates, especially short-chain aliphatic and benzene derivatives, as well as excellent stability under extreme conditions such as high temperature (85 °C) and acidic conditions. AXE also exhibited good stability over a range of NaCl, MgSO4, and CaCl2 concentrations from 0 to 1000 mM, and the emulsifying activity even showed a slight increase at salt concentrations over 500 mM. A design-bioemulsifier system was proposed that uses AXE in combination with a variety of polysaccharides to form efficient bioemulsifier, which enhanced the emulsifying activity and further lowered the concentration of AXE needed in the complex.

Conclusions

AXE showed a great application potential as a novel bioemulsifier with excellent emulsifying ability. The AXE-based-designer bioemulsifier could be obtained in the most economical way and open broad new fields for low-cost, environmentally friendly bioemulsifiers.
Determining the clinical significance of co-colonization of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus in the intestinal tracts of patients in intensive care units: a case–control study
Authors: Yoon Young Kyung , Lee Min Jung , Ju Yongguk , Lee Sung Eun , Yang Kyung Sook , Sohn Jang Wook , Kim Min Ja
Published: October 2019

Background

The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) has become a global concern for public health. The proximity of vancomycin-resistant enterococcus (VRE) and methicillin-resistant S. aureus (MRSA) is considered to be one of the foremost risk factors for the development of VRSA. This study aimed to determine the incidence, risk factors, and clinical outcomes of intestinal co-colonization with VRE and MRSA.

Methods

A case–control study was conducted in 52-bed intensive care units (ICUs) of a university-affiliated hospital from September 2012 to October 2017. Active surveillance using rectal cultures for VRE were conducted at ICU admission and on a weekly basis. Weekly surveillance cultures for detection of rectal MRSA were also conducted in patients with VRE carriage. Patients with intestinal co-colonization of VRE and MRSA were compared with randomly selected control patients with VRE colonization alone (1:1). Vancomycin minimum inhibitory concentrations (MICs) for MRSA isolates were determined by the Etest.

Results

Of the 4679 consecutive patients, 195 cases and 924 controls were detected. The median monthly incidence and duration of intestinal co-colonization with VRE and MRSA were 2.3/1000 patient-days and 7 days, respectively. The frequency of both MRSA infections and mortality attributable to MRSA were higher in the case group than in the control group: 56.9% vs. 44.1% (P = 0.011) and 8.2% vs. 1.0% (P = 0.002), respectively. Independent risk factors for intestinal co-colonization were enteral tube feeding (odds ratio [OR], 2.09; 95% confidence interval [CI] 1.32–3.32), metabolic diseases (OR, 1.75; 95% CI 1.05–2.93), male gender (OR, 1.62; 95% CI 1.06–2.50), and Charlson comorbidity index < 3 (OR, 3.61; 95% CI 1.88–6.94). All MRSA isolates from case patients were susceptible to vancomycin (MIC ≤ 2 mg/L).

Conclusions

Our study indicates that intestinal co-colonization of VRE and MRSA occurs commonly among patients in the ICU with MRSA endemicity, which might be associated with poor clinical outcomes.
Visceral adipose accumulation increased the risk of hyperuricemia among middle-aged and elderly adults: a population-based study
Authors: Huang Xiaolin , Jiang Xiaohong , Wang Long , Chen Lu , Wu Yang , Gao Pei , Hua Fei
Published: October 2019

Background

The role of body fat distribution in uric acid metabolism is still ambiguity. We aimed to investigate the independent contribution of visceral adipose measured by visceral adiposity index and lipid accumulation product and liver fat assessed by fatty liver index to the risk of hyperuricemia.

Methods

We conducted a cross-sectional study involving 1284 participants aged ≥ 40 years old recruited from communities in Zhonglou district, Changzhou. Each participant completed a standard questionnaire, and provided blood samples for biochemical measurements. Visceral adiposity index, fatty liver index and lipid accumulation product were calculated by simple anthropometric and functional parameters. Hyperuricemia was defined as serum uric acid ≥ 420 μmol/l for males and ≥ 360 μmol/l for females.

Results

The prevalence of hyperuricemia was 15.9% and gradually increased across tertiles of adiposity-based indices. The visceral adipose-based measurements (visceral adiposity index, fatty liver index, lipid accumulation product) had better power to discriminate hyperuricemia than body mass index (BMI), waist circumference and neck circumference, and visceral adiposity index exhibited the highest power, with the area under the receiver operating characteristics curve (AUROC) of 0.662 (0.636–0.688). Multivariate logistic regression found 1.49-fold, 2.21-fold and 2.12-fold increased risk of hyperuricemia with 1-unit increment of visceral adiposity index, fatty liver index, and lipid accumulation product, respectively. Compared to tertile 1, the odds ratios of hyperuricemia for the second tertile and the third tertile of visceral adiposity index were 1.57 (1.00–2.50) and 3.11 (1.96–4.94), those of fatty liver index were 1.64 (1.05–2.68) and 3.58 (1.94–6.01), and those of lipid accumulation product were 1.93 (1.19–3.15) and 3.53 (2.05–6.09), respectively. However, no significant associations of BMI, waist circumference and neck circumference with hyperuricemia were observed.

Conclusions

Visceral adipose accumulation increased the risk of hyperuricemia, independently of BMI, waist circumference and neck circumference, among middle-aged and elderly Chinese adults.
Improving the quality of maternal and newborn health outcomes through a clinical mentorship program in the Democratic Republic of the Congo: study protocol
Authors: Xiong Xu , Carter Rebecca , Lusamba-Dikassa Paul-Samson , Kuburhanwa Elvis C. , Kimanuka Francine , Salumu Freddy , Clarysse Guy , Tutu Baudouin Kalume , Yuma Sylvain , Iyeti Alain Mboko , Hernandez Julie H. , Shaffer Jeffrey G. , Villeneuve Susie , Prual Alain , Pyne-Mercier Lee , Nigussie Assaye , Buekens Pierre
Published: October 2019

Background

The Democratic Republic of the Congo (DRC) boasts one of the highest rates of institutional deliveries in sub-Saharan Africa (80%), with eight out of every ten births also assisted by a skilled provider. However, the maternal and neonatal mortality are still among the highest in the world, which demonstrates the poor in-facility quality of maternal and newborn care. The objective of this ongoing project is to design, implement, and evaluate a clinical mentorship program in 72 health facilities in two rural provinces of Kwango and Kwilu, DRC.

Methods

This is an ongoing quasi-experimental study. In the 72 facilities, 48 facilities were assigned to the group where the clinical mentorship program is being implemented (intervention group), and 24 facilities were assigned to the group where the clinical mentorship program is not being implemented (control group). The groups were selected and assigned based on administrative criteria, taking into account the number of deliveries in each facility, the coverage of health zones, accessibility, and ease of implementation of a clinical mentorship program. The main activities are organizing and training a national team of mentors (including senior midwives, obstetricians, and pediatricians) in clinical mentoring, deploying them to mentor all health providers (mentees) performing maternal and newborn health (MNH) services, and providing in-service training in routine and Emergency Obstetrical and Newborn Care (EmONC) to the mentees in health facilities over an 18-month period. Baseline and endline assessments are carried out to evaluate the effectiveness of the clinical mentorship program on the quality of MNH care and the effective coverage of key interventions to reduce maternal and neonatal mortality. Findings will be disseminated nationwide and internationally, as scientific evidence is scarce. A national strategy, guidelines, and tools for clinical mentorship in MNH will be developed for replication in other provinces, thus benefitting the entire country.

Discussion

This is the largest project on clinical mentorship aimed to improving the quality of MNH care in Africa. This program is expected to generate one of the first pieces of scientific evidence on the effectiveness of a clinical mentorship program in MNH on a scientifically designed and sustainable model.
Getting the most from after action reviews to improve global health security
Authors: Stoto Michael A. , Nelson Christopher , Piltch-Loeb Rachael , Mayigane Landry Ndriko , Copper Frederik , Chungong Stella
Published: October 2019

Background

After Action Reviews (AARs) provide a means to observe how well preparedness systems perform in real world conditions and can help to identify – and address – gaps in national and global public health emergency preparedness (PHEP) systems. WHO has recently published guidance for voluntary AARs. This analysis builds on this guidance by reviewing evidence on the effectiveness of AARs as tools for system improvement and by summarizing some key lessons about ensuring that AARs result in meaningful learning from experience.

Results

Empirical evidence from a variety of fields suggests that AARs hold considerable promise as tools of system improvement for PHEP. Our review of the literature and practical experience demonstrates that AARs are most likely to result in meaningful learning if they focus on incidents that are selected for their learning value, involve an appropriately broad range of perspectives, are conducted with appropriate time for reflection, employ systems frameworks and rigorous tools such as facilitated lookbacks and root cause analysis, and strike a balance between attention to incident specifics vs. generalizable capacities and capabilities.

Conclusions

Employing these practices requires a PHEP system that facilitates the preparation of insightful AARs, and more generally rewards learning. The barriers to AARs fall into two categories: concerns about the cultural sensitivity and context, liability, the political response, and national security; and constraints on staff time and the lack of experience and the requisite analytical skills. Ensuring that AARs fulfill their promise as tools of system improvement will require ongoing investment and a change in mindset. The first step should be to clarify that the goal of AARs is organizational learning, not placing blame or punishing poor performance. Based on experience in other fields, the buy-in of agency and political leadership is critical in this regard. National public health systems also need support in the form of toolkits, guides, and training, as well as research on AAR methods. An AAR registry could support organizational improvement through careful post-event analysis of systems’ own events, facilitate identification and sharing of best practices across jurisdictions, and enable cross-case analyses.
Amyloid-β peptides in cerebrospinal fluid of patients with dementia with Lewy bodies
Authors: van Steenoven Inger , van der Flier Wiesje M. , Scheltens Philip , Teunissen Charlotte E. , Lemstra Afina W.
Published: October 2019

Background

One of the major challenges in diagnosing dementia with Lewy bodies (DLB) is the common co-morbid presence of amyloid pathology. To understand the putative role of altered amyloid-β (Aβ) metabolism in dementia with DLB, we analyzed levels of different cerebrospinal fluid (CSF) Aβ peptides (Aβ38, Aβ40, Aβ42) in DLB, Alzheimer’s disease (AD), and cognitively normal controls.

Methods

CSF from patients with DLB (n = 72; age 68 ± 6 years; 10%F; Mini-mental State examination (MMSE) 23 ± 4), AD (n = 38; age 68 ± 6 years; 8%F; MMSE 22 ± 5), and cognitively normal controls (n = 38; age 67 ± 7 years; 13%F; MMSE 29 ± 2) was analyzed using the Meso Scale Discovery assay for human Aβ peptides. We performed general linear models to compare CSF Aβ peptide levels between groups. Associations between CSF Aβ peptides and MMSE score at baseline and longitudinal changes over time were assessed with linear mixed models.

Results

For all three CSF Aβ peptides and compared to controls (Aβ38 2676 ± 703 pg/ml, Aβ40 6243 ± 1500 pg/ml, and Aβ42 692 ± 205 pg/ml), we observed lower levels in DLB (Aβ38 2247 ± 638, Aβ40 5432 ± 1340, and Aβ42 441 ± 185, p < 0.05), whereas AD patients showed only lower Aβ42 levels (304 ± 71, p < 0.001). The observed differences in Aβ38 and Aβ40 were independent of co-morbid AD pathology (CSF tau/Aβ42 > 0.52) and APOE genotype. Finally, lower Aβ peptide levels were associated with lower MMSE score (β = 1.02–1.11, p < 0.05).

Conclusion

We demonstrated different profiles of CSF Aβ reduction in DLB and AD. In particular, while AD is characterized by an isolated drop in Aβ42, DLB comes with reductions in Aβ38, Aβ40, and Aβ42. This suggests that amyloid metabolism is affected in DLB, even in the absence of co-morbid AD pathology.
Bovine ephemeral fever virus triggers autophagy enhancing virus replication via upregulation of the Src/JNK/AP1 and PI3K/Akt/NF-κB pathways and suppression of the PI3K/Akt/mTOR pathway
Authors: Cheng Ching-Yuan , Tseng Hsu-Hung , Chiu Hung-Chuan , Chang Ching-Dong , Nielsen Brent L. , Liu Hung-Jen
Published: October 2019

Autophagy plays an important role in cellular response to pathogens. However, the impact of the autophagy machinery on bovine ephemeral fever virus (BEFV) infection is not yet determined. A recent study in our laboratory demonstrated that BEFV triggers simultaneously the PI3K/Akt/NF-κB and Src/JNK-AP1 pathways in the stage of virus binding to enhance virus entry. In this work, we report that BEFV induces autophagy via upregulation of the PI3K/Akt/NF-κB and Src/JNK/AP1 pathways in the early to middle stages of infection and suppresses the PI3K/Akt/mTOR pathway at the late stage of infection. To activate NF-κB, BEFV promotes degradation of IκBα and activates Akt to stimulate NF-κB translocation into the nucleus. Immunoprecipitation assays revealed that BEFV disrupts Beclin 1 and Bcl-2 interaction by JNK-mediated Bcl-2 phosphorylation, thereby activating autophagy. Overexpression of Bcl-2 reversed the BEFV-induced increase in the LC3 II levels. Suppression of autophagy either by knockdown of autophagy-related genes with shRNAs or treatment with a pharmacological inhibitor 3-MA reduced BEFV replication, suggesting that BEFV-induced autophagy benefits virus replication. Our results revealed that the BEFV M protein is one of the viral proteins involved in inducing autophagy via suppression of the PI3K/Akt/mTORC1 pathway. Furthermore, degradation of p62 was observed by immunoblotting, suggesting that BEFV infection triggers a complete autophagic response. Disruption of autophagosome-lysosome fusion by depleting LAMP2 resulted in reduction of virus yield, suggesting that formation of autolysosome benefits virus production.
Systematic improvement of isobutanol production from d-xylose in engineered Saccharomyces cerevisiae
Authors: Promdonkoy Peerada , Siripong Wiparat , Downes Joe James , Tanapongpipat Sutipa , Runguphan Weerawat
Published: October 2019

As the importance of reducing carbon emissions as a means to limit the serious effects of global climate change becomes apparent, synthetic biologists and metabolic engineers are looking to develop renewable sources for transportation fuels and petroleum-derived chemicals. In recent years, microbial production of high-energy fuels has emerged as an attractive alternative to the traditional production of transportation fuels. In particular, the Baker’s yeast Saccharomyces cerevisiae, a highly versatile microbial chassis, has been engineered to produce a wide array of biofuels. Nevertheless, a key limitation of S. cerevisiae is its inability to utilize xylose, the second most abundant sugar in lignocellulosic biomass, for both growth and chemical production. Therefore, the development of a robust S. cerevisiae strain that is able to use xylose is of great importance. Here, we engineered S. cerevisiae to efficiently utilize xylose as a carbon source and produce the advanced biofuel isobutanol. Specifically, we screened xylose reductase (XR) and xylose dehydrogenase (XDH) variants from different xylose-metabolizing yeast strains to identify the XR–XDH combination with the highest activity. Overexpression of the selected XR–XDH variants, a xylose-specific sugar transporter, xylulokinase, and isobutanol pathway enzymes in conjunction with the deletions of PHO13 and GRE3 resulted in an engineered strain that is capable of producing isobutanol at a titer of 48.4 ± 2.0 mg/L (yield of 7.0 mg/g d-xylose). This is a 36-fold increase from the previous report by Brat and Boles and, to our knowledge, is the highest isobutanol yield from d-xylose in a microbial system. We hope that our work will set the stage for an economic route for the production of advanced biofuel isobutanol and enable efficient utilization of lignocellulosic biomass.
Risk factors for severe systemic sting reactions in wasp (Vespula spp.) and honeybee (Apis mellifera) venom allergic patients
Authors: Fehr Danielle , Micaletto Sara , Moehr Thomas , Schmid-Grendelmeier Peter
Published: October 2019

Background

Hymenoptera stings are a major cause of anaphylaxis. Various risk factors are discussed in literature. This study aims to investigate potential risk factors for severe sting reactions in wasp (Vespula spp.) and honeybee (Apis mellifera) venom allergic patients and analyses the correlation between diagnostic test results and the severity of the allergic reaction.

Methods

480 patients suffering from wasp or honeybee venom allergy were included in this retrospective case series. Only individuals allergic to Vespula spp. but not to other vespids such as Polistes were considered. The severity of their systemic field sting reaction was analysed with regard to the amount of specific IgE antibodies to whole venom extracts and to major allergens of honeybee and/or wasp venom. Furthermore, the following potential risk factors for severe sting reactions were examined: age, sex, latency time, skin symptoms, baseline serum tryptase levels and the concentration of venom inducing a positive intracutaneous test.

Results

The two following indicators for severe systemic sting reactions in honeybee and wasp venom allergic patients have been identified: a short latency time and the absence of skin symptoms. The patient’s age and baseline serum tryptase levels have been found to positively correlate with the grade of the sting reaction only in individuals allergic to wasp venom. No correlation could be found between the degree of sensitisation and the severity of the allergic reaction. Neither the amount of specific IgE antibodies to whole venom extracts nor to major allergens were significantly associated with the severity of the sting reaction.

Conclusion

The clinical history is essential for the allergological workup and therapeutic decision on Hymenoptera venom allergies. A short latency time and the absence of skin symptoms are indicators for severe systemic sting reactions, followed by the patient’s age and baseline serum tryptase levels.
Management of severe asthma exacerbation: guidelines from the Société Française de Médecine d’Urgence, the Société de Réanimation de Langue Française and the French Group for Pediatric Intensive Care and Emergencies
Authors: Le Conte Philippe , Terzi Nicolas , Mortamet Guillaume , Abroug Fekri , Carteaux Guillaume , Charasse Céline , Chauvin Anthony , Combes Xavier , Dauger Stéphane , Demoule Alexandre , Desmettre Thibaut , Ehrmann Stephan , Gaillard-Le Roux Bénédicte , Hamel Valérie , Jung Boris , Kepka Sabrina , L’Her Erwan , Martinez Mikaël , Milési Christophe , Morawiec Élise , Oberlin Mathieu , Plaisance Patrick , Pouyau Robin , Raherison Chantal , Ray Patrick , Schmidt Mathieu , Thille Arnaud W. , Truchot Jennifer , Valdenaire Guillaume , Vaux Julien , Viglino Damien , Voiriot Guillaume , Vrignaud Bénédicte , Jean Sandrine , Mariotte Eric , Claret Pierre-Géraud
Published: October 2019

Background

The French Emergency Medicine Society, the French Intensive Care Society and the Pediatric Intensive Care and Emergency Medicine French-Speaking Group edited guidelines on severe asthma exacerbation (SAE) in adult and pediatric patients.

Results

The guidelines were related to 5 areas: diagnosis, pharmacological treatment, oxygen therapy and ventilation, patients triage, specific considerations regarding pregnant women. The literature analysis and formulation of the guidelines were conducted according to the Grade of Recommendation Assessment, Development and Evaluation methodology. An extensive literature research was conducted based on publications indexed in PubMed™ and Cochrane™ databases. Of the 21 formalized guidelines, 4 had a high level of evidence (GRADE 1+/−) and 7 a low level of evidence (GRADE 2+/−). The GRADE method was inapplicable to 10 guidelines, which resulted in expert opinions. A strong agreement was reached for all guidelines.

Conclusion

The conjunct work of 36 experts from 3 scientific societies resulted in 21 formalized recommendations to help improving the emergency and intensive care management of adult and pediatric patients with SAE.
Endoscopic third ventriculostomy success score in predicting short-term outcome in 68 children with hydrocephalus in a resource-limited tertiary centre in sub-Saharan Africa
Authors: Morgan E. , Bankole O. B. , Mofikoya B. O. , Kanu O. O. , Ojo O. A. , Jeje E. A. , Poluyi E. O.
Published: October 2019

Background

Endoscopic third ventriculostomy (ETV) is becoming a popular option of treatment in carefully selected patients with hydrocephalus (Drake et al., Childs Nerv Syst 25:467-472, 2009). The success or possible outcome of its application in treating hydrocephalus can be predicted by employing a preoperative scoring system. An example of such a system is the endoscopic third ventriculostomy success score (ETVSS). It could form a basis for decision-making and prognostication. This study aimed to evaluate ETVSS as a preoperative predictive tool in children with hydrocephalus who satisfy the inclusion criteria for the option of ETV procedure as treatment modality.

Methodology

This is a prospective hospital-based study of 68 children under 2 years of age that presented at the Lagos University Teaching Hospital (LUTH) out of 161 children with hydrocephalus from November 2014 to April 2016. The predicted ETVSS was calculated by the addition of patients’ age, presumed aetiology and prior shunting. These children were stratified into three groups according to ETVSS as higher score predicts better ETV outcome and vice versa. They were followed up for 6 months to determine the success rate of ETV.

Results

The age of the study population ranged from 0 to 24 months with a mean age of 5.52 ± 5.48 months. 69.1% of these patients were male and 30.9% were female with a male to female ratio of 2.2:1. The mean predicted ETVSS (48.82 ± 19.20%) and actual ETV success score (56.20 ± 15.10%) using the ANOVA were significantly related (p value < 0.05).

Conclusion

This study concluded that the early outcome of ETV in children below 2 years of age with hydrocephalus is directly related to the preoperative ETVSS.
Bordering on the bipolar: a review of criteria for ICD-11 and DSM-5 persistent mood disorders
Authors: Luty Jason
Published: October 2019

The principal manuals for psychiatric diagnosis have recently been updated (ICD-11 was released in June 2018 and DSM-5 was published in 2013). A common diagnostic quandary is the classification of people with chronic low mood, especially those with repeated self-harm (‘emotionally unstable’ or ‘borderline’ personality disorder). There has been a great interest in use of type II bipolar affective disorder (‘bipolar II disorder’) as a less pejorative diagnostic alternative to ‘personality disorder’, despite the radically different treatment options for these disorders. DSM-5 (but not ICD-11) clearly distinguishes between borderline personality disorder and bipolar II disorder, indicating that intense emotional experiences (such as anger, panic or despair; irritability; anxiety) should persist for only a few hours in people with a personality disorder. Both manuals now use the term ‘borderline personality disorder’ rather than ‘emotionally unstable personality disorder’. The diagnostic criteria for cyclothymic disorder remain confusing.

LEARNING OBJECTIVES

After reading this article you will be able to:

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appreciate the key differences in diagnostic classification between persistent mood disorders: bipolar II disorder, borderline personality disorder and dysthymia

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be aware of the modest differences between ICD-10, ICD-11 and DSM-5 in diagnostic criteria for these disorders

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appreciate that intense emotional experiences need persist for only a few hours to meet criteria for DSM-5 borderline personality disorder and that persistent emotional dysregulation (e.g. irritability, impulsiveness, disinhibition) for a few days meets criteria for DSM-5 bipolar II disorder.
Membrane trafficking as an active regulator of constitutively secreted cytokines
Authors: Revelo Natalia H. , ter Beest Martin , van den Bogaart Geert
Published: October 2019

Immune-cell activation by inflammatory stimuli triggers the transcription and translation of large amounts of cytokines. The transport of newly synthesized cytokines to the plasma membrane by vesicular trafficking can be rate-limiting for the production of these cytokines, and immune cells upregulate their exocytic machinery concomitantly with increased cytokine expression in order to cope with the increasing demand for trafficking. Whereas it is logical that trafficking is rate-limiting for regulated secretion where an intracellular pool of molecules is waiting to be released, the reason for this is not obvious for constitutively secreted cytokines, such as interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-α (TNF-α). These constitutively secreted cytokines are primarily regulated at the transcriptional and/or translational level but mounting evidence presented here shows that cells might also increase or decrease the rate of post-Golgi cytokine trafficking to modulate their production. Therefore, in this Hypothesis, we ask the question: why is there a need to limit the trafficking of constitutively secreted cytokines? We propose a model where cells monitor and adjust their production rate of cytokines by sensing the intracellular level of cytokines while they are in transit to the plasma membrane. This self-regulation of cytokine production could prevent an overshooting response of acute-phase cytokines, such as IL-6, IL-12 and TNF-α, upon acute infection.
Tackling the Tibetan Plateau in a down suit: insights into thermoregulation by bar-headed geese during migration
Authors: Parr Nicole , Bishop Charles M. , Batbayar Nyambayar , Butler Patrick J. , Chua Beverly , Milsom William K. , Scott Graham R. , Hawkes Lucy A.
Published: October 2019

Birds migrating through extreme environments can experience a range of challenges while meeting the demands of flight, including highly variable ambient temperatures, humidity and oxygen levels. However, there has been limited research into avian thermoregulation during migration in extreme environments. This study aimed to investigate the effect of flight performance and high altitude on body temperature (Tb) of free-flying bar-headed geese (Anser indicus), a species that completes a high-altitude trans-Himalayan migration through very cold, hypoxic environments. We measured abdominal Tb, along with altitude (via changes in barometric pressure), heart rate and body acceleration of bar-headed geese during their migration across the Tibetan Plateau. Bar-headed geese vary the circadian rhythm of Tb in response to migration, with peak daily Tb during daytime hours outside of migration but early in the morning or overnight during migration, reflecting changes in body acceleration. However, during flight, changes in Tb were not consistent with changes in flight performance (as measured by heart rate or rate of ascent) or altitude. Overall, our results suggest that bar-headed geese are able to thermoregulate during high-altitude migration, maintaining Tb within a relatively narrow range despite appreciable variation in flight intensity and environmental conditions.
Frequency of urinary tract infection and antibiotic sensitivity of uropathogens in patients with diabetes
Authors: Zubair Kaleem Ullah , Shah Abdul Haleem , Fawwad Asher , Sabir Rubina , Butt Anum
Published: October 2019

Objective: To determine the frequency of urinary tract infections and antibiotic sensitivity among patients with diabetes.

Methods: This observational study was carried out in Microbiology Department of Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University from April 2015 to June 2016. All patients with diabetes having symptoms of UTI attending out patients department of BIDE were analyzed. All samples received in the laboratory were processed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Antimicrobial susceptibility pattern was determined by disc diffusion method.

Results: A total number of 199 urine specimens, frequency of UTI were 24 (12.06%) in male and 175 (87.94%) in female. UTIs were highly found in (age group 51-60) 70 (35.18%). Escherichia coli was the most frequent pathogen (71%), followed by Klebsiellapneumoniae (7.48%), Proteus mirabilis (1.87%), Staphylococcus aureus (9.35%), Candida (5.61%) and Candidaalbicans were (2.80%). Majority of gram negative uropathogens were shown high sensitivity towards Imipenem and Piperacillin / Tazobactam followed by Nitrofurantion, Ceftriaxone, Levofloxacin, Ofloxacine, Ciprofloxacin, Norfloxacin, Cefixime, Nalidixic acid and Cephradine. Gram positive was most sensitive to Nitrofurantionand Vancomycin followed by Piperacillin / Tazobactam, Imipenem, Cephradine, Ceftriaxone, Norfloxacin and Cefixime.

Conclusion: We observed the higher frequency of UTIs in female as compared to male participants due to poor hygiene. E.coli was the most frequent pathogen responsible for UTI in patients with diabetes, followed by Staphylococcus aureus.

doi: https://doi.org/10.12669/pjms.35.6.115

How to cite this:Zubair KU, Shah AH, Fawwad A, Sabir R, Butt A. Frequency of urinary tract infection and antibiotic sensitivity of uropathogens in patients with diabetes . Pak J Med Sci. 2019;35(6):1664-1668. doi: https://doi.org/10.12669/pjms.35.6.115

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